Infectious Disease Practitioner

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

Seroprevalence surveys suggest that, from the beginning of the pandemic to 2022, more than a third of the global population had been infected with SARS-CoV-2. As large numbers of people continue to be infected, the efficacy and duration of natural immunity, in terms of protection against SARS-CoV-2 reinfections and severe disease, are of crucial significance. The virus’s epidemiologic trajectory will be influenced by the trends in vaccine-induced and hybrid immunity.

Omicron’s immune evasion

Cases of SARS-CoV-2 reinfection are increasing around the world. According to data from the U.K. Health Security Agency, 650,000 people in England have been infected twice, and most of them were reinfected in the past 2 months. Before mid-November 2021, reinfections accounted for about 1% of reported cases, but the rate has now increased to around 10%. The reinfection risk was 16 times higher between mid-December 2021 and early January 2022. Experts believe that this spike in reinfections is related to the spread of Omicron, which overtook Delta as the dominant variant. Nonetheless, other aspects should also be considered.

Omicron’s greater propensity to spread is not unrelated to its ability to evade the body’s immune defenses. This aspect was raised in a letter recently published in the New England Journal of Medicine. The authors reported that the effectiveness of previous infection in preventing reinfection against the Alpha, Beta, and Delta variants was around 90%, but it was only 56% against Omicron.
 

Natural immunity

Natural immunity showed roughly similar effectiveness regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant. The risk of hospitalization and death was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections, compared with immunization with two doses of an mRNA vaccine, but the data are not fully consistent.

Natural immunity seems to be relatively long-lasting. Data from Denmark and Austria show no evidence that protection against reinfections wanes after 6 months. Some investigations indicate that protection against reinfection is lowest 4-5 months after initial infection and increases thereafter, a finding that might hypothetically be explained by persistent viral shedding; that is, misclassification of prolonged SARS-CoV-2 infections as reinfections. While no comparison was made against information pertaining to unvaccinated, not previously-infected individuals, preliminary data from Israel suggest that protection from reinfection can decrease from 6 to more than 12 months after the first SARS-CoV-2 infection. Taken together, epidemiologic studies indicate that protection against reinfections by natural immunity lasts over 1 year with only moderate, if any, decline over this period. Among older individuals, immunocompromised patients, and those with certain comorbidities or exposure risk (for example, health care workers), rates of reinfection may be higher. It is plausible that reinfection risk may be a function of exposure risk.

There is accumulating evidence that reinfections may be significantly less severe than primary infections with SARS-CoV-2. Reduced clinical severity of SARS-CoV-2 reinfections naturally also makes sense from a biologic point of view, inasmuch as a previously primed immune system should be better prepared for a rechallenge with this virus.
 

Vaccine-induced immunity

The short-term (<4 months) efficacy of mRNA vaccines against SARS-CoV-2 is high and varies from 94.1% (Moderna) to 95% (BioNTech/Pfizer). This has been confirmed by randomized controlled trials and was subsequently confirmed in effectiveness studies in real-world settings. Waning efficacy was observed with respect to protection against SARS-CoV-2 infections (for example, only approximately 20% after about half a year in Qatar), whereas protection against severe disease was either sustained or showed only a moderate decline.

In individuals who received two doses of the BioNTech/Pfizer vaccine at least 5 months earlier, an additional vaccine dose, a so-called booster, significantly lowered mortality and severe illness. These findings suggest that the booster restored and probably exceeded the initial short-term efficacy of the initial vaccination.

Data are still emerging regarding the efficacy of boosters against the Omicron variants. Preliminary data suggest a far lower ability to restore protection from infection and vaccination. However, fatalities and hospitalizations remain low.
 

Natural immunity vs. vaccine-induced immunity

Comparisons of natural immunity with vaccine-induced immunity are complicated by a series of biases and by combinations of biases – for example, the biases of comparisons between infected and uninfected, plus the biases of comparisons between vaccinated and nonvaccinated, with strong potential selection biases and confounding. Of particular note, the proportion of people previously infected and/or vaccinated may influence estimates of effectiveness. Regarding this point, one study compared unvaccinated patients with a prior SARS-CoV-2 infection and vaccinated individuals followed up from a week after the second vaccine dose onward versus a group of unvaccinated, not previously infected individuals. The findings showed that, compared with unvaccinated, not previously infected individuals, the natural immunity group and the vaccinated group had similar protection of 94.8% and 92.8% against infection, of 94.1% and 94.2% against hospitalization, and of 96.4% and 94.4% against severe illness, respectively.

Hybrid immunity

The combination of a previous SARS-CoV-2 infection and a respective vaccination is called hybrid immunity. This combination seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue.

Data from Israel showed that, when the time since the last immunity-conferring event (either primary infection or vaccination) was the same, the rates of SARS-CoV-2 infections were similar in the following groups: individuals who had a previous infection and no vaccination, individuals who had an infection and were then vaccinated with a single dose after at least 3 months, and individuals who were vaccinated (two doses) and then infected. Severe disease was relatively rare overall.

Data on the efficacy of hybrid immunity point in the direction of hybrid immunity being superior, as compared with either vaccine-induced (without a booster) immunity or natural immunity alone. Timing and mode of vaccination of previously infected individuals to achieve optimal hybrid immunity are central questions that remain to be addressed in future studies.

Given that vaccination rates are continuously increasing and that, by the beginning of 2022, perhaps half or more of the global population had already been infected with SARS-CoV-2, with the vast majority of this group not being officially detected, it would appear logical that future infection waves, even with highly transmissible variants of SARS-CoV-2, may be limited with respect to their maximum potential health burden. The advent of Omicron suggests that massive surges can occur even in populations with extremely high rates of previous vaccination and variable rates of prior infections. However, even then, the accompanying burden of hospitalizations and deaths is far less than what was seen in 2020 and 2021. One may argue that the pandemic has already transitioned to the endemic phase and that Omicron is an endemic wave occurring in the setting of already widespread population immunity.

A version of this article first appeared on Medscape.com.

Seroprevalence surveys suggest that, from the beginning of the pandemic to 2022, more than a third of the global population had been infected with SARS-CoV-2. As large numbers of people continue to be infected, the efficacy and duration of natural immunity, in terms of protection against SARS-CoV-2 reinfections and severe disease, are of crucial significance. The virus’s epidemiologic trajectory will be influenced by the trends in vaccine-induced and hybrid immunity.

Omicron’s immune evasion

Cases of SARS-CoV-2 reinfection are increasing around the world. According to data from the U.K. Health Security Agency, 650,000 people in England have been infected twice, and most of them were reinfected in the past 2 months. Before mid-November 2021, reinfections accounted for about 1% of reported cases, but the rate has now increased to around 10%. The reinfection risk was 16 times higher between mid-December 2021 and early January 2022. Experts believe that this spike in reinfections is related to the spread of Omicron, which overtook Delta as the dominant variant. Nonetheless, other aspects should also be considered.

Omicron’s greater propensity to spread is not unrelated to its ability to evade the body’s immune defenses. This aspect was raised in a letter recently published in the New England Journal of Medicine. The authors reported that the effectiveness of previous infection in preventing reinfection against the Alpha, Beta, and Delta variants was around 90%, but it was only 56% against Omicron.
 

Natural immunity

Natural immunity showed roughly similar effectiveness regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant. The risk of hospitalization and death was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections, compared with immunization with two doses of an mRNA vaccine, but the data are not fully consistent.

Natural immunity seems to be relatively long-lasting. Data from Denmark and Austria show no evidence that protection against reinfections wanes after 6 months. Some investigations indicate that protection against reinfection is lowest 4-5 months after initial infection and increases thereafter, a finding that might hypothetically be explained by persistent viral shedding; that is, misclassification of prolonged SARS-CoV-2 infections as reinfections. While no comparison was made against information pertaining to unvaccinated, not previously-infected individuals, preliminary data from Israel suggest that protection from reinfection can decrease from 6 to more than 12 months after the first SARS-CoV-2 infection. Taken together, epidemiologic studies indicate that protection against reinfections by natural immunity lasts over 1 year with only moderate, if any, decline over this period. Among older individuals, immunocompromised patients, and those with certain comorbidities or exposure risk (for example, health care workers), rates of reinfection may be higher. It is plausible that reinfection risk may be a function of exposure risk.

There is accumulating evidence that reinfections may be significantly less severe than primary infections with SARS-CoV-2. Reduced clinical severity of SARS-CoV-2 reinfections naturally also makes sense from a biologic point of view, inasmuch as a previously primed immune system should be better prepared for a rechallenge with this virus.
 

Vaccine-induced immunity

The short-term (<4 months) efficacy of mRNA vaccines against SARS-CoV-2 is high and varies from 94.1% (Moderna) to 95% (BioNTech/Pfizer). This has been confirmed by randomized controlled trials and was subsequently confirmed in effectiveness studies in real-world settings. Waning efficacy was observed with respect to protection against SARS-CoV-2 infections (for example, only approximately 20% after about half a year in Qatar), whereas protection against severe disease was either sustained or showed only a moderate decline.

In individuals who received two doses of the BioNTech/Pfizer vaccine at least 5 months earlier, an additional vaccine dose, a so-called booster, significantly lowered mortality and severe illness. These findings suggest that the booster restored and probably exceeded the initial short-term efficacy of the initial vaccination.

Data are still emerging regarding the efficacy of boosters against the Omicron variants. Preliminary data suggest a far lower ability to restore protection from infection and vaccination. However, fatalities and hospitalizations remain low.
 

Natural immunity vs. vaccine-induced immunity

Comparisons of natural immunity with vaccine-induced immunity are complicated by a series of biases and by combinations of biases – for example, the biases of comparisons between infected and uninfected, plus the biases of comparisons between vaccinated and nonvaccinated, with strong potential selection biases and confounding. Of particular note, the proportion of people previously infected and/or vaccinated may influence estimates of effectiveness. Regarding this point, one study compared unvaccinated patients with a prior SARS-CoV-2 infection and vaccinated individuals followed up from a week after the second vaccine dose onward versus a group of unvaccinated, not previously infected individuals. The findings showed that, compared with unvaccinated, not previously infected individuals, the natural immunity group and the vaccinated group had similar protection of 94.8% and 92.8% against infection, of 94.1% and 94.2% against hospitalization, and of 96.4% and 94.4% against severe illness, respectively.

Hybrid immunity

The combination of a previous SARS-CoV-2 infection and a respective vaccination is called hybrid immunity. This combination seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue.

Data from Israel showed that, when the time since the last immunity-conferring event (either primary infection or vaccination) was the same, the rates of SARS-CoV-2 infections were similar in the following groups: individuals who had a previous infection and no vaccination, individuals who had an infection and were then vaccinated with a single dose after at least 3 months, and individuals who were vaccinated (two doses) and then infected. Severe disease was relatively rare overall.

Data on the efficacy of hybrid immunity point in the direction of hybrid immunity being superior, as compared with either vaccine-induced (without a booster) immunity or natural immunity alone. Timing and mode of vaccination of previously infected individuals to achieve optimal hybrid immunity are central questions that remain to be addressed in future studies.

Given that vaccination rates are continuously increasing and that, by the beginning of 2022, perhaps half or more of the global population had already been infected with SARS-CoV-2, with the vast majority of this group not being officially detected, it would appear logical that future infection waves, even with highly transmissible variants of SARS-CoV-2, may be limited with respect to their maximum potential health burden. The advent of Omicron suggests that massive surges can occur even in populations with extremely high rates of previous vaccination and variable rates of prior infections. However, even then, the accompanying burden of hospitalizations and deaths is far less than what was seen in 2020 and 2021. One may argue that the pandemic has already transitioned to the endemic phase and that Omicron is an endemic wave occurring in the setting of already widespread population immunity.

A version of this article first appeared on Medscape.com.

Seroprevalence surveys suggest that, from the beginning of the pandemic to 2022, more than a third of the global population had been infected with SARS-CoV-2. As large numbers of people continue to be infected, the efficacy and duration of natural immunity, in terms of protection against SARS-CoV-2 reinfections and severe disease, are of crucial significance. The virus’s epidemiologic trajectory will be influenced by the trends in vaccine-induced and hybrid immunity.

Omicron’s immune evasion

Cases of SARS-CoV-2 reinfection are increasing around the world. According to data from the U.K. Health Security Agency, 650,000 people in England have been infected twice, and most of them were reinfected in the past 2 months. Before mid-November 2021, reinfections accounted for about 1% of reported cases, but the rate has now increased to around 10%. The reinfection risk was 16 times higher between mid-December 2021 and early January 2022. Experts believe that this spike in reinfections is related to the spread of Omicron, which overtook Delta as the dominant variant. Nonetheless, other aspects should also be considered.

Omicron’s greater propensity to spread is not unrelated to its ability to evade the body’s immune defenses. This aspect was raised in a letter recently published in the New England Journal of Medicine. The authors reported that the effectiveness of previous infection in preventing reinfection against the Alpha, Beta, and Delta variants was around 90%, but it was only 56% against Omicron.
 

Natural immunity

Natural immunity showed roughly similar effectiveness regarding protection against reinfection across different SARS-CoV-2 variants, with the exception of the Omicron variant. The risk of hospitalization and death was also reduced in SARS-CoV-2 reinfections versus primary infections. Observational studies indicate that natural immunity may offer equal or greater protection against SARS-CoV-2 infections, compared with immunization with two doses of an mRNA vaccine, but the data are not fully consistent.

Natural immunity seems to be relatively long-lasting. Data from Denmark and Austria show no evidence that protection against reinfections wanes after 6 months. Some investigations indicate that protection against reinfection is lowest 4-5 months after initial infection and increases thereafter, a finding that might hypothetically be explained by persistent viral shedding; that is, misclassification of prolonged SARS-CoV-2 infections as reinfections. While no comparison was made against information pertaining to unvaccinated, not previously-infected individuals, preliminary data from Israel suggest that protection from reinfection can decrease from 6 to more than 12 months after the first SARS-CoV-2 infection. Taken together, epidemiologic studies indicate that protection against reinfections by natural immunity lasts over 1 year with only moderate, if any, decline over this period. Among older individuals, immunocompromised patients, and those with certain comorbidities or exposure risk (for example, health care workers), rates of reinfection may be higher. It is plausible that reinfection risk may be a function of exposure risk.

There is accumulating evidence that reinfections may be significantly less severe than primary infections with SARS-CoV-2. Reduced clinical severity of SARS-CoV-2 reinfections naturally also makes sense from a biologic point of view, inasmuch as a previously primed immune system should be better prepared for a rechallenge with this virus.
 

Vaccine-induced immunity

The short-term (<4 months) efficacy of mRNA vaccines against SARS-CoV-2 is high and varies from 94.1% (Moderna) to 95% (BioNTech/Pfizer). This has been confirmed by randomized controlled trials and was subsequently confirmed in effectiveness studies in real-world settings. Waning efficacy was observed with respect to protection against SARS-CoV-2 infections (for example, only approximately 20% after about half a year in Qatar), whereas protection against severe disease was either sustained or showed only a moderate decline.

In individuals who received two doses of the BioNTech/Pfizer vaccine at least 5 months earlier, an additional vaccine dose, a so-called booster, significantly lowered mortality and severe illness. These findings suggest that the booster restored and probably exceeded the initial short-term efficacy of the initial vaccination.

Data are still emerging regarding the efficacy of boosters against the Omicron variants. Preliminary data suggest a far lower ability to restore protection from infection and vaccination. However, fatalities and hospitalizations remain low.
 

Natural immunity vs. vaccine-induced immunity

Comparisons of natural immunity with vaccine-induced immunity are complicated by a series of biases and by combinations of biases – for example, the biases of comparisons between infected and uninfected, plus the biases of comparisons between vaccinated and nonvaccinated, with strong potential selection biases and confounding. Of particular note, the proportion of people previously infected and/or vaccinated may influence estimates of effectiveness. Regarding this point, one study compared unvaccinated patients with a prior SARS-CoV-2 infection and vaccinated individuals followed up from a week after the second vaccine dose onward versus a group of unvaccinated, not previously infected individuals. The findings showed that, compared with unvaccinated, not previously infected individuals, the natural immunity group and the vaccinated group had similar protection of 94.8% and 92.8% against infection, of 94.1% and 94.2% against hospitalization, and of 96.4% and 94.4% against severe illness, respectively.

Hybrid immunity

The combination of a previous SARS-CoV-2 infection and a respective vaccination is called hybrid immunity. This combination seems to confer the greatest protection against SARS-CoV-2 infections, but several knowledge gaps remain regarding this issue.

Data from Israel showed that, when the time since the last immunity-conferring event (either primary infection or vaccination) was the same, the rates of SARS-CoV-2 infections were similar in the following groups: individuals who had a previous infection and no vaccination, individuals who had an infection and were then vaccinated with a single dose after at least 3 months, and individuals who were vaccinated (two doses) and then infected. Severe disease was relatively rare overall.

Data on the efficacy of hybrid immunity point in the direction of hybrid immunity being superior, as compared with either vaccine-induced (without a booster) immunity or natural immunity alone. Timing and mode of vaccination of previously infected individuals to achieve optimal hybrid immunity are central questions that remain to be addressed in future studies.

Given that vaccination rates are continuously increasing and that, by the beginning of 2022, perhaps half or more of the global population had already been infected with SARS-CoV-2, with the vast majority of this group not being officially detected, it would appear logical that future infection waves, even with highly transmissible variants of SARS-CoV-2, may be limited with respect to their maximum potential health burden. The advent of Omicron suggests that massive surges can occur even in populations with extremely high rates of previous vaccination and variable rates of prior infections. However, even then, the accompanying burden of hospitalizations and deaths is far less than what was seen in 2020 and 2021. One may argue that the pandemic has already transitioned to the endemic phase and that Omicron is an endemic wave occurring in the setting of already widespread population immunity.

A version of this article first appeared on Medscape.com.

Note: In this article, “women” refers to ciswomen – those who identify as women and were assigned female sex at birth. Menopause also affects transmen and nonbinary people, but published research on the menopause experience has included only ciswomen participants.

Gina Brown was boarding an early morning flight in 2016 when suddenly she started to overheat. “As soon as I stepped on the plane, I immediately was drenched in sweat,” she said. Not knowing what to do, she stood still until a fellow female passenger noticed her alarm and asked a flight attendant to grab her a cup of ice. “Is this the first time this has happened to you?” the woman asked, and Ms. Brown nodded. “It’s called a hot flash,” the woman continued, “and you’re going to be okay.”

As soon as Ms. Brown returned from her trip, she visited her doctor for blood work and learned that her hormone levels were decreasing. “I knew something was going on, but [my provider and I] didn’t have a conversation about menopause,” she said. Ms. Brown, who is 56 years old, has been living with HIV for nearly 28 years, and is part of a growing group of women with HIV now entering menopause.

In 1996, a person diagnosed with HIV at 20 years of age could expect to live only to age 39. Because of antiretroviral therapy (ART), an HIV diagnosis is not nearly so dire. Now, someone with HIV who adheres to the ART regimen is estimated to have a lifespan close to that of the general population.

For women with HIV, this means going through menopause. Though this transition can be challenging for any woman, experiencing menopause with HIV adds another level of complication. On top of adhering to daily ART regimens, the woman must also deal with the hormonal changes of menopause and the symptoms that come with it. And the limited research in this area suggests that women with HIV and their clinicians may not be prepared.

“Those of us long-term survivors who have been around for a while never expected to be here, and I don’t think providers or the health care system expected us to be here,” said Vickie A. Lynn, PhD, 56, who has been living with HIV for 37 years and received an AIDS diagnosis in 1991. Her work focuses on health care interventions for people with HIV. “So now that we’re here, I don’t know that we have enough information or research to inform some of our treatment options.” Instead, these women are met with a series of unknowns due to limited studies and conflicting findings.
 

Earlier menopause?

The onset of menopause can be difficult to determine in women living with HIV, said Sara Looby, PhD, ANP-BC, a researcher at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Her research focuses on metabolic disorders, including bone loss, cardiovascular disease risk, and menopause in women living with HIV. This population is at an increased risk for amenorrhea, due to both behavioral and clinical factors, and sometimes this amenorrhea is mistakenly assumed to be menopause, she explained. A history of smoking, low weight, methadone use, or use of other psychotropic medications are common in women with HIV and can lead to missed periods. Some factors specific to HIV – including a low CD4 count and a history of an AIDS diagnosis – have also been linked to amenorrhea.

This is likely why research studies on the age of onset of menopause with women with HIV can reach conflicting conclusions. Some studies suggest that women with HIV tend to go through menopause 3-5 years earlier than women without HIV. Other studies suggest no difference in the age of onset in menopause between women living with and without HIV. But how menopause status has been accessed can vary from study to study, Dr. Looby said. Future research needs to consider participants’ complete menstrual and reproductive history, as well as relevant medical, social, and behavioral factors, she added, so that the findings are reliably capturing the age of onset of menopause rather than amenorrhea from other causes.

If menopause does occur earlier in women with HIV, there could be additional health implications. Estrogen regulates bone mass, and some research suggests the hormone may be cardioprotective. Estrogen is also thought to increase production of the neurotransmitter serotonin, which could affect mood and cognition. Women with HIV are already at higher risk for bone loss, cardiovascular disease, and depressed mood compared to women without HIV, Dr. Looby said, and as estrogen levels fall during menopause, these conditions may be deleteriously affected.

“If it is determined that women with HIV experience menopause at an earlier age, maybe early to mid-40s instead of 51 and older, they may be at increased risk for cardiovascular and bone conditions as well as mood symptoms associated with estrogen loss at an earlier age than women without HIV, which could be highly detrimental to their physical and mental health,” Dr. Looby said.
 

More frequent and severe menopausal symptoms?

Women with HIV may not only go through menopause earlier than women without HIV, but their symptoms may also be more frequent and more severe. In a 2017 study of both HIV-positive and HIV-negative Nigerian women, participants with HIV had more menopause symptoms overall and were three times as likely to report severe symptoms compared to women without HIV. A 2005 study conducted in New York found HIV-positive women were 24% more likely to report menopause symptoms compared to HIV-negative women in the study.

Looby’s own research has also found a similar pattern. In a study comparing 33 women with HIV to 33 women without HIV – all were close to menopause and matched for age, race, body mass index, and menstrual patterns – women with HIV reported more severe hot flashes and more days with hot flashes. These women also reported that their hot flashes interfered to a much greater degree with daily activities and quality of life compared to participants without HIV.

But studies of women with HIV who are entering menopause are rare, and most include only small numbers of women. As a result, many women with HIV do not know what to expect entering menopause. “I always say, I wish somebody would do some real research on HIV and menopause, because I want to know if it is worse for us or if it is the same,” said Ms. Brown, who works as the director of strategic partnership and community engagement at the Southern Aids Coalition in Powder Springs, Ga. “I would think it’s worse for me.”

More frequent and severe symptoms can have downstream effects, with some evidence suggesting that women with HIV who experience severe menopause symptoms are less likely to stick to their ART regimen. “There’s a clear picture emerging that menopausal symptoms in this group really matter,” said Shema Tariq, PhD, FRCP, an HIV physician-scientist at the University College London Institute for Global Health in England. “They really impact women’s well-being, as well as impacting their ability to look after their long-term condition.”
 

Providers wary of treating menopause symptoms in women with HIV

The little research we do have about women with HIV experiencing menopause suggests that this population could greatly benefit from treatment prescribed in women without HIV for menopause symptoms and conditions, including hormone replacement therapy (HRT). Women with HIV regularly experience night sweats and hot flashes during the menopause transition and may have more severe symptoms than women not living with the virus. If women with HIV also frequently enter early menopause (entering menopause before the age of 45), then this group meets two indications for hormone replacement therapy.

Despite the potential benefits of HRT in this population, some studies suggest this intervention is underutilized. In Dr. Tariq’s Positive Transitions through Menopause (PRIME) study, which explores how menopause affects more than 800 women living with HIV, only 8% of respondents reported using HRT. In a Canadian study that has not yet gone through peer review, 11.8% of perimenopausal and postmenopausal women reported ever using HRT, about half the rate of women in North America without HIV.

Provider discomfort with managing menopause-related care in women with HIV is one reason for such low HRT use in this population, Dr. Tariq said. In a survey of 88 general practitioners in the United Kingdom, nearly all (> 95%) respondents said they were comfortable managing menopause in a general population, but just 46% said they felt comfortable managing menopause in women with HIV. Their top concerns included the potential for drug-to-drug interactions between ART and HRT, missing an HIV-related diagnosis, and risks of menopausal hormone therapy in HIV. Nearly half of respondents (46%) said only specialists should be providing menopause-related care for women with HIV.

But specialists may also feel conflicted about managing menopause-related care in women with HIV, said Dr. Tariq. “If you’re looking at people who manage HIV, you’re looking primarily at infectious disease physicians and HIV physicians. We’re not trained as gynecologists. We’re not used to prescribing HRT,” she said. “And the problem is gynecologists aren’t used to managing HIV. They get nervous about prescribing anything when they see antiretroviral medication because all that people think of is a drug-drug interaction.”

This leaves women with HIV seeking care and treatment for menopause in a difficult situation, where they are “just being ping-ponged around between different health care providers,” said Susan Cole-Haley, 53, an HIV-activist in London who has been living with the virus for 23 years. “So many women with HIV have multiple health conditions and multiple health care providers, which can just make it really problematic and really exhausting in terms of getting help.”
 

Many unknowns

Providers may also be uncomfortable with prescribing hormone therapy because of alarming research in the early 2000s, which found that hormone replacement therapy increased the risk of breast cancer and cardiovascular disease. Later analyses have found no increased cardiovascular disease risk in women who were younger than 60 or were less than 10 years beyond the onset of menopause. Still, the “media frenzy” around the initial findings “has put off a whole load of patients and a whole load of clinicians from even thinking of HRT,” Dr. Tariq said.

Providers may be even more hesitant because people with HIV already have a higher risk for heart disease, due to behaviors such as smoking and HIV-specific factors. (Research has yet to tease out whether these cardiovascular effects are a result of the virus, a result of the antiretroviral therapy, or a result of both factors.) In addition, there have been no prospective studies looking directly at the efficacy and safety of hormone replacement therapy in women with HIV, so providers generally rely on the guidelines for the use of menopausal hormone therapy for women without HIV. While researchers from Canada and the United Kingdom have compiled recommendations for HRT in women with HIV, there is great need for a large-scale clinical trial to establish consistent guidelines for the use of HRT for women with HIV globally, Dr. Looby said.

There are also hormonal preparations and drug-to-drug interactions to consider, though none of the interactions identified so far rise to the level of contraindications. Because of how the liver metabolizes ART and HRT, hormone doses may need to be adjusted, or perhaps administered transdermally via a patch versus a pill form. (Estrogen delivered via skin patch may have reduced cardiovascular disease risk compared to other methods of delivery, some studies in women without HIV suggest.) These expected interactions are based on data from contraceptives, noted Elizabeth King, MD, whose research at the Women’s Health Research Institute at BC Women’s Hospital in Vancouver, B.C., focuses on menopause and HIV. Studies have not been done on drug-drug interactions between ART and HRT specifically, she said, and formulations for HRT are a bit different from contraceptives.

While these unknowns do need to be discussed in shared decision-making around starting HRT in women with HIV, they should not dissuade providers from considering the treatment, Dr. King said. “If women are having extremely troublesome symptoms, then withholding therapy that is potentially beneficial because of worries about some of the things we do not know – I don’t know if that is any better,” she said.

Many women with HIV may not want to start HRT – as was the case for Dr. Lynn. “I’ve taken a lot of medication in my time, and I really try to avoid it as much as possible,” she said. Uncertainties around drug interactions were the main concern for Dawn Averitt, 53, founder of the Well Project, an HIV nonprofit focused on women and girls. Ms. Averitt has lived with HIV for 34 years. “What if some of the things that I’m dealing with could be managed by HRT?” she said. “Or what if taking it exacerbates problems in a way that nobody knows to look for?” In this case, providers may work with patients to discuss nonhormonal treatment options for menopause symptom management.

While some women with HIV may not want HRT, “It’s important that women have that option, and from what we are seeing right now, not a lot of women are even being offered the therapy,” Dr. King said.

There are other nonhormonal treatments available for managing menopause symptoms, including selective serotonin reuptake inhibitors (SSRIs) as well as nonmedicinal interventions such as cognitive behavioral therapy, but these also have not been studied specifically in women with HIV.
 

The path forward

Dr. Tariq and Dr. Looby agreed the next step in expanding our knowledge around HIV and menopause should be to better engage women with HIV in research and clinical care around their experience with menopause. This includes studies on the symptoms they regularly experience and how these symptoms affect their quality of life, including their physical, psychological, cognitive, and social health. These studies could also help researchers and clinicians understand what these women with HIV want for their menopause care, whether that be medication, psychotherapy, and/or peer support groups. These interventions, whether pharmaceutical based or not, can then be assessed based on outcomes in women with HIV, Dr. Tariq noted.

Another important factor is increasing education, on both the patient and provider side, Dr. Looby said. Many women may not know what menopause is, what symptoms look like, and how these hormonal changes can affect their health. If providers keep an open dialogue with female patients around menopause throughout their adult care, that can better prepare women for the menopause transition and alert them to common symptoms they may experience. There also is a great need for provider education, Dr. Looby added. Infectious disease specialists may need further education on menopause management, while women’s health specialists may need additional training for managing care for patients with HIV. Ideally, this information could be shared among a team of providers, including infectious disease, primary care, and women’s health specialists, so that clinicians can collaborate in prescribing treatment for women with HIV, Dr. Looby said.

Lastly, there needs to be more research funding allocated toward answering questions related to menopause and HIV, including the age of onset of menopause in women with HIV, the severity of symptoms, how HIV may influence the menopause transition and vice versa, and regarding the effectiveness of treatment – pharmaceutical and nonpharmaceutical – for women with HIV going through the menopause transition. “If we don’t have funding for these studies, then we won’t have answers to establish clinical care guidelines necessary to support the health, well-being, and quality of life of women with HIV,” Dr. Looby said.

And the number of women living with HIV entering menopause is expected to keep growing, Dr. King added. “It was only a couple of decades ago when women were being told they wouldn’t even live to experience menopause, and now we are at a point where this is the highest proportion of menopausal women ever that we have seen in our HIV clinics,” she said. “It speaks to the success of antiretrovirals,” Dr. King acknowledged, but that also means identifying new challenges and addressing recognized gaps in care.

“We are charting a new course, in some ways,” she added. “There is a lot of work to be done.”

A version of this article first appeared on Medscape.com.

Note: In this article, “women” refers to ciswomen – those who identify as women and were assigned female sex at birth. Menopause also affects transmen and nonbinary people, but published research on the menopause experience has included only ciswomen participants.

Gina Brown was boarding an early morning flight in 2016 when suddenly she started to overheat. “As soon as I stepped on the plane, I immediately was drenched in sweat,” she said. Not knowing what to do, she stood still until a fellow female passenger noticed her alarm and asked a flight attendant to grab her a cup of ice. “Is this the first time this has happened to you?” the woman asked, and Ms. Brown nodded. “It’s called a hot flash,” the woman continued, “and you’re going to be okay.”

As soon as Ms. Brown returned from her trip, she visited her doctor for blood work and learned that her hormone levels were decreasing. “I knew something was going on, but [my provider and I] didn’t have a conversation about menopause,” she said. Ms. Brown, who is 56 years old, has been living with HIV for nearly 28 years, and is part of a growing group of women with HIV now entering menopause.

In 1996, a person diagnosed with HIV at 20 years of age could expect to live only to age 39. Because of antiretroviral therapy (ART), an HIV diagnosis is not nearly so dire. Now, someone with HIV who adheres to the ART regimen is estimated to have a lifespan close to that of the general population.

For women with HIV, this means going through menopause. Though this transition can be challenging for any woman, experiencing menopause with HIV adds another level of complication. On top of adhering to daily ART regimens, the woman must also deal with the hormonal changes of menopause and the symptoms that come with it. And the limited research in this area suggests that women with HIV and their clinicians may not be prepared.

“Those of us long-term survivors who have been around for a while never expected to be here, and I don’t think providers or the health care system expected us to be here,” said Vickie A. Lynn, PhD, 56, who has been living with HIV for 37 years and received an AIDS diagnosis in 1991. Her work focuses on health care interventions for people with HIV. “So now that we’re here, I don’t know that we have enough information or research to inform some of our treatment options.” Instead, these women are met with a series of unknowns due to limited studies and conflicting findings.
 

Earlier menopause?

The onset of menopause can be difficult to determine in women living with HIV, said Sara Looby, PhD, ANP-BC, a researcher at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Her research focuses on metabolic disorders, including bone loss, cardiovascular disease risk, and menopause in women living with HIV. This population is at an increased risk for amenorrhea, due to both behavioral and clinical factors, and sometimes this amenorrhea is mistakenly assumed to be menopause, she explained. A history of smoking, low weight, methadone use, or use of other psychotropic medications are common in women with HIV and can lead to missed periods. Some factors specific to HIV – including a low CD4 count and a history of an AIDS diagnosis – have also been linked to amenorrhea.

This is likely why research studies on the age of onset of menopause with women with HIV can reach conflicting conclusions. Some studies suggest that women with HIV tend to go through menopause 3-5 years earlier than women without HIV. Other studies suggest no difference in the age of onset in menopause between women living with and without HIV. But how menopause status has been accessed can vary from study to study, Dr. Looby said. Future research needs to consider participants’ complete menstrual and reproductive history, as well as relevant medical, social, and behavioral factors, she added, so that the findings are reliably capturing the age of onset of menopause rather than amenorrhea from other causes.

If menopause does occur earlier in women with HIV, there could be additional health implications. Estrogen regulates bone mass, and some research suggests the hormone may be cardioprotective. Estrogen is also thought to increase production of the neurotransmitter serotonin, which could affect mood and cognition. Women with HIV are already at higher risk for bone loss, cardiovascular disease, and depressed mood compared to women without HIV, Dr. Looby said, and as estrogen levels fall during menopause, these conditions may be deleteriously affected.

“If it is determined that women with HIV experience menopause at an earlier age, maybe early to mid-40s instead of 51 and older, they may be at increased risk for cardiovascular and bone conditions as well as mood symptoms associated with estrogen loss at an earlier age than women without HIV, which could be highly detrimental to their physical and mental health,” Dr. Looby said.
 

More frequent and severe menopausal symptoms?

Women with HIV may not only go through menopause earlier than women without HIV, but their symptoms may also be more frequent and more severe. In a 2017 study of both HIV-positive and HIV-negative Nigerian women, participants with HIV had more menopause symptoms overall and were three times as likely to report severe symptoms compared to women without HIV. A 2005 study conducted in New York found HIV-positive women were 24% more likely to report menopause symptoms compared to HIV-negative women in the study.

Looby’s own research has also found a similar pattern. In a study comparing 33 women with HIV to 33 women without HIV – all were close to menopause and matched for age, race, body mass index, and menstrual patterns – women with HIV reported more severe hot flashes and more days with hot flashes. These women also reported that their hot flashes interfered to a much greater degree with daily activities and quality of life compared to participants without HIV.

But studies of women with HIV who are entering menopause are rare, and most include only small numbers of women. As a result, many women with HIV do not know what to expect entering menopause. “I always say, I wish somebody would do some real research on HIV and menopause, because I want to know if it is worse for us or if it is the same,” said Ms. Brown, who works as the director of strategic partnership and community engagement at the Southern Aids Coalition in Powder Springs, Ga. “I would think it’s worse for me.”

More frequent and severe symptoms can have downstream effects, with some evidence suggesting that women with HIV who experience severe menopause symptoms are less likely to stick to their ART regimen. “There’s a clear picture emerging that menopausal symptoms in this group really matter,” said Shema Tariq, PhD, FRCP, an HIV physician-scientist at the University College London Institute for Global Health in England. “They really impact women’s well-being, as well as impacting their ability to look after their long-term condition.”
 

Providers wary of treating menopause symptoms in women with HIV

The little research we do have about women with HIV experiencing menopause suggests that this population could greatly benefit from treatment prescribed in women without HIV for menopause symptoms and conditions, including hormone replacement therapy (HRT). Women with HIV regularly experience night sweats and hot flashes during the menopause transition and may have more severe symptoms than women not living with the virus. If women with HIV also frequently enter early menopause (entering menopause before the age of 45), then this group meets two indications for hormone replacement therapy.

Despite the potential benefits of HRT in this population, some studies suggest this intervention is underutilized. In Dr. Tariq’s Positive Transitions through Menopause (PRIME) study, which explores how menopause affects more than 800 women living with HIV, only 8% of respondents reported using HRT. In a Canadian study that has not yet gone through peer review, 11.8% of perimenopausal and postmenopausal women reported ever using HRT, about half the rate of women in North America without HIV.

Provider discomfort with managing menopause-related care in women with HIV is one reason for such low HRT use in this population, Dr. Tariq said. In a survey of 88 general practitioners in the United Kingdom, nearly all (> 95%) respondents said they were comfortable managing menopause in a general population, but just 46% said they felt comfortable managing menopause in women with HIV. Their top concerns included the potential for drug-to-drug interactions between ART and HRT, missing an HIV-related diagnosis, and risks of menopausal hormone therapy in HIV. Nearly half of respondents (46%) said only specialists should be providing menopause-related care for women with HIV.

But specialists may also feel conflicted about managing menopause-related care in women with HIV, said Dr. Tariq. “If you’re looking at people who manage HIV, you’re looking primarily at infectious disease physicians and HIV physicians. We’re not trained as gynecologists. We’re not used to prescribing HRT,” she said. “And the problem is gynecologists aren’t used to managing HIV. They get nervous about prescribing anything when they see antiretroviral medication because all that people think of is a drug-drug interaction.”

This leaves women with HIV seeking care and treatment for menopause in a difficult situation, where they are “just being ping-ponged around between different health care providers,” said Susan Cole-Haley, 53, an HIV-activist in London who has been living with the virus for 23 years. “So many women with HIV have multiple health conditions and multiple health care providers, which can just make it really problematic and really exhausting in terms of getting help.”
 

Many unknowns

Providers may also be uncomfortable with prescribing hormone therapy because of alarming research in the early 2000s, which found that hormone replacement therapy increased the risk of breast cancer and cardiovascular disease. Later analyses have found no increased cardiovascular disease risk in women who were younger than 60 or were less than 10 years beyond the onset of menopause. Still, the “media frenzy” around the initial findings “has put off a whole load of patients and a whole load of clinicians from even thinking of HRT,” Dr. Tariq said.

Providers may be even more hesitant because people with HIV already have a higher risk for heart disease, due to behaviors such as smoking and HIV-specific factors. (Research has yet to tease out whether these cardiovascular effects are a result of the virus, a result of the antiretroviral therapy, or a result of both factors.) In addition, there have been no prospective studies looking directly at the efficacy and safety of hormone replacement therapy in women with HIV, so providers generally rely on the guidelines for the use of menopausal hormone therapy for women without HIV. While researchers from Canada and the United Kingdom have compiled recommendations for HRT in women with HIV, there is great need for a large-scale clinical trial to establish consistent guidelines for the use of HRT for women with HIV globally, Dr. Looby said.

There are also hormonal preparations and drug-to-drug interactions to consider, though none of the interactions identified so far rise to the level of contraindications. Because of how the liver metabolizes ART and HRT, hormone doses may need to be adjusted, or perhaps administered transdermally via a patch versus a pill form. (Estrogen delivered via skin patch may have reduced cardiovascular disease risk compared to other methods of delivery, some studies in women without HIV suggest.) These expected interactions are based on data from contraceptives, noted Elizabeth King, MD, whose research at the Women’s Health Research Institute at BC Women’s Hospital in Vancouver, B.C., focuses on menopause and HIV. Studies have not been done on drug-drug interactions between ART and HRT specifically, she said, and formulations for HRT are a bit different from contraceptives.

While these unknowns do need to be discussed in shared decision-making around starting HRT in women with HIV, they should not dissuade providers from considering the treatment, Dr. King said. “If women are having extremely troublesome symptoms, then withholding therapy that is potentially beneficial because of worries about some of the things we do not know – I don’t know if that is any better,” she said.

Many women with HIV may not want to start HRT – as was the case for Dr. Lynn. “I’ve taken a lot of medication in my time, and I really try to avoid it as much as possible,” she said. Uncertainties around drug interactions were the main concern for Dawn Averitt, 53, founder of the Well Project, an HIV nonprofit focused on women and girls. Ms. Averitt has lived with HIV for 34 years. “What if some of the things that I’m dealing with could be managed by HRT?” she said. “Or what if taking it exacerbates problems in a way that nobody knows to look for?” In this case, providers may work with patients to discuss nonhormonal treatment options for menopause symptom management.

While some women with HIV may not want HRT, “It’s important that women have that option, and from what we are seeing right now, not a lot of women are even being offered the therapy,” Dr. King said.

There are other nonhormonal treatments available for managing menopause symptoms, including selective serotonin reuptake inhibitors (SSRIs) as well as nonmedicinal interventions such as cognitive behavioral therapy, but these also have not been studied specifically in women with HIV.
 

The path forward

Dr. Tariq and Dr. Looby agreed the next step in expanding our knowledge around HIV and menopause should be to better engage women with HIV in research and clinical care around their experience with menopause. This includes studies on the symptoms they regularly experience and how these symptoms affect their quality of life, including their physical, psychological, cognitive, and social health. These studies could also help researchers and clinicians understand what these women with HIV want for their menopause care, whether that be medication, psychotherapy, and/or peer support groups. These interventions, whether pharmaceutical based or not, can then be assessed based on outcomes in women with HIV, Dr. Tariq noted.

Another important factor is increasing education, on both the patient and provider side, Dr. Looby said. Many women may not know what menopause is, what symptoms look like, and how these hormonal changes can affect their health. If providers keep an open dialogue with female patients around menopause throughout their adult care, that can better prepare women for the menopause transition and alert them to common symptoms they may experience. There also is a great need for provider education, Dr. Looby added. Infectious disease specialists may need further education on menopause management, while women’s health specialists may need additional training for managing care for patients with HIV. Ideally, this information could be shared among a team of providers, including infectious disease, primary care, and women’s health specialists, so that clinicians can collaborate in prescribing treatment for women with HIV, Dr. Looby said.

Lastly, there needs to be more research funding allocated toward answering questions related to menopause and HIV, including the age of onset of menopause in women with HIV, the severity of symptoms, how HIV may influence the menopause transition and vice versa, and regarding the effectiveness of treatment – pharmaceutical and nonpharmaceutical – for women with HIV going through the menopause transition. “If we don’t have funding for these studies, then we won’t have answers to establish clinical care guidelines necessary to support the health, well-being, and quality of life of women with HIV,” Dr. Looby said.

And the number of women living with HIV entering menopause is expected to keep growing, Dr. King added. “It was only a couple of decades ago when women were being told they wouldn’t even live to experience menopause, and now we are at a point where this is the highest proportion of menopausal women ever that we have seen in our HIV clinics,” she said. “It speaks to the success of antiretrovirals,” Dr. King acknowledged, but that also means identifying new challenges and addressing recognized gaps in care.

“We are charting a new course, in some ways,” she added. “There is a lot of work to be done.”

A version of this article first appeared on Medscape.com.

Note: In this article, “women” refers to ciswomen – those who identify as women and were assigned female sex at birth. Menopause also affects transmen and nonbinary people, but published research on the menopause experience has included only ciswomen participants.

Gina Brown was boarding an early morning flight in 2016 when suddenly she started to overheat. “As soon as I stepped on the plane, I immediately was drenched in sweat,” she said. Not knowing what to do, she stood still until a fellow female passenger noticed her alarm and asked a flight attendant to grab her a cup of ice. “Is this the first time this has happened to you?” the woman asked, and Ms. Brown nodded. “It’s called a hot flash,” the woman continued, “and you’re going to be okay.”

As soon as Ms. Brown returned from her trip, she visited her doctor for blood work and learned that her hormone levels were decreasing. “I knew something was going on, but [my provider and I] didn’t have a conversation about menopause,” she said. Ms. Brown, who is 56 years old, has been living with HIV for nearly 28 years, and is part of a growing group of women with HIV now entering menopause.

In 1996, a person diagnosed with HIV at 20 years of age could expect to live only to age 39. Because of antiretroviral therapy (ART), an HIV diagnosis is not nearly so dire. Now, someone with HIV who adheres to the ART regimen is estimated to have a lifespan close to that of the general population.

For women with HIV, this means going through menopause. Though this transition can be challenging for any woman, experiencing menopause with HIV adds another level of complication. On top of adhering to daily ART regimens, the woman must also deal with the hormonal changes of menopause and the symptoms that come with it. And the limited research in this area suggests that women with HIV and their clinicians may not be prepared.

“Those of us long-term survivors who have been around for a while never expected to be here, and I don’t think providers or the health care system expected us to be here,” said Vickie A. Lynn, PhD, 56, who has been living with HIV for 37 years and received an AIDS diagnosis in 1991. Her work focuses on health care interventions for people with HIV. “So now that we’re here, I don’t know that we have enough information or research to inform some of our treatment options.” Instead, these women are met with a series of unknowns due to limited studies and conflicting findings.
 

Earlier menopause?

The onset of menopause can be difficult to determine in women living with HIV, said Sara Looby, PhD, ANP-BC, a researcher at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. Her research focuses on metabolic disorders, including bone loss, cardiovascular disease risk, and menopause in women living with HIV. This population is at an increased risk for amenorrhea, due to both behavioral and clinical factors, and sometimes this amenorrhea is mistakenly assumed to be menopause, she explained. A history of smoking, low weight, methadone use, or use of other psychotropic medications are common in women with HIV and can lead to missed periods. Some factors specific to HIV – including a low CD4 count and a history of an AIDS diagnosis – have also been linked to amenorrhea.

This is likely why research studies on the age of onset of menopause with women with HIV can reach conflicting conclusions. Some studies suggest that women with HIV tend to go through menopause 3-5 years earlier than women without HIV. Other studies suggest no difference in the age of onset in menopause between women living with and without HIV. But how menopause status has been accessed can vary from study to study, Dr. Looby said. Future research needs to consider participants’ complete menstrual and reproductive history, as well as relevant medical, social, and behavioral factors, she added, so that the findings are reliably capturing the age of onset of menopause rather than amenorrhea from other causes.

If menopause does occur earlier in women with HIV, there could be additional health implications. Estrogen regulates bone mass, and some research suggests the hormone may be cardioprotective. Estrogen is also thought to increase production of the neurotransmitter serotonin, which could affect mood and cognition. Women with HIV are already at higher risk for bone loss, cardiovascular disease, and depressed mood compared to women without HIV, Dr. Looby said, and as estrogen levels fall during menopause, these conditions may be deleteriously affected.

“If it is determined that women with HIV experience menopause at an earlier age, maybe early to mid-40s instead of 51 and older, they may be at increased risk for cardiovascular and bone conditions as well as mood symptoms associated with estrogen loss at an earlier age than women without HIV, which could be highly detrimental to their physical and mental health,” Dr. Looby said.
 

More frequent and severe menopausal symptoms?

Women with HIV may not only go through menopause earlier than women without HIV, but their symptoms may also be more frequent and more severe. In a 2017 study of both HIV-positive and HIV-negative Nigerian women, participants with HIV had more menopause symptoms overall and were three times as likely to report severe symptoms compared to women without HIV. A 2005 study conducted in New York found HIV-positive women were 24% more likely to report menopause symptoms compared to HIV-negative women in the study.

Looby’s own research has also found a similar pattern. In a study comparing 33 women with HIV to 33 women without HIV – all were close to menopause and matched for age, race, body mass index, and menstrual patterns – women with HIV reported more severe hot flashes and more days with hot flashes. These women also reported that their hot flashes interfered to a much greater degree with daily activities and quality of life compared to participants without HIV.

But studies of women with HIV who are entering menopause are rare, and most include only small numbers of women. As a result, many women with HIV do not know what to expect entering menopause. “I always say, I wish somebody would do some real research on HIV and menopause, because I want to know if it is worse for us or if it is the same,” said Ms. Brown, who works as the director of strategic partnership and community engagement at the Southern Aids Coalition in Powder Springs, Ga. “I would think it’s worse for me.”

More frequent and severe symptoms can have downstream effects, with some evidence suggesting that women with HIV who experience severe menopause symptoms are less likely to stick to their ART regimen. “There’s a clear picture emerging that menopausal symptoms in this group really matter,” said Shema Tariq, PhD, FRCP, an HIV physician-scientist at the University College London Institute for Global Health in England. “They really impact women’s well-being, as well as impacting their ability to look after their long-term condition.”
 

Providers wary of treating menopause symptoms in women with HIV

The little research we do have about women with HIV experiencing menopause suggests that this population could greatly benefit from treatment prescribed in women without HIV for menopause symptoms and conditions, including hormone replacement therapy (HRT). Women with HIV regularly experience night sweats and hot flashes during the menopause transition and may have more severe symptoms than women not living with the virus. If women with HIV also frequently enter early menopause (entering menopause before the age of 45), then this group meets two indications for hormone replacement therapy.

Despite the potential benefits of HRT in this population, some studies suggest this intervention is underutilized. In Dr. Tariq’s Positive Transitions through Menopause (PRIME) study, which explores how menopause affects more than 800 women living with HIV, only 8% of respondents reported using HRT. In a Canadian study that has not yet gone through peer review, 11.8% of perimenopausal and postmenopausal women reported ever using HRT, about half the rate of women in North America without HIV.

Provider discomfort with managing menopause-related care in women with HIV is one reason for such low HRT use in this population, Dr. Tariq said. In a survey of 88 general practitioners in the United Kingdom, nearly all (> 95%) respondents said they were comfortable managing menopause in a general population, but just 46% said they felt comfortable managing menopause in women with HIV. Their top concerns included the potential for drug-to-drug interactions between ART and HRT, missing an HIV-related diagnosis, and risks of menopausal hormone therapy in HIV. Nearly half of respondents (46%) said only specialists should be providing menopause-related care for women with HIV.

But specialists may also feel conflicted about managing menopause-related care in women with HIV, said Dr. Tariq. “If you’re looking at people who manage HIV, you’re looking primarily at infectious disease physicians and HIV physicians. We’re not trained as gynecologists. We’re not used to prescribing HRT,” she said. “And the problem is gynecologists aren’t used to managing HIV. They get nervous about prescribing anything when they see antiretroviral medication because all that people think of is a drug-drug interaction.”

This leaves women with HIV seeking care and treatment for menopause in a difficult situation, where they are “just being ping-ponged around between different health care providers,” said Susan Cole-Haley, 53, an HIV-activist in London who has been living with the virus for 23 years. “So many women with HIV have multiple health conditions and multiple health care providers, which can just make it really problematic and really exhausting in terms of getting help.”
 

Many unknowns

Providers may also be uncomfortable with prescribing hormone therapy because of alarming research in the early 2000s, which found that hormone replacement therapy increased the risk of breast cancer and cardiovascular disease. Later analyses have found no increased cardiovascular disease risk in women who were younger than 60 or were less than 10 years beyond the onset of menopause. Still, the “media frenzy” around the initial findings “has put off a whole load of patients and a whole load of clinicians from even thinking of HRT,” Dr. Tariq said.

Providers may be even more hesitant because people with HIV already have a higher risk for heart disease, due to behaviors such as smoking and HIV-specific factors. (Research has yet to tease out whether these cardiovascular effects are a result of the virus, a result of the antiretroviral therapy, or a result of both factors.) In addition, there have been no prospective studies looking directly at the efficacy and safety of hormone replacement therapy in women with HIV, so providers generally rely on the guidelines for the use of menopausal hormone therapy for women without HIV. While researchers from Canada and the United Kingdom have compiled recommendations for HRT in women with HIV, there is great need for a large-scale clinical trial to establish consistent guidelines for the use of HRT for women with HIV globally, Dr. Looby said.

There are also hormonal preparations and drug-to-drug interactions to consider, though none of the interactions identified so far rise to the level of contraindications. Because of how the liver metabolizes ART and HRT, hormone doses may need to be adjusted, or perhaps administered transdermally via a patch versus a pill form. (Estrogen delivered via skin patch may have reduced cardiovascular disease risk compared to other methods of delivery, some studies in women without HIV suggest.) These expected interactions are based on data from contraceptives, noted Elizabeth King, MD, whose research at the Women’s Health Research Institute at BC Women’s Hospital in Vancouver, B.C., focuses on menopause and HIV. Studies have not been done on drug-drug interactions between ART and HRT specifically, she said, and formulations for HRT are a bit different from contraceptives.

While these unknowns do need to be discussed in shared decision-making around starting HRT in women with HIV, they should not dissuade providers from considering the treatment, Dr. King said. “If women are having extremely troublesome symptoms, then withholding therapy that is potentially beneficial because of worries about some of the things we do not know – I don’t know if that is any better,” she said.

Many women with HIV may not want to start HRT – as was the case for Dr. Lynn. “I’ve taken a lot of medication in my time, and I really try to avoid it as much as possible,” she said. Uncertainties around drug interactions were the main concern for Dawn Averitt, 53, founder of the Well Project, an HIV nonprofit focused on women and girls. Ms. Averitt has lived with HIV for 34 years. “What if some of the things that I’m dealing with could be managed by HRT?” she said. “Or what if taking it exacerbates problems in a way that nobody knows to look for?” In this case, providers may work with patients to discuss nonhormonal treatment options for menopause symptom management.

While some women with HIV may not want HRT, “It’s important that women have that option, and from what we are seeing right now, not a lot of women are even being offered the therapy,” Dr. King said.

There are other nonhormonal treatments available for managing menopause symptoms, including selective serotonin reuptake inhibitors (SSRIs) as well as nonmedicinal interventions such as cognitive behavioral therapy, but these also have not been studied specifically in women with HIV.
 

The path forward

Dr. Tariq and Dr. Looby agreed the next step in expanding our knowledge around HIV and menopause should be to better engage women with HIV in research and clinical care around their experience with menopause. This includes studies on the symptoms they regularly experience and how these symptoms affect their quality of life, including their physical, psychological, cognitive, and social health. These studies could also help researchers and clinicians understand what these women with HIV want for their menopause care, whether that be medication, psychotherapy, and/or peer support groups. These interventions, whether pharmaceutical based or not, can then be assessed based on outcomes in women with HIV, Dr. Tariq noted.

Another important factor is increasing education, on both the patient and provider side, Dr. Looby said. Many women may not know what menopause is, what symptoms look like, and how these hormonal changes can affect their health. If providers keep an open dialogue with female patients around menopause throughout their adult care, that can better prepare women for the menopause transition and alert them to common symptoms they may experience. There also is a great need for provider education, Dr. Looby added. Infectious disease specialists may need further education on menopause management, while women’s health specialists may need additional training for managing care for patients with HIV. Ideally, this information could be shared among a team of providers, including infectious disease, primary care, and women’s health specialists, so that clinicians can collaborate in prescribing treatment for women with HIV, Dr. Looby said.

Lastly, there needs to be more research funding allocated toward answering questions related to menopause and HIV, including the age of onset of menopause in women with HIV, the severity of symptoms, how HIV may influence the menopause transition and vice versa, and regarding the effectiveness of treatment – pharmaceutical and nonpharmaceutical – for women with HIV going through the menopause transition. “If we don’t have funding for these studies, then we won’t have answers to establish clinical care guidelines necessary to support the health, well-being, and quality of life of women with HIV,” Dr. Looby said.

And the number of women living with HIV entering menopause is expected to keep growing, Dr. King added. “It was only a couple of decades ago when women were being told they wouldn’t even live to experience menopause, and now we are at a point where this is the highest proportion of menopausal women ever that we have seen in our HIV clinics,” she said. “It speaks to the success of antiretrovirals,” Dr. King acknowledged, but that also means identifying new challenges and addressing recognized gaps in care.

“We are charting a new course, in some ways,” she added. “There is a lot of work to be done.”

A version of this article first appeared on Medscape.com.

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The stress of living through a pandemic may cause brain inflammation even in those uninfected with SARS-CoV-2, a study suggests.

Healthy individuals who tested negative for the virus that causes COVID-19 had elevated levels of inflammatory markers known to be involved in depression, stress, and mental fatigue. The study indicates a possible link between pandemic-associated stressors and neuroimmune responses.

“The most important finding is the evidence of neuroinflammation in noninfected, otherwise healthy participants, which may explain the variety of sickness-behavior-like symptoms experienced by many during the pandemic,” lead author Ludovica Brusaferri, PhD, a postdoctoral research fellow at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization.

The study was published online Feb. 16 in Brain, Behavior, and Immunity.
 

Impact of pandemic stress?

Reports of psychological distress have increased considerably in the United States during the pandemic, including among those not infected with SARS-CoV-2.

To better understand the effects of the pandemic on brain and mental health, the investigators retrospectively analyzed data collected from 57 people who were enrolled as control subjects for unrelated studies before the pandemic began.

They also enrolled 15 people living in Massachusetts during that state’s 2-month lockdown/stay-at-home order from March to May 2020, all of whom had tested negative for COVID-19 antibodies.

The investigators used PET and MRI imaging and blood sample analyses to investigate whether there were any differences in the brains of healthy people before and during the pandemic following the lockdown.

Compared with the control group, the pandemic cohort had elevated levels of 18 kDa translocator protein (TSPO) and myoinositol, inflammatory markers in the brain. Increased TSPO has been associated with depression and suicidal thoughts and elevated myoinositol has been linked to schizophrenia.

Blood levels of two inflammatory markers, interleukin-16 and monocyte chemoattractant protein-1, were also elevated in the pandemic cohort, although to a lesser extent.

TSPO levels were especially high in participants in the pandemic cohort who reported moodiness and mental and physical fatigue, compared with those reporting few or no symptoms.

“These findings provide support to a role for neuroinflammation in stress, an observation that, if replicated, might help guide the development of novel treatments focused on the reduction of brain inflammation,” study author Marco Loggia, PhD, codirector of the Center for Integrative Pain NeuroImaging at Mass General and Harvard Medical School, told this news organization.

Although the data showing increased neuroinflammation were collected when participants were under a stay-at-home order, the researchers said it’s not clear that this was the cause.

“We’re not saying it is the lockdown that was causing it,” Dr. Loggia said. “It could have been social isolation, changes in diet, or changes in exercise patterns. We don’t know exactly what the cause was so, maybe.”
 

A significant contribution

Commenting on the study for this news organization, Ning Quan, PhD, professor of biomedical science at Florida Atlantic University, Boca Raton, said although questions remain, the findings offer valuable information.

“This study contributes significantly to our understanding of how pandemic stress might impact our brain and behavior,” Dr. Quan said. “The main advance that this paper provides is that fatigue or brain fog could be induced in individuals with COVID infection during the pandemic.”

However, Dr. Quan added, the study has a number of limitations, including a small sample size, which makes it difficult to generalize the results.

“Another issue is the subjects of the study all lived in Massachusetts,” Dr. Quan added. “Subjects from different states or different countries could yield different results.”

The study was funded by the National Institutes of Health and by the Landreth Family Foundation. The study authors and Dr. Quan have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Moderna on March 23 released interim results indicating that its mRNA-1273 COVID vaccine produced “robust” neutralizing antibody titers in children aged 6 months to 6 years – levels similar to those seen in adults.

Vaccine efficacy against infection was 43.7% in children aged 6 months to 2 years and 37.5% among children aged 2-6 years, the new data from its phase 2/3 KidCOVE study show.

The company explained the lower efficacy numbers by noting that its study involving these younger children was conducted during the Omicron wave. The same decrease in efficacy against infection was reported in adults during the Omicron surge.

A majority of COVID-19 cases were mild in the approximately 6,900 children aged 6 months to 6 years in the study. No severe COVID-19 cases, hospitalizations, or deaths were reported.

The primary series of two 25-mcg doses of the vaccine given 28 days apart was generally well tolerated. Most adverse events were mild to moderate. For example, temperature greater than 38° C (>100.4° F) was reported for 17.0% of the 6-month-old to 2-year-old group and for 14.6% of the 2- to 6-year-old group. A few children, 0.2% of each group, experienced a temperature greater than 40° C (>104° F).

Moderna plans to include these response, efficacy, and safety data in an application to the Food and Drug Administration for emergency use authorization (EUA) of the vaccine in these younger children in the coming weeks.

“We now have clinical data on the performance of our vaccine from infants 6 months of age through older adults,” Moderna CEO Stephane Bancel said in a news release. He described the interim results as “good news for parents of children under 6 years of age.”
 

In other news

Moderna also announced that it began the FDA EUA submission process for a 50-μg two-dose primary series for children aged 6-12 years.

The company is also updating its EUA submission for a 100-mcg two-dose primary series for children and adolescents aged 12-18 years.

Similar to its booster research in adults, Moderna plans to evaluate the potential of a booster dose for all pediatric populations, including those aged 6 months to 6 years, 6-12 years, and adolescents. The company is evaluating both a booster dose of mRNA-1273 and its bivalent booster candidate (mRNA1273.214), which includes an Omicron variant booster and mRNA-1273.

A version of this article first appeared on Medscape.com.

Moderna on March 23 released interim results indicating that its mRNA-1273 COVID vaccine produced “robust” neutralizing antibody titers in children aged 6 months to 6 years – levels similar to those seen in adults.

Vaccine efficacy against infection was 43.7% in children aged 6 months to 2 years and 37.5% among children aged 2-6 years, the new data from its phase 2/3 KidCOVE study show.

The company explained the lower efficacy numbers by noting that its study involving these younger children was conducted during the Omicron wave. The same decrease in efficacy against infection was reported in adults during the Omicron surge.

A majority of COVID-19 cases were mild in the approximately 6,900 children aged 6 months to 6 years in the study. No severe COVID-19 cases, hospitalizations, or deaths were reported.

The primary series of two 25-mcg doses of the vaccine given 28 days apart was generally well tolerated. Most adverse events were mild to moderate. For example, temperature greater than 38° C (>100.4° F) was reported for 17.0% of the 6-month-old to 2-year-old group and for 14.6% of the 2- to 6-year-old group. A few children, 0.2% of each group, experienced a temperature greater than 40° C (>104° F).

Moderna plans to include these response, efficacy, and safety data in an application to the Food and Drug Administration for emergency use authorization (EUA) of the vaccine in these younger children in the coming weeks.

“We now have clinical data on the performance of our vaccine from infants 6 months of age through older adults,” Moderna CEO Stephane Bancel said in a news release. He described the interim results as “good news for parents of children under 6 years of age.”
 

In other news

Moderna also announced that it began the FDA EUA submission process for a 50-μg two-dose primary series for children aged 6-12 years.

The company is also updating its EUA submission for a 100-mcg two-dose primary series for children and adolescents aged 12-18 years.

Similar to its booster research in adults, Moderna plans to evaluate the potential of a booster dose for all pediatric populations, including those aged 6 months to 6 years, 6-12 years, and adolescents. The company is evaluating both a booster dose of mRNA-1273 and its bivalent booster candidate (mRNA1273.214), which includes an Omicron variant booster and mRNA-1273.

A version of this article first appeared on Medscape.com.

Moderna on March 23 released interim results indicating that its mRNA-1273 COVID vaccine produced “robust” neutralizing antibody titers in children aged 6 months to 6 years – levels similar to those seen in adults.

Vaccine efficacy against infection was 43.7% in children aged 6 months to 2 years and 37.5% among children aged 2-6 years, the new data from its phase 2/3 KidCOVE study show.

The company explained the lower efficacy numbers by noting that its study involving these younger children was conducted during the Omicron wave. The same decrease in efficacy against infection was reported in adults during the Omicron surge.

A majority of COVID-19 cases were mild in the approximately 6,900 children aged 6 months to 6 years in the study. No severe COVID-19 cases, hospitalizations, or deaths were reported.

The primary series of two 25-mcg doses of the vaccine given 28 days apart was generally well tolerated. Most adverse events were mild to moderate. For example, temperature greater than 38° C (>100.4° F) was reported for 17.0% of the 6-month-old to 2-year-old group and for 14.6% of the 2- to 6-year-old group. A few children, 0.2% of each group, experienced a temperature greater than 40° C (>104° F).

Moderna plans to include these response, efficacy, and safety data in an application to the Food and Drug Administration for emergency use authorization (EUA) of the vaccine in these younger children in the coming weeks.

“We now have clinical data on the performance of our vaccine from infants 6 months of age through older adults,” Moderna CEO Stephane Bancel said in a news release. He described the interim results as “good news for parents of children under 6 years of age.”
 

In other news

Moderna also announced that it began the FDA EUA submission process for a 50-μg two-dose primary series for children aged 6-12 years.

The company is also updating its EUA submission for a 100-mcg two-dose primary series for children and adolescents aged 12-18 years.

Similar to its booster research in adults, Moderna plans to evaluate the potential of a booster dose for all pediatric populations, including those aged 6 months to 6 years, 6-12 years, and adolescents. The company is evaluating both a booster dose of mRNA-1273 and its bivalent booster candidate (mRNA1273.214), which includes an Omicron variant booster and mRNA-1273.

A version of this article first appeared on Medscape.com.

The use of an electronic clinical decision support tool called “ePNa” reduced severity-adjusted, 30-day, all-cause mortality by 38% across 16 community hospitals in Utah, compared with predeployment levels, a 3-year, pragmatic, cluster-controlled study shows.

“We designed the ePNa specifically to require minimal input from the clinician so everything it does is already in the electronic medical record,” Nathan Dean, MD, University of Utah, Salt Lake City, told this news organization.

“So it’s actually putting the guideline recommendations into effect for physicians so that they can make better decisions by having all this information – it’s a comprehensive best practice kind of tool where best practices are likely to make the biggest difference for patients with a high severity of illness,” he added.

The study was published online in the American Journal of Respiratory and Critical Care Medicine.


 

Guideline-based tool

The ePNa makes use of pneumonia guidelines of 2007 and 2019 from the American Thoracic Society/Infectious Disease Society of America. The system was deployed into six geographic clusters of 16 Intermountain hospital EDs at 2-month intervals between December 2017 and November 2018. Simultaneous deployment was impractical, as implementation of the tool takes education, monitoring, and feedback that can be facilitated by focusing on only a few hospitals at a time.

The decision support tool gathers key patient indicators including age, fever, oxygen saturation, vital signs, and laboratory and chest imaging results to offer recommendations on care, including appropriate antibiotic therapy, microbiology studies, and whether a given patient should be sent to the intensive care unit, admitted to hospital, or may safely be discharged home.

Investigators analyzed a total of 6,848 patients, of whom 4,536 were managed for pneumonia before the ePNa was deployed and 2,312 after deployment.

The median age of patients was 67 years (interquartile range, 50-79 years). Roughly half were female and almost all were White. “Observed 30-day all-cause mortality including both outpatients and inpatients was 8.6% before deployment versus 4.8% after deployment of ePNa,” Dr. Dean and colleagues reported.

Adjusted for severity of illness, the odds ratio for lower mortality post-ePNa launch was 0.62 (95% confidence interval, 0.49-0.79; P < .0010) “and lower morality was consistent across hospital clusters.”

Compared with patients who were discharged home, reductions in mortality were greatest in patients who were directly admitted to ICUs from the ED (OR, 0.32; 95% CI, 0.14-0.77; P = .01). The OR for patients admitted to the medical floor was 0.53 (95% CI, 0.25-1.1; P = .09), which did not reach statistical significance.

Dr. Dean explained that the reductions in mortality were seen among those with the most severe illness, in whom best practices would benefit the most. In contrast, patients who are sent home on an antibiotic are at low risk for mortality while patients admitted to the medical floor may well have another, more lethal illness from which they end up dying, rather than simple pneumonia.

“For me, this was a clear demonstration that these best practices made the biggest difference in patients who were sick and who did not have any underlying disease that was going to kill them anyway,” he emphasized. On the other hand, both 30-day mortality and 7-day secondary hospital admission were higher among patients the tool recommended for hospital ward admission but who were discharged home from the ED.

“This was an unexpected finding,” Dr. Dean observed. However, as he explained, the authors reviewed 25% of randomly selected patients who fell into this subgroup and discovered that the ePNa tool was used in only about 20% of patients – “so doctors did not use the tool in the majority of this group.”

In addition, some of these patients declined hospital admission, so the doctors may have recommended that they be admitted but the patients said no. “The hypothesis here is that if they had been admitted to the hospital, they may have had a lower mortality risk,” Dr. Dean said.
 

Noticeable changes

Another noticeable change following the introduction of the ePNa tool was that guideline-concordant antibiotic prescribing increased in the 8 hours after patients presented to the ED, from 79.5% prior to the tool’s launch to 87.9%, again after adjusting for pneumonia severity (P < .001). Use of broad-spectrum antibiotics was not significantly different between the two treatment intervals, but administration of antibiotics active against methicillin-resistant Staphylococcus aureus dropped significantly between the two treatment intervals (P < .001). And the mean time from admission to the ED to the first antibiotic taken was slightly faster, improving from 159.4 minutes (95% CI, 156.9-161.9 minutes) prior to the ePNa launch to 150.9 minutes (95% CI, 144.1-157.8) post deployment (P < .001).

“Overall outpatient disposition for treatment of pneumonia from the emergency department increased from 29.2% before ePNa to 46.9% [post ePNA],” the authors noted, while a similar increase was observed in patients for whom ePNA recommended outpatient care – from 49.2% pre-ePNA to 66.6% after ePNA.

Both hospital ward admission and admission to the ICU decreased after ePNa had been introduced. Despite a significant increase in the percentage of patients being discharged home, neither 7-day secondary hospital admission nor severity-adjusted, 30-day mortality were significantly different before versus after the introduction of ePNa, the authors stressed.

A limitation of the study was that the trial was confined to a single health care system in one region of the United States with a patient population that may differ from that in other regions.
 

Reason for its success

Asked to comment on the findings, Adam Balls, MD, emergency department chair, Intermountain Medical Center, Murray, Utah, suggested that the reason the ePNa tool has been so successful at improving care for pneumonia patients is that it puts the guidelines directly into the hands of individual providers and tells them what’s going on. (Dr. Balls was not involved in the study.) “The tool allows us to take into consideration various clinical features – a patient’s oxygen requirements and whether or not they had prior complicated pneumonias that required additional antibiotics, for example – and then it makes the best determination for not only the disposition for that patient but antibiotic treatment as well,” he said in an interview.

This then allows physicians to either appropriately discharge less severely ill patients and admit those who are more ill – “and in general, just do a better job of treating pneumonia with this tool,” Dr. Balls said. He himself uses the decision support tool when attending to his own patients with pneumonia, as he feels that the tool really does make his care of these patients better. “There is a disparity around how we treat pneumonia in the U.S.

“Clinicians sometimes have a bias or a preference for certain antibiotics and we may not be appropriately treating these patients with broad-spectrum antibiotics or are perhaps using antibiotics that are not as effective based on an individual patient scenario so this is definitely a user-friendly tool that hopefully can be deployed throughout other health care systems to improve the treatment of pneumonia overall,” Dr. Balls emphasized.

A version of this article first appeared on Medscape.com.

The use of an electronic clinical decision support tool called “ePNa” reduced severity-adjusted, 30-day, all-cause mortality by 38% across 16 community hospitals in Utah, compared with predeployment levels, a 3-year, pragmatic, cluster-controlled study shows.

“We designed the ePNa specifically to require minimal input from the clinician so everything it does is already in the electronic medical record,” Nathan Dean, MD, University of Utah, Salt Lake City, told this news organization.

“So it’s actually putting the guideline recommendations into effect for physicians so that they can make better decisions by having all this information – it’s a comprehensive best practice kind of tool where best practices are likely to make the biggest difference for patients with a high severity of illness,” he added.

The study was published online in the American Journal of Respiratory and Critical Care Medicine.


 

Guideline-based tool

The ePNa makes use of pneumonia guidelines of 2007 and 2019 from the American Thoracic Society/Infectious Disease Society of America. The system was deployed into six geographic clusters of 16 Intermountain hospital EDs at 2-month intervals between December 2017 and November 2018. Simultaneous deployment was impractical, as implementation of the tool takes education, monitoring, and feedback that can be facilitated by focusing on only a few hospitals at a time.

The decision support tool gathers key patient indicators including age, fever, oxygen saturation, vital signs, and laboratory and chest imaging results to offer recommendations on care, including appropriate antibiotic therapy, microbiology studies, and whether a given patient should be sent to the intensive care unit, admitted to hospital, or may safely be discharged home.

Investigators analyzed a total of 6,848 patients, of whom 4,536 were managed for pneumonia before the ePNa was deployed and 2,312 after deployment.

The median age of patients was 67 years (interquartile range, 50-79 years). Roughly half were female and almost all were White. “Observed 30-day all-cause mortality including both outpatients and inpatients was 8.6% before deployment versus 4.8% after deployment of ePNa,” Dr. Dean and colleagues reported.

Adjusted for severity of illness, the odds ratio for lower mortality post-ePNa launch was 0.62 (95% confidence interval, 0.49-0.79; P < .0010) “and lower morality was consistent across hospital clusters.”

Compared with patients who were discharged home, reductions in mortality were greatest in patients who were directly admitted to ICUs from the ED (OR, 0.32; 95% CI, 0.14-0.77; P = .01). The OR for patients admitted to the medical floor was 0.53 (95% CI, 0.25-1.1; P = .09), which did not reach statistical significance.

Dr. Dean explained that the reductions in mortality were seen among those with the most severe illness, in whom best practices would benefit the most. In contrast, patients who are sent home on an antibiotic are at low risk for mortality while patients admitted to the medical floor may well have another, more lethal illness from which they end up dying, rather than simple pneumonia.

“For me, this was a clear demonstration that these best practices made the biggest difference in patients who were sick and who did not have any underlying disease that was going to kill them anyway,” he emphasized. On the other hand, both 30-day mortality and 7-day secondary hospital admission were higher among patients the tool recommended for hospital ward admission but who were discharged home from the ED.

“This was an unexpected finding,” Dr. Dean observed. However, as he explained, the authors reviewed 25% of randomly selected patients who fell into this subgroup and discovered that the ePNa tool was used in only about 20% of patients – “so doctors did not use the tool in the majority of this group.”

In addition, some of these patients declined hospital admission, so the doctors may have recommended that they be admitted but the patients said no. “The hypothesis here is that if they had been admitted to the hospital, they may have had a lower mortality risk,” Dr. Dean said.
 

Noticeable changes

Another noticeable change following the introduction of the ePNa tool was that guideline-concordant antibiotic prescribing increased in the 8 hours after patients presented to the ED, from 79.5% prior to the tool’s launch to 87.9%, again after adjusting for pneumonia severity (P < .001). Use of broad-spectrum antibiotics was not significantly different between the two treatment intervals, but administration of antibiotics active against methicillin-resistant Staphylococcus aureus dropped significantly between the two treatment intervals (P < .001). And the mean time from admission to the ED to the first antibiotic taken was slightly faster, improving from 159.4 minutes (95% CI, 156.9-161.9 minutes) prior to the ePNa launch to 150.9 minutes (95% CI, 144.1-157.8) post deployment (P < .001).

“Overall outpatient disposition for treatment of pneumonia from the emergency department increased from 29.2% before ePNa to 46.9% [post ePNA],” the authors noted, while a similar increase was observed in patients for whom ePNA recommended outpatient care – from 49.2% pre-ePNA to 66.6% after ePNA.

Both hospital ward admission and admission to the ICU decreased after ePNa had been introduced. Despite a significant increase in the percentage of patients being discharged home, neither 7-day secondary hospital admission nor severity-adjusted, 30-day mortality were significantly different before versus after the introduction of ePNa, the authors stressed.

A limitation of the study was that the trial was confined to a single health care system in one region of the United States with a patient population that may differ from that in other regions.
 

Reason for its success

Asked to comment on the findings, Adam Balls, MD, emergency department chair, Intermountain Medical Center, Murray, Utah, suggested that the reason the ePNa tool has been so successful at improving care for pneumonia patients is that it puts the guidelines directly into the hands of individual providers and tells them what’s going on. (Dr. Balls was not involved in the study.) “The tool allows us to take into consideration various clinical features – a patient’s oxygen requirements and whether or not they had prior complicated pneumonias that required additional antibiotics, for example – and then it makes the best determination for not only the disposition for that patient but antibiotic treatment as well,” he said in an interview.

This then allows physicians to either appropriately discharge less severely ill patients and admit those who are more ill – “and in general, just do a better job of treating pneumonia with this tool,” Dr. Balls said. He himself uses the decision support tool when attending to his own patients with pneumonia, as he feels that the tool really does make his care of these patients better. “There is a disparity around how we treat pneumonia in the U.S.

“Clinicians sometimes have a bias or a preference for certain antibiotics and we may not be appropriately treating these patients with broad-spectrum antibiotics or are perhaps using antibiotics that are not as effective based on an individual patient scenario so this is definitely a user-friendly tool that hopefully can be deployed throughout other health care systems to improve the treatment of pneumonia overall,” Dr. Balls emphasized.

A version of this article first appeared on Medscape.com.

The use of an electronic clinical decision support tool called “ePNa” reduced severity-adjusted, 30-day, all-cause mortality by 38% across 16 community hospitals in Utah, compared with predeployment levels, a 3-year, pragmatic, cluster-controlled study shows.

“We designed the ePNa specifically to require minimal input from the clinician so everything it does is already in the electronic medical record,” Nathan Dean, MD, University of Utah, Salt Lake City, told this news organization.

“So it’s actually putting the guideline recommendations into effect for physicians so that they can make better decisions by having all this information – it’s a comprehensive best practice kind of tool where best practices are likely to make the biggest difference for patients with a high severity of illness,” he added.

The study was published online in the American Journal of Respiratory and Critical Care Medicine.


 

Guideline-based tool

The ePNa makes use of pneumonia guidelines of 2007 and 2019 from the American Thoracic Society/Infectious Disease Society of America. The system was deployed into six geographic clusters of 16 Intermountain hospital EDs at 2-month intervals between December 2017 and November 2018. Simultaneous deployment was impractical, as implementation of the tool takes education, monitoring, and feedback that can be facilitated by focusing on only a few hospitals at a time.

The decision support tool gathers key patient indicators including age, fever, oxygen saturation, vital signs, and laboratory and chest imaging results to offer recommendations on care, including appropriate antibiotic therapy, microbiology studies, and whether a given patient should be sent to the intensive care unit, admitted to hospital, or may safely be discharged home.

Investigators analyzed a total of 6,848 patients, of whom 4,536 were managed for pneumonia before the ePNa was deployed and 2,312 after deployment.

The median age of patients was 67 years (interquartile range, 50-79 years). Roughly half were female and almost all were White. “Observed 30-day all-cause mortality including both outpatients and inpatients was 8.6% before deployment versus 4.8% after deployment of ePNa,” Dr. Dean and colleagues reported.

Adjusted for severity of illness, the odds ratio for lower mortality post-ePNa launch was 0.62 (95% confidence interval, 0.49-0.79; P < .0010) “and lower morality was consistent across hospital clusters.”

Compared with patients who were discharged home, reductions in mortality were greatest in patients who were directly admitted to ICUs from the ED (OR, 0.32; 95% CI, 0.14-0.77; P = .01). The OR for patients admitted to the medical floor was 0.53 (95% CI, 0.25-1.1; P = .09), which did not reach statistical significance.

Dr. Dean explained that the reductions in mortality were seen among those with the most severe illness, in whom best practices would benefit the most. In contrast, patients who are sent home on an antibiotic are at low risk for mortality while patients admitted to the medical floor may well have another, more lethal illness from which they end up dying, rather than simple pneumonia.

“For me, this was a clear demonstration that these best practices made the biggest difference in patients who were sick and who did not have any underlying disease that was going to kill them anyway,” he emphasized. On the other hand, both 30-day mortality and 7-day secondary hospital admission were higher among patients the tool recommended for hospital ward admission but who were discharged home from the ED.

“This was an unexpected finding,” Dr. Dean observed. However, as he explained, the authors reviewed 25% of randomly selected patients who fell into this subgroup and discovered that the ePNa tool was used in only about 20% of patients – “so doctors did not use the tool in the majority of this group.”

In addition, some of these patients declined hospital admission, so the doctors may have recommended that they be admitted but the patients said no. “The hypothesis here is that if they had been admitted to the hospital, they may have had a lower mortality risk,” Dr. Dean said.
 

Noticeable changes

Another noticeable change following the introduction of the ePNa tool was that guideline-concordant antibiotic prescribing increased in the 8 hours after patients presented to the ED, from 79.5% prior to the tool’s launch to 87.9%, again after adjusting for pneumonia severity (P < .001). Use of broad-spectrum antibiotics was not significantly different between the two treatment intervals, but administration of antibiotics active against methicillin-resistant Staphylococcus aureus dropped significantly between the two treatment intervals (P < .001). And the mean time from admission to the ED to the first antibiotic taken was slightly faster, improving from 159.4 minutes (95% CI, 156.9-161.9 minutes) prior to the ePNa launch to 150.9 minutes (95% CI, 144.1-157.8) post deployment (P < .001).

“Overall outpatient disposition for treatment of pneumonia from the emergency department increased from 29.2% before ePNa to 46.9% [post ePNA],” the authors noted, while a similar increase was observed in patients for whom ePNA recommended outpatient care – from 49.2% pre-ePNA to 66.6% after ePNA.

Both hospital ward admission and admission to the ICU decreased after ePNa had been introduced. Despite a significant increase in the percentage of patients being discharged home, neither 7-day secondary hospital admission nor severity-adjusted, 30-day mortality were significantly different before versus after the introduction of ePNa, the authors stressed.

A limitation of the study was that the trial was confined to a single health care system in one region of the United States with a patient population that may differ from that in other regions.
 

Reason for its success

Asked to comment on the findings, Adam Balls, MD, emergency department chair, Intermountain Medical Center, Murray, Utah, suggested that the reason the ePNa tool has been so successful at improving care for pneumonia patients is that it puts the guidelines directly into the hands of individual providers and tells them what’s going on. (Dr. Balls was not involved in the study.) “The tool allows us to take into consideration various clinical features – a patient’s oxygen requirements and whether or not they had prior complicated pneumonias that required additional antibiotics, for example – and then it makes the best determination for not only the disposition for that patient but antibiotic treatment as well,” he said in an interview.

This then allows physicians to either appropriately discharge less severely ill patients and admit those who are more ill – “and in general, just do a better job of treating pneumonia with this tool,” Dr. Balls said. He himself uses the decision support tool when attending to his own patients with pneumonia, as he feels that the tool really does make his care of these patients better. “There is a disparity around how we treat pneumonia in the U.S.

“Clinicians sometimes have a bias or a preference for certain antibiotics and we may not be appropriately treating these patients with broad-spectrum antibiotics or are perhaps using antibiotics that are not as effective based on an individual patient scenario so this is definitely a user-friendly tool that hopefully can be deployed throughout other health care systems to improve the treatment of pneumonia overall,” Dr. Balls emphasized.

A version of this article first appeared on Medscape.com.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

A version of this article first appeared on Medscape.com.

Antibiotics are among the most commonly prescribed medications in both outpatient and hospital settings. Global efforts at curbing antibiotic-resistant strains have prompted clinicians to pursue better stewardship, whereby they limit their prescribing of such medications to those who truly need them.

Yet there’s another possible means of addressing antibiotic resistance – using dietary interventions to reduce the gastrointestinal complaints that so often accompany the use of antibiotics: vomiting, nausea, diarrhea, bloating/indigestion, abdominal pain, and loss of appetite. Far from being a mere nuisance, these complications can have major ramifications.

“Often [these side effects] will result in people stopping an antibiotic they need or taking a second- or third-generation one, which potentially causes even more problems with resistance,” explained Daniel J. Merenstein, MD, a professor of family medicine at Georgetown University, Washington, who has conducted multiple trials on antibiotic stewardship and probiotics.

And it’s not just clinicians who would like to find a way around these common complaints. On lifestyle blogs such as Livestrong and Goop, medical news websites, and via academic institutions, patients can learn how the right probiotic supplement or certain fermented or high-fiber foods, for example, might spare them the upset stomach that often accompanies a course of antibiotics.

Yet according to experts in the field, there are notable questions to be answered about whether there’s evidence to support this approach.

The cost of GI discomfort

Pinpointing the exact manner by which antibiotics upend GI tracts is a complex task, according to Gail Cresci, PhD, RD, a microbiome researcher in the department of pediatric gastroenterology, hepatology, and nutrition and director of nutrition research at the Cleveland Clinic.

“A lot of different mechanisms can go awry,” Dr. Cresci said. “But normally, the good microbes are there to help keep the balance, so when that balance is gone, the pathogens can take over and lead to this disruption.”

According to Lynne V. McFarland, PhD, a recently retired infectious disease epidemiologist who now serves as a private consultant, such complications can have substantial ramifications for patients and health care systems.

“If you’re an inpatient and develop antibiotic-associated diarrhea, it usually increases the length of stay from 8 to 20 days. It also increases the cost of care. And small children who have this can get severely dehydrated, which can become life threatening.”

Proponents of probiotics

Several of the researchers who were interviewed believe there’s convincing evidence supporting probiotics for the treatment of common antibiotic-related GI complaints. In many instances, they were involved in the studies themselves.

During Dr. McFarland’s 4-decade career in probiotics research, she has participated in early animal studies with strains such as Saccharomyces boulardii and was involved in meta-analyses of their role in Clostridioides difficile infection and associated diarrhea and even as a potential GI intervention for COVID-19 patients (Antibiotics (Basel). 2021 Apr 9;10(4):408).

In mouse model studies from 2013 and 2018, Dr. Cresci and colleagues showed that the probiotic strains Lactobacillus GG and Faecalibacterium prausnitzii reduced the structural gut changes that lead to antibiotic-associated diarrhea and minimized the risk of C. difficile infection.

In a 2021 randomized controlled trial led by Merenstein, healthy participants were given a trial of amoxicillin/clavulanate (days 1-7) in conjunction with either yogurt containing the probiotic Bifidobacterium animalis subsp lactis BB-12 or control yogurt (days 1-14). After assessing feces samples over a 30-day period, they found that those who received the probiotic yogurt had a significantly smaller decrease in short-chain fatty acid levels and a more stable taxonomic microbiota profile than control persons.

Dr. Merenstein said that, on the basis of results such as these and others, he’s comfortable being relatively definitive about the value of probiotics.

“I believe it’s close to standard of care that if you’re prescribing antibiotics, especially for more than 7 days, you really need to put people on probiotics that have been studied, simply because the evidence is robust enough now,” he said.

Even for proponents, there are caveats

However, all the researchers recommending the use of probiotics did so with caveats. First and foremost, they advise clinicians that the term “probiotics” is an imprecise catchall and is essentially meaningless.

“A lot of products label themselves as probiotic. It’s a great marketing scheme, but many of the products out there aren’t really probiotics; they’re not proven with randomized control trials and don’t have the scientific background,” said Dr. McFarland. “We’ve found that the efficacy is extremely strain specific and disease specific. A strain may work for one disease and not work for another.”

In 2018, Dr. McFarland coauthored an evidence-based practical guide to help clinicians and patients identify the specific strain that works in certain indications. Dr. Cresci recommends that clinicians consult websites such as Probiotics.org or the National Institutes of Health’s database to find the strains that have been proven to work in well-designed clinical trials.

There was also agreement that, to date, the most robust data support probiotics for the treatment of antibiotic-associated diarrhea.

Although the optimal timing of probiotics is a subject of debate, most proponents agreed that the general rule is “the sooner the better.”

Dr. McFarland recommended incorporating probiotics within 24 hours of starting an antibiotic “because the damage done to your GI tract microbiome is pretty quick, and the probiotics work best if they’re established before major disruption occurs.” She added that patients should continue taking probiotics for 2-8 weeks after stopping antibiotics.

“It takes a long time for your normal flora to get restored,” she said. “It’s best to cover your bases.”

For others, the evidence is not definitive

Opinions on the value of probiotics to combat antibiotic-related GI side effects are divergent, though.

“I would not recommend the routine use of probiotics, and certainly not in the prevention of C. difficile or antibiotic-related diarrhea,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk. “I think the evidence does not support that, and I stand strongly on that recommendation.”

Dr. Johnson cited the 2020 guidelines from the American Gastroenterological Association, which offer only a conditional recommendation for the use of specific probiotics and only in preventing antibiotic-associated C. difficile infection.

Geoffrey A. Preidis, MD, PhD, an assistant professor of pediatrics in the section of gastroenterology, hepatology, and nutrition at Baylor College of Medicine, Houston, served as a coauthor of the AGA’s guidelines. He noted that after reviewing 39 published trials of approximately 10,000 patients given probiotics while receiving antibiotics, the authors “did find some evidence that specific probiotics might decrease the risk of C. difficile diarrhea, but the quality of that evidence was low.”

Dr. Preidis attributed this to the lack of well-designed multicenter trials that can isolate the effects of certain strains and determine their benefit in this application.

“The majority of published trials have not reported safety data as rigorously as these data are reported in pharmaceutical trials, so the risk of side effects could be higher than we think,” said Dr. Preidis. “As living microbes, probiotics can move from the intestines into the bloodstream, causing sepsis. Contamination in the manufacturing process has been reported. There might be other long-term effects that we are not yet aware of.”

When asked to characterize the available data on probiotics, Dr. Johnson replied, “I’d generally label it, ‘caveat emptor.’ ”

Dr. McFarland agreed that the field would benefit from better-designed studies and called out meta-analyses that pool outcomes with various strains for particular criticism.

“When researchers do that, it’s no longer valid and shouldn’t have been published, in my opinion,” she told this news organization.

‘Antibiotic diets’ as a possible approach

A compromise between the two sides may be the so-called antibiotic diet. The theory behind such diets is that foods and beverages with biome-boosting properties may be a risk-free intervention that patients can adopt to alleviate antibiotic-related side effects.

“You want your diet to include more soluble fibers to help support the good bacteria, particularly when you’re taking antibiotics,” said Dr. Cresci. “You can get this through eating fresh fruits and vegetables, whole grains, and foods that have more prebiotic, like potatoes. You can also eat fermented food, such as kefir, kombucha, kimchi, and yogurt, so you’re adding more beneficial bacteria into your intestinal tract.”

There is ample published evidence that such foods can boost microbiome diversity and decrease inflammation, including a July 2021 study in Cell. However, the protection this may confer while taking antibiotics isn’t known. Establishing a clear role for the efficacy of such interventions is made additionally difficult by the well-established limitations of conducting dietary clinical trials.

Dr. Merenstein said that there is no compelling evidence that antibiotic-related complications can be offset by changing what goes onto our dinner plates. He joked: “We can’t say, ‘Here’s amoxicillin for your ear infection, now make sure you increase your fermented food, fiber, and water.’ ”

Dr. Johnson said he’s intrigued by studies of prebiotics – fibers that boost beneficial bacteria in the GI system.

“I would love to have more findings about prebiotic identification; that is, things we could do in a healthy way to keep the gut balanced while it’s subject to a change with antibiotics,” he said. “We’re just not there yet.”

Dr. Johnson added that he generally recommends that patients taking antibiotics eat “a bland diet, avoiding things that may have been provocative in the past.”

If patients are already enjoying foods with microbiome-boosting reputations, Dr. Johnson sees “very little downside to continuing that [while on antibiotics].” However, he noted that the period in which you’re taking antibiotics isn’t ideal for trying new foods, given the lack of experience with how the gut bacteria will react.

There are data about foods to avoid while taking antibiotics, which generally fall in line with common dietary knowledge. Many patients may know not to drink grapefruit juice with certain medications, but it’s worth a reminder. Certain antibiotics may also require delaying or avoiding dairy products, although this does not apply to yogurt.

A fiber-deficient diet can aggravate microbiota collapse following antibiotics. In a 2020 study, researchers showed that people on a high-fat diet who were using antibiotics were 8.6 times more likely to have preinflammatory bowel disease than those eating low-fat foods and who had no recent history of antibiotic use. Mouse model data from the same study indicated that poor diet and antibiotics may have worked in conjunction to reduce oxygen in the gut.

Dr. McFarland noted that building a healthy microbiome is a lifelong pursuit and that several factors (for example, environmental or genetic) are out of individuals’ hands. The general public might want a quick fix – ironically, one of the main drivers behind their requesting and receiving antibiotics when they’re not indicated – but it’s likely not available to them.

“You can’t eat one salad and suddenly have a healthy gut, unfortunately.”

A version of this article first appeared on Medscape.com.

Antibiotics are among the most commonly prescribed medications in both outpatient and hospital settings. Global efforts at curbing antibiotic-resistant strains have prompted clinicians to pursue better stewardship, whereby they limit their prescribing of such medications to those who truly need them.

Yet there’s another possible means of addressing antibiotic resistance – using dietary interventions to reduce the gastrointestinal complaints that so often accompany the use of antibiotics: vomiting, nausea, diarrhea, bloating/indigestion, abdominal pain, and loss of appetite. Far from being a mere nuisance, these complications can have major ramifications.

“Often [these side effects] will result in people stopping an antibiotic they need or taking a second- or third-generation one, which potentially causes even more problems with resistance,” explained Daniel J. Merenstein, MD, a professor of family medicine at Georgetown University, Washington, who has conducted multiple trials on antibiotic stewardship and probiotics.

And it’s not just clinicians who would like to find a way around these common complaints. On lifestyle blogs such as Livestrong and Goop, medical news websites, and via academic institutions, patients can learn how the right probiotic supplement or certain fermented or high-fiber foods, for example, might spare them the upset stomach that often accompanies a course of antibiotics.

Yet according to experts in the field, there are notable questions to be answered about whether there’s evidence to support this approach.

The cost of GI discomfort

Pinpointing the exact manner by which antibiotics upend GI tracts is a complex task, according to Gail Cresci, PhD, RD, a microbiome researcher in the department of pediatric gastroenterology, hepatology, and nutrition and director of nutrition research at the Cleveland Clinic.

“A lot of different mechanisms can go awry,” Dr. Cresci said. “But normally, the good microbes are there to help keep the balance, so when that balance is gone, the pathogens can take over and lead to this disruption.”

According to Lynne V. McFarland, PhD, a recently retired infectious disease epidemiologist who now serves as a private consultant, such complications can have substantial ramifications for patients and health care systems.

“If you’re an inpatient and develop antibiotic-associated diarrhea, it usually increases the length of stay from 8 to 20 days. It also increases the cost of care. And small children who have this can get severely dehydrated, which can become life threatening.”

Proponents of probiotics

Several of the researchers who were interviewed believe there’s convincing evidence supporting probiotics for the treatment of common antibiotic-related GI complaints. In many instances, they were involved in the studies themselves.

During Dr. McFarland’s 4-decade career in probiotics research, she has participated in early animal studies with strains such as Saccharomyces boulardii and was involved in meta-analyses of their role in Clostridioides difficile infection and associated diarrhea and even as a potential GI intervention for COVID-19 patients (Antibiotics (Basel). 2021 Apr 9;10(4):408).

In mouse model studies from 2013 and 2018, Dr. Cresci and colleagues showed that the probiotic strains Lactobacillus GG and Faecalibacterium prausnitzii reduced the structural gut changes that lead to antibiotic-associated diarrhea and minimized the risk of C. difficile infection.

In a 2021 randomized controlled trial led by Merenstein, healthy participants were given a trial of amoxicillin/clavulanate (days 1-7) in conjunction with either yogurt containing the probiotic Bifidobacterium animalis subsp lactis BB-12 or control yogurt (days 1-14). After assessing feces samples over a 30-day period, they found that those who received the probiotic yogurt had a significantly smaller decrease in short-chain fatty acid levels and a more stable taxonomic microbiota profile than control persons.

Dr. Merenstein said that, on the basis of results such as these and others, he’s comfortable being relatively definitive about the value of probiotics.

“I believe it’s close to standard of care that if you’re prescribing antibiotics, especially for more than 7 days, you really need to put people on probiotics that have been studied, simply because the evidence is robust enough now,” he said.

Even for proponents, there are caveats

However, all the researchers recommending the use of probiotics did so with caveats. First and foremost, they advise clinicians that the term “probiotics” is an imprecise catchall and is essentially meaningless.

“A lot of products label themselves as probiotic. It’s a great marketing scheme, but many of the products out there aren’t really probiotics; they’re not proven with randomized control trials and don’t have the scientific background,” said Dr. McFarland. “We’ve found that the efficacy is extremely strain specific and disease specific. A strain may work for one disease and not work for another.”

In 2018, Dr. McFarland coauthored an evidence-based practical guide to help clinicians and patients identify the specific strain that works in certain indications. Dr. Cresci recommends that clinicians consult websites such as Probiotics.org or the National Institutes of Health’s database to find the strains that have been proven to work in well-designed clinical trials.

There was also agreement that, to date, the most robust data support probiotics for the treatment of antibiotic-associated diarrhea.

Although the optimal timing of probiotics is a subject of debate, most proponents agreed that the general rule is “the sooner the better.”

Dr. McFarland recommended incorporating probiotics within 24 hours of starting an antibiotic “because the damage done to your GI tract microbiome is pretty quick, and the probiotics work best if they’re established before major disruption occurs.” She added that patients should continue taking probiotics for 2-8 weeks after stopping antibiotics.

“It takes a long time for your normal flora to get restored,” she said. “It’s best to cover your bases.”

For others, the evidence is not definitive

Opinions on the value of probiotics to combat antibiotic-related GI side effects are divergent, though.

“I would not recommend the routine use of probiotics, and certainly not in the prevention of C. difficile or antibiotic-related diarrhea,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk. “I think the evidence does not support that, and I stand strongly on that recommendation.”

Dr. Johnson cited the 2020 guidelines from the American Gastroenterological Association, which offer only a conditional recommendation for the use of specific probiotics and only in preventing antibiotic-associated C. difficile infection.

Geoffrey A. Preidis, MD, PhD, an assistant professor of pediatrics in the section of gastroenterology, hepatology, and nutrition at Baylor College of Medicine, Houston, served as a coauthor of the AGA’s guidelines. He noted that after reviewing 39 published trials of approximately 10,000 patients given probiotics while receiving antibiotics, the authors “did find some evidence that specific probiotics might decrease the risk of C. difficile diarrhea, but the quality of that evidence was low.”

Dr. Preidis attributed this to the lack of well-designed multicenter trials that can isolate the effects of certain strains and determine their benefit in this application.

“The majority of published trials have not reported safety data as rigorously as these data are reported in pharmaceutical trials, so the risk of side effects could be higher than we think,” said Dr. Preidis. “As living microbes, probiotics can move from the intestines into the bloodstream, causing sepsis. Contamination in the manufacturing process has been reported. There might be other long-term effects that we are not yet aware of.”

When asked to characterize the available data on probiotics, Dr. Johnson replied, “I’d generally label it, ‘caveat emptor.’ ”

Dr. McFarland agreed that the field would benefit from better-designed studies and called out meta-analyses that pool outcomes with various strains for particular criticism.

“When researchers do that, it’s no longer valid and shouldn’t have been published, in my opinion,” she told this news organization.

‘Antibiotic diets’ as a possible approach

A compromise between the two sides may be the so-called antibiotic diet. The theory behind such diets is that foods and beverages with biome-boosting properties may be a risk-free intervention that patients can adopt to alleviate antibiotic-related side effects.

“You want your diet to include more soluble fibers to help support the good bacteria, particularly when you’re taking antibiotics,” said Dr. Cresci. “You can get this through eating fresh fruits and vegetables, whole grains, and foods that have more prebiotic, like potatoes. You can also eat fermented food, such as kefir, kombucha, kimchi, and yogurt, so you’re adding more beneficial bacteria into your intestinal tract.”

There is ample published evidence that such foods can boost microbiome diversity and decrease inflammation, including a July 2021 study in Cell. However, the protection this may confer while taking antibiotics isn’t known. Establishing a clear role for the efficacy of such interventions is made additionally difficult by the well-established limitations of conducting dietary clinical trials.

Dr. Merenstein said that there is no compelling evidence that antibiotic-related complications can be offset by changing what goes onto our dinner plates. He joked: “We can’t say, ‘Here’s amoxicillin for your ear infection, now make sure you increase your fermented food, fiber, and water.’ ”

Dr. Johnson said he’s intrigued by studies of prebiotics – fibers that boost beneficial bacteria in the GI system.

“I would love to have more findings about prebiotic identification; that is, things we could do in a healthy way to keep the gut balanced while it’s subject to a change with antibiotics,” he said. “We’re just not there yet.”

Dr. Johnson added that he generally recommends that patients taking antibiotics eat “a bland diet, avoiding things that may have been provocative in the past.”

If patients are already enjoying foods with microbiome-boosting reputations, Dr. Johnson sees “very little downside to continuing that [while on antibiotics].” However, he noted that the period in which you’re taking antibiotics isn’t ideal for trying new foods, given the lack of experience with how the gut bacteria will react.

There are data about foods to avoid while taking antibiotics, which generally fall in line with common dietary knowledge. Many patients may know not to drink grapefruit juice with certain medications, but it’s worth a reminder. Certain antibiotics may also require delaying or avoiding dairy products, although this does not apply to yogurt.

A fiber-deficient diet can aggravate microbiota collapse following antibiotics. In a 2020 study, researchers showed that people on a high-fat diet who were using antibiotics were 8.6 times more likely to have preinflammatory bowel disease than those eating low-fat foods and who had no recent history of antibiotic use. Mouse model data from the same study indicated that poor diet and antibiotics may have worked in conjunction to reduce oxygen in the gut.

Dr. McFarland noted that building a healthy microbiome is a lifelong pursuit and that several factors (for example, environmental or genetic) are out of individuals’ hands. The general public might want a quick fix – ironically, one of the main drivers behind their requesting and receiving antibiotics when they’re not indicated – but it’s likely not available to them.

“You can’t eat one salad and suddenly have a healthy gut, unfortunately.”

A version of this article first appeared on Medscape.com.

Antibiotics are among the most commonly prescribed medications in both outpatient and hospital settings. Global efforts at curbing antibiotic-resistant strains have prompted clinicians to pursue better stewardship, whereby they limit their prescribing of such medications to those who truly need them.

Yet there’s another possible means of addressing antibiotic resistance – using dietary interventions to reduce the gastrointestinal complaints that so often accompany the use of antibiotics: vomiting, nausea, diarrhea, bloating/indigestion, abdominal pain, and loss of appetite. Far from being a mere nuisance, these complications can have major ramifications.

“Often [these side effects] will result in people stopping an antibiotic they need or taking a second- or third-generation one, which potentially causes even more problems with resistance,” explained Daniel J. Merenstein, MD, a professor of family medicine at Georgetown University, Washington, who has conducted multiple trials on antibiotic stewardship and probiotics.

And it’s not just clinicians who would like to find a way around these common complaints. On lifestyle blogs such as Livestrong and Goop, medical news websites, and via academic institutions, patients can learn how the right probiotic supplement or certain fermented or high-fiber foods, for example, might spare them the upset stomach that often accompanies a course of antibiotics.

Yet according to experts in the field, there are notable questions to be answered about whether there’s evidence to support this approach.

The cost of GI discomfort

Pinpointing the exact manner by which antibiotics upend GI tracts is a complex task, according to Gail Cresci, PhD, RD, a microbiome researcher in the department of pediatric gastroenterology, hepatology, and nutrition and director of nutrition research at the Cleveland Clinic.

“A lot of different mechanisms can go awry,” Dr. Cresci said. “But normally, the good microbes are there to help keep the balance, so when that balance is gone, the pathogens can take over and lead to this disruption.”

According to Lynne V. McFarland, PhD, a recently retired infectious disease epidemiologist who now serves as a private consultant, such complications can have substantial ramifications for patients and health care systems.

“If you’re an inpatient and develop antibiotic-associated diarrhea, it usually increases the length of stay from 8 to 20 days. It also increases the cost of care. And small children who have this can get severely dehydrated, which can become life threatening.”

Proponents of probiotics

Several of the researchers who were interviewed believe there’s convincing evidence supporting probiotics for the treatment of common antibiotic-related GI complaints. In many instances, they were involved in the studies themselves.

During Dr. McFarland’s 4-decade career in probiotics research, she has participated in early animal studies with strains such as Saccharomyces boulardii and was involved in meta-analyses of their role in Clostridioides difficile infection and associated diarrhea and even as a potential GI intervention for COVID-19 patients (Antibiotics (Basel). 2021 Apr 9;10(4):408).

In mouse model studies from 2013 and 2018, Dr. Cresci and colleagues showed that the probiotic strains Lactobacillus GG and Faecalibacterium prausnitzii reduced the structural gut changes that lead to antibiotic-associated diarrhea and minimized the risk of C. difficile infection.

In a 2021 randomized controlled trial led by Merenstein, healthy participants were given a trial of amoxicillin/clavulanate (days 1-7) in conjunction with either yogurt containing the probiotic Bifidobacterium animalis subsp lactis BB-12 or control yogurt (days 1-14). After assessing feces samples over a 30-day period, they found that those who received the probiotic yogurt had a significantly smaller decrease in short-chain fatty acid levels and a more stable taxonomic microbiota profile than control persons.

Dr. Merenstein said that, on the basis of results such as these and others, he’s comfortable being relatively definitive about the value of probiotics.

“I believe it’s close to standard of care that if you’re prescribing antibiotics, especially for more than 7 days, you really need to put people on probiotics that have been studied, simply because the evidence is robust enough now,” he said.

Even for proponents, there are caveats

However, all the researchers recommending the use of probiotics did so with caveats. First and foremost, they advise clinicians that the term “probiotics” is an imprecise catchall and is essentially meaningless.

“A lot of products label themselves as probiotic. It’s a great marketing scheme, but many of the products out there aren’t really probiotics; they’re not proven with randomized control trials and don’t have the scientific background,” said Dr. McFarland. “We’ve found that the efficacy is extremely strain specific and disease specific. A strain may work for one disease and not work for another.”

In 2018, Dr. McFarland coauthored an evidence-based practical guide to help clinicians and patients identify the specific strain that works in certain indications. Dr. Cresci recommends that clinicians consult websites such as Probiotics.org or the National Institutes of Health’s database to find the strains that have been proven to work in well-designed clinical trials.

There was also agreement that, to date, the most robust data support probiotics for the treatment of antibiotic-associated diarrhea.

Although the optimal timing of probiotics is a subject of debate, most proponents agreed that the general rule is “the sooner the better.”

Dr. McFarland recommended incorporating probiotics within 24 hours of starting an antibiotic “because the damage done to your GI tract microbiome is pretty quick, and the probiotics work best if they’re established before major disruption occurs.” She added that patients should continue taking probiotics for 2-8 weeks after stopping antibiotics.

“It takes a long time for your normal flora to get restored,” she said. “It’s best to cover your bases.”

For others, the evidence is not definitive

Opinions on the value of probiotics to combat antibiotic-related GI side effects are divergent, though.

“I would not recommend the routine use of probiotics, and certainly not in the prevention of C. difficile or antibiotic-related diarrhea,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk. “I think the evidence does not support that, and I stand strongly on that recommendation.”

Dr. Johnson cited the 2020 guidelines from the American Gastroenterological Association, which offer only a conditional recommendation for the use of specific probiotics and only in preventing antibiotic-associated C. difficile infection.

Geoffrey A. Preidis, MD, PhD, an assistant professor of pediatrics in the section of gastroenterology, hepatology, and nutrition at Baylor College of Medicine, Houston, served as a coauthor of the AGA’s guidelines. He noted that after reviewing 39 published trials of approximately 10,000 patients given probiotics while receiving antibiotics, the authors “did find some evidence that specific probiotics might decrease the risk of C. difficile diarrhea, but the quality of that evidence was low.”

Dr. Preidis attributed this to the lack of well-designed multicenter trials that can isolate the effects of certain strains and determine their benefit in this application.

“The majority of published trials have not reported safety data as rigorously as these data are reported in pharmaceutical trials, so the risk of side effects could be higher than we think,” said Dr. Preidis. “As living microbes, probiotics can move from the intestines into the bloodstream, causing sepsis. Contamination in the manufacturing process has been reported. There might be other long-term effects that we are not yet aware of.”

When asked to characterize the available data on probiotics, Dr. Johnson replied, “I’d generally label it, ‘caveat emptor.’ ”

Dr. McFarland agreed that the field would benefit from better-designed studies and called out meta-analyses that pool outcomes with various strains for particular criticism.

“When researchers do that, it’s no longer valid and shouldn’t have been published, in my opinion,” she told this news organization.

‘Antibiotic diets’ as a possible approach

A compromise between the two sides may be the so-called antibiotic diet. The theory behind such diets is that foods and beverages with biome-boosting properties may be a risk-free intervention that patients can adopt to alleviate antibiotic-related side effects.

“You want your diet to include more soluble fibers to help support the good bacteria, particularly when you’re taking antibiotics,” said Dr. Cresci. “You can get this through eating fresh fruits and vegetables, whole grains, and foods that have more prebiotic, like potatoes. You can also eat fermented food, such as kefir, kombucha, kimchi, and yogurt, so you’re adding more beneficial bacteria into your intestinal tract.”

There is ample published evidence that such foods can boost microbiome diversity and decrease inflammation, including a July 2021 study in Cell. However, the protection this may confer while taking antibiotics isn’t known. Establishing a clear role for the efficacy of such interventions is made additionally difficult by the well-established limitations of conducting dietary clinical trials.

Dr. Merenstein said that there is no compelling evidence that antibiotic-related complications can be offset by changing what goes onto our dinner plates. He joked: “We can’t say, ‘Here’s amoxicillin for your ear infection, now make sure you increase your fermented food, fiber, and water.’ ”

Dr. Johnson said he’s intrigued by studies of prebiotics – fibers that boost beneficial bacteria in the GI system.

“I would love to have more findings about prebiotic identification; that is, things we could do in a healthy way to keep the gut balanced while it’s subject to a change with antibiotics,” he said. “We’re just not there yet.”

Dr. Johnson added that he generally recommends that patients taking antibiotics eat “a bland diet, avoiding things that may have been provocative in the past.”

If patients are already enjoying foods with microbiome-boosting reputations, Dr. Johnson sees “very little downside to continuing that [while on antibiotics].” However, he noted that the period in which you’re taking antibiotics isn’t ideal for trying new foods, given the lack of experience with how the gut bacteria will react.

There are data about foods to avoid while taking antibiotics, which generally fall in line with common dietary knowledge. Many patients may know not to drink grapefruit juice with certain medications, but it’s worth a reminder. Certain antibiotics may also require delaying or avoiding dairy products, although this does not apply to yogurt.

A fiber-deficient diet can aggravate microbiota collapse following antibiotics. In a 2020 study, researchers showed that people on a high-fat diet who were using antibiotics were 8.6 times more likely to have preinflammatory bowel disease than those eating low-fat foods and who had no recent history of antibiotic use. Mouse model data from the same study indicated that poor diet and antibiotics may have worked in conjunction to reduce oxygen in the gut.

Dr. McFarland noted that building a healthy microbiome is a lifelong pursuit and that several factors (for example, environmental or genetic) are out of individuals’ hands. The general public might want a quick fix – ironically, one of the main drivers behind their requesting and receiving antibiotics when they’re not indicated – but it’s likely not available to them.

“You can’t eat one salad and suddenly have a healthy gut, unfortunately.”

A version of this article first appeared on Medscape.com.

New COVID-19 cases in children fell by 23% as the latest weekly count dropped to its lowest level since July of 2021, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

During the week of March 11-17, the United States saw just under 32,000 new pediatric cases of COVID-19, a decline of 23% from the week before and the lowest figure reported since July 9-15, 2021, when the early stages of the Delta surge led to 23,551 cases, the AAP and CHA said in their weekly COVID report.

The two organizations put the total number of cases at nearly 12.8 million from the start of the pandemic to March 17, with children representing 19.0% of cases among all ages. The Centers for Disease Control and Prevention puts the cumulative number of COVID-19 cases at almost 12.0 million as of March 21, or 17.5% of the nationwide total.

COVID-related hospitalizations also continue to fall, and two new studies from the CDC put children’s experiences during the Omicron surge and the larger pandemic into perspective.

One study showed that hospitalization rates for children aged 4 years and younger during the Omicron surge were five times higher than at the peak of the Delta surge, with the highest rates occurring in infants under 6 months of age. That report was based on the CDC’s COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), which covers 99 counties across 14 states (MMWR. 2022 March 18;71[11]:429-36).

The second study compared child hospitalizations during 1 year of the COVID pandemic (Oct. 1, 2020, to Sept. 30, 2021) with three influenza seasons (2017-2018 through 2019-2020). The pre-Omicron hospitalization rate for those under age 18 years, 48.2 per 100,000 children, was higher than any of the three flu seasons: 33.5 per 100,000 in 2017-2018, 33.8 in 2018-2019, and 41.7 for 2019-2020, the investigators said in a medRxiv preprint.

Most of the increased COVID burden fell on adolescents aged 12-17, they said. The COVID hospitalization rate for that age group was 59.9 per 100,000, versus 12.2-14.1 for influenza, while children aged 5-11 had a COVID-related rate of 25.0 and flu-related rates of 24.3-31.7, and those aged 0-4 had rates of 66.8 for COVID and 70.9-91.5 for the flu, Miranda J. Delahoy of the CDC’s COVID-19 Response Team and associates reported.

rfranki@mdedge.com

New COVID-19 cases in children fell by 23% as the latest weekly count dropped to its lowest level since July of 2021, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

During the week of March 11-17, the United States saw just under 32,000 new pediatric cases of COVID-19, a decline of 23% from the week before and the lowest figure reported since July 9-15, 2021, when the early stages of the Delta surge led to 23,551 cases, the AAP and CHA said in their weekly COVID report.

The two organizations put the total number of cases at nearly 12.8 million from the start of the pandemic to March 17, with children representing 19.0% of cases among all ages. The Centers for Disease Control and Prevention puts the cumulative number of COVID-19 cases at almost 12.0 million as of March 21, or 17.5% of the nationwide total.

COVID-related hospitalizations also continue to fall, and two new studies from the CDC put children’s experiences during the Omicron surge and the larger pandemic into perspective.

One study showed that hospitalization rates for children aged 4 years and younger during the Omicron surge were five times higher than at the peak of the Delta surge, with the highest rates occurring in infants under 6 months of age. That report was based on the CDC’s COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), which covers 99 counties across 14 states (MMWR. 2022 March 18;71[11]:429-36).

The second study compared child hospitalizations during 1 year of the COVID pandemic (Oct. 1, 2020, to Sept. 30, 2021) with three influenza seasons (2017-2018 through 2019-2020). The pre-Omicron hospitalization rate for those under age 18 years, 48.2 per 100,000 children, was higher than any of the three flu seasons: 33.5 per 100,000 in 2017-2018, 33.8 in 2018-2019, and 41.7 for 2019-2020, the investigators said in a medRxiv preprint.

Most of the increased COVID burden fell on adolescents aged 12-17, they said. The COVID hospitalization rate for that age group was 59.9 per 100,000, versus 12.2-14.1 for influenza, while children aged 5-11 had a COVID-related rate of 25.0 and flu-related rates of 24.3-31.7, and those aged 0-4 had rates of 66.8 for COVID and 70.9-91.5 for the flu, Miranda J. Delahoy of the CDC’s COVID-19 Response Team and associates reported.

rfranki@mdedge.com

New COVID-19 cases in children fell by 23% as the latest weekly count dropped to its lowest level since July of 2021, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

During the week of March 11-17, the United States saw just under 32,000 new pediatric cases of COVID-19, a decline of 23% from the week before and the lowest figure reported since July 9-15, 2021, when the early stages of the Delta surge led to 23,551 cases, the AAP and CHA said in their weekly COVID report.

The two organizations put the total number of cases at nearly 12.8 million from the start of the pandemic to March 17, with children representing 19.0% of cases among all ages. The Centers for Disease Control and Prevention puts the cumulative number of COVID-19 cases at almost 12.0 million as of March 21, or 17.5% of the nationwide total.

COVID-related hospitalizations also continue to fall, and two new studies from the CDC put children’s experiences during the Omicron surge and the larger pandemic into perspective.

One study showed that hospitalization rates for children aged 4 years and younger during the Omicron surge were five times higher than at the peak of the Delta surge, with the highest rates occurring in infants under 6 months of age. That report was based on the CDC’s COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), which covers 99 counties across 14 states (MMWR. 2022 March 18;71[11]:429-36).

The second study compared child hospitalizations during 1 year of the COVID pandemic (Oct. 1, 2020, to Sept. 30, 2021) with three influenza seasons (2017-2018 through 2019-2020). The pre-Omicron hospitalization rate for those under age 18 years, 48.2 per 100,000 children, was higher than any of the three flu seasons: 33.5 per 100,000 in 2017-2018, 33.8 in 2018-2019, and 41.7 for 2019-2020, the investigators said in a medRxiv preprint.

Most of the increased COVID burden fell on adolescents aged 12-17, they said. The COVID hospitalization rate for that age group was 59.9 per 100,000, versus 12.2-14.1 for influenza, while children aged 5-11 had a COVID-related rate of 25.0 and flu-related rates of 24.3-31.7, and those aged 0-4 had rates of 66.8 for COVID and 70.9-91.5 for the flu, Miranda J. Delahoy of the CDC’s COVID-19 Response Team and associates reported.

rfranki@mdedge.com

People who recover from a mild case of COVID-19 appear to have an increased risk for subsequent new-onset type 2 diabetes but not other types of diabetes, new data suggest.

“If confirmed, the results of the present study indicate that diabetes screening in individuals who have recovered from even mild COVID-19 should be recommended,” say Wolfgang Rathmann, MD, of the Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany, and colleagues.

The findings, from a nationwide primary care database in Germany, were recently published in Diabetologia.

These primary care data align with those from other studies of more seriously ill patients with COVID-19 that found increased rates of type 2 diabetes diagnoses in the subsequent months following illness, they point out.

“COVID-19 infection may lead to diabetes by upregulation of the immune system after remission, which may induce pancreatic beta-cell dysfunction and insulin resistance, or patients may have been at risk for developing diabetes due to having obesity or prediabetes, and the stress COVID-19 put on their bodies sped it up,” said Dr. Rathmann in a press release.

However, because the patients with COVID-19 in the study were only followed for about 3 months, “further follow-up is needed to understand whether type 2 diabetes after mild COVID-19 is just temporary and can be reversed after they have fully recovered or whether it leads to a chronic condition,” he noted.
 

Increase in type 2 diabetes 3 months after mild COVID-19

The retrospective cohort analysis was performed using data from the Disease Analyzer, a representative panel of 1,171 physician practices in Germany, from March 2020 to January 2021, with follow-up through July 2021.

Individuals with a history of COVID-19 or diabetes and those taking corticosteroids within 30 days after the index dates were excluded.

A total of 35,865 patients with confirmed SARS-CoV-2 infection were propensity score-matched on a one-to-one basis for sex, age, health insurance, and comorbidities with those who had acute respiratory tract infections (controls) but were COVID-19 negative. Median follow-up was 119 days for the COVID-19 group and 161 days for controls.

There was a 28% increased risk of type 2 diabetes for those who had COVID-19 versus controls (15.8 per 1,000 person-years vs. 12.3 per 1,000 person-years, respectively, which was significantly different, and an incidence rate ratio of 1.28).

The incidence of other types of diabetes or unspecified diabetes for the COVID-19 and control groups did not differ significantly (4.3 per 1,000 person-years vs. 3.7 per 1,000 person-years; IRR, 1.17).

Similar findings were seen in sensitivity analyses by glucose-lowering medication prescriptions and by ICD-10 codes.

Although type 2 diabetes is not likely to be a problem for the vast majority of people who have mild COVID-19, the authors recommend that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms such as fatigue, frequent urination, and increased thirst, and seek treatment right away.

CoviDiab registry tracking type 1 and type 2 diabetes

Over the course of the pandemic, there have been conflicting data on whether COVID-19 induces or reveals a propensity for type 1 and type 2 diabetes.

The CoviDiab global registry is tracking this and will include diabetes type for adults and children.

The aim is to have “as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c,” coprincipal investigator Francesco Rubino, MD, of King’s College London, previously told this news organization.

“By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19.”

Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or the hyperglycemia may be stress-induced and temporary.

The German Diabetes Center is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State of North Rhine-Westphalia. Dr. Rathmann has reported receiving consulting fees for attending educational sessions or advisory boards for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk and institutional research grants from Novo Nordisk outside of the topic of the current work.

A version of this article first appeared on Medscape.com.

People who recover from a mild case of COVID-19 appear to have an increased risk for subsequent new-onset type 2 diabetes but not other types of diabetes, new data suggest.

“If confirmed, the results of the present study indicate that diabetes screening in individuals who have recovered from even mild COVID-19 should be recommended,” say Wolfgang Rathmann, MD, of the Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany, and colleagues.

The findings, from a nationwide primary care database in Germany, were recently published in Diabetologia.

These primary care data align with those from other studies of more seriously ill patients with COVID-19 that found increased rates of type 2 diabetes diagnoses in the subsequent months following illness, they point out.

“COVID-19 infection may lead to diabetes by upregulation of the immune system after remission, which may induce pancreatic beta-cell dysfunction and insulin resistance, or patients may have been at risk for developing diabetes due to having obesity or prediabetes, and the stress COVID-19 put on their bodies sped it up,” said Dr. Rathmann in a press release.

However, because the patients with COVID-19 in the study were only followed for about 3 months, “further follow-up is needed to understand whether type 2 diabetes after mild COVID-19 is just temporary and can be reversed after they have fully recovered or whether it leads to a chronic condition,” he noted.
 

Increase in type 2 diabetes 3 months after mild COVID-19

The retrospective cohort analysis was performed using data from the Disease Analyzer, a representative panel of 1,171 physician practices in Germany, from March 2020 to January 2021, with follow-up through July 2021.

Individuals with a history of COVID-19 or diabetes and those taking corticosteroids within 30 days after the index dates were excluded.

A total of 35,865 patients with confirmed SARS-CoV-2 infection were propensity score-matched on a one-to-one basis for sex, age, health insurance, and comorbidities with those who had acute respiratory tract infections (controls) but were COVID-19 negative. Median follow-up was 119 days for the COVID-19 group and 161 days for controls.

There was a 28% increased risk of type 2 diabetes for those who had COVID-19 versus controls (15.8 per 1,000 person-years vs. 12.3 per 1,000 person-years, respectively, which was significantly different, and an incidence rate ratio of 1.28).

The incidence of other types of diabetes or unspecified diabetes for the COVID-19 and control groups did not differ significantly (4.3 per 1,000 person-years vs. 3.7 per 1,000 person-years; IRR, 1.17).

Similar findings were seen in sensitivity analyses by glucose-lowering medication prescriptions and by ICD-10 codes.

Although type 2 diabetes is not likely to be a problem for the vast majority of people who have mild COVID-19, the authors recommend that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms such as fatigue, frequent urination, and increased thirst, and seek treatment right away.

CoviDiab registry tracking type 1 and type 2 diabetes

Over the course of the pandemic, there have been conflicting data on whether COVID-19 induces or reveals a propensity for type 1 and type 2 diabetes.

The CoviDiab global registry is tracking this and will include diabetes type for adults and children.

The aim is to have “as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c,” coprincipal investigator Francesco Rubino, MD, of King’s College London, previously told this news organization.

“By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19.”

Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or the hyperglycemia may be stress-induced and temporary.

The German Diabetes Center is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State of North Rhine-Westphalia. Dr. Rathmann has reported receiving consulting fees for attending educational sessions or advisory boards for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk and institutional research grants from Novo Nordisk outside of the topic of the current work.

A version of this article first appeared on Medscape.com.

People who recover from a mild case of COVID-19 appear to have an increased risk for subsequent new-onset type 2 diabetes but not other types of diabetes, new data suggest.

“If confirmed, the results of the present study indicate that diabetes screening in individuals who have recovered from even mild COVID-19 should be recommended,” say Wolfgang Rathmann, MD, of the Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany, and colleagues.

The findings, from a nationwide primary care database in Germany, were recently published in Diabetologia.

These primary care data align with those from other studies of more seriously ill patients with COVID-19 that found increased rates of type 2 diabetes diagnoses in the subsequent months following illness, they point out.

“COVID-19 infection may lead to diabetes by upregulation of the immune system after remission, which may induce pancreatic beta-cell dysfunction and insulin resistance, or patients may have been at risk for developing diabetes due to having obesity or prediabetes, and the stress COVID-19 put on their bodies sped it up,” said Dr. Rathmann in a press release.

However, because the patients with COVID-19 in the study were only followed for about 3 months, “further follow-up is needed to understand whether type 2 diabetes after mild COVID-19 is just temporary and can be reversed after they have fully recovered or whether it leads to a chronic condition,” he noted.
 

Increase in type 2 diabetes 3 months after mild COVID-19

The retrospective cohort analysis was performed using data from the Disease Analyzer, a representative panel of 1,171 physician practices in Germany, from March 2020 to January 2021, with follow-up through July 2021.

Individuals with a history of COVID-19 or diabetes and those taking corticosteroids within 30 days after the index dates were excluded.

A total of 35,865 patients with confirmed SARS-CoV-2 infection were propensity score-matched on a one-to-one basis for sex, age, health insurance, and comorbidities with those who had acute respiratory tract infections (controls) but were COVID-19 negative. Median follow-up was 119 days for the COVID-19 group and 161 days for controls.

There was a 28% increased risk of type 2 diabetes for those who had COVID-19 versus controls (15.8 per 1,000 person-years vs. 12.3 per 1,000 person-years, respectively, which was significantly different, and an incidence rate ratio of 1.28).

The incidence of other types of diabetes or unspecified diabetes for the COVID-19 and control groups did not differ significantly (4.3 per 1,000 person-years vs. 3.7 per 1,000 person-years; IRR, 1.17).

Similar findings were seen in sensitivity analyses by glucose-lowering medication prescriptions and by ICD-10 codes.

Although type 2 diabetes is not likely to be a problem for the vast majority of people who have mild COVID-19, the authors recommend that anyone who has recovered from COVID-19 be aware of the warning signs and symptoms such as fatigue, frequent urination, and increased thirst, and seek treatment right away.

CoviDiab registry tracking type 1 and type 2 diabetes

Over the course of the pandemic, there have been conflicting data on whether COVID-19 induces or reveals a propensity for type 1 and type 2 diabetes.

The CoviDiab global registry is tracking this and will include diabetes type for adults and children.

The aim is to have “as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c,” coprincipal investigator Francesco Rubino, MD, of King’s College London, previously told this news organization.

“By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19.”

Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or the hyperglycemia may be stress-induced and temporary.

The German Diabetes Center is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State of North Rhine-Westphalia. Dr. Rathmann has reported receiving consulting fees for attending educational sessions or advisory boards for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk and institutional research grants from Novo Nordisk outside of the topic of the current work.

A version of this article first appeared on Medscape.com.