MDedge Infectious Disease

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

Moderna probably will not have clinical trial results anytime soon on how its COVID-19 vaccine affects children and adolescents, according to the company CEO and a federal official.

The Moderna vaccine was authorized for use in December and is now being given to people 18 and over. But children would receive lower doses, so new clinical trials must be done, Moderna CEO Stephane Bancel said at the JPMorgan virtual Health Care Conference on Monday.

Clinical trials on children 11 and younger “will take much longer, because we have to age deescalate and start at a lower dose. So we should not anticipate clinical data in 2021, but more in 2022,” Ms. Bancel said, according to Business Insider.

Moderna’s clinical trials for 12- to 17-year-olds started 4 weeks ago, but the company is having trouble getting enough participants, said Moncef Slaoui, PhD, the scientific head of Operation Warp Speed, the U.S. government’s vaccine effort. That could delay Food and Drug Administration approval, he said.

“It’s really very important for all of us, for all the population in America, to realize that we can’t have that indication unless adolescents aged 12-18 decide to participate,” Dr. Slaoui said, according to USA Today.

He said the adolescent trials are getting only about 800 volunteers a month, but need at least 3,000 volunteers to complete the study, USA Today reported. Parents interested in having their child participate can check eligibility and sign at this website.

The Pfizer/BioNTech vaccine won authorization for use in 16- to 17-year-olds as well as adults.

The coronavirus doesn’t appear to have as serious complications for children as for adults.

“At this time, it appears that severe illness due to COVID-19 is rare among children,” the American Association of Pediatrics says. “However, there is an urgent need to collect more data on longer-term impacts of the pandemic on children, including ways the virus may harm the long-term physical health of infected children, as well as its emotional and mental health effects.”

The association says 179 children had died of COVID-related reasons in 43 states and New York City as of Dec. 31, 2020. That’s about 0.06% of total COVID deaths, it says.

But children do get sick. As of Jan. 7, 2021, nearly 2.3 million children had tested positive for COVID-19 since the start of the pandemic, the association says.

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

New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.

Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.

However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.

The results were published online Jan. 7 in MedRxiv.

Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.

“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent  story by Reuters.
 

Consider the big picture

“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.

One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”

“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
 

Interim findings

The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.

Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).

“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
 

Cautious optimism?

“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”

In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.

“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.

Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”

Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”

Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.

The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.

Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
 

Backing from the British

Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.

Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.

“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”

Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.

Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.

“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).

Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”

Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”

“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.

Awaiting peer review

“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.

“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”

“We need to make sure these findings, as outlined, hold up,” he said.

In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”

The REMAP-CAP study is ongoing and updated results will be provided online.

Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.

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

New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.

Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.

However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.

The results were published online Jan. 7 in MedRxiv.

Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.

“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent  story by Reuters.
 

Consider the big picture

“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.

One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”

“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
 

Interim findings

The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.

Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).

“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
 

Cautious optimism?

“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”

In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.

“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.

Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”

Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”

Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.

The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.

Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
 

Backing from the British

Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.

Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.

“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”

Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.

Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.

“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).

Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”

Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”

“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.

Awaiting peer review

“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.

“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”

“We need to make sure these findings, as outlined, hold up,” he said.

In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”

The REMAP-CAP study is ongoing and updated results will be provided online.

Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.

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

New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.

Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.

However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.

The results were published online Jan. 7 in MedRxiv.

Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.

“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent  story by Reuters.
 

Consider the big picture

“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.

One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”

“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
 

Interim findings

The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.

Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).

“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
 

Cautious optimism?

“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”

In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.

“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.

Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”

Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”

Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.

The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.

Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
 

Backing from the British

Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.

Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.

“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”

Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.

Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.

“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).

Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”

Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”

“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.

Awaiting peer review

“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.

“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”

“We need to make sure these findings, as outlined, hold up,” he said.

In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”

The REMAP-CAP study is ongoing and updated results will be provided online.

Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.

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

When Margot Gage-Witvliet began feeling run down after her family returned from a trip to the Netherlands in late February 2020, she initially chalked up her symptoms to jet lag. Three days later, however, her situation went from concerning to alarming as she struggled to breathe. “It felt like there was an elephant sitting on my chest,” she said.

Her husband and daughters also became ill with COVID-19, but Ms. Gage-Witvliet was the only one in her family who didn’t get better. After an early improvement, a rare coronavirus-induced tonic-clonic seizure in early April sent her spiraling back down. Ms. Gage-Witvliet spent the next several weeks in bed with the curtains drawn, unable to tolerate light or sound.

Today, Ms. Gage-Witvliet’s life looks nothing like it did 6 months ago when she first got sick. As one of COVID-19’s so called long-haulers, she continues to struggle with crushing fatigue, brain fog, and headaches – symptoms that worsen when she pushes herself to do more. Across the country, as many as 1 in 10 COVID-19 patients are reporting illnesses that continue for weeks and months after their initial diagnosis. Nearly all report neurologic issues like Ms. Gage-Witvliet, as well as shortness of breath and psychiatric concerns.

For Avindra Nath, MD, a neurologist at the National Institutes of Health, the experience of these long-haul COVID-19 patients feels familiar and reminds him of myalgic encephalomyelitis, also known as chronic fatigue syndrome.

Dr. Nath has long been interested in the lingering neurologic issues connected to chronic fatigue. An estimated three-quarters of all patients with chronic fatigue syndrome report that their symptoms started after a viral infection, and they suffer unrelenting exhaustion, difficulties regulating pulse and blood pressure, aches and pains, and brain fog. When Dr. Nath first read about the novel coronavirus, he began to worry that the virus would trigger symptoms in a subset of those infected. Hearing about the experiences of long-haulers like Ms. Gage-Witvliet raised his suspicions even more.

Unlike COVID-19 long-haulers, however, many patients with chronic fatigue syndrome go at least a year with these symptoms before receiving a diagnosis, according to a British survey. That means researchers have had few opportunities to study the early stages of the syndrome. “When we see patients with myalgic encephalomyelitis, whatever infection they might have had occurred in the remote past, so there’s no way for us to know how they got infected with it, what the infection was, or what the effects of it were in that early phase. We’re seeing them 2 years afterward,” Dr. Nath said.

Dr. Nath quickly realized that studying patients like Ms. Gage-Witvliet would give physicians and scientists a unique opportunity to understand not only long-term outcomes of COVID-19 infections, but also other postviral syndromes, including chronic fatigue syndrome at their earliest stages. It’s why Dr. Nath has spent the past several months scrambling to launch two NIH studies to examine the phenomenon.

Although Dr. Nath said that the parallels between COVID-19 long-haulers and those with chronic fatigue syndrome are obvious, he cautions against assuming that they are the same phenomenon. Some long-haulers might simply be taking a much slower path to recovery, or they might have a condition that looks similar on the surface but differs from chronic fatigue syndrome on a molecular level. But even if Dr. Nath fails to see links to chronic fatigue syndrome, with more than 92.5 million documented cases of COVID-19 around the world, the work will be relevant to the substantial number of infected individuals who don’t recover quickly.

“With so many people having exposure to the same virus over a similar time period, we really have the opportunity to look at these manifestations and at the very least to understand postviral syndromes,” said Mady Hornig, MD, a psychiatrist at Columbia University, New York.

The origins of chronic fatigue syndrome date back to 1985, when the Centers for Disease Control and Prevention received a request from two physicians – Paul Cheney, MD, and Daniel Peterson, MD – to investigate a mysterious disease outbreak in Nevada. In November 1984, residents in and around the idyllic vacation spot of Incline Village, a small town tucked into the north shore of Lake Tahoe, had begun reporting flu-like symptoms that persisted for weeks, even months. The doctors had searched high and low for a cause, but they couldn’t figure out what was making their patients sick.

They reported a range of symptoms – including muscle aches and pains, low-grade fevers, sore throats, and headaches – but everyone said that crippling fatigue was the most debilitating issue. This wasn’t the kind of fatigue that could be cured by a nap or even a long holiday. No matter how much their patients slept – and some were almost completely bedbound – their fatigue didn’t abate. What’s more, the fatigue got worse whenever they tried to push themselves to do more. Puzzled, the CDC sent two epidemic intelligence service (EIS) officers to try to get to the bottom of what might be happening.


 

Muscle aches and pains with crippling fatigue

After their visit to Incline Village, however, the CDC was just as perplexed as Dr. Cheney and Dr. Peterson. Many of the people with the condition reported flu-like symptoms right around the time they first got sick, and the physicians’ leading hypothesis was that the outbreak and its lasting symptoms were caused by chronic Epstein-Barr virus infection. But neither the CDC nor anyone else could identify the infection or any other microbial cause. The two EIS officers duly wrote up a report for the CDC’s flagship publication, Morbidity and Mortality Weekly ReportI, titled “Chronic Fatigue Possibly Related to Epstein-Barr Virus – Nevada”.

That investigators focused on the fatigue aspect made sense, says Leonard A. Jason, PhD, professor of psychology at DePaul University and director of the Center for Community Research, both in Chicago, because it was one of the few symptoms shared by all the individuals studied and it was also the most debilitating. But that focus – and the name “chronic fatigue syndrome” – led to broad public dismissal of the condition’s severity, as did an editorial note in MMWR urging physicians to look for “more definable, and possibly treatable, conditions.” Subsequent research failed to confirm a specific link to the Epstein-Barr virus, which only added to the condition’s phony reputation. Rather than being considered a potentially disabling illness, it was disregarded as a “yuppie flu” or a fancy name for malingering.

“It’s not a surprise that patients are being dismissed because there’s already this sort of grandfathered-in sense that fatigue is not real,” said Jennifer Frankovich, MD, a pediatric rheumatologist at Stanford (Calif.) University’s Lucile Packard Children’s Hospital in Palo Alto. “I’m sure that’s frustrating for them to be tired and then to have the clinician not believe them or dismiss them or think they’re making it up. It would be more helpful to the families to say: ‘You know what, we don’t know, we do not have the answer, and we believe you.’ ”
 

A syndrome’s shame

As time passed, patient advocacy groups began pushing back against the negative way the condition was being perceived. This criticism came as organizations like the CDC worked to develop a set of diagnostic criteria that researchers and clinicians dealing with chronic fatigue syndrome could use. With such a heterogeneous group of patients and symptoms, the task was no small challenge. The discussions, which took place over nearly 2 decades, played a key role in helping scientists home in on the single factor that was central to chronic fatigue: postexertional malaise.

“This is quite unique for chronic fatigue syndrome. With other diseases, yes, you may have fatigue as one of the components of the disease, but postexertional fatigue is very specific,” said Alain Moreau, PhD, a molecular biologist at the University of Montreal.

Of course, plenty of people have pushed themselves too hard physically and paid the price the next day. But those with chronic fatigue syndrome weren’t running marathons. To them, exertion could be anything from getting the mail to reading a book. Nor could the resulting exhaustion be resolved by an afternoon on the couch or a long vacation.

“If they do these activities, they can crash for weeks, even months,” Dr. Moreau said. It was deep, persistent, and – for 40% of those with chronic fatigue syndrome – disabling. In 2015, a study group from the Institute of Medicine proposed renaming chronic fatigue to “systemic exercise intolerance disease” because of the centrality of this symptom. Although that effort mostly stalled, their report did bring the condition out of its historic place as a scientific backwater. What resulted was an uptick in research on chronic fatigue syndrome, which helped define some of the physiological issues that either contribute to or result from the condition.

Researchers had long known about the link between infection and fatigue, said Dr. Frankovich. Work included mysterious outbreaks like the one in Lake Tahoe and well-documented issues like the wave of encephalitis lethargica (a condition that leaves patients in an almost vegetative state) that followed the 1918 H1N1 influenza pandemic.

“As a clinician, when you see someone who comes in with a chronic infection, they’re tired. I think that’s why, in the chronic-fatigue world, people are desperately looking for the infection so we can treat it, and maybe these poor suffering people will feel better,” Dr. Frankovich added. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Immunologic symptoms

Given the close link between a nonspecific viral illness and the onset of symptoms in chronic fatigue syndrome, scientists like Dr. Hornig opted to focus on immunologic symptoms. In a 2015 analysis published in Science, Dr. Hornig and colleagues showed that immune problems can be found in the earliest stages of chronic fatigue syndrome, and that they change as the illness progresses. Patients who had been sick for less than 3 years showed significant increases in levels of both pro- and anti-inflammatory cytokines, and the factor most strongly correlated to this inability to regulate cytokine levels was the duration of symptoms, not their severity. A series of other studies also revealed problems with regulation of the immune system, although no one could show what might have set these problems in motion.

Other researchers found signs of mitochondrial dysfunction in those with chronic fatigue syndrome. Because mitochondria make energy for cells, it wasn’t an intellectual stretch to believe that glitches in this process could contribute to fatigue. As early as 1991, scientists had discovered signs of mitochondrial degeneration in muscle biopsies from people with chronic fatigue syndrome. Subsequent studies showed that those affected by chronic fatigue were missing segments of mitochondrial DNA and had significantly reduced levels of mitochondrial activity. Although exercise normally improves mitochondrial functioning, the opposite appears to happen in chronic fatigue.

To Dr. Nath, these dual hypotheses aren’t necessarily mutually exclusive. Some studies have hinted that infection with the common human herpesvirus–6 (HHV-6) can lead to an autoimmune condition in which the body makes antibodies against the mitochondria. Mitochondria also play a key role in the ability of the innate immune system to produce interferon and other proinflammatory cytokines. It might also be that the link between immune and mitochondrial problems is more convoluted than originally thought, or that the two systems are affected independent of one another, Dr. Nath said.

Finding answers, especially those that could lead to potential treatments, wouldn’t be easy, however. In 2016, the NIH launched an in-depth study of a small number of individuals with chronic fatigue, hoping to find clues about what the condition was and how it might be treated.

For scientists like Dr. Nath, the NIH study provided a way to get at the underlying biology of chronic fatigue syndrome. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Chronic post-SARS syndrome

In March 2020, retired physician Harvey Moldofsky, MD, began receiving inquiries about a 2011 study he and his colleague, John Patcai, MD, had published in BMC Neurology about something they dubbed “chronic post-SARS syndrome.” The small case-control study, which involved mainly health care workers in Toronto, received little attention when it was first published, but with COVID-19, it was suddenly relevant.

Early clusters of similar cases in Miami made local physicians desperate for Dr. Moldofsky’s expertise. Luckily, he was nearby; he had fled the frigid Canadian winter for the warmth of Sarasota, Fla.

“I had people from various countries around the world writing to me and asking what they should do. And of course I don’t have any answers,” he said. But the study contained one of the world’s only references to the syndrome.

In 2003, a woman arrived in Toronto from Hong Kong. She didn’t know it at the time, but her preairport stay at the Hotel Metropole had infected her with the first SARS (severe acute respiratory syndrome) coronavirus. Her subsequent hospitalization in Toronto sparked a city-wide outbreak of SARS in which 273 people became ill and 44 died. Many of those affected were health care workers, including nurses and respiratory therapists. Although most eventually returned to work, a subset couldn’t. They complained of energy-sapping fatigue, poor sleep, brain fog, and assorted body aches and pains that persisted for more than 18 months. The aches and pains brought them to the attention of Dr. Moldofsky, then director of the Centre for the Study of Pain at the University of Toronto.

His primary interest at the time was fibromyalgia, which caused symptoms similar to those reported by the original SARS long-haulers. Intrigued, Dr. Moldofsky agreed to take a look. Their chest x-rays were clear and the nurses showed no signs of lingering viral infection. Dr. Moldofsky could see that the nurses were ill and suffering, but no lab tests or anything else could identify what was causing their symptoms.

In 2011, Dr. Moldofsky and Dr. Patcai found a strong overlap between chronic SARS, fibromyalgia, and chronic fatigue syndrome when they compared 22 patients with long-term SARS issues with 21 who had fibromyalgia. “Their problems are exactly the same. They have strange symptoms and nobody can figure out what they’re about. And these symptoms are aches and pains, and they have trouble thinking and concentrating,” Dr. Moldofsky said. Reports of COVID-19 long-haulers didn’t surprise Dr. Moldofsky, and he immediately recognized that Nath’s intention to follow these patients could provide insights into both fibromyalgia and chronic fatigue syndrome.

That’s exactly what Dr. Nath is proposing with the two NIH studies. One will focus solely on the neurologic impacts of COVID-19, including stroke, loss of taste and smell, and brain fog. The other will bring patients who have had COVID-19 symptoms for at least 6 months to the NIH Clinical Center for an inpatient stay during which they will undergo detailed physiologic tests.

Scientists around the world are launching their own post–COVID-19 studies. Dr. Moreau’s group in Montreal has laid the groundwork for such an endeavor, and the CoroNerve group in the United Kingdom is monitoring neurologic complications from the coronavirus. Many of them have the same goals as the NIH studies: Leverage the large number of COVID-19 long-haulers to better understand the earliest stages of postviral syndrome.

“At this juncture, after all the reports that we’ve seen so far, I think it’s very unlikely that there will be no relationship whatsoever between COVID-19 and chronic fatigue syndrome,” Dr. Hornig said. “I think there certainly will be some, but again, what’s the scope, what’s the size? And then, of course, even more importantly, if it is happening, what is the mechanism and how is it happening?”

For people like Ms. Gage-Witvliet, the answers can’t come soon enough. For the first time in more than a decade, the full-time professor of epidemiology didn’t prepare to teach this year because she simply can’t. It’s too taxing for her brain to deal with impromptu student questions. Ms. Gage-Witvliet hopes that, by sharing her own experiences with post COVID-19, she can help others.

“In my work, I use data to give a voice to people who don’t have a voice,” she said. “Now, I am one of those people.”

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

When Margot Gage-Witvliet began feeling run down after her family returned from a trip to the Netherlands in late February 2020, she initially chalked up her symptoms to jet lag. Three days later, however, her situation went from concerning to alarming as she struggled to breathe. “It felt like there was an elephant sitting on my chest,” she said.

Her husband and daughters also became ill with COVID-19, but Ms. Gage-Witvliet was the only one in her family who didn’t get better. After an early improvement, a rare coronavirus-induced tonic-clonic seizure in early April sent her spiraling back down. Ms. Gage-Witvliet spent the next several weeks in bed with the curtains drawn, unable to tolerate light or sound.

Today, Ms. Gage-Witvliet’s life looks nothing like it did 6 months ago when she first got sick. As one of COVID-19’s so called long-haulers, she continues to struggle with crushing fatigue, brain fog, and headaches – symptoms that worsen when she pushes herself to do more. Across the country, as many as 1 in 10 COVID-19 patients are reporting illnesses that continue for weeks and months after their initial diagnosis. Nearly all report neurologic issues like Ms. Gage-Witvliet, as well as shortness of breath and psychiatric concerns.

For Avindra Nath, MD, a neurologist at the National Institutes of Health, the experience of these long-haul COVID-19 patients feels familiar and reminds him of myalgic encephalomyelitis, also known as chronic fatigue syndrome.

Dr. Nath has long been interested in the lingering neurologic issues connected to chronic fatigue. An estimated three-quarters of all patients with chronic fatigue syndrome report that their symptoms started after a viral infection, and they suffer unrelenting exhaustion, difficulties regulating pulse and blood pressure, aches and pains, and brain fog. When Dr. Nath first read about the novel coronavirus, he began to worry that the virus would trigger symptoms in a subset of those infected. Hearing about the experiences of long-haulers like Ms. Gage-Witvliet raised his suspicions even more.

Unlike COVID-19 long-haulers, however, many patients with chronic fatigue syndrome go at least a year with these symptoms before receiving a diagnosis, according to a British survey. That means researchers have had few opportunities to study the early stages of the syndrome. “When we see patients with myalgic encephalomyelitis, whatever infection they might have had occurred in the remote past, so there’s no way for us to know how they got infected with it, what the infection was, or what the effects of it were in that early phase. We’re seeing them 2 years afterward,” Dr. Nath said.

Dr. Nath quickly realized that studying patients like Ms. Gage-Witvliet would give physicians and scientists a unique opportunity to understand not only long-term outcomes of COVID-19 infections, but also other postviral syndromes, including chronic fatigue syndrome at their earliest stages. It’s why Dr. Nath has spent the past several months scrambling to launch two NIH studies to examine the phenomenon.

Although Dr. Nath said that the parallels between COVID-19 long-haulers and those with chronic fatigue syndrome are obvious, he cautions against assuming that they are the same phenomenon. Some long-haulers might simply be taking a much slower path to recovery, or they might have a condition that looks similar on the surface but differs from chronic fatigue syndrome on a molecular level. But even if Dr. Nath fails to see links to chronic fatigue syndrome, with more than 92.5 million documented cases of COVID-19 around the world, the work will be relevant to the substantial number of infected individuals who don’t recover quickly.

“With so many people having exposure to the same virus over a similar time period, we really have the opportunity to look at these manifestations and at the very least to understand postviral syndromes,” said Mady Hornig, MD, a psychiatrist at Columbia University, New York.

The origins of chronic fatigue syndrome date back to 1985, when the Centers for Disease Control and Prevention received a request from two physicians – Paul Cheney, MD, and Daniel Peterson, MD – to investigate a mysterious disease outbreak in Nevada. In November 1984, residents in and around the idyllic vacation spot of Incline Village, a small town tucked into the north shore of Lake Tahoe, had begun reporting flu-like symptoms that persisted for weeks, even months. The doctors had searched high and low for a cause, but they couldn’t figure out what was making their patients sick.

They reported a range of symptoms – including muscle aches and pains, low-grade fevers, sore throats, and headaches – but everyone said that crippling fatigue was the most debilitating issue. This wasn’t the kind of fatigue that could be cured by a nap or even a long holiday. No matter how much their patients slept – and some were almost completely bedbound – their fatigue didn’t abate. What’s more, the fatigue got worse whenever they tried to push themselves to do more. Puzzled, the CDC sent two epidemic intelligence service (EIS) officers to try to get to the bottom of what might be happening.


 

Muscle aches and pains with crippling fatigue

After their visit to Incline Village, however, the CDC was just as perplexed as Dr. Cheney and Dr. Peterson. Many of the people with the condition reported flu-like symptoms right around the time they first got sick, and the physicians’ leading hypothesis was that the outbreak and its lasting symptoms were caused by chronic Epstein-Barr virus infection. But neither the CDC nor anyone else could identify the infection or any other microbial cause. The two EIS officers duly wrote up a report for the CDC’s flagship publication, Morbidity and Mortality Weekly ReportI, titled “Chronic Fatigue Possibly Related to Epstein-Barr Virus – Nevada”.

That investigators focused on the fatigue aspect made sense, says Leonard A. Jason, PhD, professor of psychology at DePaul University and director of the Center for Community Research, both in Chicago, because it was one of the few symptoms shared by all the individuals studied and it was also the most debilitating. But that focus – and the name “chronic fatigue syndrome” – led to broad public dismissal of the condition’s severity, as did an editorial note in MMWR urging physicians to look for “more definable, and possibly treatable, conditions.” Subsequent research failed to confirm a specific link to the Epstein-Barr virus, which only added to the condition’s phony reputation. Rather than being considered a potentially disabling illness, it was disregarded as a “yuppie flu” or a fancy name for malingering.

“It’s not a surprise that patients are being dismissed because there’s already this sort of grandfathered-in sense that fatigue is not real,” said Jennifer Frankovich, MD, a pediatric rheumatologist at Stanford (Calif.) University’s Lucile Packard Children’s Hospital in Palo Alto. “I’m sure that’s frustrating for them to be tired and then to have the clinician not believe them or dismiss them or think they’re making it up. It would be more helpful to the families to say: ‘You know what, we don’t know, we do not have the answer, and we believe you.’ ”
 

A syndrome’s shame

As time passed, patient advocacy groups began pushing back against the negative way the condition was being perceived. This criticism came as organizations like the CDC worked to develop a set of diagnostic criteria that researchers and clinicians dealing with chronic fatigue syndrome could use. With such a heterogeneous group of patients and symptoms, the task was no small challenge. The discussions, which took place over nearly 2 decades, played a key role in helping scientists home in on the single factor that was central to chronic fatigue: postexertional malaise.

“This is quite unique for chronic fatigue syndrome. With other diseases, yes, you may have fatigue as one of the components of the disease, but postexertional fatigue is very specific,” said Alain Moreau, PhD, a molecular biologist at the University of Montreal.

Of course, plenty of people have pushed themselves too hard physically and paid the price the next day. But those with chronic fatigue syndrome weren’t running marathons. To them, exertion could be anything from getting the mail to reading a book. Nor could the resulting exhaustion be resolved by an afternoon on the couch or a long vacation.

“If they do these activities, they can crash for weeks, even months,” Dr. Moreau said. It was deep, persistent, and – for 40% of those with chronic fatigue syndrome – disabling. In 2015, a study group from the Institute of Medicine proposed renaming chronic fatigue to “systemic exercise intolerance disease” because of the centrality of this symptom. Although that effort mostly stalled, their report did bring the condition out of its historic place as a scientific backwater. What resulted was an uptick in research on chronic fatigue syndrome, which helped define some of the physiological issues that either contribute to or result from the condition.

Researchers had long known about the link between infection and fatigue, said Dr. Frankovich. Work included mysterious outbreaks like the one in Lake Tahoe and well-documented issues like the wave of encephalitis lethargica (a condition that leaves patients in an almost vegetative state) that followed the 1918 H1N1 influenza pandemic.

“As a clinician, when you see someone who comes in with a chronic infection, they’re tired. I think that’s why, in the chronic-fatigue world, people are desperately looking for the infection so we can treat it, and maybe these poor suffering people will feel better,” Dr. Frankovich added. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Immunologic symptoms

Given the close link between a nonspecific viral illness and the onset of symptoms in chronic fatigue syndrome, scientists like Dr. Hornig opted to focus on immunologic symptoms. In a 2015 analysis published in Science, Dr. Hornig and colleagues showed that immune problems can be found in the earliest stages of chronic fatigue syndrome, and that they change as the illness progresses. Patients who had been sick for less than 3 years showed significant increases in levels of both pro- and anti-inflammatory cytokines, and the factor most strongly correlated to this inability to regulate cytokine levels was the duration of symptoms, not their severity. A series of other studies also revealed problems with regulation of the immune system, although no one could show what might have set these problems in motion.

Other researchers found signs of mitochondrial dysfunction in those with chronic fatigue syndrome. Because mitochondria make energy for cells, it wasn’t an intellectual stretch to believe that glitches in this process could contribute to fatigue. As early as 1991, scientists had discovered signs of mitochondrial degeneration in muscle biopsies from people with chronic fatigue syndrome. Subsequent studies showed that those affected by chronic fatigue were missing segments of mitochondrial DNA and had significantly reduced levels of mitochondrial activity. Although exercise normally improves mitochondrial functioning, the opposite appears to happen in chronic fatigue.

To Dr. Nath, these dual hypotheses aren’t necessarily mutually exclusive. Some studies have hinted that infection with the common human herpesvirus–6 (HHV-6) can lead to an autoimmune condition in which the body makes antibodies against the mitochondria. Mitochondria also play a key role in the ability of the innate immune system to produce interferon and other proinflammatory cytokines. It might also be that the link between immune and mitochondrial problems is more convoluted than originally thought, or that the two systems are affected independent of one another, Dr. Nath said.

Finding answers, especially those that could lead to potential treatments, wouldn’t be easy, however. In 2016, the NIH launched an in-depth study of a small number of individuals with chronic fatigue, hoping to find clues about what the condition was and how it might be treated.

For scientists like Dr. Nath, the NIH study provided a way to get at the underlying biology of chronic fatigue syndrome. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Chronic post-SARS syndrome

In March 2020, retired physician Harvey Moldofsky, MD, began receiving inquiries about a 2011 study he and his colleague, John Patcai, MD, had published in BMC Neurology about something they dubbed “chronic post-SARS syndrome.” The small case-control study, which involved mainly health care workers in Toronto, received little attention when it was first published, but with COVID-19, it was suddenly relevant.

Early clusters of similar cases in Miami made local physicians desperate for Dr. Moldofsky’s expertise. Luckily, he was nearby; he had fled the frigid Canadian winter for the warmth of Sarasota, Fla.

“I had people from various countries around the world writing to me and asking what they should do. And of course I don’t have any answers,” he said. But the study contained one of the world’s only references to the syndrome.

In 2003, a woman arrived in Toronto from Hong Kong. She didn’t know it at the time, but her preairport stay at the Hotel Metropole had infected her with the first SARS (severe acute respiratory syndrome) coronavirus. Her subsequent hospitalization in Toronto sparked a city-wide outbreak of SARS in which 273 people became ill and 44 died. Many of those affected were health care workers, including nurses and respiratory therapists. Although most eventually returned to work, a subset couldn’t. They complained of energy-sapping fatigue, poor sleep, brain fog, and assorted body aches and pains that persisted for more than 18 months. The aches and pains brought them to the attention of Dr. Moldofsky, then director of the Centre for the Study of Pain at the University of Toronto.

His primary interest at the time was fibromyalgia, which caused symptoms similar to those reported by the original SARS long-haulers. Intrigued, Dr. Moldofsky agreed to take a look. Their chest x-rays were clear and the nurses showed no signs of lingering viral infection. Dr. Moldofsky could see that the nurses were ill and suffering, but no lab tests or anything else could identify what was causing their symptoms.

In 2011, Dr. Moldofsky and Dr. Patcai found a strong overlap between chronic SARS, fibromyalgia, and chronic fatigue syndrome when they compared 22 patients with long-term SARS issues with 21 who had fibromyalgia. “Their problems are exactly the same. They have strange symptoms and nobody can figure out what they’re about. And these symptoms are aches and pains, and they have trouble thinking and concentrating,” Dr. Moldofsky said. Reports of COVID-19 long-haulers didn’t surprise Dr. Moldofsky, and he immediately recognized that Nath’s intention to follow these patients could provide insights into both fibromyalgia and chronic fatigue syndrome.

That’s exactly what Dr. Nath is proposing with the two NIH studies. One will focus solely on the neurologic impacts of COVID-19, including stroke, loss of taste and smell, and brain fog. The other will bring patients who have had COVID-19 symptoms for at least 6 months to the NIH Clinical Center for an inpatient stay during which they will undergo detailed physiologic tests.

Scientists around the world are launching their own post–COVID-19 studies. Dr. Moreau’s group in Montreal has laid the groundwork for such an endeavor, and the CoroNerve group in the United Kingdom is monitoring neurologic complications from the coronavirus. Many of them have the same goals as the NIH studies: Leverage the large number of COVID-19 long-haulers to better understand the earliest stages of postviral syndrome.

“At this juncture, after all the reports that we’ve seen so far, I think it’s very unlikely that there will be no relationship whatsoever between COVID-19 and chronic fatigue syndrome,” Dr. Hornig said. “I think there certainly will be some, but again, what’s the scope, what’s the size? And then, of course, even more importantly, if it is happening, what is the mechanism and how is it happening?”

For people like Ms. Gage-Witvliet, the answers can’t come soon enough. For the first time in more than a decade, the full-time professor of epidemiology didn’t prepare to teach this year because she simply can’t. It’s too taxing for her brain to deal with impromptu student questions. Ms. Gage-Witvliet hopes that, by sharing her own experiences with post COVID-19, she can help others.

“In my work, I use data to give a voice to people who don’t have a voice,” she said. “Now, I am one of those people.”

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

When Margot Gage-Witvliet began feeling run down after her family returned from a trip to the Netherlands in late February 2020, she initially chalked up her symptoms to jet lag. Three days later, however, her situation went from concerning to alarming as she struggled to breathe. “It felt like there was an elephant sitting on my chest,” she said.

Her husband and daughters also became ill with COVID-19, but Ms. Gage-Witvliet was the only one in her family who didn’t get better. After an early improvement, a rare coronavirus-induced tonic-clonic seizure in early April sent her spiraling back down. Ms. Gage-Witvliet spent the next several weeks in bed with the curtains drawn, unable to tolerate light or sound.

Today, Ms. Gage-Witvliet’s life looks nothing like it did 6 months ago when she first got sick. As one of COVID-19’s so called long-haulers, she continues to struggle with crushing fatigue, brain fog, and headaches – symptoms that worsen when she pushes herself to do more. Across the country, as many as 1 in 10 COVID-19 patients are reporting illnesses that continue for weeks and months after their initial diagnosis. Nearly all report neurologic issues like Ms. Gage-Witvliet, as well as shortness of breath and psychiatric concerns.

For Avindra Nath, MD, a neurologist at the National Institutes of Health, the experience of these long-haul COVID-19 patients feels familiar and reminds him of myalgic encephalomyelitis, also known as chronic fatigue syndrome.

Dr. Nath has long been interested in the lingering neurologic issues connected to chronic fatigue. An estimated three-quarters of all patients with chronic fatigue syndrome report that their symptoms started after a viral infection, and they suffer unrelenting exhaustion, difficulties regulating pulse and blood pressure, aches and pains, and brain fog. When Dr. Nath first read about the novel coronavirus, he began to worry that the virus would trigger symptoms in a subset of those infected. Hearing about the experiences of long-haulers like Ms. Gage-Witvliet raised his suspicions even more.

Unlike COVID-19 long-haulers, however, many patients with chronic fatigue syndrome go at least a year with these symptoms before receiving a diagnosis, according to a British survey. That means researchers have had few opportunities to study the early stages of the syndrome. “When we see patients with myalgic encephalomyelitis, whatever infection they might have had occurred in the remote past, so there’s no way for us to know how they got infected with it, what the infection was, or what the effects of it were in that early phase. We’re seeing them 2 years afterward,” Dr. Nath said.

Dr. Nath quickly realized that studying patients like Ms. Gage-Witvliet would give physicians and scientists a unique opportunity to understand not only long-term outcomes of COVID-19 infections, but also other postviral syndromes, including chronic fatigue syndrome at their earliest stages. It’s why Dr. Nath has spent the past several months scrambling to launch two NIH studies to examine the phenomenon.

Although Dr. Nath said that the parallels between COVID-19 long-haulers and those with chronic fatigue syndrome are obvious, he cautions against assuming that they are the same phenomenon. Some long-haulers might simply be taking a much slower path to recovery, or they might have a condition that looks similar on the surface but differs from chronic fatigue syndrome on a molecular level. But even if Dr. Nath fails to see links to chronic fatigue syndrome, with more than 92.5 million documented cases of COVID-19 around the world, the work will be relevant to the substantial number of infected individuals who don’t recover quickly.

“With so many people having exposure to the same virus over a similar time period, we really have the opportunity to look at these manifestations and at the very least to understand postviral syndromes,” said Mady Hornig, MD, a psychiatrist at Columbia University, New York.

The origins of chronic fatigue syndrome date back to 1985, when the Centers for Disease Control and Prevention received a request from two physicians – Paul Cheney, MD, and Daniel Peterson, MD – to investigate a mysterious disease outbreak in Nevada. In November 1984, residents in and around the idyllic vacation spot of Incline Village, a small town tucked into the north shore of Lake Tahoe, had begun reporting flu-like symptoms that persisted for weeks, even months. The doctors had searched high and low for a cause, but they couldn’t figure out what was making their patients sick.

They reported a range of symptoms – including muscle aches and pains, low-grade fevers, sore throats, and headaches – but everyone said that crippling fatigue was the most debilitating issue. This wasn’t the kind of fatigue that could be cured by a nap or even a long holiday. No matter how much their patients slept – and some were almost completely bedbound – their fatigue didn’t abate. What’s more, the fatigue got worse whenever they tried to push themselves to do more. Puzzled, the CDC sent two epidemic intelligence service (EIS) officers to try to get to the bottom of what might be happening.


 

Muscle aches and pains with crippling fatigue

After their visit to Incline Village, however, the CDC was just as perplexed as Dr. Cheney and Dr. Peterson. Many of the people with the condition reported flu-like symptoms right around the time they first got sick, and the physicians’ leading hypothesis was that the outbreak and its lasting symptoms were caused by chronic Epstein-Barr virus infection. But neither the CDC nor anyone else could identify the infection or any other microbial cause. The two EIS officers duly wrote up a report for the CDC’s flagship publication, Morbidity and Mortality Weekly ReportI, titled “Chronic Fatigue Possibly Related to Epstein-Barr Virus – Nevada”.

That investigators focused on the fatigue aspect made sense, says Leonard A. Jason, PhD, professor of psychology at DePaul University and director of the Center for Community Research, both in Chicago, because it was one of the few symptoms shared by all the individuals studied and it was also the most debilitating. But that focus – and the name “chronic fatigue syndrome” – led to broad public dismissal of the condition’s severity, as did an editorial note in MMWR urging physicians to look for “more definable, and possibly treatable, conditions.” Subsequent research failed to confirm a specific link to the Epstein-Barr virus, which only added to the condition’s phony reputation. Rather than being considered a potentially disabling illness, it was disregarded as a “yuppie flu” or a fancy name for malingering.

“It’s not a surprise that patients are being dismissed because there’s already this sort of grandfathered-in sense that fatigue is not real,” said Jennifer Frankovich, MD, a pediatric rheumatologist at Stanford (Calif.) University’s Lucile Packard Children’s Hospital in Palo Alto. “I’m sure that’s frustrating for them to be tired and then to have the clinician not believe them or dismiss them or think they’re making it up. It would be more helpful to the families to say: ‘You know what, we don’t know, we do not have the answer, and we believe you.’ ”
 

A syndrome’s shame

As time passed, patient advocacy groups began pushing back against the negative way the condition was being perceived. This criticism came as organizations like the CDC worked to develop a set of diagnostic criteria that researchers and clinicians dealing with chronic fatigue syndrome could use. With such a heterogeneous group of patients and symptoms, the task was no small challenge. The discussions, which took place over nearly 2 decades, played a key role in helping scientists home in on the single factor that was central to chronic fatigue: postexertional malaise.

“This is quite unique for chronic fatigue syndrome. With other diseases, yes, you may have fatigue as one of the components of the disease, but postexertional fatigue is very specific,” said Alain Moreau, PhD, a molecular biologist at the University of Montreal.

Of course, plenty of people have pushed themselves too hard physically and paid the price the next day. But those with chronic fatigue syndrome weren’t running marathons. To them, exertion could be anything from getting the mail to reading a book. Nor could the resulting exhaustion be resolved by an afternoon on the couch or a long vacation.

“If they do these activities, they can crash for weeks, even months,” Dr. Moreau said. It was deep, persistent, and – for 40% of those with chronic fatigue syndrome – disabling. In 2015, a study group from the Institute of Medicine proposed renaming chronic fatigue to “systemic exercise intolerance disease” because of the centrality of this symptom. Although that effort mostly stalled, their report did bring the condition out of its historic place as a scientific backwater. What resulted was an uptick in research on chronic fatigue syndrome, which helped define some of the physiological issues that either contribute to or result from the condition.

Researchers had long known about the link between infection and fatigue, said Dr. Frankovich. Work included mysterious outbreaks like the one in Lake Tahoe and well-documented issues like the wave of encephalitis lethargica (a condition that leaves patients in an almost vegetative state) that followed the 1918 H1N1 influenza pandemic.

“As a clinician, when you see someone who comes in with a chronic infection, they’re tired. I think that’s why, in the chronic-fatigue world, people are desperately looking for the infection so we can treat it, and maybe these poor suffering people will feel better,” Dr. Frankovich added. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Immunologic symptoms

Given the close link between a nonspecific viral illness and the onset of symptoms in chronic fatigue syndrome, scientists like Dr. Hornig opted to focus on immunologic symptoms. In a 2015 analysis published in Science, Dr. Hornig and colleagues showed that immune problems can be found in the earliest stages of chronic fatigue syndrome, and that they change as the illness progresses. Patients who had been sick for less than 3 years showed significant increases in levels of both pro- and anti-inflammatory cytokines, and the factor most strongly correlated to this inability to regulate cytokine levels was the duration of symptoms, not their severity. A series of other studies also revealed problems with regulation of the immune system, although no one could show what might have set these problems in motion.

Other researchers found signs of mitochondrial dysfunction in those with chronic fatigue syndrome. Because mitochondria make energy for cells, it wasn’t an intellectual stretch to believe that glitches in this process could contribute to fatigue. As early as 1991, scientists had discovered signs of mitochondrial degeneration in muscle biopsies from people with chronic fatigue syndrome. Subsequent studies showed that those affected by chronic fatigue were missing segments of mitochondrial DNA and had significantly reduced levels of mitochondrial activity. Although exercise normally improves mitochondrial functioning, the opposite appears to happen in chronic fatigue.

To Dr. Nath, these dual hypotheses aren’t necessarily mutually exclusive. Some studies have hinted that infection with the common human herpesvirus–6 (HHV-6) can lead to an autoimmune condition in which the body makes antibodies against the mitochondria. Mitochondria also play a key role in the ability of the innate immune system to produce interferon and other proinflammatory cytokines. It might also be that the link between immune and mitochondrial problems is more convoluted than originally thought, or that the two systems are affected independent of one another, Dr. Nath said.

Finding answers, especially those that could lead to potential treatments, wouldn’t be easy, however. In 2016, the NIH launched an in-depth study of a small number of individuals with chronic fatigue, hoping to find clues about what the condition was and how it might be treated.

For scientists like Dr. Nath, the NIH study provided a way to get at the underlying biology of chronic fatigue syndrome. Then the pandemic struck, giving him yet another opportunity to study postviral syndromes.
 

Chronic post-SARS syndrome

In March 2020, retired physician Harvey Moldofsky, MD, began receiving inquiries about a 2011 study he and his colleague, John Patcai, MD, had published in BMC Neurology about something they dubbed “chronic post-SARS syndrome.” The small case-control study, which involved mainly health care workers in Toronto, received little attention when it was first published, but with COVID-19, it was suddenly relevant.

Early clusters of similar cases in Miami made local physicians desperate for Dr. Moldofsky’s expertise. Luckily, he was nearby; he had fled the frigid Canadian winter for the warmth of Sarasota, Fla.

“I had people from various countries around the world writing to me and asking what they should do. And of course I don’t have any answers,” he said. But the study contained one of the world’s only references to the syndrome.

In 2003, a woman arrived in Toronto from Hong Kong. She didn’t know it at the time, but her preairport stay at the Hotel Metropole had infected her with the first SARS (severe acute respiratory syndrome) coronavirus. Her subsequent hospitalization in Toronto sparked a city-wide outbreak of SARS in which 273 people became ill and 44 died. Many of those affected were health care workers, including nurses and respiratory therapists. Although most eventually returned to work, a subset couldn’t. They complained of energy-sapping fatigue, poor sleep, brain fog, and assorted body aches and pains that persisted for more than 18 months. The aches and pains brought them to the attention of Dr. Moldofsky, then director of the Centre for the Study of Pain at the University of Toronto.

His primary interest at the time was fibromyalgia, which caused symptoms similar to those reported by the original SARS long-haulers. Intrigued, Dr. Moldofsky agreed to take a look. Their chest x-rays were clear and the nurses showed no signs of lingering viral infection. Dr. Moldofsky could see that the nurses were ill and suffering, but no lab tests or anything else could identify what was causing their symptoms.

In 2011, Dr. Moldofsky and Dr. Patcai found a strong overlap between chronic SARS, fibromyalgia, and chronic fatigue syndrome when they compared 22 patients with long-term SARS issues with 21 who had fibromyalgia. “Their problems are exactly the same. They have strange symptoms and nobody can figure out what they’re about. And these symptoms are aches and pains, and they have trouble thinking and concentrating,” Dr. Moldofsky said. Reports of COVID-19 long-haulers didn’t surprise Dr. Moldofsky, and he immediately recognized that Nath’s intention to follow these patients could provide insights into both fibromyalgia and chronic fatigue syndrome.

That’s exactly what Dr. Nath is proposing with the two NIH studies. One will focus solely on the neurologic impacts of COVID-19, including stroke, loss of taste and smell, and brain fog. The other will bring patients who have had COVID-19 symptoms for at least 6 months to the NIH Clinical Center for an inpatient stay during which they will undergo detailed physiologic tests.

Scientists around the world are launching their own post–COVID-19 studies. Dr. Moreau’s group in Montreal has laid the groundwork for such an endeavor, and the CoroNerve group in the United Kingdom is monitoring neurologic complications from the coronavirus. Many of them have the same goals as the NIH studies: Leverage the large number of COVID-19 long-haulers to better understand the earliest stages of postviral syndrome.

“At this juncture, after all the reports that we’ve seen so far, I think it’s very unlikely that there will be no relationship whatsoever between COVID-19 and chronic fatigue syndrome,” Dr. Hornig said. “I think there certainly will be some, but again, what’s the scope, what’s the size? And then, of course, even more importantly, if it is happening, what is the mechanism and how is it happening?”

For people like Ms. Gage-Witvliet, the answers can’t come soon enough. For the first time in more than a decade, the full-time professor of epidemiology didn’t prepare to teach this year because she simply can’t. It’s too taxing for her brain to deal with impromptu student questions. Ms. Gage-Witvliet hopes that, by sharing her own experiences with post COVID-19, she can help others.

“In my work, I use data to give a voice to people who don’t have a voice,” she said. “Now, I am one of those people.”

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

Among the multiple vaccine candidates around the globe, next up in the arsenal against COVID-19 is likely the single-dose Ad26.COV2.S vaccine in development from Johnson & Johnson/Janssen, infectious disease experts predict.

And it got closer with promising interim phase 1/2a trial results, published online Jan. 13 in The New England Journal of Medicine.

A single Ad26.COV2.S dose was associated with S-binding and neutralizing antibodies in more than 90% of the participants. The finding was observed in both adults aged 18-55 years and participants 65 and older, as well as for participants given low-dose or high-dose vaccinations.

The results also suggest a durable vaccine response. “The take-home message [includes] a high neutralizing antibody responder rate to a single dose of our Ad26.COV2.S COVID-19 vaccine candidate. In addition, we see that these responses and antibody titers are stable for at least 71 days,” senior study author Hanneke Schuitemaker, PhD, global head of viral vaccine discovery and translational medicine at Johnson & Johnson in Leiden, the Netherlands, said in an interview.

If the single-dose Johnson & Johnson product gains Food and Drug Administration emergency use authorization (EUA), it could significantly boost the number of overall immunizations available. Less stringent storage requirements – only regular refrigeration vs. a need to freeze the Pfizer/BioNTech and Moderna COVID-19 vaccines – is another potential advantage. The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 36°-46 °F (2°-8 °C).

“Phase 1-2 trial data on the J&J vaccine: If it works as well as the mRNA options, it will have substantial advantages,” Jeremy Faust, MD, an emergency room physician affiliated with Brigham & Women’s Hospital and Harvard Medical School, Boston, tweeted on Jan. 13.

Unlike the Pfizer/BioNTech and Moderna messenger RNA vaccines, the Johnson & Johnson product is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.
 

Phase 3 efficacy/safety results pending

Under normal circumstances, phase 3 trial results would not be anticipated within weeks of phase 1/2a trial findings. However, the urgency of the COVID-19 pandemic accelerated the vaccine development process, so preclinical trials were conducted simultaneously and not sequentially. For this reason, phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and a company executive told Reuters that the rollout is on track for March.

“We hope to report data from our first phase 3 study, ENSEMBLE, in which we are testing the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February,” Dr. Schuitemaker said. 

In the meantime, the phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results have drawn positive reactions.

“Data is highly encouraging and supports the single inoculation approach that makes this vaccine unique,” Carlos del Rio, executive associate dean for Emory University at Grady in Atlanta, wrote in a tweet on Jan. 13.

“Encouraging COVID vaccine data from J&J published [Jan. 13]. Solid antibody, CD4 T cell, and CD8 T cell responses – a nice trifecta of vaccine immune responses to see! And safe!” tweeted Shane Crotty, PhD, vaccine scientist and professor at the La Jolla (Calif.) Institute for Immunology.

 

First results in 800+ participants

At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.

A total of 402 people in the younger age cohort and 403 in the 65 and older group received a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose 56 days later for a separate trial, ENSEMBLE2, designed to compare safety and efficacy between single- and double-dose regimens. Results of that trial are still pending.
 

Safety profile

A single dose was associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. They also found that grade 3 adverse events decreased with increasing age.

Injection site pain on the day of immunization or the next day was the most common local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% of the low-dose vaccine group and 39% of the high-dose cohort. Fatigue, headache, and myalgia were the most common grade 1 or 2 solicited systemic adverse events reported.

Five serious adverse events were reported, including four that investigators deemed unrelated to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that resulted in hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours.

“These data confirm our previous experience with vaccine candidates based on our Ad26 viral vector platform in the younger age group. The almost similar performance in older adults is promising,” Dr. Schuitemaker said.

A potential limitation of the phase 1/2a trial is “the lack of representation of minority groups,” the researchers noted. Johnson & Johnson is working on improving the diversity of study participants “with respect to groups that seem to be affected most by the COVID-19 pandemic.”
 

AstraZeneca/Oxford vaccine status

The AstraZeneca/Oxford AZD1222 vaccine in development received approval for use in the United Kingdom on Dec. 30. The approval came after Public Health England said the country was facing “unprecedented” levels of infections, the BBC reported. AstraZeneca applied for European Medical Agency approval earlier in the week of Jan. 10, which could lead to more widespread use across Europe.

The status of the vaccine remains uncertain in the United States. A phase 3 trial that started in August was paused for about 6 weeks in September and October after an adverse event in a British volunteer halted studies worldwide. On Oct. 23, the FDA permitted researchers to continue the trial with approximately 40,000 participants.

There was some suggestion in the clinical trials that a half dose of the AstraZeneca vaccine was more effective than a full dose, 90% vs. 62%, but some irregularities in the research require further investigation.

Although the AstraZeneca vaccine is delivered to cells by an adenovirus – as with the Johnson & Johnson product – it is designed to be delivered in two doses 28 days apart, like the administration schedule of the Moderna mRNA vaccine.
 

A need for speed, and more doses

Regardless of which vaccine product is next to gain an EUA in the United States, many experts agree the COVID-19 vaccine rollouts so far have been problematic, at a time when cases are climbing to record-breaking levels, and likely more related to logistics over administration of the vaccine than production of the doses.

“Lots of doses being manufactured. In December 20 million, January 40 million, February 80 million and J&J hopefully soon to add to the count. The shortage is the number arms not getting vaccinated. Freezers do not get COVID. They do not need all those vaccines,” Daniel Griffin, MD, PhD, an infectious disease expert in Port Washington, N.Y., tweeted on Jan. 12.

“Unfortunately, the rollout has not gone smoothly, partly due to a lack of resources for this distribution phase we’re in,” Andrew T. Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah, Salt Lake City, said during a media briefing Jan. 14 sponsored by the Infectious Diseases Society of America (IDSA).

“We’re concerned about the mismatch between the number of people who are being told they are eligible and the amount of vaccine that is being distributed,” he said.

Complicating the rollout is a directive from U.S. Health and Human Services Secretary Alex Azar that states should start vaccinating everyone 65 and older as well as those with underlying conditions.

Expanding distribution to the 15% of Americans in just this age group is a big challenge, Dr. Pavia said. “We have enough vaccine maybe to vaccinate 40 million by the end of this month. There is a huge disconnect, and that creates a lot of problems.”

“One of the biggest problems is we are trying to do this mass vaccination program in the middle of the biggest surge we’ve ever seen,” Julie Vaishampayan, MD, MPH, chair of the IDSA Public Health Committee, said during the briefing. Without sufficient time for public health officials to plan for vaccinating a larger population, “people will come and stand in extremely long lines.”

Trying to expand immunization access without a proportionate increase in available doses prompted Dr. Vaishampayan to share an analogy from a colleague: “We are trying to fill a lake with a garden hose. Rather than making the lake bigger, what we really need is more water.”

Dr. Pavia emphasized that infectious disease experts “know the measures that work.” Not using masks, physical distancing, and hand hygiene, he said, “is a bit like knowing that really good shark repellents will be available in summer, so I’m going to jump into the ocean covered in blood while the great whites are swimming around.”

An official at the World Health Organization agreed. “Vaccines are coming online and I do believe vaccines will make a huge difference. But they are not here yet in enough quantities and in enough people to make that difference,” Michael Ryan, MB, WHO executive director of health emergencies, said during an online media briefing Jan. 13, held in conjunction with Emory University.

Dr. Ryan predicted that “we’ve got weeks if not months ahead of us in which our weapon is our knowledge ... what we know about this virus, its transmission, and stopping that transmission.

“And as the vaccines roll in, we can hopefully end this horrific pandemic.”

Dr. Schuitemaker reports grants from BARDA during the conduct of the study; personal fees and other from Janssen Vaccines and Prevention, a J&J company, outside the submitted work. Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services funded the phase 1/2a study.

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

Among the multiple vaccine candidates around the globe, next up in the arsenal against COVID-19 is likely the single-dose Ad26.COV2.S vaccine in development from Johnson & Johnson/Janssen, infectious disease experts predict.

And it got closer with promising interim phase 1/2a trial results, published online Jan. 13 in The New England Journal of Medicine.

A single Ad26.COV2.S dose was associated with S-binding and neutralizing antibodies in more than 90% of the participants. The finding was observed in both adults aged 18-55 years and participants 65 and older, as well as for participants given low-dose or high-dose vaccinations.

The results also suggest a durable vaccine response. “The take-home message [includes] a high neutralizing antibody responder rate to a single dose of our Ad26.COV2.S COVID-19 vaccine candidate. In addition, we see that these responses and antibody titers are stable for at least 71 days,” senior study author Hanneke Schuitemaker, PhD, global head of viral vaccine discovery and translational medicine at Johnson & Johnson in Leiden, the Netherlands, said in an interview.

If the single-dose Johnson & Johnson product gains Food and Drug Administration emergency use authorization (EUA), it could significantly boost the number of overall immunizations available. Less stringent storage requirements – only regular refrigeration vs. a need to freeze the Pfizer/BioNTech and Moderna COVID-19 vaccines – is another potential advantage. The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 36°-46 °F (2°-8 °C).

“Phase 1-2 trial data on the J&J vaccine: If it works as well as the mRNA options, it will have substantial advantages,” Jeremy Faust, MD, an emergency room physician affiliated with Brigham & Women’s Hospital and Harvard Medical School, Boston, tweeted on Jan. 13.

Unlike the Pfizer/BioNTech and Moderna messenger RNA vaccines, the Johnson & Johnson product is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.
 

Phase 3 efficacy/safety results pending

Under normal circumstances, phase 3 trial results would not be anticipated within weeks of phase 1/2a trial findings. However, the urgency of the COVID-19 pandemic accelerated the vaccine development process, so preclinical trials were conducted simultaneously and not sequentially. For this reason, phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and a company executive told Reuters that the rollout is on track for March.

“We hope to report data from our first phase 3 study, ENSEMBLE, in which we are testing the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February,” Dr. Schuitemaker said. 

In the meantime, the phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results have drawn positive reactions.

“Data is highly encouraging and supports the single inoculation approach that makes this vaccine unique,” Carlos del Rio, executive associate dean for Emory University at Grady in Atlanta, wrote in a tweet on Jan. 13.

“Encouraging COVID vaccine data from J&J published [Jan. 13]. Solid antibody, CD4 T cell, and CD8 T cell responses – a nice trifecta of vaccine immune responses to see! And safe!” tweeted Shane Crotty, PhD, vaccine scientist and professor at the La Jolla (Calif.) Institute for Immunology.

 

First results in 800+ participants

At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.

A total of 402 people in the younger age cohort and 403 in the 65 and older group received a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose 56 days later for a separate trial, ENSEMBLE2, designed to compare safety and efficacy between single- and double-dose regimens. Results of that trial are still pending.
 

Safety profile

A single dose was associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. They also found that grade 3 adverse events decreased with increasing age.

Injection site pain on the day of immunization or the next day was the most common local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% of the low-dose vaccine group and 39% of the high-dose cohort. Fatigue, headache, and myalgia were the most common grade 1 or 2 solicited systemic adverse events reported.

Five serious adverse events were reported, including four that investigators deemed unrelated to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that resulted in hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours.

“These data confirm our previous experience with vaccine candidates based on our Ad26 viral vector platform in the younger age group. The almost similar performance in older adults is promising,” Dr. Schuitemaker said.

A potential limitation of the phase 1/2a trial is “the lack of representation of minority groups,” the researchers noted. Johnson & Johnson is working on improving the diversity of study participants “with respect to groups that seem to be affected most by the COVID-19 pandemic.”
 

AstraZeneca/Oxford vaccine status

The AstraZeneca/Oxford AZD1222 vaccine in development received approval for use in the United Kingdom on Dec. 30. The approval came after Public Health England said the country was facing “unprecedented” levels of infections, the BBC reported. AstraZeneca applied for European Medical Agency approval earlier in the week of Jan. 10, which could lead to more widespread use across Europe.

The status of the vaccine remains uncertain in the United States. A phase 3 trial that started in August was paused for about 6 weeks in September and October after an adverse event in a British volunteer halted studies worldwide. On Oct. 23, the FDA permitted researchers to continue the trial with approximately 40,000 participants.

There was some suggestion in the clinical trials that a half dose of the AstraZeneca vaccine was more effective than a full dose, 90% vs. 62%, but some irregularities in the research require further investigation.

Although the AstraZeneca vaccine is delivered to cells by an adenovirus – as with the Johnson & Johnson product – it is designed to be delivered in two doses 28 days apart, like the administration schedule of the Moderna mRNA vaccine.
 

A need for speed, and more doses

Regardless of which vaccine product is next to gain an EUA in the United States, many experts agree the COVID-19 vaccine rollouts so far have been problematic, at a time when cases are climbing to record-breaking levels, and likely more related to logistics over administration of the vaccine than production of the doses.

“Lots of doses being manufactured. In December 20 million, January 40 million, February 80 million and J&J hopefully soon to add to the count. The shortage is the number arms not getting vaccinated. Freezers do not get COVID. They do not need all those vaccines,” Daniel Griffin, MD, PhD, an infectious disease expert in Port Washington, N.Y., tweeted on Jan. 12.

“Unfortunately, the rollout has not gone smoothly, partly due to a lack of resources for this distribution phase we’re in,” Andrew T. Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah, Salt Lake City, said during a media briefing Jan. 14 sponsored by the Infectious Diseases Society of America (IDSA).

“We’re concerned about the mismatch between the number of people who are being told they are eligible and the amount of vaccine that is being distributed,” he said.

Complicating the rollout is a directive from U.S. Health and Human Services Secretary Alex Azar that states should start vaccinating everyone 65 and older as well as those with underlying conditions.

Expanding distribution to the 15% of Americans in just this age group is a big challenge, Dr. Pavia said. “We have enough vaccine maybe to vaccinate 40 million by the end of this month. There is a huge disconnect, and that creates a lot of problems.”

“One of the biggest problems is we are trying to do this mass vaccination program in the middle of the biggest surge we’ve ever seen,” Julie Vaishampayan, MD, MPH, chair of the IDSA Public Health Committee, said during the briefing. Without sufficient time for public health officials to plan for vaccinating a larger population, “people will come and stand in extremely long lines.”

Trying to expand immunization access without a proportionate increase in available doses prompted Dr. Vaishampayan to share an analogy from a colleague: “We are trying to fill a lake with a garden hose. Rather than making the lake bigger, what we really need is more water.”

Dr. Pavia emphasized that infectious disease experts “know the measures that work.” Not using masks, physical distancing, and hand hygiene, he said, “is a bit like knowing that really good shark repellents will be available in summer, so I’m going to jump into the ocean covered in blood while the great whites are swimming around.”

An official at the World Health Organization agreed. “Vaccines are coming online and I do believe vaccines will make a huge difference. But they are not here yet in enough quantities and in enough people to make that difference,” Michael Ryan, MB, WHO executive director of health emergencies, said during an online media briefing Jan. 13, held in conjunction with Emory University.

Dr. Ryan predicted that “we’ve got weeks if not months ahead of us in which our weapon is our knowledge ... what we know about this virus, its transmission, and stopping that transmission.

“And as the vaccines roll in, we can hopefully end this horrific pandemic.”

Dr. Schuitemaker reports grants from BARDA during the conduct of the study; personal fees and other from Janssen Vaccines and Prevention, a J&J company, outside the submitted work. Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services funded the phase 1/2a study.

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

Among the multiple vaccine candidates around the globe, next up in the arsenal against COVID-19 is likely the single-dose Ad26.COV2.S vaccine in development from Johnson & Johnson/Janssen, infectious disease experts predict.

And it got closer with promising interim phase 1/2a trial results, published online Jan. 13 in The New England Journal of Medicine.

A single Ad26.COV2.S dose was associated with S-binding and neutralizing antibodies in more than 90% of the participants. The finding was observed in both adults aged 18-55 years and participants 65 and older, as well as for participants given low-dose or high-dose vaccinations.

The results also suggest a durable vaccine response. “The take-home message [includes] a high neutralizing antibody responder rate to a single dose of our Ad26.COV2.S COVID-19 vaccine candidate. In addition, we see that these responses and antibody titers are stable for at least 71 days,” senior study author Hanneke Schuitemaker, PhD, global head of viral vaccine discovery and translational medicine at Johnson & Johnson in Leiden, the Netherlands, said in an interview.

If the single-dose Johnson & Johnson product gains Food and Drug Administration emergency use authorization (EUA), it could significantly boost the number of overall immunizations available. Less stringent storage requirements – only regular refrigeration vs. a need to freeze the Pfizer/BioNTech and Moderna COVID-19 vaccines – is another potential advantage. The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 36°-46 °F (2°-8 °C).

“Phase 1-2 trial data on the J&J vaccine: If it works as well as the mRNA options, it will have substantial advantages,” Jeremy Faust, MD, an emergency room physician affiliated with Brigham & Women’s Hospital and Harvard Medical School, Boston, tweeted on Jan. 13.

Unlike the Pfizer/BioNTech and Moderna messenger RNA vaccines, the Johnson & Johnson product is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.
 

Phase 3 efficacy/safety results pending

Under normal circumstances, phase 3 trial results would not be anticipated within weeks of phase 1/2a trial findings. However, the urgency of the COVID-19 pandemic accelerated the vaccine development process, so preclinical trials were conducted simultaneously and not sequentially. For this reason, phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and a company executive told Reuters that the rollout is on track for March.

“We hope to report data from our first phase 3 study, ENSEMBLE, in which we are testing the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February,” Dr. Schuitemaker said. 

In the meantime, the phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results have drawn positive reactions.

“Data is highly encouraging and supports the single inoculation approach that makes this vaccine unique,” Carlos del Rio, executive associate dean for Emory University at Grady in Atlanta, wrote in a tweet on Jan. 13.

“Encouraging COVID vaccine data from J&J published [Jan. 13]. Solid antibody, CD4 T cell, and CD8 T cell responses – a nice trifecta of vaccine immune responses to see! And safe!” tweeted Shane Crotty, PhD, vaccine scientist and professor at the La Jolla (Calif.) Institute for Immunology.

 

First results in 800+ participants

At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.

A total of 402 people in the younger age cohort and 403 in the 65 and older group received a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose 56 days later for a separate trial, ENSEMBLE2, designed to compare safety and efficacy between single- and double-dose regimens. Results of that trial are still pending.
 

Safety profile

A single dose was associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. They also found that grade 3 adverse events decreased with increasing age.

Injection site pain on the day of immunization or the next day was the most common local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% of the low-dose vaccine group and 39% of the high-dose cohort. Fatigue, headache, and myalgia were the most common grade 1 or 2 solicited systemic adverse events reported.

Five serious adverse events were reported, including four that investigators deemed unrelated to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that resulted in hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours.

“These data confirm our previous experience with vaccine candidates based on our Ad26 viral vector platform in the younger age group. The almost similar performance in older adults is promising,” Dr. Schuitemaker said.

A potential limitation of the phase 1/2a trial is “the lack of representation of minority groups,” the researchers noted. Johnson & Johnson is working on improving the diversity of study participants “with respect to groups that seem to be affected most by the COVID-19 pandemic.”
 

AstraZeneca/Oxford vaccine status

The AstraZeneca/Oxford AZD1222 vaccine in development received approval for use in the United Kingdom on Dec. 30. The approval came after Public Health England said the country was facing “unprecedented” levels of infections, the BBC reported. AstraZeneca applied for European Medical Agency approval earlier in the week of Jan. 10, which could lead to more widespread use across Europe.

The status of the vaccine remains uncertain in the United States. A phase 3 trial that started in August was paused for about 6 weeks in September and October after an adverse event in a British volunteer halted studies worldwide. On Oct. 23, the FDA permitted researchers to continue the trial with approximately 40,000 participants.

There was some suggestion in the clinical trials that a half dose of the AstraZeneca vaccine was more effective than a full dose, 90% vs. 62%, but some irregularities in the research require further investigation.

Although the AstraZeneca vaccine is delivered to cells by an adenovirus – as with the Johnson & Johnson product – it is designed to be delivered in two doses 28 days apart, like the administration schedule of the Moderna mRNA vaccine.
 

A need for speed, and more doses

Regardless of which vaccine product is next to gain an EUA in the United States, many experts agree the COVID-19 vaccine rollouts so far have been problematic, at a time when cases are climbing to record-breaking levels, and likely more related to logistics over administration of the vaccine than production of the doses.

“Lots of doses being manufactured. In December 20 million, January 40 million, February 80 million and J&J hopefully soon to add to the count. The shortage is the number arms not getting vaccinated. Freezers do not get COVID. They do not need all those vaccines,” Daniel Griffin, MD, PhD, an infectious disease expert in Port Washington, N.Y., tweeted on Jan. 12.

“Unfortunately, the rollout has not gone smoothly, partly due to a lack of resources for this distribution phase we’re in,” Andrew T. Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah, Salt Lake City, said during a media briefing Jan. 14 sponsored by the Infectious Diseases Society of America (IDSA).

“We’re concerned about the mismatch between the number of people who are being told they are eligible and the amount of vaccine that is being distributed,” he said.

Complicating the rollout is a directive from U.S. Health and Human Services Secretary Alex Azar that states should start vaccinating everyone 65 and older as well as those with underlying conditions.

Expanding distribution to the 15% of Americans in just this age group is a big challenge, Dr. Pavia said. “We have enough vaccine maybe to vaccinate 40 million by the end of this month. There is a huge disconnect, and that creates a lot of problems.”

“One of the biggest problems is we are trying to do this mass vaccination program in the middle of the biggest surge we’ve ever seen,” Julie Vaishampayan, MD, MPH, chair of the IDSA Public Health Committee, said during the briefing. Without sufficient time for public health officials to plan for vaccinating a larger population, “people will come and stand in extremely long lines.”

Trying to expand immunization access without a proportionate increase in available doses prompted Dr. Vaishampayan to share an analogy from a colleague: “We are trying to fill a lake with a garden hose. Rather than making the lake bigger, what we really need is more water.”

Dr. Pavia emphasized that infectious disease experts “know the measures that work.” Not using masks, physical distancing, and hand hygiene, he said, “is a bit like knowing that really good shark repellents will be available in summer, so I’m going to jump into the ocean covered in blood while the great whites are swimming around.”

An official at the World Health Organization agreed. “Vaccines are coming online and I do believe vaccines will make a huge difference. But they are not here yet in enough quantities and in enough people to make that difference,” Michael Ryan, MB, WHO executive director of health emergencies, said during an online media briefing Jan. 13, held in conjunction with Emory University.

Dr. Ryan predicted that “we’ve got weeks if not months ahead of us in which our weapon is our knowledge ... what we know about this virus, its transmission, and stopping that transmission.

“And as the vaccines roll in, we can hopefully end this horrific pandemic.”

Dr. Schuitemaker reports grants from BARDA during the conduct of the study; personal fees and other from Janssen Vaccines and Prevention, a J&J company, outside the submitted work. Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services funded the phase 1/2a study.

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

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Pregnancy complications in women with pityriasis rosea (PR) were relatively minor, and included no cases of miscarriage, abortion, or fetal death, according to a review of 33 patients.

“Though generally considered benign, PR may be associated with an increased risk of birth complications if acquired during pregnancy,” and previous studies have shown increased rates of complications including miscarriage and neonatal hypotonia in these patients, wrote Julian Stashower of the University of Virginia, Charlottesville, and colleagues.

In a retrospective study published in the Journal of the American Academy of Dermatology, the researchers assessed pregnancy outcomes in women who developed PR during pregnancy. They were identified from medical records at three institutions between September 2010 and June 2020. Diagnosis of PR, a papulosquamous skin eruption associated with human herpesvirus (HHV)–6/7 reactivation, was based on history and physical examination.

Overall, 8 of the 33 women (24%) had birth complications; the rates of preterm delivery, spontaneous pregnancy loss in clinically detectable pregnancies, and oligohydramnios were 6%, 0%, and 3%, respectively. The average onset of PR during pregnancy was earlier among women with complications, compared with those without complications (10.75 weeks’ gestation vs. 15.21 weeks’ gestation), but the difference was not statistically significant.

The researchers noted that their findings differed from the most recent study of PR in pregnancy, which included 60 patients and found a notably higher incidence of overall birth complications (50%), as well as higher incidence of neonatal hypotonia (25%), and miscarriage (13%).

The previous study also showed an increased risk of birth complications when PR onset occurred prior to 15 weeks’ gestation, but the current study did not reflect that finding, they wrote.

The current study findings were limited by several factors including the small sample size, retrospective design, and lack of confirmation of PR with HHV-6/7 testing, as well as lack of exclusion of atypical PR cases, the researchers noted. However, the results suggest that birth complications associated with PR may be lower than previously reported. “Further research is needed to guide future care and fully elucidate this possible association, which has important implications for both pregnant women with PR and their providers.”

The study received no outside funding. The researchers had no financial conflict to disclose.

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

Several updates in the strategy for prevention of and treatment of sexually transmitted infections were recently published in the United States.

Among these are the U.S. Department of Health and Human Services’ first “Sexually Transmitted Infections (STIs) National Strategic Plan for the United States,” which has a strong encompassing vision.

• Prevent New STIs.
• Improve the health of people by reducing adverse outcomes of STIs.
• Accelerate progress in STI research, technology, and innovation.
• Reduce STI-related health disparities and health inequities.
• Achieve integrated, coordinated efforts that address the STI epidemic.¹

In my opinion, family physicians have important roles to play in order for each of these goals to be achieved.Unfortunately, there are approximately 20 million new cases of STIs each year, and the U.S. has seen increases in the rates of STIs in the past decade.

“Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others,” according to a new recommendation statement from the USPSTF.² STIs may lead to serious health consequences for patients, cause harms to a mother and infant during pregnancy, and lead to cases of cancer among other concerning outcomes. As such, following the HHS new national strategic plan is critical for us to address the needs of our communities.
 

Preventing new STIs

Family physicians can be vital in achieving the first goal of the plan by helping to prevent new STIs. In August 2020, the USPSTF updated its guideline on behavioral counseling interventions to prevent STIs. In my opinion, the USPSTF offers some practical improvements from the earlier version of this guideline.

The task force provides a grade B recommendation that all sexually active adolescents and adults at increased risk for STIs be provided with behavioral counseling to prevent STIs. The guideline indicates that behavioral counseling interventions reduce the likelihood of those at increased risk for acquiring STIs.²

The 2014 guideline had recommended intensive interventions with a minimum of 30 minutes of counseling. Many family physicians may have found this previous recommendation impractical to implement. These updated recommendations now include a variety of interventions, such as those that take less than 30 minutes.

Although interventions with more than 120 minutes of contact time had the most effect, those with less than 30 minutes still demonstrated statistically significant fewer acquisitions of STIs during follow-up. These options include in-person counseling, and providing written materials, websites, videos, and telephone and text support to patients. These interventions can be delivered directly by the family physician, or patients may be referred to other settings or the media interventions.

The task force’s updated recommendation statement refers to a variety of resources that can be used to identify these interventions. Many of the studies reviewed for this guideline were conducted in STI clinics, and the guideline authors recommended further studies in primary care as opportunities for more generalizability.

In addition to behavioral counseling for STI prevention, family physicians can help prevent STIs in their patients through HPV vaccination and HIV pre-exposure prophylaxis (PrEP provision) within their practices. As the first contact for health care for many patients, we have an opportunity to significantly impact this first goal of prevention.
 

Treating STIs

Within the second goal of the national strategic plan is treatment of STIs, which family physicians should include in their practices as well as the diagnosis of STIs.

In December 2020, an update to the CDC’s treatment guideline for gonococcal infection was released. Prior to the publishing of this updated recommendation, the CDC recommended combination therapy of 250 mg intramuscular (IM) dose of ceftriaxone and either doxycycline or azithromycin. This recommendation has been changed to a single 500-mg IM dose of ceftriaxone for uncomplicated urogenital, anorectal, and pharyngeal gonorrhea. If chlamydia cannot be excluded, then the addition of oral doxycycline 100 mg twice daily for 7 days is recommended for nonpregnant persons, and 1 g oral azithromycin for pregnant persons. The previous treatment was recommended based on a concern for gonococcal resistance.

This updated guideline reflects increasing concerns for antimicrobial stewardship and emerging azithromycin resistance. It does not recommend a test-of-cure for urogenital or rectal gonorrhea, though did recommend a test-of-cure 7-14 days after treatment of pharyngeal gonorrhea. The guideline also recommends testing for reinfection 3-12 months after treatment as the rate of reinfection ranges from 7% to 12% among those previously treated.³

For some offices, the provision of the IM injection may be challenging, though having this medication in stock with the possibility of provision can greatly improve access and ease of treatment for patients. Family physicians can incorporate these updated recommendations along with those for other STIs such as chlamydia and syphilis with standing orders for treatment and testing within their offices.
 

Accelerating progress in STI research

Family physicians can also support the national strategic plan by participating in studies looking at the impact of behavioral counseling in the primary care office as opposed to in STI clinics. In addition, by following the STI treatment and screening guidelines, family physicians will contribute to the body of knowledge of prevalence, treatment failure, and reinfection rates of STIs. We can also help advance the research by providing feedback on interventions that have success within our practices.

Reducing STI-related health disparities and inequities

Family physicians are also in important places to support the strategic plan’s fourth goal of reducing health disparities and health inequities.

If we continue to ask the questions to identify those at high risk and ensure that we are offering appropriate STI prevention, care, and treatment services within our clinics, we can expand access to all who need services and improve equity. By offering these services within the primary care office, we may be able to decrease the stigma some may feel going to an STI clinic for services.

By incorporating additional screening and counseling in our practices we may identify some patients who were not aware that they were at risk for an STI and offer them preventive services.
 

Achieving integrated and coordinated efforts

Finally, as many family physicians have integrated practices, we are uniquely poised to support the fifth goal of the strategic plan of achieving integrated and coordinated efforts addressing the STI epidemic. In our practices we can participate in, lead, and refer to programs for substance use disorders, viral hepatitis, STIs, and HIV as part of full scope primary care.

Family physicians and other primary care providers should work to support the entire strategic plan to ensure that we are fully caring for our patients and communities and stopping the past decade’s increase in STIs. We have an opportunity to use this strategy and make a large impact in our communities.
 

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program at Humboldt Park, Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at fpnews@mdedge.com.

References

1. U.S. Department of Health and Human Services. 2020. Sexually Transmitted Infections National Strategic Plan for the United States: 2021-2025. Washington.

2. U.S. Preventive Services Task Force. Behavioral counseling interventions to prevent sexually transmitted infections: U.S. Preventive Services Task Force Recommendation Statement. JAMA. 2020;324(7):674-81. doi: 10.1001/jama.2020.13095.

3. St. Cyr S et al. Update to CDC’s Treatment Guideline for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1911-6. doi: 10.15585/mmwr.mm6950a6external_icon.

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

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

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

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

The American Diabetes Association, along with 18 other organizations, has sent a letter to the U.S. Centers for Disease Control and Prevention urging them to rank people with type 1 diabetes as equally high risk for COVID-19 severity, and therefore vaccination, as those with type 2 diabetes.

On Jan. 12, the CDC recommended states vaccinate all Americans over age 65 and those with underlying health conditions that make them more vulnerable to COVID-19.

Currently, type 2 diabetes is listed among 12 conditions that place adults “at increased risk of severe illness from the virus that causes COVID-19,” with the latter defined as “hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”

On the other hand, the autoimmune condition type 1 diabetes is among 11 conditions the CDC says “might be at increased risk” for COVID-19, but limited data were available at the time of the last update on Dec. 23, 2020.

“States are utilizing the CDC risk classification when designing their vaccine distribution plans. This raises an obvious concern as it could result in the approximately 1.6 million with type 1 diabetes receiving the vaccination later than others with the same risk,” states the ADA letter, sent to the CDC on Jan. 13.

Representatives from the Endocrine Society, American Association of Clinical Endocrinology, Pediatric Endocrine Society, Association of Diabetes Care & Education Specialists, and JDRF, among others, cosigned the letter.
 

Newer data show those with type 1 diabetes at equally high risk

While acknowledging that “early data did not provide as much clarity about the extent to which those with type 1 diabetes are at high risk,” the ADA says newer evidence has emerged, as previously reported by this news organization, that “convincingly demonstrates that COVID-19 severity is more than tripled in individuals with type 1 diabetes.”

The letter also cites another study showing that people with type 1 diabetes “have a 3.3-fold greater risk of severe illness, are 3.9 times more likely to be hospitalized with COVID-19, and have a 3-fold increase in mortality compared to those without type 1 diabetes.”

Those risks, they note, are comparable to the increased risk established for those with type 2 diabetes, as shown in a third study from Scotland, published last month.

Asked for comment, CDC representative Kirsten Nordlund said in an interview, “This list is a living document that will be periodically updated by CDC, and it could rapidly change as the science evolves.”

In addition, Ms. Nordlund said, “Decisions about transitioning to subsequent phases should depend on supply; demand; equitable vaccine distribution; and local, state, or territorial context.”

“Phased vaccine recommendations are meant to be fluid and not restrictive for jurisdictions. It is not necessary to vaccinate all individuals in one phase before initiating the next phase; phases may overlap,” she noted. More information is available here.
 

Tennessee gives type 1 and type 2 diabetes equal priority for vaccination

Meanwhile, at least one state, Tennessee, has updated its guidance to include both types of diabetes as being priority for COVID-19 vaccination.

Vanderbilt University pediatric endocrinologist Justin M. Gregory, MD, said in an interview: “I was thrilled when our state modified its guidance on December 30th to include both type 1 and type 2 diabetes in the ‘high-risk category.’ Other states have not modified that guidance though.”

It’s unclear how this might play out on the ground, noted Dr. Gregory, who led one of the three studies demonstrating increased COVID-19 risk for people with type 1 diabetes.

“To tell you the truth, I don’t really know how individual organizations dispensing the vaccination [will handle] people who come to their facility saying they have ‘diabetes.’ Individual states set the vaccine-dispensing guidance and individual county health departments and health care systems mirror that guidance,” he said.

Thus, he added, “Although it’s possible an individual nurse may take the ‘I’ll ask you no questions, and you’ll tell me no lies’ approach if someone with type 1 diabetes says they have ‘diabetes’, websites and health department–recorded telephone messages are going to tell people with type 1 diabetes they have to wait further back in line if that is what their state’s guidance directs.”

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

Three-quarters of patients hospitalized with COVID-19 were still experiencing at least one symptom of the infection 6 months after being discharged, according to a follow-up study involving 1,733 patients.

“Patients with COVID-19 had symptoms of fatigue or muscle weakness, sleep difficulties, and anxiety or depression,” and those with “more severe illness during their hospital stay had increasingly impaired pulmonary diffusion capacities and abnormal chest imaging manifestations,” Chaolin Huang, MD, of Jin Yin-tan Hospital in Wuhan, China, and associates wrote in the Lancet.

Fatigue or muscle weakness, reported by 63% of patients, was the most common symptom, followed by sleep difficulties, hair loss, and smell disorder. Altogether, 76% of those examined 6 months after discharge from Jin Yin-tan hospital – the first designated for patients with COVID-19 in Wuhan – reported at least one symptom, they said.

Symptoms were more common in women than men: 81% vs. 73% had at least one symptom, and 66% vs. 59% had fatigue or muscle weakness. Women were also more likely than men to report anxiety or depression at follow-up: 28% vs. 18% (23% overall), the investigators said.

Patients with the most severe COVID-19 were 2.4 times as likely to report any symptom later, compared with those who had the least severe levels of infection. Among the 349 participants who completed a lung function test at follow-up, lung diffusion impairment was seen in 56% of those with the most severe illness and 22% of those with the lowest level, Dr. Huang and associates reported.

In a different subset of 94 patients from whom plasma samples were collected, the “seropositivity and median titres of the neutralising antibodies were significantly lower than at the acute phase,” raising concern for reinfection, they said.

The results of the study, the investigators noted, “support that those with severe disease need post-discharge care. Longer follow-up studies in a larger population are necessary to understand the full spectrum of health consequences from COVID-19.”

rfranki@mdedge.com

Three-quarters of patients hospitalized with COVID-19 were still experiencing at least one symptom of the infection 6 months after being discharged, according to a follow-up study involving 1,733 patients.

“Patients with COVID-19 had symptoms of fatigue or muscle weakness, sleep difficulties, and anxiety or depression,” and those with “more severe illness during their hospital stay had increasingly impaired pulmonary diffusion capacities and abnormal chest imaging manifestations,” Chaolin Huang, MD, of Jin Yin-tan Hospital in Wuhan, China, and associates wrote in the Lancet.

Fatigue or muscle weakness, reported by 63% of patients, was the most common symptom, followed by sleep difficulties, hair loss, and smell disorder. Altogether, 76% of those examined 6 months after discharge from Jin Yin-tan hospital – the first designated for patients with COVID-19 in Wuhan – reported at least one symptom, they said.

Symptoms were more common in women than men: 81% vs. 73% had at least one symptom, and 66% vs. 59% had fatigue or muscle weakness. Women were also more likely than men to report anxiety or depression at follow-up: 28% vs. 18% (23% overall), the investigators said.

Patients with the most severe COVID-19 were 2.4 times as likely to report any symptom later, compared with those who had the least severe levels of infection. Among the 349 participants who completed a lung function test at follow-up, lung diffusion impairment was seen in 56% of those with the most severe illness and 22% of those with the lowest level, Dr. Huang and associates reported.

In a different subset of 94 patients from whom plasma samples were collected, the “seropositivity and median titres of the neutralising antibodies were significantly lower than at the acute phase,” raising concern for reinfection, they said.

The results of the study, the investigators noted, “support that those with severe disease need post-discharge care. Longer follow-up studies in a larger population are necessary to understand the full spectrum of health consequences from COVID-19.”

rfranki@mdedge.com

Three-quarters of patients hospitalized with COVID-19 were still experiencing at least one symptom of the infection 6 months after being discharged, according to a follow-up study involving 1,733 patients.

“Patients with COVID-19 had symptoms of fatigue or muscle weakness, sleep difficulties, and anxiety or depression,” and those with “more severe illness during their hospital stay had increasingly impaired pulmonary diffusion capacities and abnormal chest imaging manifestations,” Chaolin Huang, MD, of Jin Yin-tan Hospital in Wuhan, China, and associates wrote in the Lancet.

Fatigue or muscle weakness, reported by 63% of patients, was the most common symptom, followed by sleep difficulties, hair loss, and smell disorder. Altogether, 76% of those examined 6 months after discharge from Jin Yin-tan hospital – the first designated for patients with COVID-19 in Wuhan – reported at least one symptom, they said.

Symptoms were more common in women than men: 81% vs. 73% had at least one symptom, and 66% vs. 59% had fatigue or muscle weakness. Women were also more likely than men to report anxiety or depression at follow-up: 28% vs. 18% (23% overall), the investigators said.

Patients with the most severe COVID-19 were 2.4 times as likely to report any symptom later, compared with those who had the least severe levels of infection. Among the 349 participants who completed a lung function test at follow-up, lung diffusion impairment was seen in 56% of those with the most severe illness and 22% of those with the lowest level, Dr. Huang and associates reported.

In a different subset of 94 patients from whom plasma samples were collected, the “seropositivity and median titres of the neutralising antibodies were significantly lower than at the acute phase,” raising concern for reinfection, they said.

The results of the study, the investigators noted, “support that those with severe disease need post-discharge care. Longer follow-up studies in a larger population are necessary to understand the full spectrum of health consequences from COVID-19.”

rfranki@mdedge.com

While the direct toll of the COVID-19 pandemic is being tallied and shared on the nightly news, the indirect effects will undoubtedly take years to fully measure.

Floaria Bicher/iStock/Getty Images Plus

In two papers published online Jan. 11 in the Journal of the American College of Cardiology, researchers have started the process of quantifying the impact of the pandemic on the care of patients with cardiovascular disease (CVD).

In the first study, Rishi Wadhera, MD, MPP, MPhil, and colleagues from the Beth Israel Deaconess Medical Center and Harvard Medical School in Boston examined population-level data to determine how deaths from cardiovascular causes changed in the United States in the early months of the pandemic relative to the same periods in 2019.

In a second paper, Andrew J. Einstein, MD, PhD, from Columbia University Irving Medical Center/New York–Presbyterian Hospital and colleagues looked at the pandemic’s international impact on the diagnosis of heart disease.

Using data from the National Center for Health Statistics, Dr. Wadhera and colleagues compared death rates from cardiovascular causes in the United States from March 18, 2020, to June 2, 2020, (the first wave of the pandemic) and from Jan. 1, 2020, to March 17, 2020, (the period just before the pandemic started) and compared them to the same periods in 2019. ICD codes were used to identify underlying causes of death.

Relative to 2019, they found a significant increase in deaths from ischemic heart disease nationally (1.11; 95% confidence interval, 1.04-1.18), as well as an increase in deaths caused by hypertensive disease (1.17; 95% CI, 1.09-1.26). There was no apparent increase in deaths from heart failure, cerebrovascular disease, or other diseases of the circulatory system.

When they looked just at New York City, the area hit hardest during the early part of the pandemic, the relative increases in deaths from ischemic heart disease were more pronounced.

Deaths from ischemic heart disease or hypertensive diseases jumped 139% and 164%, respectively, between March 18, 2020, and June 2, 2020.

More modest increases in deaths were seen in the remainder of New York state, New Jersey, Michigan and Illinois, while Massachusetts and Louisiana did not see a change in cardiovascular deaths.

Several studies from different parts of the world have indicated a 40%-50% drop in hospitalization for myocardial infarction in the initial months of the pandemic, said Dr. Wadhera in an interview.

“We wanted to understand where did all the heart attacks go? And we worried that patients with urgent heart conditions were not seeking the medical care they needed. I think our data suggest that this may have been the case,” reported Dr. Wadhera.  

“This very much reflects the reality of what we’re seeing on the ground,” he told this news organization. “After the initial surge ended, when hospital volumes began to return to normal, we saw patients come into the hospital who clearly had a heart attack during the surge months – and were now experiencing complications of that event – because they had initially not come into the hospital due to concerns about exposure to the virus.”

A limitation of their data, he stressed, is whether some deaths coded as CVD deaths were really deaths from undiagnosed COVID-19. “It’s possible that some portion of the increased deaths we observed really reflect the cardiovascular complications of undiagnosed COVID-19, because we know that testing was quite limited during the early first surge of cases.”

“I think that basically three factors – patients avoiding the health care system because of fear of getting COVID, health care systems being strained and overwhelmed leading to the deferral of cardiovascular care and semi-elective procedures, and the cardiovascular complications of COVID-19 itself – all probably collectively contributed to the rise in cardiovascular deaths that we observed,” said Dr. Wadhera.

In an accompanying editorial, Michael N. Young, MD, Geisel School of Medicine at Dartmouth, Lebanon, N.H., and colleagues write that these data, taken together with an earlier study showing an increase in out-of-hospital cardiac arrests at the pandemic peak in New York City, “support the notion of excess fatalities due to unattended comorbid illnesses.” That said, attribution of death in the COVID era “remains problematic.”

In the second article, Andrew Einstein, MD, PhD, and the INCAPS COVID Investigators Group took a broader approach and looked at the impact of COVID-19 on cardiac diagnostic procedures in over 100 countries.

The INCAPS (International Atomic Energy Agency Noninvasive Cardiology Protocols Study) group has for the past decade conducted numerous studies addressing the use of best practices and worldwide practice variation in CVD diagnosis.

For this effort, they sent a survey link to INCAPS participants worldwide, ultimately including 909 survey responses from 108 countries in the final analysis.

Compared with March 2019, overall procedure volume decreased 42% in March 2020 and 64% in April 2020.

The greatest decreases were seen in stress testing (78%) and transesophageal echocardiography (76%), both procedures, noted Dr. Einstein, associated with a greater risk of aerosolization.

“Whether as we reset after COVID we return to the same place in terms of the use of cardiovascular diagnostic testing remains to be seen, but it certainly poses an opportunity to improve our utilization of various modes of testing,” said Dr. Einstein.

Using regression analysis, Dr. Einstein and colleagues were able to see that sites located in low-income and lower-middle-income countries saw an additional 22% reduction in cardiac procedures and less availability of personal protective equipment (PPE) and telehealth.

Fifty-two percent of survey respondents reported significant shortages of N95 masks early in the pandemic, with fewer issues in supplies of gloves, gowns, and face shields. Lower-income countries were more likely to face significant PPE shortages and less likely to be able to implement telehealth strategies to make up for reduced in-person care. PPE shortage itself, however, was not related to lower procedural volume on multivariable regression.

“It all really begs the question of whether there is more that the world can do to help out the developing world in terms of managing the pandemic in all its facets,” said Dr. Einstein in an interview, adding he was “shocked” to learn how difficult it was for some lower-income countries to get sufficient PPE.
 

Did shutdowns go too far?

Calling this a “remarkable study,” an editorial written by Darryl P. Leong, MBBS, PhD, John W. Eikelboom, MBBS, and Salim Yusuf, MBBS, DPhil, all from McMaster University, Hamilton, Ont., suggests that perhaps health systems in some places went too far in closing down during the first wave of the pandemic, naming specifically Canada, Eastern Europe, and Saudi Arabia as examples.

“Although these measures were taken to prepare for the worst, overwhelming numbers of patients with COVID-19 did not materialize during the first wave of the pandemic in these countries. It is possible that delaying so-called nonessential services may have been unnecessary and potentially harmful, because it likely led to delays in providing care for the treatment of serious non–COVID-19 illnesses.”

Since then, more experience and more data have largely allowed hospital systems to “tackle the ebb and flow” of COVID-19 cases in ways that limit shutdowns of important health services, they said.

Given the more pronounced effect in low- and middle-income countries, they stressed the need to focus resources on ways to promote prevention and treatment that do not rely on diagnostic procedures.

“This calls for more emphasis on developing efficient systems of telehealth, especially in poorer countries or in remote settings in all countries,” Dr. Leong and colleagues conclude.

Dr. Wadhera has reported research support from the National Heart, Lung, and Blood Institute, along with fellow senior author Robert W. Yeh, MD, MBA, who has also received personal fees and grants from several companies not related to the submitted work. Dr. Einstein, Dr. Leong, Dr. Eikelboom, and Dr. Yusuf have reported no relevant financial relationships.

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

While the direct toll of the COVID-19 pandemic is being tallied and shared on the nightly news, the indirect effects will undoubtedly take years to fully measure.

Floaria Bicher/iStock/Getty Images Plus

In two papers published online Jan. 11 in the Journal of the American College of Cardiology, researchers have started the process of quantifying the impact of the pandemic on the care of patients with cardiovascular disease (CVD).

In the first study, Rishi Wadhera, MD, MPP, MPhil, and colleagues from the Beth Israel Deaconess Medical Center and Harvard Medical School in Boston examined population-level data to determine how deaths from cardiovascular causes changed in the United States in the early months of the pandemic relative to the same periods in 2019.

In a second paper, Andrew J. Einstein, MD, PhD, from Columbia University Irving Medical Center/New York–Presbyterian Hospital and colleagues looked at the pandemic’s international impact on the diagnosis of heart disease.

Using data from the National Center for Health Statistics, Dr. Wadhera and colleagues compared death rates from cardiovascular causes in the United States from March 18, 2020, to June 2, 2020, (the first wave of the pandemic) and from Jan. 1, 2020, to March 17, 2020, (the period just before the pandemic started) and compared them to the same periods in 2019. ICD codes were used to identify underlying causes of death.

Relative to 2019, they found a significant increase in deaths from ischemic heart disease nationally (1.11; 95% confidence interval, 1.04-1.18), as well as an increase in deaths caused by hypertensive disease (1.17; 95% CI, 1.09-1.26). There was no apparent increase in deaths from heart failure, cerebrovascular disease, or other diseases of the circulatory system.

When they looked just at New York City, the area hit hardest during the early part of the pandemic, the relative increases in deaths from ischemic heart disease were more pronounced.

Deaths from ischemic heart disease or hypertensive diseases jumped 139% and 164%, respectively, between March 18, 2020, and June 2, 2020.

More modest increases in deaths were seen in the remainder of New York state, New Jersey, Michigan and Illinois, while Massachusetts and Louisiana did not see a change in cardiovascular deaths.

Several studies from different parts of the world have indicated a 40%-50% drop in hospitalization for myocardial infarction in the initial months of the pandemic, said Dr. Wadhera in an interview.

“We wanted to understand where did all the heart attacks go? And we worried that patients with urgent heart conditions were not seeking the medical care they needed. I think our data suggest that this may have been the case,” reported Dr. Wadhera.  

“This very much reflects the reality of what we’re seeing on the ground,” he told this news organization. “After the initial surge ended, when hospital volumes began to return to normal, we saw patients come into the hospital who clearly had a heart attack during the surge months – and were now experiencing complications of that event – because they had initially not come into the hospital due to concerns about exposure to the virus.”

A limitation of their data, he stressed, is whether some deaths coded as CVD deaths were really deaths from undiagnosed COVID-19. “It’s possible that some portion of the increased deaths we observed really reflect the cardiovascular complications of undiagnosed COVID-19, because we know that testing was quite limited during the early first surge of cases.”

“I think that basically three factors – patients avoiding the health care system because of fear of getting COVID, health care systems being strained and overwhelmed leading to the deferral of cardiovascular care and semi-elective procedures, and the cardiovascular complications of COVID-19 itself – all probably collectively contributed to the rise in cardiovascular deaths that we observed,” said Dr. Wadhera.

In an accompanying editorial, Michael N. Young, MD, Geisel School of Medicine at Dartmouth, Lebanon, N.H., and colleagues write that these data, taken together with an earlier study showing an increase in out-of-hospital cardiac arrests at the pandemic peak in New York City, “support the notion of excess fatalities due to unattended comorbid illnesses.” That said, attribution of death in the COVID era “remains problematic.”

In the second article, Andrew Einstein, MD, PhD, and the INCAPS COVID Investigators Group took a broader approach and looked at the impact of COVID-19 on cardiac diagnostic procedures in over 100 countries.

The INCAPS (International Atomic Energy Agency Noninvasive Cardiology Protocols Study) group has for the past decade conducted numerous studies addressing the use of best practices and worldwide practice variation in CVD diagnosis.

For this effort, they sent a survey link to INCAPS participants worldwide, ultimately including 909 survey responses from 108 countries in the final analysis.

Compared with March 2019, overall procedure volume decreased 42% in March 2020 and 64% in April 2020.

The greatest decreases were seen in stress testing (78%) and transesophageal echocardiography (76%), both procedures, noted Dr. Einstein, associated with a greater risk of aerosolization.

“Whether as we reset after COVID we return to the same place in terms of the use of cardiovascular diagnostic testing remains to be seen, but it certainly poses an opportunity to improve our utilization of various modes of testing,” said Dr. Einstein.

Using regression analysis, Dr. Einstein and colleagues were able to see that sites located in low-income and lower-middle-income countries saw an additional 22% reduction in cardiac procedures and less availability of personal protective equipment (PPE) and telehealth.

Fifty-two percent of survey respondents reported significant shortages of N95 masks early in the pandemic, with fewer issues in supplies of gloves, gowns, and face shields. Lower-income countries were more likely to face significant PPE shortages and less likely to be able to implement telehealth strategies to make up for reduced in-person care. PPE shortage itself, however, was not related to lower procedural volume on multivariable regression.

“It all really begs the question of whether there is more that the world can do to help out the developing world in terms of managing the pandemic in all its facets,” said Dr. Einstein in an interview, adding he was “shocked” to learn how difficult it was for some lower-income countries to get sufficient PPE.
 

Did shutdowns go too far?

Calling this a “remarkable study,” an editorial written by Darryl P. Leong, MBBS, PhD, John W. Eikelboom, MBBS, and Salim Yusuf, MBBS, DPhil, all from McMaster University, Hamilton, Ont., suggests that perhaps health systems in some places went too far in closing down during the first wave of the pandemic, naming specifically Canada, Eastern Europe, and Saudi Arabia as examples.

“Although these measures were taken to prepare for the worst, overwhelming numbers of patients with COVID-19 did not materialize during the first wave of the pandemic in these countries. It is possible that delaying so-called nonessential services may have been unnecessary and potentially harmful, because it likely led to delays in providing care for the treatment of serious non–COVID-19 illnesses.”

Since then, more experience and more data have largely allowed hospital systems to “tackle the ebb and flow” of COVID-19 cases in ways that limit shutdowns of important health services, they said.

Given the more pronounced effect in low- and middle-income countries, they stressed the need to focus resources on ways to promote prevention and treatment that do not rely on diagnostic procedures.

“This calls for more emphasis on developing efficient systems of telehealth, especially in poorer countries or in remote settings in all countries,” Dr. Leong and colleagues conclude.

Dr. Wadhera has reported research support from the National Heart, Lung, and Blood Institute, along with fellow senior author Robert W. Yeh, MD, MBA, who has also received personal fees and grants from several companies not related to the submitted work. Dr. Einstein, Dr. Leong, Dr. Eikelboom, and Dr. Yusuf have reported no relevant financial relationships.

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

While the direct toll of the COVID-19 pandemic is being tallied and shared on the nightly news, the indirect effects will undoubtedly take years to fully measure.

Floaria Bicher/iStock/Getty Images Plus

In two papers published online Jan. 11 in the Journal of the American College of Cardiology, researchers have started the process of quantifying the impact of the pandemic on the care of patients with cardiovascular disease (CVD).

In the first study, Rishi Wadhera, MD, MPP, MPhil, and colleagues from the Beth Israel Deaconess Medical Center and Harvard Medical School in Boston examined population-level data to determine how deaths from cardiovascular causes changed in the United States in the early months of the pandemic relative to the same periods in 2019.

In a second paper, Andrew J. Einstein, MD, PhD, from Columbia University Irving Medical Center/New York–Presbyterian Hospital and colleagues looked at the pandemic’s international impact on the diagnosis of heart disease.

Using data from the National Center for Health Statistics, Dr. Wadhera and colleagues compared death rates from cardiovascular causes in the United States from March 18, 2020, to June 2, 2020, (the first wave of the pandemic) and from Jan. 1, 2020, to March 17, 2020, (the period just before the pandemic started) and compared them to the same periods in 2019. ICD codes were used to identify underlying causes of death.

Relative to 2019, they found a significant increase in deaths from ischemic heart disease nationally (1.11; 95% confidence interval, 1.04-1.18), as well as an increase in deaths caused by hypertensive disease (1.17; 95% CI, 1.09-1.26). There was no apparent increase in deaths from heart failure, cerebrovascular disease, or other diseases of the circulatory system.

When they looked just at New York City, the area hit hardest during the early part of the pandemic, the relative increases in deaths from ischemic heart disease were more pronounced.

Deaths from ischemic heart disease or hypertensive diseases jumped 139% and 164%, respectively, between March 18, 2020, and June 2, 2020.

More modest increases in deaths were seen in the remainder of New York state, New Jersey, Michigan and Illinois, while Massachusetts and Louisiana did not see a change in cardiovascular deaths.

Several studies from different parts of the world have indicated a 40%-50% drop in hospitalization for myocardial infarction in the initial months of the pandemic, said Dr. Wadhera in an interview.

“We wanted to understand where did all the heart attacks go? And we worried that patients with urgent heart conditions were not seeking the medical care they needed. I think our data suggest that this may have been the case,” reported Dr. Wadhera.  

“This very much reflects the reality of what we’re seeing on the ground,” he told this news organization. “After the initial surge ended, when hospital volumes began to return to normal, we saw patients come into the hospital who clearly had a heart attack during the surge months – and were now experiencing complications of that event – because they had initially not come into the hospital due to concerns about exposure to the virus.”

A limitation of their data, he stressed, is whether some deaths coded as CVD deaths were really deaths from undiagnosed COVID-19. “It’s possible that some portion of the increased deaths we observed really reflect the cardiovascular complications of undiagnosed COVID-19, because we know that testing was quite limited during the early first surge of cases.”

“I think that basically three factors – patients avoiding the health care system because of fear of getting COVID, health care systems being strained and overwhelmed leading to the deferral of cardiovascular care and semi-elective procedures, and the cardiovascular complications of COVID-19 itself – all probably collectively contributed to the rise in cardiovascular deaths that we observed,” said Dr. Wadhera.

In an accompanying editorial, Michael N. Young, MD, Geisel School of Medicine at Dartmouth, Lebanon, N.H., and colleagues write that these data, taken together with an earlier study showing an increase in out-of-hospital cardiac arrests at the pandemic peak in New York City, “support the notion of excess fatalities due to unattended comorbid illnesses.” That said, attribution of death in the COVID era “remains problematic.”

In the second article, Andrew Einstein, MD, PhD, and the INCAPS COVID Investigators Group took a broader approach and looked at the impact of COVID-19 on cardiac diagnostic procedures in over 100 countries.

The INCAPS (International Atomic Energy Agency Noninvasive Cardiology Protocols Study) group has for the past decade conducted numerous studies addressing the use of best practices and worldwide practice variation in CVD diagnosis.

For this effort, they sent a survey link to INCAPS participants worldwide, ultimately including 909 survey responses from 108 countries in the final analysis.

Compared with March 2019, overall procedure volume decreased 42% in March 2020 and 64% in April 2020.

The greatest decreases were seen in stress testing (78%) and transesophageal echocardiography (76%), both procedures, noted Dr. Einstein, associated with a greater risk of aerosolization.

“Whether as we reset after COVID we return to the same place in terms of the use of cardiovascular diagnostic testing remains to be seen, but it certainly poses an opportunity to improve our utilization of various modes of testing,” said Dr. Einstein.

Using regression analysis, Dr. Einstein and colleagues were able to see that sites located in low-income and lower-middle-income countries saw an additional 22% reduction in cardiac procedures and less availability of personal protective equipment (PPE) and telehealth.

Fifty-two percent of survey respondents reported significant shortages of N95 masks early in the pandemic, with fewer issues in supplies of gloves, gowns, and face shields. Lower-income countries were more likely to face significant PPE shortages and less likely to be able to implement telehealth strategies to make up for reduced in-person care. PPE shortage itself, however, was not related to lower procedural volume on multivariable regression.

“It all really begs the question of whether there is more that the world can do to help out the developing world in terms of managing the pandemic in all its facets,” said Dr. Einstein in an interview, adding he was “shocked” to learn how difficult it was for some lower-income countries to get sufficient PPE.
 

Did shutdowns go too far?

Calling this a “remarkable study,” an editorial written by Darryl P. Leong, MBBS, PhD, John W. Eikelboom, MBBS, and Salim Yusuf, MBBS, DPhil, all from McMaster University, Hamilton, Ont., suggests that perhaps health systems in some places went too far in closing down during the first wave of the pandemic, naming specifically Canada, Eastern Europe, and Saudi Arabia as examples.

“Although these measures were taken to prepare for the worst, overwhelming numbers of patients with COVID-19 did not materialize during the first wave of the pandemic in these countries. It is possible that delaying so-called nonessential services may have been unnecessary and potentially harmful, because it likely led to delays in providing care for the treatment of serious non–COVID-19 illnesses.”

Since then, more experience and more data have largely allowed hospital systems to “tackle the ebb and flow” of COVID-19 cases in ways that limit shutdowns of important health services, they said.

Given the more pronounced effect in low- and middle-income countries, they stressed the need to focus resources on ways to promote prevention and treatment that do not rely on diagnostic procedures.

“This calls for more emphasis on developing efficient systems of telehealth, especially in poorer countries or in remote settings in all countries,” Dr. Leong and colleagues conclude.

Dr. Wadhera has reported research support from the National Heart, Lung, and Blood Institute, along with fellow senior author Robert W. Yeh, MD, MBA, who has also received personal fees and grants from several companies not related to the submitted work. Dr. Einstein, Dr. Leong, Dr. Eikelboom, and Dr. Yusuf have reported no relevant financial relationships.

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

In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.

The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.

The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
 

Goal-setting

There are five main goals outlined in the plan, according to the HHS:

• Prevent new hepatitis infections.
• Improve hepatitis-related health outcomes of people with viral hepatitis.
• Reduce hepatitis-related disparities and health inequities.
• Improve hepatitis surveillance and data use.
• Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.

“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.

mlesney@mdedge.com

In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.

The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.

The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
 

Goal-setting

There are five main goals outlined in the plan, according to the HHS:

• Prevent new hepatitis infections.
• Improve hepatitis-related health outcomes of people with viral hepatitis.
• Reduce hepatitis-related disparities and health inequities.
• Improve hepatitis surveillance and data use.
• Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.

“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.

mlesney@mdedge.com

In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.

The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.

The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
 

Goal-setting

There are five main goals outlined in the plan, according to the HHS:

• Prevent new hepatitis infections.
• Improve hepatitis-related health outcomes of people with viral hepatitis.
• Reduce hepatitis-related disparities and health inequities.
• Improve hepatitis surveillance and data use.
• Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.

“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.

mlesney@mdedge.com