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In Case You Missed It: COVID
Reported COVID-19 symptoms by hospitalization status
Why are many of my patients doing better during the pandemic?
The COVID-19 pandemic has, like it or not, made experimental labs rats out of us all.
Since the U.S. “shutdown” began in March, we have all had to adjust to a situation in which we are home more, stuck seeing less of our friends, exercising less, often eating and drinking more, or using recreational substances more – in part because of the severe stress. We have been ripped away from many of the social “anchors” of our weeks; that is, the spiritual, social and physical, and tactile supports that sustain and motivate us in our lives.
And yet, many of us, of all ages, stripes, and colors are thriving. Why is that so? Without necessarily being fully fledged, card carrying misanthropes, many of us are actually not bereft when forced to spend some alone time.
We may be self-starters and have hobbies and interests that we may have neglected but can fall back on with alacrity. Activities such as gardening, cooking, reading, working at our day jobs, listening to music, streaming TV, and so on are now more available to us.
The pandemic has produced unforeseen side effects, such as decreased pollution, less seismic “noise” on our planet, increasingly bold activity by wild life, and we can actually hear bird songs in our yards. Likewise, the social isolation has enabled us to focus more on “back burner” projects and to motivate us toward accessing and achieving other internally driven goals.
Also, to many, it has provided a surprising and unexpected privilege to meaningfully connect while in close quarters with spouses, children, and other loved ones, which has improved and cemented relationships under some level of duress, perhaps.
Similarly, and perhaps surprisingly, in addition to the above reasons, many of our patients with chronic mental illness may be functioning reasonably well, too, even better than their “walking wounded” loved ones and peers. They may be reaping the rewards of many years of consistent biopsychosocial support in strong mental health programs.
But another reason might be the lowered expectations. I’m just so much more relaxed; I’ve got this.” And certainly the Freudian “schadenfreude” defense has something to do with this as well. Seeing family members lose their jobs, become financially vulnerable, being unable to or stymied from demonstrating mastery in many different situations and skill sets elicit the empathy and galvanizes the support of well-managed patients with mental illness – already used to existential threats – for their generally higher functioning loved ones.
As one of my struggling patients said, “Welcome to my world!” Years of hardship, lack of intimate relationships because of social anxiety, and psychotic level obsessive-compulsive disorder have trained, indeed, inured her to the daily pain, constriction, and misery of social isolation. Her life, despite working full time, has remained static, while younger siblings have married, started a family, moved away. She is still living at home with her elderly parents. They now worry about catching COVID-19, while she is now their protector with roles reversed, doing their shopping, and providing moral support and encouragement for the whole family.
Many of us have lost jobs, been furloughed, seen our dreams disappear, and are unable to pay rent or mortgages. Those with chronic mental illness, especially those living in states with a strong social safety net, are continuing to receive their Social Security disability checks, and maintain their in-home health and family supports. They also have continued their adherence with the mental health system structure by continuing with telemedicine therapy and regular medications or monthly intramuscular shots. Their families are especially cognizant of the need for ongoing structure and stability, which is now easier to provide. And what of those patients who endured severe anxiety and panic disorders in their prepandemic states? It is true that many do require higher doses of their anxiolytics, especially benzodiazepines. They do know how to “roll with the punches” with their lifetime experience, as opposed to the “newbies” whose incipient anxiety is brought to the forefront and who might not even recognize these debilitating symptoms and are not keen, for reasons of stigma, to be seen by a mental health expert unless compelled to.
It is up to us as psychiatrists and other mental health clinicians to minimize dependence on those medications by using alternative non–dependence-forming anxiolytics and encouraging our patients to hone and develop the skills from cognitive-behavioral therapy. COVID-19 is just one more stressor, superimposed on many others, and unlikely to precipitate any “tipping point” in functioning, even if there are significant losses among loved ones to the virus.
How about our child and adolescent patients? As a rule of thumb, those with anxiety disorders, social anxiety, selective mutism – and those experiencing challenges and bullying in the rough and tumble world of schools – are doing significantly better. Those with ADHD and impulse control disorders, however, might be struggling with school, especially with Zoom calls and very high distractibility, boredom, and motivational challenges. They may need their doses of medications adjusted up, and their parents are struggling. The risk for unwitnessed and unmonitored abuse in home situations is higher.
Those with chronic mental illness often do have increased risk factors for COVID-19 that might be compounded by their psychopharmacologic treatment for conditions/behaviors such as diabetes, obesity, cardiovascular disease, and substance use. By proactively monitoring those comorbid disorders in a multimodal treatment program, we can help mitigate those baseline challenges.
This aspect of the COVID-19 pandemic is, alas, likely to prove to be an illusory positive “blip” on the radar screen for many with chronic mental illness. Nevertheless, the self-knowledge and awareness of hidden strengths rather than weakness, resilience rather than shrinking from challenges, is not insignificant. This “flight into normality” may be a change that can be internalized and nurtured once vaccines are available and life on planet Earth returns to a new normal.
Dr. Tofler is affiliated with Kaiser Permanente Psychiatry in Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.
The COVID-19 pandemic has, like it or not, made experimental labs rats out of us all.
Since the U.S. “shutdown” began in March, we have all had to adjust to a situation in which we are home more, stuck seeing less of our friends, exercising less, often eating and drinking more, or using recreational substances more – in part because of the severe stress. We have been ripped away from many of the social “anchors” of our weeks; that is, the spiritual, social and physical, and tactile supports that sustain and motivate us in our lives.
And yet, many of us, of all ages, stripes, and colors are thriving. Why is that so? Without necessarily being fully fledged, card carrying misanthropes, many of us are actually not bereft when forced to spend some alone time.
We may be self-starters and have hobbies and interests that we may have neglected but can fall back on with alacrity. Activities such as gardening, cooking, reading, working at our day jobs, listening to music, streaming TV, and so on are now more available to us.
The pandemic has produced unforeseen side effects, such as decreased pollution, less seismic “noise” on our planet, increasingly bold activity by wild life, and we can actually hear bird songs in our yards. Likewise, the social isolation has enabled us to focus more on “back burner” projects and to motivate us toward accessing and achieving other internally driven goals.
Also, to many, it has provided a surprising and unexpected privilege to meaningfully connect while in close quarters with spouses, children, and other loved ones, which has improved and cemented relationships under some level of duress, perhaps.
Similarly, and perhaps surprisingly, in addition to the above reasons, many of our patients with chronic mental illness may be functioning reasonably well, too, even better than their “walking wounded” loved ones and peers. They may be reaping the rewards of many years of consistent biopsychosocial support in strong mental health programs.
But another reason might be the lowered expectations. I’m just so much more relaxed; I’ve got this.” And certainly the Freudian “schadenfreude” defense has something to do with this as well. Seeing family members lose their jobs, become financially vulnerable, being unable to or stymied from demonstrating mastery in many different situations and skill sets elicit the empathy and galvanizes the support of well-managed patients with mental illness – already used to existential threats – for their generally higher functioning loved ones.
As one of my struggling patients said, “Welcome to my world!” Years of hardship, lack of intimate relationships because of social anxiety, and psychotic level obsessive-compulsive disorder have trained, indeed, inured her to the daily pain, constriction, and misery of social isolation. Her life, despite working full time, has remained static, while younger siblings have married, started a family, moved away. She is still living at home with her elderly parents. They now worry about catching COVID-19, while she is now their protector with roles reversed, doing their shopping, and providing moral support and encouragement for the whole family.
Many of us have lost jobs, been furloughed, seen our dreams disappear, and are unable to pay rent or mortgages. Those with chronic mental illness, especially those living in states with a strong social safety net, are continuing to receive their Social Security disability checks, and maintain their in-home health and family supports. They also have continued their adherence with the mental health system structure by continuing with telemedicine therapy and regular medications or monthly intramuscular shots. Their families are especially cognizant of the need for ongoing structure and stability, which is now easier to provide. And what of those patients who endured severe anxiety and panic disorders in their prepandemic states? It is true that many do require higher doses of their anxiolytics, especially benzodiazepines. They do know how to “roll with the punches” with their lifetime experience, as opposed to the “newbies” whose incipient anxiety is brought to the forefront and who might not even recognize these debilitating symptoms and are not keen, for reasons of stigma, to be seen by a mental health expert unless compelled to.
It is up to us as psychiatrists and other mental health clinicians to minimize dependence on those medications by using alternative non–dependence-forming anxiolytics and encouraging our patients to hone and develop the skills from cognitive-behavioral therapy. COVID-19 is just one more stressor, superimposed on many others, and unlikely to precipitate any “tipping point” in functioning, even if there are significant losses among loved ones to the virus.
How about our child and adolescent patients? As a rule of thumb, those with anxiety disorders, social anxiety, selective mutism – and those experiencing challenges and bullying in the rough and tumble world of schools – are doing significantly better. Those with ADHD and impulse control disorders, however, might be struggling with school, especially with Zoom calls and very high distractibility, boredom, and motivational challenges. They may need their doses of medications adjusted up, and their parents are struggling. The risk for unwitnessed and unmonitored abuse in home situations is higher.
Those with chronic mental illness often do have increased risk factors for COVID-19 that might be compounded by their psychopharmacologic treatment for conditions/behaviors such as diabetes, obesity, cardiovascular disease, and substance use. By proactively monitoring those comorbid disorders in a multimodal treatment program, we can help mitigate those baseline challenges.
This aspect of the COVID-19 pandemic is, alas, likely to prove to be an illusory positive “blip” on the radar screen for many with chronic mental illness. Nevertheless, the self-knowledge and awareness of hidden strengths rather than weakness, resilience rather than shrinking from challenges, is not insignificant. This “flight into normality” may be a change that can be internalized and nurtured once vaccines are available and life on planet Earth returns to a new normal.
Dr. Tofler is affiliated with Kaiser Permanente Psychiatry in Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.
The COVID-19 pandemic has, like it or not, made experimental labs rats out of us all.
Since the U.S. “shutdown” began in March, we have all had to adjust to a situation in which we are home more, stuck seeing less of our friends, exercising less, often eating and drinking more, or using recreational substances more – in part because of the severe stress. We have been ripped away from many of the social “anchors” of our weeks; that is, the spiritual, social and physical, and tactile supports that sustain and motivate us in our lives.
And yet, many of us, of all ages, stripes, and colors are thriving. Why is that so? Without necessarily being fully fledged, card carrying misanthropes, many of us are actually not bereft when forced to spend some alone time.
We may be self-starters and have hobbies and interests that we may have neglected but can fall back on with alacrity. Activities such as gardening, cooking, reading, working at our day jobs, listening to music, streaming TV, and so on are now more available to us.
The pandemic has produced unforeseen side effects, such as decreased pollution, less seismic “noise” on our planet, increasingly bold activity by wild life, and we can actually hear bird songs in our yards. Likewise, the social isolation has enabled us to focus more on “back burner” projects and to motivate us toward accessing and achieving other internally driven goals.
Also, to many, it has provided a surprising and unexpected privilege to meaningfully connect while in close quarters with spouses, children, and other loved ones, which has improved and cemented relationships under some level of duress, perhaps.
Similarly, and perhaps surprisingly, in addition to the above reasons, many of our patients with chronic mental illness may be functioning reasonably well, too, even better than their “walking wounded” loved ones and peers. They may be reaping the rewards of many years of consistent biopsychosocial support in strong mental health programs.
But another reason might be the lowered expectations. I’m just so much more relaxed; I’ve got this.” And certainly the Freudian “schadenfreude” defense has something to do with this as well. Seeing family members lose their jobs, become financially vulnerable, being unable to or stymied from demonstrating mastery in many different situations and skill sets elicit the empathy and galvanizes the support of well-managed patients with mental illness – already used to existential threats – for their generally higher functioning loved ones.
As one of my struggling patients said, “Welcome to my world!” Years of hardship, lack of intimate relationships because of social anxiety, and psychotic level obsessive-compulsive disorder have trained, indeed, inured her to the daily pain, constriction, and misery of social isolation. Her life, despite working full time, has remained static, while younger siblings have married, started a family, moved away. She is still living at home with her elderly parents. They now worry about catching COVID-19, while she is now their protector with roles reversed, doing their shopping, and providing moral support and encouragement for the whole family.
Many of us have lost jobs, been furloughed, seen our dreams disappear, and are unable to pay rent or mortgages. Those with chronic mental illness, especially those living in states with a strong social safety net, are continuing to receive their Social Security disability checks, and maintain their in-home health and family supports. They also have continued their adherence with the mental health system structure by continuing with telemedicine therapy and regular medications or monthly intramuscular shots. Their families are especially cognizant of the need for ongoing structure and stability, which is now easier to provide. And what of those patients who endured severe anxiety and panic disorders in their prepandemic states? It is true that many do require higher doses of their anxiolytics, especially benzodiazepines. They do know how to “roll with the punches” with their lifetime experience, as opposed to the “newbies” whose incipient anxiety is brought to the forefront and who might not even recognize these debilitating symptoms and are not keen, for reasons of stigma, to be seen by a mental health expert unless compelled to.
It is up to us as psychiatrists and other mental health clinicians to minimize dependence on those medications by using alternative non–dependence-forming anxiolytics and encouraging our patients to hone and develop the skills from cognitive-behavioral therapy. COVID-19 is just one more stressor, superimposed on many others, and unlikely to precipitate any “tipping point” in functioning, even if there are significant losses among loved ones to the virus.
How about our child and adolescent patients? As a rule of thumb, those with anxiety disorders, social anxiety, selective mutism – and those experiencing challenges and bullying in the rough and tumble world of schools – are doing significantly better. Those with ADHD and impulse control disorders, however, might be struggling with school, especially with Zoom calls and very high distractibility, boredom, and motivational challenges. They may need their doses of medications adjusted up, and their parents are struggling. The risk for unwitnessed and unmonitored abuse in home situations is higher.
Those with chronic mental illness often do have increased risk factors for COVID-19 that might be compounded by their psychopharmacologic treatment for conditions/behaviors such as diabetes, obesity, cardiovascular disease, and substance use. By proactively monitoring those comorbid disorders in a multimodal treatment program, we can help mitigate those baseline challenges.
This aspect of the COVID-19 pandemic is, alas, likely to prove to be an illusory positive “blip” on the radar screen for many with chronic mental illness. Nevertheless, the self-knowledge and awareness of hidden strengths rather than weakness, resilience rather than shrinking from challenges, is not insignificant. This “flight into normality” may be a change that can be internalized and nurtured once vaccines are available and life on planet Earth returns to a new normal.
Dr. Tofler is affiliated with Kaiser Permanente Psychiatry in Los Angeles. He also is a visiting faculty member in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. Dr. Tofler has no conflicts of interest.
Being a pediatric hospitalist during the COVID-19 pandemic
“Times of great calamity and confusion have been productive for the greatest minds. The purest ore is produced from the hottest furnace. The brightest thunderbolt is elicited from the darkest storm.” – Charles Caleb Colton
I walk inside the pediatric unit of our hospital, only to be welcomed by an eerie silence. There are a handful of nurses at the nursing station, faces covered with masks sitting 6 feet apart and quietly working on their computers. The resident work lounge also depicts a similar picture of emptiness. Just over a month ago, these halls were bustling with children, parents, consultants, and a host of ancillary staff. I recall times in which I was running around from one patient room to another talking to families and attending to patient needs. For the past 2 months I have often spent hours alone in my office waiting to see a patient. This is the new norm for many of us.
Across the board in hospitals, pediatric census has dropped since the start of the COVID-19 pandemic. Reasons for these are nonspecific but may include fear among parents of “exposure” to the virus by bringing their sick children to the hospital to get evaluated for other concerns. A few patients that we have seen in our hospital are sicker when they have arrived because their parents avoided seeking medical care earlier, plagued by the same fear. Social distancing and school closure have also limited the amount of infectious diseases going around, which are responsible for a bulk of pediatric admissions.
While many of us are still coming in to see the limited number of patients we have, we are not in the true sense frontline providers during this pandemic. There have been limited cases of COVID-19 in children, most of which – fortunately – present with mild symptoms. Although multisystem inflammatory syndrome in children (MIS-C) is a new disease that COVID-19 has brought us closer to, many of us have yet to see our first case because of its rarity.
I have read through the news daily in the past few months to find many adult provider physicians succumbing to COVID-19 and felt a pang of guilt. My social media is full of heartbreaking stories as adult hospitalists are having difficult conversations with families and supporting them through this unknown territory, often sacrificing their own safety. I feel so proud of them and my profession. My heart tells me, though, I personally may not be living up to the true calling I was expected to have as a physician.
As pediatric hospitalists, while we sit and wait for this pandemic to pass, we have been ruminating on and anxious about our future. As census drops, there is a financial strain that many of us are feeling. Job cuts and furloughing of health care workers in our surroundings leave us with a sense of insecurity and low morale. Many small inpatient pediatric units have had to be shut down temporarily either so they could be used for adult patients or because of lack of pediatric patients. Limiting staffing to avoid exposure and cohorting providers has also been a challenge.
A big question that has risen in these times is how to ensure productivity and stay useful while at the same time being prepared for the unknown that lies ahead. The economics of medicine is staring hard at our years of hard work, questioning the need for our specialty in the first place.
In smaller community settings, the closure of pediatric units has put an additional strain on the overall framework of the community, parents, and referring primary care providers. With the absence of local resources, children who have needed care have had to be transferred to bigger referral centers that are still taking care of pediatric patients. On one end of the spectrum there is concern for pediatric inpatient units not being productive enough for the hospital, but that coexists with a worry that, as we pass through this pandemic, we could see more hospitalizations for vaccine-preventable illnesses, child abuse/medical neglect, and respiratory syncytial virus plus COVID.
The question remains about how best to cope and use this time of uncertainty to be productive and prepare for the worst. A few solutions and suggestions are highlighted below.
- Helping adult providers: Many pediatric hospitalist colleagues in highly affected states have filled the increasing need for clinicians and taken care of adult patients. As pediatric units have closed, providers have continued to offer care where it is needed. Pediatric hospitalists have used this time to take urgent refresher courses in advanced cardiac life support and adult critical care. In states that are not as severely hit, many pediatric hospitalists have utilized this time to plan and prepare protocols for the future as information continues coming in regarding MIS-C and COVID-19 in pediatric patients.
- Use of telemedicine: With the ease in restrictions for use of telemedicine in many states, pediatric hospitalists can consider using it to restructure their staffing model whenever feasible. This can help in cohorting and allowing high risk and quarantined providers to work from home. This model simultaneously provides opportunities for pediatric hospitalists to continue providing their services, while at the same time decreasing financial burden on their institution.
- Reaching out to the community: Engaging with the community during these times can help ensure services and options remain available to our referral providers and patients for pediatric services. Information about COVID-19 can be widely disseminated. We can also play our part by continuing to encourage parents in our maximum capacity to obtain care for their children when needed and to not avoid the hospital because of fears of exposure.
- Supporting each other: There is no doubt that these times are unsettling for the pediatric hospitalist community, and the uncertainty that surrounds us can feel crippling. Strong team building is imperative in these times. While we may not be frequently meeting in work lounges and sharing meals, a good sense of support and camaraderie will go a long way in building morale for the future. Seeking mental health resources if needed is essential for us and should not be looked at with shame or guilt. This is something that many of us have never seen before, and it is okay to ask for help. Seeking help is and always will be a sign of strength.
Today, as I envision myself walking in the hospital on the other side of this pandemic I see a cheerful pediatric unit, smiling faces without masks, my 3-year-old patient cruising around the hallways in a toy car, our therapy dog walking around bringing joy to many, and many healthy patients feeling better and ready to go home. A time when we are not scared to hug each other, shake hands, or share emotion. When our teams are stronger and more well bonded. A time when parents are not scared to bring their sick children to the hospital. Will it be many months before this happens? I don’t know. But I do know that the children I take care of are known for their resilience. I will live up to them today by practicing the same.
Dr. Fatima is a pediatric hospitalist at Wesley Children’s Hospital and assistant professor of pediatrics at Kansas University School of Medicine, both in Wichita. Her research interests include medical errors, medical education, and high-value care.
“Times of great calamity and confusion have been productive for the greatest minds. The purest ore is produced from the hottest furnace. The brightest thunderbolt is elicited from the darkest storm.” – Charles Caleb Colton
I walk inside the pediatric unit of our hospital, only to be welcomed by an eerie silence. There are a handful of nurses at the nursing station, faces covered with masks sitting 6 feet apart and quietly working on their computers. The resident work lounge also depicts a similar picture of emptiness. Just over a month ago, these halls were bustling with children, parents, consultants, and a host of ancillary staff. I recall times in which I was running around from one patient room to another talking to families and attending to patient needs. For the past 2 months I have often spent hours alone in my office waiting to see a patient. This is the new norm for many of us.
Across the board in hospitals, pediatric census has dropped since the start of the COVID-19 pandemic. Reasons for these are nonspecific but may include fear among parents of “exposure” to the virus by bringing their sick children to the hospital to get evaluated for other concerns. A few patients that we have seen in our hospital are sicker when they have arrived because their parents avoided seeking medical care earlier, plagued by the same fear. Social distancing and school closure have also limited the amount of infectious diseases going around, which are responsible for a bulk of pediatric admissions.
While many of us are still coming in to see the limited number of patients we have, we are not in the true sense frontline providers during this pandemic. There have been limited cases of COVID-19 in children, most of which – fortunately – present with mild symptoms. Although multisystem inflammatory syndrome in children (MIS-C) is a new disease that COVID-19 has brought us closer to, many of us have yet to see our first case because of its rarity.
I have read through the news daily in the past few months to find many adult provider physicians succumbing to COVID-19 and felt a pang of guilt. My social media is full of heartbreaking stories as adult hospitalists are having difficult conversations with families and supporting them through this unknown territory, often sacrificing their own safety. I feel so proud of them and my profession. My heart tells me, though, I personally may not be living up to the true calling I was expected to have as a physician.
As pediatric hospitalists, while we sit and wait for this pandemic to pass, we have been ruminating on and anxious about our future. As census drops, there is a financial strain that many of us are feeling. Job cuts and furloughing of health care workers in our surroundings leave us with a sense of insecurity and low morale. Many small inpatient pediatric units have had to be shut down temporarily either so they could be used for adult patients or because of lack of pediatric patients. Limiting staffing to avoid exposure and cohorting providers has also been a challenge.
A big question that has risen in these times is how to ensure productivity and stay useful while at the same time being prepared for the unknown that lies ahead. The economics of medicine is staring hard at our years of hard work, questioning the need for our specialty in the first place.
In smaller community settings, the closure of pediatric units has put an additional strain on the overall framework of the community, parents, and referring primary care providers. With the absence of local resources, children who have needed care have had to be transferred to bigger referral centers that are still taking care of pediatric patients. On one end of the spectrum there is concern for pediatric inpatient units not being productive enough for the hospital, but that coexists with a worry that, as we pass through this pandemic, we could see more hospitalizations for vaccine-preventable illnesses, child abuse/medical neglect, and respiratory syncytial virus plus COVID.
The question remains about how best to cope and use this time of uncertainty to be productive and prepare for the worst. A few solutions and suggestions are highlighted below.
- Helping adult providers: Many pediatric hospitalist colleagues in highly affected states have filled the increasing need for clinicians and taken care of adult patients. As pediatric units have closed, providers have continued to offer care where it is needed. Pediatric hospitalists have used this time to take urgent refresher courses in advanced cardiac life support and adult critical care. In states that are not as severely hit, many pediatric hospitalists have utilized this time to plan and prepare protocols for the future as information continues coming in regarding MIS-C and COVID-19 in pediatric patients.
- Use of telemedicine: With the ease in restrictions for use of telemedicine in many states, pediatric hospitalists can consider using it to restructure their staffing model whenever feasible. This can help in cohorting and allowing high risk and quarantined providers to work from home. This model simultaneously provides opportunities for pediatric hospitalists to continue providing their services, while at the same time decreasing financial burden on their institution.
- Reaching out to the community: Engaging with the community during these times can help ensure services and options remain available to our referral providers and patients for pediatric services. Information about COVID-19 can be widely disseminated. We can also play our part by continuing to encourage parents in our maximum capacity to obtain care for their children when needed and to not avoid the hospital because of fears of exposure.
- Supporting each other: There is no doubt that these times are unsettling for the pediatric hospitalist community, and the uncertainty that surrounds us can feel crippling. Strong team building is imperative in these times. While we may not be frequently meeting in work lounges and sharing meals, a good sense of support and camaraderie will go a long way in building morale for the future. Seeking mental health resources if needed is essential for us and should not be looked at with shame or guilt. This is something that many of us have never seen before, and it is okay to ask for help. Seeking help is and always will be a sign of strength.
Today, as I envision myself walking in the hospital on the other side of this pandemic I see a cheerful pediatric unit, smiling faces without masks, my 3-year-old patient cruising around the hallways in a toy car, our therapy dog walking around bringing joy to many, and many healthy patients feeling better and ready to go home. A time when we are not scared to hug each other, shake hands, or share emotion. When our teams are stronger and more well bonded. A time when parents are not scared to bring their sick children to the hospital. Will it be many months before this happens? I don’t know. But I do know that the children I take care of are known for their resilience. I will live up to them today by practicing the same.
Dr. Fatima is a pediatric hospitalist at Wesley Children’s Hospital and assistant professor of pediatrics at Kansas University School of Medicine, both in Wichita. Her research interests include medical errors, medical education, and high-value care.
“Times of great calamity and confusion have been productive for the greatest minds. The purest ore is produced from the hottest furnace. The brightest thunderbolt is elicited from the darkest storm.” – Charles Caleb Colton
I walk inside the pediatric unit of our hospital, only to be welcomed by an eerie silence. There are a handful of nurses at the nursing station, faces covered with masks sitting 6 feet apart and quietly working on their computers. The resident work lounge also depicts a similar picture of emptiness. Just over a month ago, these halls were bustling with children, parents, consultants, and a host of ancillary staff. I recall times in which I was running around from one patient room to another talking to families and attending to patient needs. For the past 2 months I have often spent hours alone in my office waiting to see a patient. This is the new norm for many of us.
Across the board in hospitals, pediatric census has dropped since the start of the COVID-19 pandemic. Reasons for these are nonspecific but may include fear among parents of “exposure” to the virus by bringing their sick children to the hospital to get evaluated for other concerns. A few patients that we have seen in our hospital are sicker when they have arrived because their parents avoided seeking medical care earlier, plagued by the same fear. Social distancing and school closure have also limited the amount of infectious diseases going around, which are responsible for a bulk of pediatric admissions.
While many of us are still coming in to see the limited number of patients we have, we are not in the true sense frontline providers during this pandemic. There have been limited cases of COVID-19 in children, most of which – fortunately – present with mild symptoms. Although multisystem inflammatory syndrome in children (MIS-C) is a new disease that COVID-19 has brought us closer to, many of us have yet to see our first case because of its rarity.
I have read through the news daily in the past few months to find many adult provider physicians succumbing to COVID-19 and felt a pang of guilt. My social media is full of heartbreaking stories as adult hospitalists are having difficult conversations with families and supporting them through this unknown territory, often sacrificing their own safety. I feel so proud of them and my profession. My heart tells me, though, I personally may not be living up to the true calling I was expected to have as a physician.
As pediatric hospitalists, while we sit and wait for this pandemic to pass, we have been ruminating on and anxious about our future. As census drops, there is a financial strain that many of us are feeling. Job cuts and furloughing of health care workers in our surroundings leave us with a sense of insecurity and low morale. Many small inpatient pediatric units have had to be shut down temporarily either so they could be used for adult patients or because of lack of pediatric patients. Limiting staffing to avoid exposure and cohorting providers has also been a challenge.
A big question that has risen in these times is how to ensure productivity and stay useful while at the same time being prepared for the unknown that lies ahead. The economics of medicine is staring hard at our years of hard work, questioning the need for our specialty in the first place.
In smaller community settings, the closure of pediatric units has put an additional strain on the overall framework of the community, parents, and referring primary care providers. With the absence of local resources, children who have needed care have had to be transferred to bigger referral centers that are still taking care of pediatric patients. On one end of the spectrum there is concern for pediatric inpatient units not being productive enough for the hospital, but that coexists with a worry that, as we pass through this pandemic, we could see more hospitalizations for vaccine-preventable illnesses, child abuse/medical neglect, and respiratory syncytial virus plus COVID.
The question remains about how best to cope and use this time of uncertainty to be productive and prepare for the worst. A few solutions and suggestions are highlighted below.
- Helping adult providers: Many pediatric hospitalist colleagues in highly affected states have filled the increasing need for clinicians and taken care of adult patients. As pediatric units have closed, providers have continued to offer care where it is needed. Pediatric hospitalists have used this time to take urgent refresher courses in advanced cardiac life support and adult critical care. In states that are not as severely hit, many pediatric hospitalists have utilized this time to plan and prepare protocols for the future as information continues coming in regarding MIS-C and COVID-19 in pediatric patients.
- Use of telemedicine: With the ease in restrictions for use of telemedicine in many states, pediatric hospitalists can consider using it to restructure their staffing model whenever feasible. This can help in cohorting and allowing high risk and quarantined providers to work from home. This model simultaneously provides opportunities for pediatric hospitalists to continue providing their services, while at the same time decreasing financial burden on their institution.
- Reaching out to the community: Engaging with the community during these times can help ensure services and options remain available to our referral providers and patients for pediatric services. Information about COVID-19 can be widely disseminated. We can also play our part by continuing to encourage parents in our maximum capacity to obtain care for their children when needed and to not avoid the hospital because of fears of exposure.
- Supporting each other: There is no doubt that these times are unsettling for the pediatric hospitalist community, and the uncertainty that surrounds us can feel crippling. Strong team building is imperative in these times. While we may not be frequently meeting in work lounges and sharing meals, a good sense of support and camaraderie will go a long way in building morale for the future. Seeking mental health resources if needed is essential for us and should not be looked at with shame or guilt. This is something that many of us have never seen before, and it is okay to ask for help. Seeking help is and always will be a sign of strength.
Today, as I envision myself walking in the hospital on the other side of this pandemic I see a cheerful pediatric unit, smiling faces without masks, my 3-year-old patient cruising around the hallways in a toy car, our therapy dog walking around bringing joy to many, and many healthy patients feeling better and ready to go home. A time when we are not scared to hug each other, shake hands, or share emotion. When our teams are stronger and more well bonded. A time when parents are not scared to bring their sick children to the hospital. Will it be many months before this happens? I don’t know. But I do know that the children I take care of are known for their resilience. I will live up to them today by practicing the same.
Dr. Fatima is a pediatric hospitalist at Wesley Children’s Hospital and assistant professor of pediatrics at Kansas University School of Medicine, both in Wichita. Her research interests include medical errors, medical education, and high-value care.
When viruses collide: Flu season during pandemic
The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.
Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.
“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”
With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.
Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”
That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.
Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
Flu vaccine ‘extra important’
The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.
The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.
But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
Risks of coinfection
About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.
“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”
Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
Distinguishing COVID-19 from flu
Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.
Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.
“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.
But even after that, symptoms can be difficult to distinguish.
“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”
But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”
Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.
Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.
In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”
Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”
The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”
That may be somewhat welcome as flu season arrives.
The physicians interviewed have no relevant disclosures.
The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.
Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.
“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”
With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.
Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”
That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.
Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
Flu vaccine ‘extra important’
The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.
The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.
But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
Risks of coinfection
About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.
“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”
Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
Distinguishing COVID-19 from flu
Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.
Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.
“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.
But even after that, symptoms can be difficult to distinguish.
“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”
But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”
Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.
Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.
In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”
Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”
The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”
That may be somewhat welcome as flu season arrives.
The physicians interviewed have no relevant disclosures.
The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.
Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.
“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”
With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.
Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”
That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.
Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
Flu vaccine ‘extra important’
The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.
The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.
But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
Risks of coinfection
About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.
“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”
Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
Distinguishing COVID-19 from flu
Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.
Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.
“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.
But even after that, symptoms can be difficult to distinguish.
“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”
But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”
Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.
Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.
In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”
Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”
The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”
That may be somewhat welcome as flu season arrives.
The physicians interviewed have no relevant disclosures.
As COVID-19 cases increase in children, deaths remain low
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The cumulative number of pediatric cases reported up to that date was 442,785, or 9.3% of the total COVID-19 case load of more than 4.76 million among all ages. There have been only 92 pediatric deaths, however, which works out to just 0.06% of the 154,279 reported for all ages, the AAP and the CHA said Aug. 24 in their most recent update.
Child hospitalizations also were on the low side, representing 1.7% (4,062) of the cumulative total of 234,810 admissions among all ages as of Aug. 20, based on data from 21 states and New York City.
Nationally, the cumulative number of reported child cases is now up to 583 per 100,000 children, and that figure covers 49 states, Washington, D.C., Guam, New York City, and Puerto Rico.
There is some disagreement among the states, though, about the definition of “child.” Most states use an age range of 0-17, 0-18, or 0-19, but Florida and Utah go with a range of 0-14 years while South Carolina and Tennessee consider humans aged 0-20 years to be children. Other data limitations involve Texas, which has reported age distribution for only 8% of all cases, and New York, which is not reporting the age distribution of statewide cases, the AAP/CHA report noted.
The definition of child isn’t the only thing that varies between the states. The cumulative case rate for Tennessee, the highest in the country at 1,315 per 100,000 children, is 10 times that of Vermont, which is the lowest at 131 per 100,000, the AAP and CHA said. Vermont reports child COVID-19 cases using an age range of 0-19 years.
The other states with rates over 1,000 cases per 100,000 children are Arizona (1,300), which had the highest rate a week ago; South Carolina (1,214); Louisiana (1,127); Mississippi (1,120); and Nevada (1,068). Those with rates below 200 cases per 100,000 children are Maine (150), New Hampshire (175), and Hawaii (188), according to this week’s report.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The cumulative number of pediatric cases reported up to that date was 442,785, or 9.3% of the total COVID-19 case load of more than 4.76 million among all ages. There have been only 92 pediatric deaths, however, which works out to just 0.06% of the 154,279 reported for all ages, the AAP and the CHA said Aug. 24 in their most recent update.
Child hospitalizations also were on the low side, representing 1.7% (4,062) of the cumulative total of 234,810 admissions among all ages as of Aug. 20, based on data from 21 states and New York City.
Nationally, the cumulative number of reported child cases is now up to 583 per 100,000 children, and that figure covers 49 states, Washington, D.C., Guam, New York City, and Puerto Rico.
There is some disagreement among the states, though, about the definition of “child.” Most states use an age range of 0-17, 0-18, or 0-19, but Florida and Utah go with a range of 0-14 years while South Carolina and Tennessee consider humans aged 0-20 years to be children. Other data limitations involve Texas, which has reported age distribution for only 8% of all cases, and New York, which is not reporting the age distribution of statewide cases, the AAP/CHA report noted.
The definition of child isn’t the only thing that varies between the states. The cumulative case rate for Tennessee, the highest in the country at 1,315 per 100,000 children, is 10 times that of Vermont, which is the lowest at 131 per 100,000, the AAP and CHA said. Vermont reports child COVID-19 cases using an age range of 0-19 years.
The other states with rates over 1,000 cases per 100,000 children are Arizona (1,300), which had the highest rate a week ago; South Carolina (1,214); Louisiana (1,127); Mississippi (1,120); and Nevada (1,068). Those with rates below 200 cases per 100,000 children are Maine (150), New Hampshire (175), and Hawaii (188), according to this week’s report.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The cumulative number of pediatric cases reported up to that date was 442,785, or 9.3% of the total COVID-19 case load of more than 4.76 million among all ages. There have been only 92 pediatric deaths, however, which works out to just 0.06% of the 154,279 reported for all ages, the AAP and the CHA said Aug. 24 in their most recent update.
Child hospitalizations also were on the low side, representing 1.7% (4,062) of the cumulative total of 234,810 admissions among all ages as of Aug. 20, based on data from 21 states and New York City.
Nationally, the cumulative number of reported child cases is now up to 583 per 100,000 children, and that figure covers 49 states, Washington, D.C., Guam, New York City, and Puerto Rico.
There is some disagreement among the states, though, about the definition of “child.” Most states use an age range of 0-17, 0-18, or 0-19, but Florida and Utah go with a range of 0-14 years while South Carolina and Tennessee consider humans aged 0-20 years to be children. Other data limitations involve Texas, which has reported age distribution for only 8% of all cases, and New York, which is not reporting the age distribution of statewide cases, the AAP/CHA report noted.
The definition of child isn’t the only thing that varies between the states. The cumulative case rate for Tennessee, the highest in the country at 1,315 per 100,000 children, is 10 times that of Vermont, which is the lowest at 131 per 100,000, the AAP and CHA said. Vermont reports child COVID-19 cases using an age range of 0-19 years.
The other states with rates over 1,000 cases per 100,000 children are Arizona (1,300), which had the highest rate a week ago; South Carolina (1,214); Louisiana (1,127); Mississippi (1,120); and Nevada (1,068). Those with rates below 200 cases per 100,000 children are Maine (150), New Hampshire (175), and Hawaii (188), according to this week’s report.
Coronavirus-associated aspergillosis increased 30-day mortality risk
Researchers are beginning to make some headway in identifying the role of secondary infections in the course and outcomes of COVID-19.
Patients who are on ventilatory support for severe COVID-19 infections appear to be at high risk for invasive pulmonary aspergillosis, which in a small prospective study was associated with a more than threefold risk for 30-day mortality. The findings were published online in Clinical Infectious Diseases.
Among 108 patients with COVID-19 on mechanical ventilation in one of three intensive care units, 30 (27.7%) were diagnosed with coronavirus-associated pulmonary aspergillosis (CAPA) based on consensus definitions similar to those used to diagnose influenza-associated pulmonary aspergillosis (IAPA).
Of the patients with CAPA, 44% died within 30 days of ICU admission, compared with 19% of patients who did not meet the criteria for aspergillosis (P = .002). This difference translated into an odds ratio (OR) for death with CAPA of 3.55 (P = .014), reported Michele Bartoletti, MD, PhD, of the infectious diseases unit at Sant’Orsola Malpighi Hospital in Bologna, Italy, and colleagues.
When the investigators applied a proposed definition of putative invasive pulmonary aspergillosis, or “PIPA” to the same patients, the 30-day mortality rate jumped to 74% vs. 26% for patients without PIPA (P < .001), with an OR of 11.60 (P < .001). “We found a high incidence of CAPA among critically ill COVID-19 patients and that its occurrence seems to change the natural history of disease,” they wrote.
“[T]he study from Bartoletti et al. alerts the clinical audience to be aware of CAPA and take appropriate (and where needed repetitive) actions that fits their clinical setting,” Roger J. Brüggemann, PharmD, of the department of pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands, and colleagues wrote in an editorial accompanying the study.
Diagnosis challenging
At the best of times, the diagnosis of pulmonary aspergillosis is difficult, subject to both false-positive and false-negative results, said a critical care specialist who was not involved in the study.
“Critically ill patients are susceptible to having aspergillus, so in reading the article, my only concerns are that I don’t know how accurate the testing is, and I don’t know if their population is truly different from a general population of patients in the ICU,” Daniel R. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital in Detroit, said in an interview.
As seen in ICU patients with severe influenza or other viral infections, patients with severe COVID-19 disease are susceptible to secondary infections, he said, making it difficult to know whether the worse outcomes seen in patients with COVID-19 and presumed aspergillosis are a reflection of their being more critically ill or whether the secondary infections themselves account for the difference in mortality.
Three ICUs
Dr. Bartoletti and colleagues conducted a study on all adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation in three ICUs in Bologna.
All patients included in the study were screened for invasive pulmonary aspergillosis with bronchoalveolar lavage and galactomannan detection and cultures. The lavage was performed on ICU admission, one day from the first day of mechanical ventilation, and if patients had evidence of clinical disease progression.
Samples that tested positive for galactomannan, a component of the aspergillus cell wall, were stored and later analyzed with a commercial quantitative real-time polymerase chain reaction assay for aspergillus; these results were not reported to clinicians on the patient floors.
The investigators defined invasive pulmonary aspergillosis according to a recently proposed definition for CAPA. This definition applies to COVID-19–positive patients admitted to an ICU with pulmonary infiltrates and at least one of the following:
- A serum galactomannan > 0.5.
- Bronchoalveolar lavage galactomannan > 1.0.
- Positive aspergillus bronchoalveolar lavage culture or cavitating infiltrate not attributed to another cause in the area of the pulmonary infiltrate.
They compared the CAPA diagnostic criteria with those of PIPA criteria as described by Stijn J. Blot, PhD, and colleagues in study published in the American Journal of Respiratory and Critical Care Medicine (2012 Jul 1;186(1):56-64).
A total of 108 patients were screened for aspergillosis, with a median age of 64. The majority of patients (78%) were male. The median age-adjusted Charlson Comorbidity Index was 2.5 (range 1-4). The median Sequential Organ Failure Assessment (SOFA) score at ICU admission was 4 (range 3-5).
As noted, probable aspergillosis by CAPA criteria was diagnosed in 30 patients (27.7%), with the diagnosis made after a median of 4 days after intubation and a median of 14 days from onset of COVID-19 symptoms.
The incidence rate of probable CAPA was 38.83 per 10,000 ICU patient days.
A comparison of clinical characteristics of patients with and without probable CAPA showed that only chronic steroid therapy at ≥ 16 mg/day prednisone for at least 15 days was significantly associated with risk for CAPA (P = .02).
At a median follow-up of 31 days, 54 patients (50%) had been discharged, 44 (41%) had died, and the remaining patients were still on follow-up.
As noted before, the mortality rate with 30 days of ICU admission was 44% for patients with probable CAPA vs. 19% for patients without. Among patients deemed to have PIPA, 74% died within 30 days of admission, compared with 26% without PIPA.
In a logistic regression model, the association of CAPA with increased risk for 30-day mortality remained even after adjustment for the need for renal replacement therapy (OR 3.02, P = .015) and SOFA score at ICU admission (OR 1.38, P = .004).
In a logistic regression using the PIPA rather than CAPA definition, the OR for 30-day mortality was 11.60 (P = .001).
Prognostic marker
The investigators noted that bronchoalveolar lavage galactomannan index appeared to be predictive of death. Each 1-point increase in the index was associated with 1.41-fold increase in the risk for 30-day mortality (P = .0070), a relationship that held up after adjustment for age, need for renal replacement therapy, and SOFA score.
Sixteen patients who met the CAPA definition received antifungal therapy, primarily voriconazole. The use of voriconazole was associated with a nonsignificant trend toward lower mortality.
They noted that the heavy use of immunomodulating agents in the patients in their study may have contributed to the high prevalence of CAPA.
Dr. Ouellette agreed that many of the therapies used to treat COVID-19 in the ICU are experimental, and that agents used to suppress the cytokine storm that is believed to contribute to disease severity may increase risk for secondary infections such as invasive aspergillosis.
“Many of our treatments may be associated with adverse consequences,” he said. “There is a trend toward treating patients with COVID-19 pneumonia with corticosteroids, and certainly that could have an immunosuppressant effect and predispose patients to secondary infections.”
He noted that the World Health Organization recommendations current in March 2020, when the pandemic began in earnest in the United States, advised against the use of corticosteroids, likely because of a lack of evidence of efficacy and concerns about risk for secondary infections.
“Regardless of the strategic choice made, all efforts should be put into improving our ability to reliably identify patients that may benefit from therapeutic interventions, which include host and risk factors, clinical factors and CAPA disease markers,” Dr. Brüggemann and colleagues wrote in their editorial.
The study was performed without external funding. The authors and Dr. Ouellette reported no conflicts of interest. Dr. Brüggemann and coauthors report grants and/or personal fees from various companies outside the submitted work.
SOURCE: Bartoletti M et al. Clin Infect Dis. 2020 Jul 28. doi: 10.1093/cid/ciaa1065.
Researchers are beginning to make some headway in identifying the role of secondary infections in the course and outcomes of COVID-19.
Patients who are on ventilatory support for severe COVID-19 infections appear to be at high risk for invasive pulmonary aspergillosis, which in a small prospective study was associated with a more than threefold risk for 30-day mortality. The findings were published online in Clinical Infectious Diseases.
Among 108 patients with COVID-19 on mechanical ventilation in one of three intensive care units, 30 (27.7%) were diagnosed with coronavirus-associated pulmonary aspergillosis (CAPA) based on consensus definitions similar to those used to diagnose influenza-associated pulmonary aspergillosis (IAPA).
Of the patients with CAPA, 44% died within 30 days of ICU admission, compared with 19% of patients who did not meet the criteria for aspergillosis (P = .002). This difference translated into an odds ratio (OR) for death with CAPA of 3.55 (P = .014), reported Michele Bartoletti, MD, PhD, of the infectious diseases unit at Sant’Orsola Malpighi Hospital in Bologna, Italy, and colleagues.
When the investigators applied a proposed definition of putative invasive pulmonary aspergillosis, or “PIPA” to the same patients, the 30-day mortality rate jumped to 74% vs. 26% for patients without PIPA (P < .001), with an OR of 11.60 (P < .001). “We found a high incidence of CAPA among critically ill COVID-19 patients and that its occurrence seems to change the natural history of disease,” they wrote.
“[T]he study from Bartoletti et al. alerts the clinical audience to be aware of CAPA and take appropriate (and where needed repetitive) actions that fits their clinical setting,” Roger J. Brüggemann, PharmD, of the department of pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands, and colleagues wrote in an editorial accompanying the study.
Diagnosis challenging
At the best of times, the diagnosis of pulmonary aspergillosis is difficult, subject to both false-positive and false-negative results, said a critical care specialist who was not involved in the study.
“Critically ill patients are susceptible to having aspergillus, so in reading the article, my only concerns are that I don’t know how accurate the testing is, and I don’t know if their population is truly different from a general population of patients in the ICU,” Daniel R. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital in Detroit, said in an interview.
As seen in ICU patients with severe influenza or other viral infections, patients with severe COVID-19 disease are susceptible to secondary infections, he said, making it difficult to know whether the worse outcomes seen in patients with COVID-19 and presumed aspergillosis are a reflection of their being more critically ill or whether the secondary infections themselves account for the difference in mortality.
Three ICUs
Dr. Bartoletti and colleagues conducted a study on all adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation in three ICUs in Bologna.
All patients included in the study were screened for invasive pulmonary aspergillosis with bronchoalveolar lavage and galactomannan detection and cultures. The lavage was performed on ICU admission, one day from the first day of mechanical ventilation, and if patients had evidence of clinical disease progression.
Samples that tested positive for galactomannan, a component of the aspergillus cell wall, were stored and later analyzed with a commercial quantitative real-time polymerase chain reaction assay for aspergillus; these results were not reported to clinicians on the patient floors.
The investigators defined invasive pulmonary aspergillosis according to a recently proposed definition for CAPA. This definition applies to COVID-19–positive patients admitted to an ICU with pulmonary infiltrates and at least one of the following:
- A serum galactomannan > 0.5.
- Bronchoalveolar lavage galactomannan > 1.0.
- Positive aspergillus bronchoalveolar lavage culture or cavitating infiltrate not attributed to another cause in the area of the pulmonary infiltrate.
They compared the CAPA diagnostic criteria with those of PIPA criteria as described by Stijn J. Blot, PhD, and colleagues in study published in the American Journal of Respiratory and Critical Care Medicine (2012 Jul 1;186(1):56-64).
A total of 108 patients were screened for aspergillosis, with a median age of 64. The majority of patients (78%) were male. The median age-adjusted Charlson Comorbidity Index was 2.5 (range 1-4). The median Sequential Organ Failure Assessment (SOFA) score at ICU admission was 4 (range 3-5).
As noted, probable aspergillosis by CAPA criteria was diagnosed in 30 patients (27.7%), with the diagnosis made after a median of 4 days after intubation and a median of 14 days from onset of COVID-19 symptoms.
The incidence rate of probable CAPA was 38.83 per 10,000 ICU patient days.
A comparison of clinical characteristics of patients with and without probable CAPA showed that only chronic steroid therapy at ≥ 16 mg/day prednisone for at least 15 days was significantly associated with risk for CAPA (P = .02).
At a median follow-up of 31 days, 54 patients (50%) had been discharged, 44 (41%) had died, and the remaining patients were still on follow-up.
As noted before, the mortality rate with 30 days of ICU admission was 44% for patients with probable CAPA vs. 19% for patients without. Among patients deemed to have PIPA, 74% died within 30 days of admission, compared with 26% without PIPA.
In a logistic regression model, the association of CAPA with increased risk for 30-day mortality remained even after adjustment for the need for renal replacement therapy (OR 3.02, P = .015) and SOFA score at ICU admission (OR 1.38, P = .004).
In a logistic regression using the PIPA rather than CAPA definition, the OR for 30-day mortality was 11.60 (P = .001).
Prognostic marker
The investigators noted that bronchoalveolar lavage galactomannan index appeared to be predictive of death. Each 1-point increase in the index was associated with 1.41-fold increase in the risk for 30-day mortality (P = .0070), a relationship that held up after adjustment for age, need for renal replacement therapy, and SOFA score.
Sixteen patients who met the CAPA definition received antifungal therapy, primarily voriconazole. The use of voriconazole was associated with a nonsignificant trend toward lower mortality.
They noted that the heavy use of immunomodulating agents in the patients in their study may have contributed to the high prevalence of CAPA.
Dr. Ouellette agreed that many of the therapies used to treat COVID-19 in the ICU are experimental, and that agents used to suppress the cytokine storm that is believed to contribute to disease severity may increase risk for secondary infections such as invasive aspergillosis.
“Many of our treatments may be associated with adverse consequences,” he said. “There is a trend toward treating patients with COVID-19 pneumonia with corticosteroids, and certainly that could have an immunosuppressant effect and predispose patients to secondary infections.”
He noted that the World Health Organization recommendations current in March 2020, when the pandemic began in earnest in the United States, advised against the use of corticosteroids, likely because of a lack of evidence of efficacy and concerns about risk for secondary infections.
“Regardless of the strategic choice made, all efforts should be put into improving our ability to reliably identify patients that may benefit from therapeutic interventions, which include host and risk factors, clinical factors and CAPA disease markers,” Dr. Brüggemann and colleagues wrote in their editorial.
The study was performed without external funding. The authors and Dr. Ouellette reported no conflicts of interest. Dr. Brüggemann and coauthors report grants and/or personal fees from various companies outside the submitted work.
SOURCE: Bartoletti M et al. Clin Infect Dis. 2020 Jul 28. doi: 10.1093/cid/ciaa1065.
Researchers are beginning to make some headway in identifying the role of secondary infections in the course and outcomes of COVID-19.
Patients who are on ventilatory support for severe COVID-19 infections appear to be at high risk for invasive pulmonary aspergillosis, which in a small prospective study was associated with a more than threefold risk for 30-day mortality. The findings were published online in Clinical Infectious Diseases.
Among 108 patients with COVID-19 on mechanical ventilation in one of three intensive care units, 30 (27.7%) were diagnosed with coronavirus-associated pulmonary aspergillosis (CAPA) based on consensus definitions similar to those used to diagnose influenza-associated pulmonary aspergillosis (IAPA).
Of the patients with CAPA, 44% died within 30 days of ICU admission, compared with 19% of patients who did not meet the criteria for aspergillosis (P = .002). This difference translated into an odds ratio (OR) for death with CAPA of 3.55 (P = .014), reported Michele Bartoletti, MD, PhD, of the infectious diseases unit at Sant’Orsola Malpighi Hospital in Bologna, Italy, and colleagues.
When the investigators applied a proposed definition of putative invasive pulmonary aspergillosis, or “PIPA” to the same patients, the 30-day mortality rate jumped to 74% vs. 26% for patients without PIPA (P < .001), with an OR of 11.60 (P < .001). “We found a high incidence of CAPA among critically ill COVID-19 patients and that its occurrence seems to change the natural history of disease,” they wrote.
“[T]he study from Bartoletti et al. alerts the clinical audience to be aware of CAPA and take appropriate (and where needed repetitive) actions that fits their clinical setting,” Roger J. Brüggemann, PharmD, of the department of pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands, and colleagues wrote in an editorial accompanying the study.
Diagnosis challenging
At the best of times, the diagnosis of pulmonary aspergillosis is difficult, subject to both false-positive and false-negative results, said a critical care specialist who was not involved in the study.
“Critically ill patients are susceptible to having aspergillus, so in reading the article, my only concerns are that I don’t know how accurate the testing is, and I don’t know if their population is truly different from a general population of patients in the ICU,” Daniel R. Ouellette, MD, FCCP, associate director of medical critical care at Henry Ford Hospital in Detroit, said in an interview.
As seen in ICU patients with severe influenza or other viral infections, patients with severe COVID-19 disease are susceptible to secondary infections, he said, making it difficult to know whether the worse outcomes seen in patients with COVID-19 and presumed aspergillosis are a reflection of their being more critically ill or whether the secondary infections themselves account for the difference in mortality.
Three ICUs
Dr. Bartoletti and colleagues conducted a study on all adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation in three ICUs in Bologna.
All patients included in the study were screened for invasive pulmonary aspergillosis with bronchoalveolar lavage and galactomannan detection and cultures. The lavage was performed on ICU admission, one day from the first day of mechanical ventilation, and if patients had evidence of clinical disease progression.
Samples that tested positive for galactomannan, a component of the aspergillus cell wall, were stored and later analyzed with a commercial quantitative real-time polymerase chain reaction assay for aspergillus; these results were not reported to clinicians on the patient floors.
The investigators defined invasive pulmonary aspergillosis according to a recently proposed definition for CAPA. This definition applies to COVID-19–positive patients admitted to an ICU with pulmonary infiltrates and at least one of the following:
- A serum galactomannan > 0.5.
- Bronchoalveolar lavage galactomannan > 1.0.
- Positive aspergillus bronchoalveolar lavage culture or cavitating infiltrate not attributed to another cause in the area of the pulmonary infiltrate.
They compared the CAPA diagnostic criteria with those of PIPA criteria as described by Stijn J. Blot, PhD, and colleagues in study published in the American Journal of Respiratory and Critical Care Medicine (2012 Jul 1;186(1):56-64).
A total of 108 patients were screened for aspergillosis, with a median age of 64. The majority of patients (78%) were male. The median age-adjusted Charlson Comorbidity Index was 2.5 (range 1-4). The median Sequential Organ Failure Assessment (SOFA) score at ICU admission was 4 (range 3-5).
As noted, probable aspergillosis by CAPA criteria was diagnosed in 30 patients (27.7%), with the diagnosis made after a median of 4 days after intubation and a median of 14 days from onset of COVID-19 symptoms.
The incidence rate of probable CAPA was 38.83 per 10,000 ICU patient days.
A comparison of clinical characteristics of patients with and without probable CAPA showed that only chronic steroid therapy at ≥ 16 mg/day prednisone for at least 15 days was significantly associated with risk for CAPA (P = .02).
At a median follow-up of 31 days, 54 patients (50%) had been discharged, 44 (41%) had died, and the remaining patients were still on follow-up.
As noted before, the mortality rate with 30 days of ICU admission was 44% for patients with probable CAPA vs. 19% for patients without. Among patients deemed to have PIPA, 74% died within 30 days of admission, compared with 26% without PIPA.
In a logistic regression model, the association of CAPA with increased risk for 30-day mortality remained even after adjustment for the need for renal replacement therapy (OR 3.02, P = .015) and SOFA score at ICU admission (OR 1.38, P = .004).
In a logistic regression using the PIPA rather than CAPA definition, the OR for 30-day mortality was 11.60 (P = .001).
Prognostic marker
The investigators noted that bronchoalveolar lavage galactomannan index appeared to be predictive of death. Each 1-point increase in the index was associated with 1.41-fold increase in the risk for 30-day mortality (P = .0070), a relationship that held up after adjustment for age, need for renal replacement therapy, and SOFA score.
Sixteen patients who met the CAPA definition received antifungal therapy, primarily voriconazole. The use of voriconazole was associated with a nonsignificant trend toward lower mortality.
They noted that the heavy use of immunomodulating agents in the patients in their study may have contributed to the high prevalence of CAPA.
Dr. Ouellette agreed that many of the therapies used to treat COVID-19 in the ICU are experimental, and that agents used to suppress the cytokine storm that is believed to contribute to disease severity may increase risk for secondary infections such as invasive aspergillosis.
“Many of our treatments may be associated with adverse consequences,” he said. “There is a trend toward treating patients with COVID-19 pneumonia with corticosteroids, and certainly that could have an immunosuppressant effect and predispose patients to secondary infections.”
He noted that the World Health Organization recommendations current in March 2020, when the pandemic began in earnest in the United States, advised against the use of corticosteroids, likely because of a lack of evidence of efficacy and concerns about risk for secondary infections.
“Regardless of the strategic choice made, all efforts should be put into improving our ability to reliably identify patients that may benefit from therapeutic interventions, which include host and risk factors, clinical factors and CAPA disease markers,” Dr. Brüggemann and colleagues wrote in their editorial.
The study was performed without external funding. The authors and Dr. Ouellette reported no conflicts of interest. Dr. Brüggemann and coauthors report grants and/or personal fees from various companies outside the submitted work.
SOURCE: Bartoletti M et al. Clin Infect Dis. 2020 Jul 28. doi: 10.1093/cid/ciaa1065.
FROM CLINICAL INFECTIOUS DISEASES
First evidence of SARS-CoV-2 in heart cells
SARS-CoV-2 has been found in cardiac tissue of a child from Brazil with multisystem inflammatory syndrome (MIS-C) related to COVID-19 who presented with myocarditis and died of heart failure.
It’s believed to be the first evidence of direct infection of heart muscle cells by the virus; viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.
The case was described in a report published online August 20 in The Lancet Child & Adolescent Health.
“The presence of the virus in various cell types of cardiac tissue, as evidenced by electron microscopy, shows that myocarditis in this case is likely a direct inflammatory response to the virus infection in the heart,” first author Marisa Dolhnikoff, MD, department of pathology, University of São Paulo, said in an interview.
There have been previous reports in adults with COVID-19 of both SARS-CoV-2 RNA by reverse transcription–polymerase chain reaction (RT-PCR) and viral particles by electron microscopy in cardiac tissue from endomyocardial specimens, the researchers noted. One of these reports, published in April by Tavazzi and colleagues, “detected viral particles in cardiac macrophages in an adult patient with acute cardiac injury associated with COVID-19; no viral particles were seen in cardiomyocytes or endothelial cells.
“Our case report is the first to our knowledge to document the presence of viral particles in the cardiac tissue of a child affected by MIS-C,” they added. “Moreover, viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.”
‘Concerning’ case report
“This is a concerning report as it shows for the first time that the virus can actually invade the heart muscle cells themselves,” C. Michael Gibson, MD, CEO of the Baim Institute for Clinical Research in Boston, said in an interview.
“Previous reports of COVID-19 and the heart found that the virus was in the area outside the heart muscle cells. We do not know yet the relative contribution of the inflammatory cells invading the heart, the release of blood-borne inflammatory mediators, and the virus inside the heart muscle cells themselves to heart damage,” Dr. Gibson said.
The patient was a previously healthy 11-year-old girl of African descent with MIS-C related to COVID-19. She developed cardiac failure and died after 1 day in the hospital, despite aggressive treatment.
SARS-CoV-2 RNA was detected on a postmortem nasopharyngeal swab and in cardiac and pulmonary tissues by RT-PCR.
Postmortem ultrasound examination of the heart showed a “hyperechogenic and diffusely thickened endocardium (mean thickness, 10 mm), a thickened myocardium (18 mm thick in the left ventricle), and a small pericardial effusion,” Dr. Dolhnikoff and colleagues reported.
Histopathologic exam revealed myocarditis, pericarditis, and endocarditis characterized by infiltration of inflammatory cells. Inflammation was mainly interstitial and perivascular, associated with foci of cardiomyocyte necrosis and was mainly composed of CD68+ macrophages, a few CD45+ lymphocytes, and a few neutrophils and eosinophils.
Electron microscopy of cardiac tissue revealed spherical viral particles in shape and size consistent with the Coronaviridae family in the extracellular compartment and within cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts.
Microthrombi in the pulmonary arterioles and renal glomerular capillaries were also seen at autopsy. SARS-CoV-2–associated pneumonia was mild.
Lymphoid depletion and signs of hemophagocytosis were observed in the spleen and lymph nodes. Acute tubular necrosis in the kidneys and hepatic centrilobular necrosis, secondary to shock, were also seen. Brain tissue showed microglial reactivity.
“Fortunately, MIS-C is a rare event and, although it can be severe and life threatening, most children recover,” Dr. Dolhnikoff commented.
“This case report comes at a time when the scientific community around the world calls attention to MIS-C and the need for it to be quickly recognized and treated by the pediatric community. Evidence of a direct relation between the virus and myocarditis confirms that MIS-C is one of the possible forms of presentation of COVID-19 and that the heart may be the target organ. It also alerts clinicians to possible cardiac sequelae in these children,” she added.
Experts weigh in
Scott Aydin, MD, medical director of pediatric cardiac intensive care, Mount Sinai Kravis Children’s Hospital in New York City, said that this case report is “unfortunately not all that surprising.
“Since the initial presentations of MIS-C several months ago, we have suspected mechanisms of direct and indirect injury to the myocardium. This important work is just the next step in further understanding the mechanisms of how COVID-19 creates havoc in the human body and the choices of possible therapies we have to treat children with COVID-19 and MIS-C,” said Dr. Aydin, who was not involved with the case report.
Anish Koka, MD, a cardiologist in private practice in Philadelphia, noted that, in these cases, endomyocardial biopsy is “rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis.”
“While reports like this are sure to spawn viral tweets, it’s vital to understand that it’s not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in,” Dr. Koka said in an interview.
He noted that, in the case of the young girl who died, it took high PCR-cycle threshold values to isolate virus from the lung and heart samples.
“This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs,” said Dr. Koka, who was also not associated with the case report.
This research had no specific funding. The authors declared no competing interests. Dr. Aydin disclosed no relevant financial relationships. Dr. Koka disclosed financial relationships with Boehringer Ingelheim and Jardiance.
This article first appeared on Medscape.com.
SARS-CoV-2 has been found in cardiac tissue of a child from Brazil with multisystem inflammatory syndrome (MIS-C) related to COVID-19 who presented with myocarditis and died of heart failure.
It’s believed to be the first evidence of direct infection of heart muscle cells by the virus; viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.
The case was described in a report published online August 20 in The Lancet Child & Adolescent Health.
“The presence of the virus in various cell types of cardiac tissue, as evidenced by electron microscopy, shows that myocarditis in this case is likely a direct inflammatory response to the virus infection in the heart,” first author Marisa Dolhnikoff, MD, department of pathology, University of São Paulo, said in an interview.
There have been previous reports in adults with COVID-19 of both SARS-CoV-2 RNA by reverse transcription–polymerase chain reaction (RT-PCR) and viral particles by electron microscopy in cardiac tissue from endomyocardial specimens, the researchers noted. One of these reports, published in April by Tavazzi and colleagues, “detected viral particles in cardiac macrophages in an adult patient with acute cardiac injury associated with COVID-19; no viral particles were seen in cardiomyocytes or endothelial cells.
“Our case report is the first to our knowledge to document the presence of viral particles in the cardiac tissue of a child affected by MIS-C,” they added. “Moreover, viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.”
‘Concerning’ case report
“This is a concerning report as it shows for the first time that the virus can actually invade the heart muscle cells themselves,” C. Michael Gibson, MD, CEO of the Baim Institute for Clinical Research in Boston, said in an interview.
“Previous reports of COVID-19 and the heart found that the virus was in the area outside the heart muscle cells. We do not know yet the relative contribution of the inflammatory cells invading the heart, the release of blood-borne inflammatory mediators, and the virus inside the heart muscle cells themselves to heart damage,” Dr. Gibson said.
The patient was a previously healthy 11-year-old girl of African descent with MIS-C related to COVID-19. She developed cardiac failure and died after 1 day in the hospital, despite aggressive treatment.
SARS-CoV-2 RNA was detected on a postmortem nasopharyngeal swab and in cardiac and pulmonary tissues by RT-PCR.
Postmortem ultrasound examination of the heart showed a “hyperechogenic and diffusely thickened endocardium (mean thickness, 10 mm), a thickened myocardium (18 mm thick in the left ventricle), and a small pericardial effusion,” Dr. Dolhnikoff and colleagues reported.
Histopathologic exam revealed myocarditis, pericarditis, and endocarditis characterized by infiltration of inflammatory cells. Inflammation was mainly interstitial and perivascular, associated with foci of cardiomyocyte necrosis and was mainly composed of CD68+ macrophages, a few CD45+ lymphocytes, and a few neutrophils and eosinophils.
Electron microscopy of cardiac tissue revealed spherical viral particles in shape and size consistent with the Coronaviridae family in the extracellular compartment and within cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts.
Microthrombi in the pulmonary arterioles and renal glomerular capillaries were also seen at autopsy. SARS-CoV-2–associated pneumonia was mild.
Lymphoid depletion and signs of hemophagocytosis were observed in the spleen and lymph nodes. Acute tubular necrosis in the kidneys and hepatic centrilobular necrosis, secondary to shock, were also seen. Brain tissue showed microglial reactivity.
“Fortunately, MIS-C is a rare event and, although it can be severe and life threatening, most children recover,” Dr. Dolhnikoff commented.
“This case report comes at a time when the scientific community around the world calls attention to MIS-C and the need for it to be quickly recognized and treated by the pediatric community. Evidence of a direct relation between the virus and myocarditis confirms that MIS-C is one of the possible forms of presentation of COVID-19 and that the heart may be the target organ. It also alerts clinicians to possible cardiac sequelae in these children,” she added.
Experts weigh in
Scott Aydin, MD, medical director of pediatric cardiac intensive care, Mount Sinai Kravis Children’s Hospital in New York City, said that this case report is “unfortunately not all that surprising.
“Since the initial presentations of MIS-C several months ago, we have suspected mechanisms of direct and indirect injury to the myocardium. This important work is just the next step in further understanding the mechanisms of how COVID-19 creates havoc in the human body and the choices of possible therapies we have to treat children with COVID-19 and MIS-C,” said Dr. Aydin, who was not involved with the case report.
Anish Koka, MD, a cardiologist in private practice in Philadelphia, noted that, in these cases, endomyocardial biopsy is “rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis.”
“While reports like this are sure to spawn viral tweets, it’s vital to understand that it’s not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in,” Dr. Koka said in an interview.
He noted that, in the case of the young girl who died, it took high PCR-cycle threshold values to isolate virus from the lung and heart samples.
“This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs,” said Dr. Koka, who was also not associated with the case report.
This research had no specific funding. The authors declared no competing interests. Dr. Aydin disclosed no relevant financial relationships. Dr. Koka disclosed financial relationships with Boehringer Ingelheim and Jardiance.
This article first appeared on Medscape.com.
SARS-CoV-2 has been found in cardiac tissue of a child from Brazil with multisystem inflammatory syndrome (MIS-C) related to COVID-19 who presented with myocarditis and died of heart failure.
It’s believed to be the first evidence of direct infection of heart muscle cells by the virus; viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.
The case was described in a report published online August 20 in The Lancet Child & Adolescent Health.
“The presence of the virus in various cell types of cardiac tissue, as evidenced by electron microscopy, shows that myocarditis in this case is likely a direct inflammatory response to the virus infection in the heart,” first author Marisa Dolhnikoff, MD, department of pathology, University of São Paulo, said in an interview.
There have been previous reports in adults with COVID-19 of both SARS-CoV-2 RNA by reverse transcription–polymerase chain reaction (RT-PCR) and viral particles by electron microscopy in cardiac tissue from endomyocardial specimens, the researchers noted. One of these reports, published in April by Tavazzi and colleagues, “detected viral particles in cardiac macrophages in an adult patient with acute cardiac injury associated with COVID-19; no viral particles were seen in cardiomyocytes or endothelial cells.
“Our case report is the first to our knowledge to document the presence of viral particles in the cardiac tissue of a child affected by MIS-C,” they added. “Moreover, viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.”
‘Concerning’ case report
“This is a concerning report as it shows for the first time that the virus can actually invade the heart muscle cells themselves,” C. Michael Gibson, MD, CEO of the Baim Institute for Clinical Research in Boston, said in an interview.
“Previous reports of COVID-19 and the heart found that the virus was in the area outside the heart muscle cells. We do not know yet the relative contribution of the inflammatory cells invading the heart, the release of blood-borne inflammatory mediators, and the virus inside the heart muscle cells themselves to heart damage,” Dr. Gibson said.
The patient was a previously healthy 11-year-old girl of African descent with MIS-C related to COVID-19. She developed cardiac failure and died after 1 day in the hospital, despite aggressive treatment.
SARS-CoV-2 RNA was detected on a postmortem nasopharyngeal swab and in cardiac and pulmonary tissues by RT-PCR.
Postmortem ultrasound examination of the heart showed a “hyperechogenic and diffusely thickened endocardium (mean thickness, 10 mm), a thickened myocardium (18 mm thick in the left ventricle), and a small pericardial effusion,” Dr. Dolhnikoff and colleagues reported.
Histopathologic exam revealed myocarditis, pericarditis, and endocarditis characterized by infiltration of inflammatory cells. Inflammation was mainly interstitial and perivascular, associated with foci of cardiomyocyte necrosis and was mainly composed of CD68+ macrophages, a few CD45+ lymphocytes, and a few neutrophils and eosinophils.
Electron microscopy of cardiac tissue revealed spherical viral particles in shape and size consistent with the Coronaviridae family in the extracellular compartment and within cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts.
Microthrombi in the pulmonary arterioles and renal glomerular capillaries were also seen at autopsy. SARS-CoV-2–associated pneumonia was mild.
Lymphoid depletion and signs of hemophagocytosis were observed in the spleen and lymph nodes. Acute tubular necrosis in the kidneys and hepatic centrilobular necrosis, secondary to shock, were also seen. Brain tissue showed microglial reactivity.
“Fortunately, MIS-C is a rare event and, although it can be severe and life threatening, most children recover,” Dr. Dolhnikoff commented.
“This case report comes at a time when the scientific community around the world calls attention to MIS-C and the need for it to be quickly recognized and treated by the pediatric community. Evidence of a direct relation between the virus and myocarditis confirms that MIS-C is one of the possible forms of presentation of COVID-19 and that the heart may be the target organ. It also alerts clinicians to possible cardiac sequelae in these children,” she added.
Experts weigh in
Scott Aydin, MD, medical director of pediatric cardiac intensive care, Mount Sinai Kravis Children’s Hospital in New York City, said that this case report is “unfortunately not all that surprising.
“Since the initial presentations of MIS-C several months ago, we have suspected mechanisms of direct and indirect injury to the myocardium. This important work is just the next step in further understanding the mechanisms of how COVID-19 creates havoc in the human body and the choices of possible therapies we have to treat children with COVID-19 and MIS-C,” said Dr. Aydin, who was not involved with the case report.
Anish Koka, MD, a cardiologist in private practice in Philadelphia, noted that, in these cases, endomyocardial biopsy is “rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis.”
“While reports like this are sure to spawn viral tweets, it’s vital to understand that it’s not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in,” Dr. Koka said in an interview.
He noted that, in the case of the young girl who died, it took high PCR-cycle threshold values to isolate virus from the lung and heart samples.
“This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs,” said Dr. Koka, who was also not associated with the case report.
This research had no specific funding. The authors declared no competing interests. Dr. Aydin disclosed no relevant financial relationships. Dr. Koka disclosed financial relationships with Boehringer Ingelheim and Jardiance.
This article first appeared on Medscape.com.
Famotidine associated with benefits in hospitalized COVID patients in another trial
It also demonstrated lower levels of serum markers for severe disease.
The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.
“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”
In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.
Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.
The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.
In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).
Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m2, chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.
“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”
In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H2 blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”
Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”
Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).
“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”
Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.
SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.
It also demonstrated lower levels of serum markers for severe disease.
The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.
“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”
In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.
Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.
The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.
In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).
Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m2, chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.
“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”
In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H2 blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”
Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”
Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).
“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”
Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.
SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.
It also demonstrated lower levels of serum markers for severe disease.
The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.
“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”
In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.
Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.
The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.
In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).
Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m2, chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.
“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”
In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H2 blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”
Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”
Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).
“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”
Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.
SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.
REPORTING FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
Key clinical point: Among hospitalized COVID-19 patients, famotidine use was associated with a reduction in death and either death or intubation.
Major finding: The use of famotidine was associated with a decreased risk of in-hospital mortality (OR, 0.37; P = .021), as well as the combined endpoint of death or intubation (OR, 0.47; P = .040).
Study details: A single-center observational study of 83 patients hospitalized with COVID-19.
Disclosures: The researchers reported having no financial disclosures.
Source: Mather J et al. 2020 Aug 14. Am J Gastroenterol.
FDA approves clinical trials for cannabinoid drug designed to reduce COVID-19 lung inflammation
The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.
ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.
The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.
Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.
“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”
ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.
Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.
If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19.
If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said. Phase three would start at the end of 2021.
Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
This article first appeared on Medscape.com.
The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.
ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.
The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.
Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.
“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”
ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.
Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.
If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19.
If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said. Phase three would start at the end of 2021.
Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
This article first appeared on Medscape.com.
The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.
ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.
The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.
Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.
“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”
ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.
Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.
If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19.
If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said. Phase three would start at the end of 2021.
Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
This article first appeared on Medscape.com.
Study confirms it’s possible to catch COVID-19 twice
Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.
The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.
On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.
The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.
Experts with the World Health Organization responded to the case at a news briefing.
“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.
A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.
“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
Past experience guides present
Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.
This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.
It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.
“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.
There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.
Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
Good news
That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.
That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.
But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.
“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.
“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.
It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.
Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.
Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.
“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”
A version of this article originally appeared on WebMD.com.
Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.
The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.
On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.
The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.
Experts with the World Health Organization responded to the case at a news briefing.
“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.
A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.
“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
Past experience guides present
Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.
This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.
It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.
“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.
There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.
Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
Good news
That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.
That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.
But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.
“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.
“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.
It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.
Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.
Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.
“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”
A version of this article originally appeared on WebMD.com.
Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.
The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.
On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.
The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.
Experts with the World Health Organization responded to the case at a news briefing.
“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.
A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.
“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
Past experience guides present
Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.
This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.
It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.
“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.
There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.
Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
Good news
That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.
That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.
But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.
“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.
“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.
It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.
Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.
Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.
“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”
A version of this article originally appeared on WebMD.com.