CHEST Physician

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

Rheumatologists the world over are joining forces to create a COVID-19 rheumatology registry designed to help both patients and providers learn from each other regarding management of rheumatologic diseases and risk of infection among patients who are commonly on chronic immunosuppressive medications.

The COVID-19 Global Rheumatology Alliance, a consortium supported by more than 50 major clinical societies and foundations, quickly grew from messages on social media platforms to a multinational group focused on the common goal of helping to “guide rheumatology clinicians in assessing and treating patients with rheumatologic disease and in evaluating the risk of infection in patients on immunosuppression.”

As of this writing, the rheumatology registry is still being assembled, and organizers are currently seeking approvals from various authorities. As of March 17, 2020, the Institutional Review Board (IRB) at the University of California, San Francisco, has determined that the registry is exempt from IRB approval requirements, a finding that should apply elsewhere in the United States, according to the registry website.

When it is fully up and running, clinicians will be able to report to the secure website on any and all cases of patients with rheumatologic disorders who present with COVID-19 of any severity, including patients with mild disease or asymptomatic patients who test positive.

“We are aiming for 5 to 10 minutes to input the data. We don’t want to drag them away from their clinical duties too much, but if clinicians are able to spare a few minutes to put in details about a patient, then that’s going to help build our knowledge and it’s going to help them with other patients,” said Philip Robinson, MBChB, associate professor of medicine at the University of Queensland in Brisbane, Australia, and the chief architect of the registry.

The data will be deindentified, with no protected health care information required or included, and made available to the global rheumatology community, but the registry will not offer clinical advice, Dr. Robinson said in an interview.

“This is observational data, it’s not randomized, but our approach is that some data is better than no data,” he said.

He also cautioned that the data will need careful interpretation, because information about patients with mild symptoms may offer false reassurances about the severity or extent of infection.

“For example, the patients with severe cases may be in the ICU, and can’t tell their doctors that they’re on methotrexate, so you can see how we need to be really careful about the messages from that data and not misinterpret it,” he said.

The COVID-19 rheumatology registry was inspired by a similar effort in the gastroenterology community, the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE-IBD) registry. Patients with inflammatory bowel disease are often treated with immunosuppressive biologic agents familiar to the rheumatology community, such as infliximab (Remicade and biosimilars) and adalimumab (Humira and biosimilars), and methotrexate.

As of this morning, March 19, 2020, I’m still working.

Granted, there aren’t a lot of people who want to come in. My schedule has dropped to 3-5 follow-ups per day and no new patients.

I can understand people not wanting to expose themselves unnecessarily right now.

But, I’m still a doctor. What drove me to study for the MCAT, apply to med school 2 years in a row, and then survive medical school, internship, residency, and fellowship ... is still there.

Like I said in my 1987 personal statement, I still want to help people. I’d feel remiss if (provided I don’t have COVID-19) I didn’t show up for work each day, ready to care for any who need me. It’s part of who I am, what I do, and what I believe in.

I’m sure my colleagues in family practice, internal medicine, and pulmonology are swamped right now, but neurologists with primarily outpatient practices are taking a back seat except for a handful of patients.

My small office has been set up for my staff to work remotely in a pinch since 2016, so that was easy to enact. The three of us cover the phones the way we always have, and I see patients here.

With the relaxing of telehealth requirements for Medicare that were announced on March 17, I’m setting up to “see” patients remotely.

The whole situation seems bizarre and surreal.

It’s easy for anyone to read too much into anything. A brief tickle in my throat when I wake up, or a sneeze, or a few coughs, suddenly trigger a flurry of “could I have it?” thoughts. Fortunately, they fade when things quickly return to normal, but a few weeks ago I wouldn’t have thought anything of them at all.

Inevitably, I and pretty much everyone else will be exposed to or catch the virus. It’s what virions do. Unless you absolutely isolate yourself on a desert island, it will happen. When it does, you can only hope for the best.

I’m here for my patients today and will be as long as they need me. Unless I have to go into quarantine, of course. And even then, if able, I’ll do the best I can to treat them remotely.

That’s all I could ever want.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

As of this morning, March 19, 2020, I’m still working.

Granted, there aren’t a lot of people who want to come in. My schedule has dropped to 3-5 follow-ups per day and no new patients.

I can understand people not wanting to expose themselves unnecessarily right now.

But, I’m still a doctor. What drove me to study for the MCAT, apply to med school 2 years in a row, and then survive medical school, internship, residency, and fellowship ... is still there.

Like I said in my 1987 personal statement, I still want to help people. I’d feel remiss if (provided I don’t have COVID-19) I didn’t show up for work each day, ready to care for any who need me. It’s part of who I am, what I do, and what I believe in.

I’m sure my colleagues in family practice, internal medicine, and pulmonology are swamped right now, but neurologists with primarily outpatient practices are taking a back seat except for a handful of patients.

My small office has been set up for my staff to work remotely in a pinch since 2016, so that was easy to enact. The three of us cover the phones the way we always have, and I see patients here.

With the relaxing of telehealth requirements for Medicare that were announced on March 17, I’m setting up to “see” patients remotely.

The whole situation seems bizarre and surreal.

It’s easy for anyone to read too much into anything. A brief tickle in my throat when I wake up, or a sneeze, or a few coughs, suddenly trigger a flurry of “could I have it?” thoughts. Fortunately, they fade when things quickly return to normal, but a few weeks ago I wouldn’t have thought anything of them at all.

Inevitably, I and pretty much everyone else will be exposed to or catch the virus. It’s what virions do. Unless you absolutely isolate yourself on a desert island, it will happen. When it does, you can only hope for the best.

I’m here for my patients today and will be as long as they need me. Unless I have to go into quarantine, of course. And even then, if able, I’ll do the best I can to treat them remotely.

That’s all I could ever want.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

As of this morning, March 19, 2020, I’m still working.

Granted, there aren’t a lot of people who want to come in. My schedule has dropped to 3-5 follow-ups per day and no new patients.

I can understand people not wanting to expose themselves unnecessarily right now.

But, I’m still a doctor. What drove me to study for the MCAT, apply to med school 2 years in a row, and then survive medical school, internship, residency, and fellowship ... is still there.

Like I said in my 1987 personal statement, I still want to help people. I’d feel remiss if (provided I don’t have COVID-19) I didn’t show up for work each day, ready to care for any who need me. It’s part of who I am, what I do, and what I believe in.

I’m sure my colleagues in family practice, internal medicine, and pulmonology are swamped right now, but neurologists with primarily outpatient practices are taking a back seat except for a handful of patients.

My small office has been set up for my staff to work remotely in a pinch since 2016, so that was easy to enact. The three of us cover the phones the way we always have, and I see patients here.

With the relaxing of telehealth requirements for Medicare that were announced on March 17, I’m setting up to “see” patients remotely.

The whole situation seems bizarre and surreal.

It’s easy for anyone to read too much into anything. A brief tickle in my throat when I wake up, or a sneeze, or a few coughs, suddenly trigger a flurry of “could I have it?” thoughts. Fortunately, they fade when things quickly return to normal, but a few weeks ago I wouldn’t have thought anything of them at all.

Inevitably, I and pretty much everyone else will be exposed to or catch the virus. It’s what virions do. Unless you absolutely isolate yourself on a desert island, it will happen. When it does, you can only hope for the best.

I’m here for my patients today and will be as long as they need me. Unless I have to go into quarantine, of course. And even then, if able, I’ll do the best I can to treat them remotely.

That’s all I could ever want.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Newly updated guidance on treating patients with the novel coronavirus (COVID-19) has been published by the World Health Organization.

While it can’t replace clinical judgment or specialist consultation, the new guidance may help strengthen the clinical management of patients when COVID-19 is suspected, according to its authors.

The guidance, adapted from an earlier edition focused on the management of suspected Middle East respiratory syndrome coronavirus (MERS-CoV), covers best practices for triage, infection prevention and control, and optimized supportive care for mild, severe, or critical coronavirus disease 2019 (COVID-19).

“This guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival,” the authors wrote in the guidance.

Newly updated guidance on treating patients with the novel coronavirus (COVID-19) has been published by the World Health Organization.

While it can’t replace clinical judgment or specialist consultation, the new guidance may help strengthen the clinical management of patients when COVID-19 is suspected, according to its authors.

The guidance, adapted from an earlier edition focused on the management of suspected Middle East respiratory syndrome coronavirus (MERS-CoV), covers best practices for triage, infection prevention and control, and optimized supportive care for mild, severe, or critical coronavirus disease 2019 (COVID-19).

“This guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival,” the authors wrote in the guidance.

Newly updated guidance on treating patients with the novel coronavirus (COVID-19) has been published by the World Health Organization.

While it can’t replace clinical judgment or specialist consultation, the new guidance may help strengthen the clinical management of patients when COVID-19 is suspected, according to its authors.

The guidance, adapted from an earlier edition focused on the management of suspected Middle East respiratory syndrome coronavirus (MERS-CoV), covers best practices for triage, infection prevention and control, and optimized supportive care for mild, severe, or critical coronavirus disease 2019 (COVID-19).

“This guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival,” the authors wrote in the guidance.

No difference in the primary endpoint of the time to clinical improvement was seen in an open-label trial of the antiretroviral drug lopinavir-ritonavir versus standard of care in adult patients hospitalized with severe COVID-19.

The median time to clinical improvement – defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever was first – was 16 days in both groups (hazard ratio, 1.31; 95% confidence interval 0.95-1.85; P = .09).

Although a numerically lower number of deaths were recorded at 28 days (19.2% vs. 25%) with the antiretroviral treatment versus standard of care, a similar percentage of patients had detectable levels of viral RNA in throat swabs taken at various time points during the study, Chinese researchers reported in the New England Journal of Medicine.

Bai Cao, M.D, from the China-Japan Friendship Hospital and Chinese Academy of Medical Sciences, both in Beijing, and associates, performed a randomized, controlled, trial of 199 adult patients hospitalized at the Jin Yin-Tan Hospital in Wuhan in Hubei Province, China.

For inclusion, patients had to have laboratory confirmed infection with SARS-Cov-2, the virus that causes COVID-19; pneumonia confirmed by chest imaging; and severely reduced oxygen saturation (94% or less while breathing ambient air or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen of less than 300 mm Hg).

Patients were randomized to receive either a combination of lopinavir (400 mg) and ritonavir (100 mg) twice a day on top of standard care (n = 99) or to standard care alone (n = 100) for 14 days. “Because of the emergency nature of the trial, placebos of lopinavir-ritonavir were not prepared,” Dr. Cao et al. explained, noting that standard care consisted of supplemental oxygen, ventilation, antibiotic treatment, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation.

While the trial did not meet its primary endpoint, Dr. Cao et al. reported that patients in the lopinavir-ritonavir group had a shorter stay in the intensive care unit than did those in the standard-care group, at a median of 6 versus 11 days. They also reported that the duration from randomization to hospital discharge was numerically shorter, at a median of 12 versus 14 days. Furthermore, there was a higher percentage of patients with clinical improvement at day 14 in the lopinavir-ritonavir group than in the standard-care group (45.5% vs. 30.0%)

“The trial was initiated in rapid response to the COVID-19 public health emergency, at which time there was very limited information about clinical outcomes in hospitalized patients with COVID-19,” the researchers observed. “The question of whether earlier lopinavir-ritonavir treatment in COVID-19 could have clinical benefit is an important one that requires further study,” they wrote.

Among the trial’s limitations are it was not blinded and the researchers do not have data on the lopinavir exposure levels in the trial participants.

“This was a heroic effort” in a “particularly challenging population,” Lindsey R. Baden, MD, and Eric J. Rubin, MD, stated in an editorial accompanying the article (Baden LR and Rubin EJ. New Engl J Med. March 18, 2020. doi: 10.1056/NEJMe2005477). “Unfortunately, the trial results were disappointing,” they noted.

“The secondary end points provide both reason for hope and reason for discouragement,” wrote Dr. Baden and Dr. Rubin. The lack of effect on viral shedding, however, “strongly [suggests] that it did not have the activity desired” they observed.

Dr. Baden and Dr. Rubin commented that one of the important takeaways from the trial is that “the investigators appropriately prioritized speed, designing a trial that could rapidly produce an answer.” They continued that the investigators had shown that “rapidly initiated, high-quality randomized clinical trials are possible in epidemic conditions” and that results of such trials, whether they are positive or negative, “will be central to clinical care as the dangerous coronavirus outbreak continues.”

As it stands, more than 100 trials are listed in the ClinicalTrials.gov database as testing a wide range of different treatment approaches for COVID-19. These include trials investigating if sarilumab, hydroxychloroquine, fingolimod, bevacizumab, and losartan might have a role to play. There are also trials looking at the potential of other antiviral agents, such as Gilead’s investigational drug remdesivir, which has shown to have in vitro and in vivo activity against many emerging viral pathogens that cause Ebola, Middle Eastern Respiratory Syndrome, and Severe Acute Respiratory Syndrome.

Dr. Cao’s trial was supported by grants from Major Projects of National Science and Technology on New Drug Creation and Development and from the Chinese Academy of Medical Sciences (CAMS) Emergency Project of Covid-19, and a National Science Grant for Distinguished Young Scholars.

All authors had no financial conflicts of interest to disclose.

Dr. Baden is the director of clinical research in the Division of Infectious Diseases at the Brigham and Women’s Hospital and the director of infectious diseases at the Dana-Farber Cancer Institute. He is a deputy editor of the New England Journal of Medicine and chair of the FDA’s Antimicrobial Drug Advisory Committee. He is involved in HIV vaccine clinical trials and has received research grants from the Ragon Institute, the National Institutes of Health/National Institute of Allergy and Infectious Diseases, and the Gates Foundation.

Dr. Rubin is employed by the New England Journal of Medicine as editor-in-chief. He is an associate physician at Brigham and Women’s Hospital and is chair and Irene Heinz Given Professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health.

SOURCE: Cao B et al. New Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282.

No difference in the primary endpoint of the time to clinical improvement was seen in an open-label trial of the antiretroviral drug lopinavir-ritonavir versus standard of care in adult patients hospitalized with severe COVID-19.

The median time to clinical improvement – defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever was first – was 16 days in both groups (hazard ratio, 1.31; 95% confidence interval 0.95-1.85; P = .09).

Although a numerically lower number of deaths were recorded at 28 days (19.2% vs. 25%) with the antiretroviral treatment versus standard of care, a similar percentage of patients had detectable levels of viral RNA in throat swabs taken at various time points during the study, Chinese researchers reported in the New England Journal of Medicine.

Bai Cao, M.D, from the China-Japan Friendship Hospital and Chinese Academy of Medical Sciences, both in Beijing, and associates, performed a randomized, controlled, trial of 199 adult patients hospitalized at the Jin Yin-Tan Hospital in Wuhan in Hubei Province, China.

For inclusion, patients had to have laboratory confirmed infection with SARS-Cov-2, the virus that causes COVID-19; pneumonia confirmed by chest imaging; and severely reduced oxygen saturation (94% or less while breathing ambient air or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen of less than 300 mm Hg).

Patients were randomized to receive either a combination of lopinavir (400 mg) and ritonavir (100 mg) twice a day on top of standard care (n = 99) or to standard care alone (n = 100) for 14 days. “Because of the emergency nature of the trial, placebos of lopinavir-ritonavir were not prepared,” Dr. Cao et al. explained, noting that standard care consisted of supplemental oxygen, ventilation, antibiotic treatment, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation.

While the trial did not meet its primary endpoint, Dr. Cao et al. reported that patients in the lopinavir-ritonavir group had a shorter stay in the intensive care unit than did those in the standard-care group, at a median of 6 versus 11 days. They also reported that the duration from randomization to hospital discharge was numerically shorter, at a median of 12 versus 14 days. Furthermore, there was a higher percentage of patients with clinical improvement at day 14 in the lopinavir-ritonavir group than in the standard-care group (45.5% vs. 30.0%)

“The trial was initiated in rapid response to the COVID-19 public health emergency, at which time there was very limited information about clinical outcomes in hospitalized patients with COVID-19,” the researchers observed. “The question of whether earlier lopinavir-ritonavir treatment in COVID-19 could have clinical benefit is an important one that requires further study,” they wrote.

Among the trial’s limitations are it was not blinded and the researchers do not have data on the lopinavir exposure levels in the trial participants.

“This was a heroic effort” in a “particularly challenging population,” Lindsey R. Baden, MD, and Eric J. Rubin, MD, stated in an editorial accompanying the article (Baden LR and Rubin EJ. New Engl J Med. March 18, 2020. doi: 10.1056/NEJMe2005477). “Unfortunately, the trial results were disappointing,” they noted.

“The secondary end points provide both reason for hope and reason for discouragement,” wrote Dr. Baden and Dr. Rubin. The lack of effect on viral shedding, however, “strongly [suggests] that it did not have the activity desired” they observed.

Dr. Baden and Dr. Rubin commented that one of the important takeaways from the trial is that “the investigators appropriately prioritized speed, designing a trial that could rapidly produce an answer.” They continued that the investigators had shown that “rapidly initiated, high-quality randomized clinical trials are possible in epidemic conditions” and that results of such trials, whether they are positive or negative, “will be central to clinical care as the dangerous coronavirus outbreak continues.”

As it stands, more than 100 trials are listed in the ClinicalTrials.gov database as testing a wide range of different treatment approaches for COVID-19. These include trials investigating if sarilumab, hydroxychloroquine, fingolimod, bevacizumab, and losartan might have a role to play. There are also trials looking at the potential of other antiviral agents, such as Gilead’s investigational drug remdesivir, which has shown to have in vitro and in vivo activity against many emerging viral pathogens that cause Ebola, Middle Eastern Respiratory Syndrome, and Severe Acute Respiratory Syndrome.

Dr. Cao’s trial was supported by grants from Major Projects of National Science and Technology on New Drug Creation and Development and from the Chinese Academy of Medical Sciences (CAMS) Emergency Project of Covid-19, and a National Science Grant for Distinguished Young Scholars.

All authors had no financial conflicts of interest to disclose.

Dr. Baden is the director of clinical research in the Division of Infectious Diseases at the Brigham and Women’s Hospital and the director of infectious diseases at the Dana-Farber Cancer Institute. He is a deputy editor of the New England Journal of Medicine and chair of the FDA’s Antimicrobial Drug Advisory Committee. He is involved in HIV vaccine clinical trials and has received research grants from the Ragon Institute, the National Institutes of Health/National Institute of Allergy and Infectious Diseases, and the Gates Foundation.

Dr. Rubin is employed by the New England Journal of Medicine as editor-in-chief. He is an associate physician at Brigham and Women’s Hospital and is chair and Irene Heinz Given Professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health.

SOURCE: Cao B et al. New Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282.

No difference in the primary endpoint of the time to clinical improvement was seen in an open-label trial of the antiretroviral drug lopinavir-ritonavir versus standard of care in adult patients hospitalized with severe COVID-19.

The median time to clinical improvement – defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever was first – was 16 days in both groups (hazard ratio, 1.31; 95% confidence interval 0.95-1.85; P = .09).

Although a numerically lower number of deaths were recorded at 28 days (19.2% vs. 25%) with the antiretroviral treatment versus standard of care, a similar percentage of patients had detectable levels of viral RNA in throat swabs taken at various time points during the study, Chinese researchers reported in the New England Journal of Medicine.

Bai Cao, M.D, from the China-Japan Friendship Hospital and Chinese Academy of Medical Sciences, both in Beijing, and associates, performed a randomized, controlled, trial of 199 adult patients hospitalized at the Jin Yin-Tan Hospital in Wuhan in Hubei Province, China.

For inclusion, patients had to have laboratory confirmed infection with SARS-Cov-2, the virus that causes COVID-19; pneumonia confirmed by chest imaging; and severely reduced oxygen saturation (94% or less while breathing ambient air or a ratio of the partial pressure of oxygen to the fraction of inspired oxygen of less than 300 mm Hg).

Patients were randomized to receive either a combination of lopinavir (400 mg) and ritonavir (100 mg) twice a day on top of standard care (n = 99) or to standard care alone (n = 100) for 14 days. “Because of the emergency nature of the trial, placebos of lopinavir-ritonavir were not prepared,” Dr. Cao et al. explained, noting that standard care consisted of supplemental oxygen, ventilation, antibiotic treatment, vasopressor support, renal-replacement therapy, and extracorporeal membrane oxygenation.

While the trial did not meet its primary endpoint, Dr. Cao et al. reported that patients in the lopinavir-ritonavir group had a shorter stay in the intensive care unit than did those in the standard-care group, at a median of 6 versus 11 days. They also reported that the duration from randomization to hospital discharge was numerically shorter, at a median of 12 versus 14 days. Furthermore, there was a higher percentage of patients with clinical improvement at day 14 in the lopinavir-ritonavir group than in the standard-care group (45.5% vs. 30.0%)

“The trial was initiated in rapid response to the COVID-19 public health emergency, at which time there was very limited information about clinical outcomes in hospitalized patients with COVID-19,” the researchers observed. “The question of whether earlier lopinavir-ritonavir treatment in COVID-19 could have clinical benefit is an important one that requires further study,” they wrote.

Among the trial’s limitations are it was not blinded and the researchers do not have data on the lopinavir exposure levels in the trial participants.

“This was a heroic effort” in a “particularly challenging population,” Lindsey R. Baden, MD, and Eric J. Rubin, MD, stated in an editorial accompanying the article (Baden LR and Rubin EJ. New Engl J Med. March 18, 2020. doi: 10.1056/NEJMe2005477). “Unfortunately, the trial results were disappointing,” they noted.

“The secondary end points provide both reason for hope and reason for discouragement,” wrote Dr. Baden and Dr. Rubin. The lack of effect on viral shedding, however, “strongly [suggests] that it did not have the activity desired” they observed.

Dr. Baden and Dr. Rubin commented that one of the important takeaways from the trial is that “the investigators appropriately prioritized speed, designing a trial that could rapidly produce an answer.” They continued that the investigators had shown that “rapidly initiated, high-quality randomized clinical trials are possible in epidemic conditions” and that results of such trials, whether they are positive or negative, “will be central to clinical care as the dangerous coronavirus outbreak continues.”

As it stands, more than 100 trials are listed in the ClinicalTrials.gov database as testing a wide range of different treatment approaches for COVID-19. These include trials investigating if sarilumab, hydroxychloroquine, fingolimod, bevacizumab, and losartan might have a role to play. There are also trials looking at the potential of other antiviral agents, such as Gilead’s investigational drug remdesivir, which has shown to have in vitro and in vivo activity against many emerging viral pathogens that cause Ebola, Middle Eastern Respiratory Syndrome, and Severe Acute Respiratory Syndrome.

Dr. Cao’s trial was supported by grants from Major Projects of National Science and Technology on New Drug Creation and Development and from the Chinese Academy of Medical Sciences (CAMS) Emergency Project of Covid-19, and a National Science Grant for Distinguished Young Scholars.

All authors had no financial conflicts of interest to disclose.

Dr. Baden is the director of clinical research in the Division of Infectious Diseases at the Brigham and Women’s Hospital and the director of infectious diseases at the Dana-Farber Cancer Institute. He is a deputy editor of the New England Journal of Medicine and chair of the FDA’s Antimicrobial Drug Advisory Committee. He is involved in HIV vaccine clinical trials and has received research grants from the Ragon Institute, the National Institutes of Health/National Institute of Allergy and Infectious Diseases, and the Gates Foundation.

Dr. Rubin is employed by the New England Journal of Medicine as editor-in-chief. He is an associate physician at Brigham and Women’s Hospital and is chair and Irene Heinz Given Professor of Immunology and Infectious Diseases at the Harvard T.H. Chan School of Public Health.

SOURCE: Cao B et al. New Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282.

PHOENIX, ARIZ. – Cardiovascular deaths and death rates related to atrial fibrillation have risen since 1999, with significant acceleration following 2009, results from a cross-sectional analysis of national data show.

Doug Brunk/MDedge News

“AFib is the most common arrhythmia disorder in the United States and it is estimated that it will effect more than 12 million Americans by 2030,” Yoshihiro Tanaka, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “The predicted lifetime risk ranges from 25% to 35%, and AFib is associated with an increased risk for heart failure, stroke, and death.”

A recent review reported that declines in total heart disease mortality rates in the United States have plateaued since 2011 (JAMA 2019;322[8]:780-2). However, it is not well understood what factors such as AFib contribute to this rate of plateau. In an effort to quantify U.S. trends in AFib-related CVD death rates, Dr. Tanaka and colleagues conducted a serial cross-sectional analysis of death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER) database during 1999-2017.

Outcomes included age-adjusted mortality per 100,000 based on the 2000 U.S. standard population. The researchers also used joinpoint regression to calculate the average annual percentage change over time and conducted subgroup analyses by race and sex and across two age groups: 35-64 years and 65-84 years.

In all, 522,104 AFib-related CVD deaths were identified during 1999-2017. Dr. Tanaka reported that age-adjusted mortality increased from 16.0 per 100,000 persons in 1999 to 22.2 per 100,000 person in 2017, with an acceleration following an inflection point in 2009. Specifically, the average annual percentage change in AFib-related CVD deaths rose from 0.4% in 2009 to 3.5% in 2017 (P < .001). “These increases were consistent across all race-sex subgroups,” said Dr. Tanaka, of the department of preventive medicine at Northwestern University, Chicago. “Relative increases were also greater in younger compared with older adults, although the absolute number of deaths in younger adults was less.”

The researchers observed that age-adjusted mortality increased across blacks and whites in both age groups, with a more pronounced increase among black and white men. Black men had the highest age-adjusted mortality among persons aged 35-64 (6.5 per 100,000 persons, compared with 4.2 among white men, 2.8 in black women, and 1.6 in white women 1.6 per 100,000). At the same time, white men had the highest age-adjusted mortality rate among those aged 65-84 years (112.5 per 100,000 persons, compared with 87.7 in black men, 77.4 in white women, and 61.3 in black women).

In an interview, one of the session’s moderators, Alvaro Alonso, MD, PhD, said that the study’s reliance on mortality data is a limitation. “You have to be careful with that, because it’s not the whole picture,” said Dr. Alonso, professor of epidemiology at the Rollins School of Public Health at Emory University, Atlanta. “It could be an underestimation of what is going on. The increase in recent years is probably due to a higher awareness of AFib as a risk factor for stroke; it’s more on the radar. Also, around 2009-2010, we started having new anticoagulants for AFib. It’s getting diagnosed more. When you look at coronary heart disease and stroke, there has been a decrease over time. In mortality and incidence of AFib, we don’t have that. That’s probably because we don’t know very much about what the risk factors for AFib are and how to prevent it.”

Dr. Tanaka said that the cause of increase in AFib-related CVD mortality can be classified into two major categories: a balance between case fatality of AFib and the prevalence of AFib. “The case fatality rate should have decreased over the last years,” he said at the meeting, which was sponsored by the American Heart Association. “In contrast, in the context of the aging of the population, the prevalence of AFib increased over the past years. Contributing factors include increasing awareness of AFib, a change in coding between ICD-9 and ICD-10, and a change in coding practices by physicians.”

Strengths of the study, he said, include its large sample size and the fact that the researchers were able to capture data from all death certificates filed in the United States. Limitations include the fact that the data “do not identify if changes in age-adjusted mortality rates are due to changing incidence or to case fatality rates,” he said. “CDC WONDER does not allow us to explore causes of these descriptive findings, but this would be an important next step.”

Dr. Tanaka reported having no financial disclosures.

[email protected]

SOURCE: Tanaka Y. EPI/Lifestyle 2020, Session 5, Abstract 15.

PHOENIX, ARIZ. – Cardiovascular deaths and death rates related to atrial fibrillation have risen since 1999, with significant acceleration following 2009, results from a cross-sectional analysis of national data show.

Doug Brunk/MDedge News

“AFib is the most common arrhythmia disorder in the United States and it is estimated that it will effect more than 12 million Americans by 2030,” Yoshihiro Tanaka, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “The predicted lifetime risk ranges from 25% to 35%, and AFib is associated with an increased risk for heart failure, stroke, and death.”

A recent review reported that declines in total heart disease mortality rates in the United States have plateaued since 2011 (JAMA 2019;322[8]:780-2). However, it is not well understood what factors such as AFib contribute to this rate of plateau. In an effort to quantify U.S. trends in AFib-related CVD death rates, Dr. Tanaka and colleagues conducted a serial cross-sectional analysis of death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER) database during 1999-2017.

Outcomes included age-adjusted mortality per 100,000 based on the 2000 U.S. standard population. The researchers also used joinpoint regression to calculate the average annual percentage change over time and conducted subgroup analyses by race and sex and across two age groups: 35-64 years and 65-84 years.

In all, 522,104 AFib-related CVD deaths were identified during 1999-2017. Dr. Tanaka reported that age-adjusted mortality increased from 16.0 per 100,000 persons in 1999 to 22.2 per 100,000 person in 2017, with an acceleration following an inflection point in 2009. Specifically, the average annual percentage change in AFib-related CVD deaths rose from 0.4% in 2009 to 3.5% in 2017 (P < .001). “These increases were consistent across all race-sex subgroups,” said Dr. Tanaka, of the department of preventive medicine at Northwestern University, Chicago. “Relative increases were also greater in younger compared with older adults, although the absolute number of deaths in younger adults was less.”

The researchers observed that age-adjusted mortality increased across blacks and whites in both age groups, with a more pronounced increase among black and white men. Black men had the highest age-adjusted mortality among persons aged 35-64 (6.5 per 100,000 persons, compared with 4.2 among white men, 2.8 in black women, and 1.6 in white women 1.6 per 100,000). At the same time, white men had the highest age-adjusted mortality rate among those aged 65-84 years (112.5 per 100,000 persons, compared with 87.7 in black men, 77.4 in white women, and 61.3 in black women).

In an interview, one of the session’s moderators, Alvaro Alonso, MD, PhD, said that the study’s reliance on mortality data is a limitation. “You have to be careful with that, because it’s not the whole picture,” said Dr. Alonso, professor of epidemiology at the Rollins School of Public Health at Emory University, Atlanta. “It could be an underestimation of what is going on. The increase in recent years is probably due to a higher awareness of AFib as a risk factor for stroke; it’s more on the radar. Also, around 2009-2010, we started having new anticoagulants for AFib. It’s getting diagnosed more. When you look at coronary heart disease and stroke, there has been a decrease over time. In mortality and incidence of AFib, we don’t have that. That’s probably because we don’t know very much about what the risk factors for AFib are and how to prevent it.”

Dr. Tanaka said that the cause of increase in AFib-related CVD mortality can be classified into two major categories: a balance between case fatality of AFib and the prevalence of AFib. “The case fatality rate should have decreased over the last years,” he said at the meeting, which was sponsored by the American Heart Association. “In contrast, in the context of the aging of the population, the prevalence of AFib increased over the past years. Contributing factors include increasing awareness of AFib, a change in coding between ICD-9 and ICD-10, and a change in coding practices by physicians.”

Strengths of the study, he said, include its large sample size and the fact that the researchers were able to capture data from all death certificates filed in the United States. Limitations include the fact that the data “do not identify if changes in age-adjusted mortality rates are due to changing incidence or to case fatality rates,” he said. “CDC WONDER does not allow us to explore causes of these descriptive findings, but this would be an important next step.”

Dr. Tanaka reported having no financial disclosures.

[email protected]

SOURCE: Tanaka Y. EPI/Lifestyle 2020, Session 5, Abstract 15.

PHOENIX, ARIZ. – Cardiovascular deaths and death rates related to atrial fibrillation have risen since 1999, with significant acceleration following 2009, results from a cross-sectional analysis of national data show.

Doug Brunk/MDedge News

“AFib is the most common arrhythmia disorder in the United States and it is estimated that it will effect more than 12 million Americans by 2030,” Yoshihiro Tanaka, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting. “The predicted lifetime risk ranges from 25% to 35%, and AFib is associated with an increased risk for heart failure, stroke, and death.”

A recent review reported that declines in total heart disease mortality rates in the United States have plateaued since 2011 (JAMA 2019;322[8]:780-2). However, it is not well understood what factors such as AFib contribute to this rate of plateau. In an effort to quantify U.S. trends in AFib-related CVD death rates, Dr. Tanaka and colleagues conducted a serial cross-sectional analysis of death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (WONDER) database during 1999-2017.

Outcomes included age-adjusted mortality per 100,000 based on the 2000 U.S. standard population. The researchers also used joinpoint regression to calculate the average annual percentage change over time and conducted subgroup analyses by race and sex and across two age groups: 35-64 years and 65-84 years.

In all, 522,104 AFib-related CVD deaths were identified during 1999-2017. Dr. Tanaka reported that age-adjusted mortality increased from 16.0 per 100,000 persons in 1999 to 22.2 per 100,000 person in 2017, with an acceleration following an inflection point in 2009. Specifically, the average annual percentage change in AFib-related CVD deaths rose from 0.4% in 2009 to 3.5% in 2017 (P < .001). “These increases were consistent across all race-sex subgroups,” said Dr. Tanaka, of the department of preventive medicine at Northwestern University, Chicago. “Relative increases were also greater in younger compared with older adults, although the absolute number of deaths in younger adults was less.”

The researchers observed that age-adjusted mortality increased across blacks and whites in both age groups, with a more pronounced increase among black and white men. Black men had the highest age-adjusted mortality among persons aged 35-64 (6.5 per 100,000 persons, compared with 4.2 among white men, 2.8 in black women, and 1.6 in white women 1.6 per 100,000). At the same time, white men had the highest age-adjusted mortality rate among those aged 65-84 years (112.5 per 100,000 persons, compared with 87.7 in black men, 77.4 in white women, and 61.3 in black women).

In an interview, one of the session’s moderators, Alvaro Alonso, MD, PhD, said that the study’s reliance on mortality data is a limitation. “You have to be careful with that, because it’s not the whole picture,” said Dr. Alonso, professor of epidemiology at the Rollins School of Public Health at Emory University, Atlanta. “It could be an underestimation of what is going on. The increase in recent years is probably due to a higher awareness of AFib as a risk factor for stroke; it’s more on the radar. Also, around 2009-2010, we started having new anticoagulants for AFib. It’s getting diagnosed more. When you look at coronary heart disease and stroke, there has been a decrease over time. In mortality and incidence of AFib, we don’t have that. That’s probably because we don’t know very much about what the risk factors for AFib are and how to prevent it.”

Dr. Tanaka said that the cause of increase in AFib-related CVD mortality can be classified into two major categories: a balance between case fatality of AFib and the prevalence of AFib. “The case fatality rate should have decreased over the last years,” he said at the meeting, which was sponsored by the American Heart Association. “In contrast, in the context of the aging of the population, the prevalence of AFib increased over the past years. Contributing factors include increasing awareness of AFib, a change in coding between ICD-9 and ICD-10, and a change in coding practices by physicians.”

Strengths of the study, he said, include its large sample size and the fact that the researchers were able to capture data from all death certificates filed in the United States. Limitations include the fact that the data “do not identify if changes in age-adjusted mortality rates are due to changing incidence or to case fatality rates,” he said. “CDC WONDER does not allow us to explore causes of these descriptive findings, but this would be an important next step.”

Dr. Tanaka reported having no financial disclosures.

[email protected]

SOURCE: Tanaka Y. EPI/Lifestyle 2020, Session 5, Abstract 15.

Amid the growing SARS-CoV-2 pandemic, currently in its expansive growth phase in the United States, the American Gastroenterological Association (AGA), the American Association for the Study of Liver Diseases (AASLD), the American College of Gastroenterology (ACG), and the American Society for Gastrointestinal Endoscopy (ASGE) have jointly released “COVID-19 Clinical Insights for Our Community of Gastroenterologists and Gastroenterology Care Providers,” which can be found on the websites of the various societies.

“The purpose of this communication is to jointly provide you with up to date COVID-19 information in order to maintain the highest level of health and safety for our patients, staff, community, and ourselves,” according to the AGA website announcement.

In particular, the societies point out that there is recent evidence suggesting the potential for coronavirus transmission through droplets and perhaps fecal shedding, which pose potential risks in particular during endoscopy and colonoscopy procedures to other patients, endoscopy personnel, and practitioners.

Relevant clinical factors related to COVID-19 are discussed, including the fact that asymptomatic spread can occur during the prodromal phase (the mean incubation period is approximately 5 days, with a range of 0-14 days), with viral shedding greatest when symptoms begin.

Between 20% and 30% of patients with COVID-19 infection show abnormal liver enzymes. In addition, COVID-19 patients show drops in their leukocyte counts, and elevated white blood cell counts is a poor prognostic sign, according to the release.

The Centers for Disease Control and Prevention lists vulnerable populations at the greatest risk for more serious outcomes; these include the elderly and those with severe chronic health conditions, such as heart disease, lung disease, diabetes, decompensated cirrhosis, HIV with low CD4 counts, and immunosuppression (including liver and other solid organ transplant recipients), are at higher risk of developing more serious illness. In addition pregnancy may provide added risk.
 

Specific advice for the gastroenterology profession

The joint statement urges that practitioners strongly consider rescheduling elective nonurgent endoscopic procedures, although some nonurgent procedures are higher priority and may need to be performed, including cancer evaluations, prosthetic removals, and evaluation of significant symptoms. “Of note, the Surgeon General on 3/14/20 advised hospitals to postpone all elective surgeries,” the document states.

Patient concerns

In all cases, patients should be prescreened for high-risk exposure or symptoms. This includes asking about history of fever or respiratory symptoms, family members or close contacts with similar symptoms, any contact with a confirmed case of COVID-19, and recent travel to a high-risk area. “Avoid bringing patients (or their escorts) into the medical facility who are over age 65 or have one of the CDC recognized risks listed above,” the societies advise.

Check body temperature of the patient upon arrival at endoscopy unit or clinic, and keep all patients at an appropriate distance from each other (6 feet is recommended) throughout the entire time in the endoscopy unit.

“For COVID-19 positive patients, or those awaiting test results, isolation precautions should be taken with procedures performed in negative pressure rooms,” according to the statement.

In addition, use telemedicine where possible in elective cases, and consider phone follow-up after any procedures at 7 and 14 days to ask about new diagnosis of COVID-19 or development of its symptoms, .

Those patients who are on immunosuppressive drugs for inflammatory bowel disease and autoimmune hepatitis should continue taking their medications because the risk of disease flare outweighs the chance of contracting coronavirus, according to the document. In addition, these patients should be advised to follow CDC guidelines for at-risk groups by avoiding crowds and limiting travel.
 

Protection of practitioners

Key factors in ensuring practitioner safety and maintaining practice functionality are discussed by the joint document. In particular, appropriate personal protective equipment (PPE) should be worn by all members of the endoscopy team: gloves, mask, eye shield/goggles, face shields, and gown, but practitioners should also be aware of how to put on and take off PPE appropriately.

“Conservation of PPE is critical. Only essential personnel should be present in cases. Consider extended use or reuse of surgical masks and eye protection in accordance with hospital policies,” the document recommends.

“It is important to address our collective staff needs and institute policies that protect our workforce.” To that end, the document recommends that centers should strategically assign available personnel in order to minimize concomitant exposure of those with similar or unique skill sets. This includes the use of nonphysician practitioners and fellows that cannot participate in cases for screening and triaging patients, or performing virtual visits.

Coming at a time of pandemic, when gastrointestinal symptoms have been recognized as a more common symptom of COVID-19 than previously expected and liver damage has been noted as a potential repercussion of SARS-CoV-2 infection, these clinical insights provide a template for gastroenterologists and related professionals for dealing with their patients and keeping themselves safe under dramatically changed circumstances.

The partnered organizations, AASLD, ACG, AGA, and ASGE, are committed to providing updated COVID-19 information as appropriate. However: “Given the evolving and fluid nature of the situation, institutions, hospitals and clinics have also been formulating their own local guidelines, so we urge you to follow the evolving CDC recommendations and your local requirements,” according to the AGA website announcement.

In addition to the joint communication, the society websites each offer additional COVID-19 information. The AGA practice updates on the COVID-19 webpage provides information about announcements, such as the cancellation of Digestive Disease Week^® in May, a location for AGA members to discuss their COVID-19 experiences and share advice, and links to the CDC COVID-19 updates.
 

[email protected]

SOURCE: American Gastroenterological Association et al. March 2020, COVID-19 Clinical Insights for Our Community of Gastroenterologists and Gastroenterology Care Providers.

Amid the growing SARS-CoV-2 pandemic, currently in its expansive growth phase in the United States, the American Gastroenterological Association (AGA), the American Association for the Study of Liver Diseases (AASLD), the American College of Gastroenterology (ACG), and the American Society for Gastrointestinal Endoscopy (ASGE) have jointly released “COVID-19 Clinical Insights for Our Community of Gastroenterologists and Gastroenterology Care Providers,” which can be found on the websites of the various societies.

“The purpose of this communication is to jointly provide you with up to date COVID-19 information in order to maintain the highest level of health and safety for our patients, staff, community, and ourselves,” according to the AGA website announcement.

In particular, the societies point out that there is recent evidence suggesting the potential for coronavirus transmission through droplets and perhaps fecal shedding, which pose potential risks in particular during endoscopy and colonoscopy procedures to other patients, endoscopy personnel, and practitioners.

Relevant clinical factors related to COVID-19 are discussed, including the fact that asymptomatic spread can occur during the prodromal phase (the mean incubation period is approximately 5 days, with a range of 0-14 days), with viral shedding greatest when symptoms begin.

Between 20% and 30% of patients with COVID-19 infection show abnormal liver enzymes. In addition, COVID-19 patients show drops in their leukocyte counts, and elevated white blood cell counts is a poor prognostic sign, according to the release.

The Centers for Disease Control and Prevention lists vulnerable populations at the greatest risk for more serious outcomes; these include the elderly and those with severe chronic health conditions, such as heart disease, lung disease, diabetes, decompensated cirrhosis, HIV with low CD4 counts, and immunosuppression (including liver and other solid organ transplant recipients), are at higher risk of developing more serious illness. In addition pregnancy may provide added risk.
 

Specific advice for the gastroenterology profession

The joint statement urges that practitioners strongly consider rescheduling elective nonurgent endoscopic procedures, although some nonurgent procedures are higher priority and may need to be performed, including cancer evaluations, prosthetic removals, and evaluation of significant symptoms. “Of note, the Surgeon General on 3/14/20 advised hospitals to postpone all elective surgeries,” the document states.

Patient concerns

In all cases, patients should be prescreened for high-risk exposure or symptoms. This includes asking about history of fever or respiratory symptoms, family members or close contacts with similar symptoms, any contact with a confirmed case of COVID-19, and recent travel to a high-risk area. “Avoid bringing patients (or their escorts) into the medical facility who are over age 65 or have one of the CDC recognized risks listed above,” the societies advise.

Check body temperature of the patient upon arrival at endoscopy unit or clinic, and keep all patients at an appropriate distance from each other (6 feet is recommended) throughout the entire time in the endoscopy unit.

“For COVID-19 positive patients, or those awaiting test results, isolation precautions should be taken with procedures performed in negative pressure rooms,” according to the statement.

In addition, use telemedicine where possible in elective cases, and consider phone follow-up after any procedures at 7 and 14 days to ask about new diagnosis of COVID-19 or development of its symptoms, .

Those patients who are on immunosuppressive drugs for inflammatory bowel disease and autoimmune hepatitis should continue taking their medications because the risk of disease flare outweighs the chance of contracting coronavirus, according to the document. In addition, these patients should be advised to follow CDC guidelines for at-risk groups by avoiding crowds and limiting travel.
 

Protection of practitioners

Key factors in ensuring practitioner safety and maintaining practice functionality are discussed by the joint document. In particular, appropriate personal protective equipment (PPE) should be worn by all members of the endoscopy team: gloves, mask, eye shield/goggles, face shields, and gown, but practitioners should also be aware of how to put on and take off PPE appropriately.

“Conservation of PPE is critical. Only essential personnel should be present in cases. Consider extended use or reuse of surgical masks and eye protection in accordance with hospital policies,” the document recommends.

“It is important to address our collective staff needs and institute policies that protect our workforce.” To that end, the document recommends that centers should strategically assign available personnel in order to minimize concomitant exposure of those with similar or unique skill sets. This includes the use of nonphysician practitioners and fellows that cannot participate in cases for screening and triaging patients, or performing virtual visits.

Coming at a time of pandemic, when gastrointestinal symptoms have been recognized as a more common symptom of COVID-19 than previously expected and liver damage has been noted as a potential repercussion of SARS-CoV-2 infection, these clinical insights provide a template for gastroenterologists and related professionals for dealing with their patients and keeping themselves safe under dramatically changed circumstances.

The partnered organizations, AASLD, ACG, AGA, and ASGE, are committed to providing updated COVID-19 information as appropriate. However: “Given the evolving and fluid nature of the situation, institutions, hospitals and clinics have also been formulating their own local guidelines, so we urge you to follow the evolving CDC recommendations and your local requirements,” according to the AGA website announcement.

In addition to the joint communication, the society websites each offer additional COVID-19 information. The AGA practice updates on the COVID-19 webpage provides information about announcements, such as the cancellation of Digestive Disease Week^® in May, a location for AGA members to discuss their COVID-19 experiences and share advice, and links to the CDC COVID-19 updates.
 

[email protected]

SOURCE: American Gastroenterological Association et al. March 2020, COVID-19 Clinical Insights for Our Community of Gastroenterologists and Gastroenterology Care Providers.

Amid the growing SARS-CoV-2 pandemic, currently in its expansive growth phase in the United States, the American Gastroenterological Association (AGA), the American Association for the Study of Liver Diseases (AASLD), the American College of Gastroenterology (ACG), and the American Society for Gastrointestinal Endoscopy (ASGE) have jointly released “COVID-19 Clinical Insights for Our Community of Gastroenterologists and Gastroenterology Care Providers,” which can be found on the websites of the various societies.

“The purpose of this communication is to jointly provide you with up to date COVID-19 information in order to maintain the highest level of health and safety for our patients, staff, community, and ourselves,” according to the AGA website announcement.

In particular, the societies point out that there is recent evidence suggesting the potential for coronavirus transmission through droplets and perhaps fecal shedding, which pose potential risks in particular during endoscopy and colonoscopy procedures to other patients, endoscopy personnel, and practitioners.

Relevant clinical factors related to COVID-19 are discussed, including the fact that asymptomatic spread can occur during the prodromal phase (the mean incubation period is approximately 5 days, with a range of 0-14 days), with viral shedding greatest when symptoms begin.

Between 20% and 30% of patients with COVID-19 infection show abnormal liver enzymes. In addition, COVID-19 patients show drops in their leukocyte counts, and elevated white blood cell counts is a poor prognostic sign, according to the release.

The Centers for Disease Control and Prevention lists vulnerable populations at the greatest risk for more serious outcomes; these include the elderly and those with severe chronic health conditions, such as heart disease, lung disease, diabetes, decompensated cirrhosis, HIV with low CD4 counts, and immunosuppression (including liver and other solid organ transplant recipients), are at higher risk of developing more serious illness. In addition pregnancy may provide added risk.
 

Specific advice for the gastroenterology profession

The joint statement urges that practitioners strongly consider rescheduling elective nonurgent endoscopic procedures, although some nonurgent procedures are higher priority and may need to be performed, including cancer evaluations, prosthetic removals, and evaluation of significant symptoms. “Of note, the Surgeon General on 3/14/20 advised hospitals to postpone all elective surgeries,” the document states.

Patient concerns

In all cases, patients should be prescreened for high-risk exposure or symptoms. This includes asking about history of fever or respiratory symptoms, family members or close contacts with similar symptoms, any contact with a confirmed case of COVID-19, and recent travel to a high-risk area. “Avoid bringing patients (or their escorts) into the medical facility who are over age 65 or have one of the CDC recognized risks listed above,” the societies advise.

Check body temperature of the patient upon arrival at endoscopy unit or clinic, and keep all patients at an appropriate distance from each other (6 feet is recommended) throughout the entire time in the endoscopy unit.

“For COVID-19 positive patients, or those awaiting test results, isolation precautions should be taken with procedures performed in negative pressure rooms,” according to the statement.

In addition, use telemedicine where possible in elective cases, and consider phone follow-up after any procedures at 7 and 14 days to ask about new diagnosis of COVID-19 or development of its symptoms, .

Those patients who are on immunosuppressive drugs for inflammatory bowel disease and autoimmune hepatitis should continue taking their medications because the risk of disease flare outweighs the chance of contracting coronavirus, according to the document. In addition, these patients should be advised to follow CDC guidelines for at-risk groups by avoiding crowds and limiting travel.
 

Protection of practitioners

Key factors in ensuring practitioner safety and maintaining practice functionality are discussed by the joint document. In particular, appropriate personal protective equipment (PPE) should be worn by all members of the endoscopy team: gloves, mask, eye shield/goggles, face shields, and gown, but practitioners should also be aware of how to put on and take off PPE appropriately.

“Conservation of PPE is critical. Only essential personnel should be present in cases. Consider extended use or reuse of surgical masks and eye protection in accordance with hospital policies,” the document recommends.

“It is important to address our collective staff needs and institute policies that protect our workforce.” To that end, the document recommends that centers should strategically assign available personnel in order to minimize concomitant exposure of those with similar or unique skill sets. This includes the use of nonphysician practitioners and fellows that cannot participate in cases for screening and triaging patients, or performing virtual visits.

Coming at a time of pandemic, when gastrointestinal symptoms have been recognized as a more common symptom of COVID-19 than previously expected and liver damage has been noted as a potential repercussion of SARS-CoV-2 infection, these clinical insights provide a template for gastroenterologists and related professionals for dealing with their patients and keeping themselves safe under dramatically changed circumstances.

The partnered organizations, AASLD, ACG, AGA, and ASGE, are committed to providing updated COVID-19 information as appropriate. However: “Given the evolving and fluid nature of the situation, institutions, hospitals and clinics have also been formulating their own local guidelines, so we urge you to follow the evolving CDC recommendations and your local requirements,” according to the AGA website announcement.

In addition to the joint communication, the society websites each offer additional COVID-19 information. The AGA practice updates on the COVID-19 webpage provides information about announcements, such as the cancellation of Digestive Disease Week^® in May, a location for AGA members to discuss their COVID-19 experiences and share advice, and links to the CDC COVID-19 updates.
 

[email protected]

SOURCE: American Gastroenterological Association et al. March 2020, COVID-19 Clinical Insights for Our Community of Gastroenterologists and Gastroenterology Care Providers.

Patients with COVID-19 may be at risk for liver injury, but mechanisms of damage remain unclear, according to investigators.

Proposed mechanisms include direct virus-induced effects, immune-induced damage due to excessive inflammatory responses, and drug-induced injury, reported lead author Ling Xu of Huazhong University of Science and Technology, Wuhan, China, and colleagues.

“From a clinical perspective, in addition to actively dealing with the primary disease caused by coronavirus infection, attention should also be paid to monitor the occurrence of liver injury, and to the application of drugs which may induce liver damage,” the investigators wrote in Liver International. “Patients with liver damage are advised to be treated with drugs that could both protect liver functions and inhibit inflammatory responses, such as ammonium glycyrrhizinate, which may, in turn, accelerate the process of disease recovery.”

The review of liver injury associated with major pathogenic coronaviruses included severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emergent SARS-CoV-2, which causes COVID-19.

In cases of COVID-19, reported incidence of liver injury ranges from 15% to 53%, based on elevations of alanine transaminase (ALT) and aspartate aminotransferase (AST), along with slightly elevated bilirubin levels. In severe cases, albumin decreases have also been documented.

Liver injury appears to be significantly more common among those with severe infection. In one cohort of 82 patients who died from COVID-19, the incidence of liver injury was 78%, while another study of 36 nonsurvivors reported a rate of 58%.

According to the investigators, both bile duct epithelial cells and liver cells express angiotensin converting enzyme II (ACE2), which is an entry receptor for SARS-CoV-2; however, expression of ACE2 in bile duct cells is “much higher” than in liver cells, and comparable with alveolar type 2 cells in the lungs.

“Bile duct epithelial cells are known to play important roles in liver regeneration and immune response,” the investigators noted.

Beyond direct- and immune-induced effects of COVID-19, postmortem findings suggest that drug-induced liver injury may also be a possibility, with a number of theoretical culprits, including antibiotics, steroids, and antivirals. Although the investigators emphasized that data are insufficient to pinpoint an exact agent, they highlighted a recent preprint study, which reported a significantly higher rate of lopinavir/ritonavir administration among patients with abnormal liver function, compared with those who had normal liver function (56.1% vs. 25%; P = .009).

“Drug-induced liver injury during the treatment of coronavirus infection should not be ignored and needs to be carefully investigated,” the investigators concluded.

Fundamental Research Funds for the Central Universities supported the work. The investigators reported no conflicts of interest.

SOURCE: Xu L et al. Liver Int. 2020 Mar 14. doi: 10.1111/liv.14435.

Patients with COVID-19 may be at risk for liver injury, but mechanisms of damage remain unclear, according to investigators.

Proposed mechanisms include direct virus-induced effects, immune-induced damage due to excessive inflammatory responses, and drug-induced injury, reported lead author Ling Xu of Huazhong University of Science and Technology, Wuhan, China, and colleagues.

“From a clinical perspective, in addition to actively dealing with the primary disease caused by coronavirus infection, attention should also be paid to monitor the occurrence of liver injury, and to the application of drugs which may induce liver damage,” the investigators wrote in Liver International. “Patients with liver damage are advised to be treated with drugs that could both protect liver functions and inhibit inflammatory responses, such as ammonium glycyrrhizinate, which may, in turn, accelerate the process of disease recovery.”

The review of liver injury associated with major pathogenic coronaviruses included severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emergent SARS-CoV-2, which causes COVID-19.

In cases of COVID-19, reported incidence of liver injury ranges from 15% to 53%, based on elevations of alanine transaminase (ALT) and aspartate aminotransferase (AST), along with slightly elevated bilirubin levels. In severe cases, albumin decreases have also been documented.

Liver injury appears to be significantly more common among those with severe infection. In one cohort of 82 patients who died from COVID-19, the incidence of liver injury was 78%, while another study of 36 nonsurvivors reported a rate of 58%.

According to the investigators, both bile duct epithelial cells and liver cells express angiotensin converting enzyme II (ACE2), which is an entry receptor for SARS-CoV-2; however, expression of ACE2 in bile duct cells is “much higher” than in liver cells, and comparable with alveolar type 2 cells in the lungs.

“Bile duct epithelial cells are known to play important roles in liver regeneration and immune response,” the investigators noted.

Beyond direct- and immune-induced effects of COVID-19, postmortem findings suggest that drug-induced liver injury may also be a possibility, with a number of theoretical culprits, including antibiotics, steroids, and antivirals. Although the investigators emphasized that data are insufficient to pinpoint an exact agent, they highlighted a recent preprint study, which reported a significantly higher rate of lopinavir/ritonavir administration among patients with abnormal liver function, compared with those who had normal liver function (56.1% vs. 25%; P = .009).

“Drug-induced liver injury during the treatment of coronavirus infection should not be ignored and needs to be carefully investigated,” the investigators concluded.

Fundamental Research Funds for the Central Universities supported the work. The investigators reported no conflicts of interest.

SOURCE: Xu L et al. Liver Int. 2020 Mar 14. doi: 10.1111/liv.14435.

Patients with COVID-19 may be at risk for liver injury, but mechanisms of damage remain unclear, according to investigators.

Proposed mechanisms include direct virus-induced effects, immune-induced damage due to excessive inflammatory responses, and drug-induced injury, reported lead author Ling Xu of Huazhong University of Science and Technology, Wuhan, China, and colleagues.

“From a clinical perspective, in addition to actively dealing with the primary disease caused by coronavirus infection, attention should also be paid to monitor the occurrence of liver injury, and to the application of drugs which may induce liver damage,” the investigators wrote in Liver International. “Patients with liver damage are advised to be treated with drugs that could both protect liver functions and inhibit inflammatory responses, such as ammonium glycyrrhizinate, which may, in turn, accelerate the process of disease recovery.”

The review of liver injury associated with major pathogenic coronaviruses included severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emergent SARS-CoV-2, which causes COVID-19.

In cases of COVID-19, reported incidence of liver injury ranges from 15% to 53%, based on elevations of alanine transaminase (ALT) and aspartate aminotransferase (AST), along with slightly elevated bilirubin levels. In severe cases, albumin decreases have also been documented.

Liver injury appears to be significantly more common among those with severe infection. In one cohort of 82 patients who died from COVID-19, the incidence of liver injury was 78%, while another study of 36 nonsurvivors reported a rate of 58%.

According to the investigators, both bile duct epithelial cells and liver cells express angiotensin converting enzyme II (ACE2), which is an entry receptor for SARS-CoV-2; however, expression of ACE2 in bile duct cells is “much higher” than in liver cells, and comparable with alveolar type 2 cells in the lungs.

“Bile duct epithelial cells are known to play important roles in liver regeneration and immune response,” the investigators noted.

Beyond direct- and immune-induced effects of COVID-19, postmortem findings suggest that drug-induced liver injury may also be a possibility, with a number of theoretical culprits, including antibiotics, steroids, and antivirals. Although the investigators emphasized that data are insufficient to pinpoint an exact agent, they highlighted a recent preprint study, which reported a significantly higher rate of lopinavir/ritonavir administration among patients with abnormal liver function, compared with those who had normal liver function (56.1% vs. 25%; P = .009).

“Drug-induced liver injury during the treatment of coronavirus infection should not be ignored and needs to be carefully investigated,” the investigators concluded.

Fundamental Research Funds for the Central Universities supported the work. The investigators reported no conflicts of interest.

SOURCE: Xu L et al. Liver Int. 2020 Mar 14. doi: 10.1111/liv.14435.

Combination apatinib and vinorelbine “may have potential” for treating patients with wild-type, advanced non–small cell lung cancer (NSCLC) who failed at least two prior lines of chemotherapy, according to researchers.

In a phase 2 trial, apatinib plus vinorelbine produced an overall response rate of 36.7% and a disease control rate of 76.7%. Nearly half of patients required dose reductions, and 17% discontinued treatment due to adverse events.

Xiangyu Zhang, MD, of Hunan Cancer Hospital in Changsha, China, and colleagues conducted this trial (NCT03652857) and detailed the results in JAMA Network Open.

The researchers noted that there is no standard treatment strategy for patients who have advanced NSCLC without actionable mutations and have failed two or more lines of chemotherapy. So the team tested apatinib plus vinorelbine in 30 such patients.

The patients’ median age was 63 years (range, 34-78 years), 60% were men, and 90% had stage IV disease. They had received a median of 2 (range, 2-5) prior lines of chemotherapy.

In this study, patients received apatinib at 500 mg once daily and vinorelbine at 60 mg/m² once weekly. The dose of apatinib could be interrupted or reduced to manage adverse events. Patients could receive 250 mg or 500 mg on alternate days or 250 mg once daily. Patients were treated until they progressed, withdrew, or had unacceptable adverse events.
 

Results

Patients were treated for a median of 4 months (range, 1-22 months), and the median follow-up was 11 months (range, 4.5-14.1 months). Most patients (n = 25) continued treatment until they progressed, 17 were able to remain on the 500-mg dose of apatinib, 13 received the 250-mg dose of apatinib, and 5 patients discontinued treatment due to adverse events.

The overall response rate was 36.7%, and the disease control rate, defined as the proportion of patients with complete response, partial response, and stable disease, was 76.7%. There were no complete responses, 11 partial responses, 12 patients with stable disease, and 7 patients who progressed. Rates of response, disease control, and progression were similar whether patients received the 500-mg dose of apatinib or the 250-mg dose.

The median progression-free survival was 4.5 months, and the median overall survival was 10 months.

Hand-foot syndrome was the most common adverse event, with grade 1-2 hand-foot syndrome occurring in 13 patients (43%), grade 3 occurring in 5 patients (17%), and grade 4 occurring in 1 patient (3%).

The adverse events that led to treatment discontinuation were grade 3 weakness (n = 1), pleural effusion (n = 1), fungal infection (n = 1), and grade 3 hand-foot syndrome (n = 2). There were no fatal adverse events.

“[The] combination of apatinib and oral vinorelbine has promising efficacy and manageable toxic effects as a third-line or subsequent-line treatment in patients with driver variation-negative advanced NCSLC,” the researchers concluded. “Further evaluation of this combination in phase 3 trials is warranted.”

The current study was funded by grants from the National Natural Science Foundation of China and the Hunan Natural Science Foundation. The researchers disclosed no conflicts of interest.

[email protected]

SOURCE: Zhang X et al. JAMA Netw Open. 2020;3(3):e201226. doi: 10.1001/jamanetworkopen.2020.12.

Combination apatinib and vinorelbine “may have potential” for treating patients with wild-type, advanced non–small cell lung cancer (NSCLC) who failed at least two prior lines of chemotherapy, according to researchers.

In a phase 2 trial, apatinib plus vinorelbine produced an overall response rate of 36.7% and a disease control rate of 76.7%. Nearly half of patients required dose reductions, and 17% discontinued treatment due to adverse events.

Xiangyu Zhang, MD, of Hunan Cancer Hospital in Changsha, China, and colleagues conducted this trial (NCT03652857) and detailed the results in JAMA Network Open.

The researchers noted that there is no standard treatment strategy for patients who have advanced NSCLC without actionable mutations and have failed two or more lines of chemotherapy. So the team tested apatinib plus vinorelbine in 30 such patients.

The patients’ median age was 63 years (range, 34-78 years), 60% were men, and 90% had stage IV disease. They had received a median of 2 (range, 2-5) prior lines of chemotherapy.

In this study, patients received apatinib at 500 mg once daily and vinorelbine at 60 mg/m² once weekly. The dose of apatinib could be interrupted or reduced to manage adverse events. Patients could receive 250 mg or 500 mg on alternate days or 250 mg once daily. Patients were treated until they progressed, withdrew, or had unacceptable adverse events.
 

Results

Patients were treated for a median of 4 months (range, 1-22 months), and the median follow-up was 11 months (range, 4.5-14.1 months). Most patients (n = 25) continued treatment until they progressed, 17 were able to remain on the 500-mg dose of apatinib, 13 received the 250-mg dose of apatinib, and 5 patients discontinued treatment due to adverse events.

The overall response rate was 36.7%, and the disease control rate, defined as the proportion of patients with complete response, partial response, and stable disease, was 76.7%. There were no complete responses, 11 partial responses, 12 patients with stable disease, and 7 patients who progressed. Rates of response, disease control, and progression were similar whether patients received the 500-mg dose of apatinib or the 250-mg dose.

The median progression-free survival was 4.5 months, and the median overall survival was 10 months.

Hand-foot syndrome was the most common adverse event, with grade 1-2 hand-foot syndrome occurring in 13 patients (43%), grade 3 occurring in 5 patients (17%), and grade 4 occurring in 1 patient (3%).

The adverse events that led to treatment discontinuation were grade 3 weakness (n = 1), pleural effusion (n = 1), fungal infection (n = 1), and grade 3 hand-foot syndrome (n = 2). There were no fatal adverse events.

“[The] combination of apatinib and oral vinorelbine has promising efficacy and manageable toxic effects as a third-line or subsequent-line treatment in patients with driver variation-negative advanced NCSLC,” the researchers concluded. “Further evaluation of this combination in phase 3 trials is warranted.”

The current study was funded by grants from the National Natural Science Foundation of China and the Hunan Natural Science Foundation. The researchers disclosed no conflicts of interest.

[email protected]

SOURCE: Zhang X et al. JAMA Netw Open. 2020;3(3):e201226. doi: 10.1001/jamanetworkopen.2020.12.

Combination apatinib and vinorelbine “may have potential” for treating patients with wild-type, advanced non–small cell lung cancer (NSCLC) who failed at least two prior lines of chemotherapy, according to researchers.

In a phase 2 trial, apatinib plus vinorelbine produced an overall response rate of 36.7% and a disease control rate of 76.7%. Nearly half of patients required dose reductions, and 17% discontinued treatment due to adverse events.

Xiangyu Zhang, MD, of Hunan Cancer Hospital in Changsha, China, and colleagues conducted this trial (NCT03652857) and detailed the results in JAMA Network Open.

The researchers noted that there is no standard treatment strategy for patients who have advanced NSCLC without actionable mutations and have failed two or more lines of chemotherapy. So the team tested apatinib plus vinorelbine in 30 such patients.

The patients’ median age was 63 years (range, 34-78 years), 60% were men, and 90% had stage IV disease. They had received a median of 2 (range, 2-5) prior lines of chemotherapy.

In this study, patients received apatinib at 500 mg once daily and vinorelbine at 60 mg/m² once weekly. The dose of apatinib could be interrupted or reduced to manage adverse events. Patients could receive 250 mg or 500 mg on alternate days or 250 mg once daily. Patients were treated until they progressed, withdrew, or had unacceptable adverse events.
 

Results

Patients were treated for a median of 4 months (range, 1-22 months), and the median follow-up was 11 months (range, 4.5-14.1 months). Most patients (n = 25) continued treatment until they progressed, 17 were able to remain on the 500-mg dose of apatinib, 13 received the 250-mg dose of apatinib, and 5 patients discontinued treatment due to adverse events.

The overall response rate was 36.7%, and the disease control rate, defined as the proportion of patients with complete response, partial response, and stable disease, was 76.7%. There were no complete responses, 11 partial responses, 12 patients with stable disease, and 7 patients who progressed. Rates of response, disease control, and progression were similar whether patients received the 500-mg dose of apatinib or the 250-mg dose.

The median progression-free survival was 4.5 months, and the median overall survival was 10 months.

Hand-foot syndrome was the most common adverse event, with grade 1-2 hand-foot syndrome occurring in 13 patients (43%), grade 3 occurring in 5 patients (17%), and grade 4 occurring in 1 patient (3%).

The adverse events that led to treatment discontinuation were grade 3 weakness (n = 1), pleural effusion (n = 1), fungal infection (n = 1), and grade 3 hand-foot syndrome (n = 2). There were no fatal adverse events.

“[The] combination of apatinib and oral vinorelbine has promising efficacy and manageable toxic effects as a third-line or subsequent-line treatment in patients with driver variation-negative advanced NCSLC,” the researchers concluded. “Further evaluation of this combination in phase 3 trials is warranted.”

The current study was funded by grants from the National Natural Science Foundation of China and the Hunan Natural Science Foundation. The researchers disclosed no conflicts of interest.

[email protected]

SOURCE: Zhang X et al. JAMA Netw Open. 2020;3(3):e201226. doi: 10.1001/jamanetworkopen.2020.12.

In a JAMA Live Stream interview, Anthony S. Fauci, MD, a key member of the White House Coronavirus Task Force, urged resolve, rather than panic, as the coronavirus pandemic takes hold in the United States.

Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.

The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.

“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”

He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”

Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
 

Stress test on the health care system

Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.

In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”

The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.

Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
 

Returning to work after COVID-19 infection

Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.

“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.

Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
 

Higher risk reported in cardiac patients

Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.

Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.

He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
 

Potential therapies

Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.

Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”

[email protected]

In a JAMA Live Stream interview, Anthony S. Fauci, MD, a key member of the White House Coronavirus Task Force, urged resolve, rather than panic, as the coronavirus pandemic takes hold in the United States.

Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.

The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.

“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”

He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”

Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
 

Stress test on the health care system

Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.

In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”

The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.

Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
 

Returning to work after COVID-19 infection

Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.

“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.

Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
 

Higher risk reported in cardiac patients

Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.

Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.

He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
 

Potential therapies

Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.

Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”

[email protected]

In a JAMA Live Stream interview, Anthony S. Fauci, MD, a key member of the White House Coronavirus Task Force, urged resolve, rather than panic, as the coronavirus pandemic takes hold in the United States.

Dr. Fauci got into the details of what is known, what is unknown, what is being done in laboratories, and what clinical elements are still not understood about this disease.

The next several weeks, he said, are likely to tell the tale of whether our health care system is up to the challenge of care for the most ill among those who will be affected by COVID-19.

“It shouldn’t panic or frighten us, but we have to know we’re dealing with a very serious problem that we have to address, and we have to deal with it in a very bold way,” said Dr. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.

Speaking in an interview with JAMA Editor in Chief Howard Bauchner, MD, Dr. Fauci said the situation favors action over fear. “Let’s apply that energy to doing the things that we know can mitigate this.”

He added that he heard the message loud and clear from health care leaders in Italy and France during a World Health Organization coronavirus call earlier in the day. Officials in those countries, he said, were “almost pleading with the rest of the world to please take this very seriously, because it happens all of a sudden – very abruptly. ... The best time to mitigate is before that happens, because if you wait until after it happens you’re playing catch-up.”

Dr. Bauchner, noting that strict social distancing has been underway in many parts of the United States for several days, posited that, by early April, “We’ll really have a sense if we can manage in terms of serious illness.” Seattle, New York, Boston, and the San Francisco Bay Area may experience demand that outstrips ICU capacity at that point, but the rest of the country, he said, “is doing relatively well.”
 

Stress test on the health care system

Dr. Fauci agreed with this statement and added: “We’re going to know – for better or worse – whether we have enough of what it takes to be able to practice the kind of medicine that we optimally would want to practice.

In the matter of a week or 2 ... I think we’ll get a feel for whether or not we really have enough of the supplies that it takes.”

The well-publicized regional shortages in personal protective equipment (PPE) are forcing tough choices in some areas. As expedited – and even drive-through – testing begins, some of the demand for testing-related PPE may abate, especially if protocols include self-administration of nasal swabs, he noted.

Dr. Fauci added that the strategic national stockpile of medical supplies and equipment has not yet been tapped, “but you need to backfill that as quickly as you can once you start drawing from the strategic national stockpile.”
 

Returning to work after COVID-19 infection

Regarding the thorny question of when health care workers should be permitted to return to work after coronavirus infection, “it’s an evolving story,” said Dr. Fauci. Current guidance advises that health care providers stay away from work until two negative tests after resolution of fever and improvement of respiratory symptoms, or 3 fever-free days.

“We are approaching a point where you’re going to get enough people who are getting infected that we aren’t going to be able to do that,” he said. Depending on the stress to the health care system in a given locality, he said that facilities are going to have to “decide with good judgment” when health care workers go back on the job after coronavirus infection.

Asked how soon an individual would reliably test positive for COVID-19 after exposure, Dr. Fauci said, “We don’t know the answer to that. ... We can surmise it ...” He noted that it’s a median of about 5 days with a range of 2 to 14 days, before an infected individual becomes symptomatic. “I can say it’s not going to happen immediately,” he added, noting that he wouldn’t expect to see a positive test until about 2 days after exposure at the earliest. “When you get to the point where you are symptomatic, you’re almost certainly going to be positive then. ... This is just an extrapolation,” rather than conclusions drawn from solid data, he emphasized.
 

Higher risk reported in cardiac patients

Dr. Bauchner, who was relaying questions sent in from physicians during the live-streamed interview, asked about a newly issued joint statement from the American Heart Association, American College of Cardiology, and the Heart Failure Society of America, which on March 17 affirmed that individuals on ACE inhibitors and angiotensin receptor blockers (ARBs) continue that therapy if they should become ill with COVID-19. The European Society of Cardiology issued a similar recommendation a few days prior.

Despite these societies’ statements, Dr. Fauci pointed to population-level data in Italy as suggesting that the case isn’t yet closed. “We really need to get data, and we need to get data fast. There’s a mechanistic rationale for the concern. It’s there, and it’s firm,” he said. The theoretical concern is that ACE inhibitors can upregulate expression of the ACE-2 protein on cell membranes, which is the entry point for SARS-Cov-2 to enter cells.

He added that he remains concerned about the number of coronavirus fatalities of patients in Italy who had hypertension as their only, or primary, underlying health problem.“That to me was a bit of a red flag,” he said. “Patients with hypertension almost certainly had a physician, and the physician almost certainly treated that person with medication. Why should someone who has hypertension that was well controlled have a much greater chance of dying?” he asked, noting that “I look at a person with well-controlled hypertension as a relatively healthy person. I don’t know what the answer is, but somebody has to look very carefully,” ideally by means of a natural history study that identifies medications used by those who died from coronavirus.
 

Potential therapies

Regarding potential therapies for COVID-19, Dr. Fauci acknowledged the social media buzz and flurry of medical letters and case reports about the use of hydroxychloroquine (Plaquenil) to treat active infection. He said that he and other researchers are “in active discussion” about how best to study the efficacy and safety of hydroxychloroquine, but he also acknowledged that many treating clinicians will use hydroxychloroquine empirically in the absence of other treatments with proven efficacy.

Clinical trials underway in China for antiviral medication are facing some enrollment challenges currently “because people want to get the drug,” said Dr. Fauci. “They don’t want to be in the trial; they just want to get the drug.” Though each of two trials has targeted approximately 500 participants as the number needed for sufficient statistical power, Dr. Fauci urged Chinese data safety monitoring boards to “take a close look” at the data already accrued for the several hundred patients who have already enrolled for the studies “to see if there’s any hint of efficacy.”

[email protected]

Clinical manifestations of COVID-19 infection among children in mainland China generally have been less severe than those among adults, but children of all ages – and infants in particular – are vulnerable to infection, according to a review of 2,143 cases.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Further, infection patterns in the nationwide series of all pediatric patients reported to the Chinese Center for Disease Control and Prevention from Jan. 16 to Feb. 8, 2020, provide strong evidence of human-to-human transmission, Yuanyuan Dong, MPH, a research assistant at Shanghai Children’s Medical Center, Shanghai Jiao Tong University, China, and colleagues reported in Pediatrics.

Of the 2,143 patients included in the review, 57% were boys and the median age was 7 years; 34% had laboratory-confirmed infection and 67% had suspected infection. More than 90% had asymptomatic, mild, or moderate disease (4%, 51%, and 39%, respectively), and 46% were from Hubei Province, where the first cases were reported, the investigators found.

The median time from illness onset to diagnosis was 2 days, and there was a trend of rapid increase of disease at the early stage of the epidemic – with rapid spread from Hubei Province to surrounding provinces – followed by a gradual and steady decrease, they noted.

“The total number of pediatric patients increased remarkably between mid-January and early February, peaked around February 1, and then declined since early February 2020,” they wrote. The proportion of severe and critical cases was 11% for infants under 1 year of age, compared with 7% for those aged 1-5 years; 4% for those aged 6-10 years; 4% for those 11-15 years; and 3% for those 16 years and older.

As of Feb. 8, 2020, only one child in this group of study patients died and most cases of COVID-19 symptoms were mild. There were many fewer severe and critical cases among the children (6%), compared with those reported in adult patients in other studies (19%). “It suggests that, compared with adult patients, clinical manifestations of children’s COVID-19 may be less severe,” the investigators suggested.

“As most of these children were likely to expose themselves to family members and/or other children with COVID-19, it clearly indicates person-to-person transmission ” of novel coronavirus 2019, they said, adding that similar evidence of such transmission also has been reported from studies of adult patients.

The reasons for reduced severity in children versus adults remain unclear, but may be related to both exposure and host factors, Ms. Dong and associates said. “Children were usually well cared for at home and might have relatively [fewer] opportunities to expose themselves to pathogens and/or sick patients.”

The findings demonstrate a pediatric distribution that varied across time and space, with most cases concentrated in the Hubei province and surrounding areas. No significant gender-related difference in infection rates was observed, and although the median patient age was 7 years, the range was 1 day to 18 years, suggesting that “all ages at childhood were susceptible” to the virus, they added.

The declining number of cases over time further suggests that disease control measures implemented by the government were effective, and that cases will “continue to decline, and finally stop in the near future unless sustained human-to-human transmissions occur,” Ms. Dong and associates concluded.

In an accompanying editorial, Andrea T. Cruz, MD, of Baylor College of Medicine, Houston, and Steven L. Zeichner, MD, PhD, of the University of Virginia, Charlottesville, said the findings regarding reduced severity among children versus adults with novel coronavirus 2019 infection are consistent with data on non-COVID-19 coronavirus.

They pointed out that Ms. Dong and associates did find that 13% of virologically-confirmed cases had asymptomatic infection, “a rate that almost certainly understates the true rate of asymptomatic infection, since many asymptomatic children are unlikely to be tested.”

Of the symptomatic children, “5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults) and 0.6% progressed to acute respiratory distress syndrome (ARDS) or multiorgan system dysfunction”; this also is at a lower rate than seen in adults, they said.

Very young children –infants or children in preschool – were more likely to have severe clinical manifestations than children who were older.

Thus, it appears that certain subpopulations of children are at increased risk for more significant COVID-19 illness: “younger age, underlying pulmonary pathology, and immunocompromising conditions,” Dr. Cruz and Dr. Zeichner suggested.

The two editorialists said the findings suggest children “may play a major role in community-based viral transmission.” Evidence suggests that children may have more upper respiratory tract involvement and that fecal shedding may occur for several weeks after diagnosis; this raises concerns about fecal-oral transmission, particularly for infants and children, and about viral replication in the gastrointestinal tract, they said. This has substantial implications for community spread in day care centers, schools, and in the home.

A great deal has been learned about COVID-19 in a short time, but there still is much to learn about the effect of the virus on children, the impact of children on viral spread, and about possible vertical transmission, they said.

“Widespread availability of testing will allow for us to more accurately describe the spectrum of illness and may result in adjustment of the apparent morbidity and mortality rate as fewer ill individuals are diagnosed,” Dr. Cruz and Dr. Zeichner wrote, adding that “rigorously gauging the impact of COVID-19 on children will be important to accurately model the pandemic and to ensure that appropriate resources are allocated to children requiring care.”

They noted that understanding differences in children versus adults with COVID-19 “can yield important insights into disease pathogenesis, informing management and the development of therapeutics.”

This study was partially supported by the Science and Technology Commission of Shanghai Municipality. The authors reported having no disclosures. Dr. Cruz and Dr. Zeichner are associate editors for Pediatrics. Dr. Cruz reported having no disclosures. Dr. Zeichner is an inventor of new technologies for the rapid production of vaccines, for which the University of Virginia has filed patent applications.

[email protected]

SOURCE: Dong Y et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0702; Cruz A and Zeichner S. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0834.

Clinical manifestations of COVID-19 infection among children in mainland China generally have been less severe than those among adults, but children of all ages – and infants in particular – are vulnerable to infection, according to a review of 2,143 cases.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Further, infection patterns in the nationwide series of all pediatric patients reported to the Chinese Center for Disease Control and Prevention from Jan. 16 to Feb. 8, 2020, provide strong evidence of human-to-human transmission, Yuanyuan Dong, MPH, a research assistant at Shanghai Children’s Medical Center, Shanghai Jiao Tong University, China, and colleagues reported in Pediatrics.

Of the 2,143 patients included in the review, 57% were boys and the median age was 7 years; 34% had laboratory-confirmed infection and 67% had suspected infection. More than 90% had asymptomatic, mild, or moderate disease (4%, 51%, and 39%, respectively), and 46% were from Hubei Province, where the first cases were reported, the investigators found.

The median time from illness onset to diagnosis was 2 days, and there was a trend of rapid increase of disease at the early stage of the epidemic – with rapid spread from Hubei Province to surrounding provinces – followed by a gradual and steady decrease, they noted.

“The total number of pediatric patients increased remarkably between mid-January and early February, peaked around February 1, and then declined since early February 2020,” they wrote. The proportion of severe and critical cases was 11% for infants under 1 year of age, compared with 7% for those aged 1-5 years; 4% for those aged 6-10 years; 4% for those 11-15 years; and 3% for those 16 years and older.

As of Feb. 8, 2020, only one child in this group of study patients died and most cases of COVID-19 symptoms were mild. There were many fewer severe and critical cases among the children (6%), compared with those reported in adult patients in other studies (19%). “It suggests that, compared with adult patients, clinical manifestations of children’s COVID-19 may be less severe,” the investigators suggested.

“As most of these children were likely to expose themselves to family members and/or other children with COVID-19, it clearly indicates person-to-person transmission ” of novel coronavirus 2019, they said, adding that similar evidence of such transmission also has been reported from studies of adult patients.

The reasons for reduced severity in children versus adults remain unclear, but may be related to both exposure and host factors, Ms. Dong and associates said. “Children were usually well cared for at home and might have relatively [fewer] opportunities to expose themselves to pathogens and/or sick patients.”

The findings demonstrate a pediatric distribution that varied across time and space, with most cases concentrated in the Hubei province and surrounding areas. No significant gender-related difference in infection rates was observed, and although the median patient age was 7 years, the range was 1 day to 18 years, suggesting that “all ages at childhood were susceptible” to the virus, they added.

The declining number of cases over time further suggests that disease control measures implemented by the government were effective, and that cases will “continue to decline, and finally stop in the near future unless sustained human-to-human transmissions occur,” Ms. Dong and associates concluded.

In an accompanying editorial, Andrea T. Cruz, MD, of Baylor College of Medicine, Houston, and Steven L. Zeichner, MD, PhD, of the University of Virginia, Charlottesville, said the findings regarding reduced severity among children versus adults with novel coronavirus 2019 infection are consistent with data on non-COVID-19 coronavirus.

They pointed out that Ms. Dong and associates did find that 13% of virologically-confirmed cases had asymptomatic infection, “a rate that almost certainly understates the true rate of asymptomatic infection, since many asymptomatic children are unlikely to be tested.”

Of the symptomatic children, “5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults) and 0.6% progressed to acute respiratory distress syndrome (ARDS) or multiorgan system dysfunction”; this also is at a lower rate than seen in adults, they said.

Very young children –infants or children in preschool – were more likely to have severe clinical manifestations than children who were older.

Thus, it appears that certain subpopulations of children are at increased risk for more significant COVID-19 illness: “younger age, underlying pulmonary pathology, and immunocompromising conditions,” Dr. Cruz and Dr. Zeichner suggested.

The two editorialists said the findings suggest children “may play a major role in community-based viral transmission.” Evidence suggests that children may have more upper respiratory tract involvement and that fecal shedding may occur for several weeks after diagnosis; this raises concerns about fecal-oral transmission, particularly for infants and children, and about viral replication in the gastrointestinal tract, they said. This has substantial implications for community spread in day care centers, schools, and in the home.

A great deal has been learned about COVID-19 in a short time, but there still is much to learn about the effect of the virus on children, the impact of children on viral spread, and about possible vertical transmission, they said.

“Widespread availability of testing will allow for us to more accurately describe the spectrum of illness and may result in adjustment of the apparent morbidity and mortality rate as fewer ill individuals are diagnosed,” Dr. Cruz and Dr. Zeichner wrote, adding that “rigorously gauging the impact of COVID-19 on children will be important to accurately model the pandemic and to ensure that appropriate resources are allocated to children requiring care.”

They noted that understanding differences in children versus adults with COVID-19 “can yield important insights into disease pathogenesis, informing management and the development of therapeutics.”

This study was partially supported by the Science and Technology Commission of Shanghai Municipality. The authors reported having no disclosures. Dr. Cruz and Dr. Zeichner are associate editors for Pediatrics. Dr. Cruz reported having no disclosures. Dr. Zeichner is an inventor of new technologies for the rapid production of vaccines, for which the University of Virginia has filed patent applications.

[email protected]

SOURCE: Dong Y et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0702; Cruz A and Zeichner S. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0834.

Clinical manifestations of COVID-19 infection among children in mainland China generally have been less severe than those among adults, but children of all ages – and infants in particular – are vulnerable to infection, according to a review of 2,143 cases.

CDC/ Dr. Fred Murphy; Sylvia Whitfield

Further, infection patterns in the nationwide series of all pediatric patients reported to the Chinese Center for Disease Control and Prevention from Jan. 16 to Feb. 8, 2020, provide strong evidence of human-to-human transmission, Yuanyuan Dong, MPH, a research assistant at Shanghai Children’s Medical Center, Shanghai Jiao Tong University, China, and colleagues reported in Pediatrics.

Of the 2,143 patients included in the review, 57% were boys and the median age was 7 years; 34% had laboratory-confirmed infection and 67% had suspected infection. More than 90% had asymptomatic, mild, or moderate disease (4%, 51%, and 39%, respectively), and 46% were from Hubei Province, where the first cases were reported, the investigators found.

The median time from illness onset to diagnosis was 2 days, and there was a trend of rapid increase of disease at the early stage of the epidemic – with rapid spread from Hubei Province to surrounding provinces – followed by a gradual and steady decrease, they noted.

“The total number of pediatric patients increased remarkably between mid-January and early February, peaked around February 1, and then declined since early February 2020,” they wrote. The proportion of severe and critical cases was 11% for infants under 1 year of age, compared with 7% for those aged 1-5 years; 4% for those aged 6-10 years; 4% for those 11-15 years; and 3% for those 16 years and older.

As of Feb. 8, 2020, only one child in this group of study patients died and most cases of COVID-19 symptoms were mild. There were many fewer severe and critical cases among the children (6%), compared with those reported in adult patients in other studies (19%). “It suggests that, compared with adult patients, clinical manifestations of children’s COVID-19 may be less severe,” the investigators suggested.

“As most of these children were likely to expose themselves to family members and/or other children with COVID-19, it clearly indicates person-to-person transmission ” of novel coronavirus 2019, they said, adding that similar evidence of such transmission also has been reported from studies of adult patients.

The reasons for reduced severity in children versus adults remain unclear, but may be related to both exposure and host factors, Ms. Dong and associates said. “Children were usually well cared for at home and might have relatively [fewer] opportunities to expose themselves to pathogens and/or sick patients.”

The findings demonstrate a pediatric distribution that varied across time and space, with most cases concentrated in the Hubei province and surrounding areas. No significant gender-related difference in infection rates was observed, and although the median patient age was 7 years, the range was 1 day to 18 years, suggesting that “all ages at childhood were susceptible” to the virus, they added.

The declining number of cases over time further suggests that disease control measures implemented by the government were effective, and that cases will “continue to decline, and finally stop in the near future unless sustained human-to-human transmissions occur,” Ms. Dong and associates concluded.

In an accompanying editorial, Andrea T. Cruz, MD, of Baylor College of Medicine, Houston, and Steven L. Zeichner, MD, PhD, of the University of Virginia, Charlottesville, said the findings regarding reduced severity among children versus adults with novel coronavirus 2019 infection are consistent with data on non-COVID-19 coronavirus.

They pointed out that Ms. Dong and associates did find that 13% of virologically-confirmed cases had asymptomatic infection, “a rate that almost certainly understates the true rate of asymptomatic infection, since many asymptomatic children are unlikely to be tested.”

Of the symptomatic children, “5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults) and 0.6% progressed to acute respiratory distress syndrome (ARDS) or multiorgan system dysfunction”; this also is at a lower rate than seen in adults, they said.

Very young children –infants or children in preschool – were more likely to have severe clinical manifestations than children who were older.

Thus, it appears that certain subpopulations of children are at increased risk for more significant COVID-19 illness: “younger age, underlying pulmonary pathology, and immunocompromising conditions,” Dr. Cruz and Dr. Zeichner suggested.

The two editorialists said the findings suggest children “may play a major role in community-based viral transmission.” Evidence suggests that children may have more upper respiratory tract involvement and that fecal shedding may occur for several weeks after diagnosis; this raises concerns about fecal-oral transmission, particularly for infants and children, and about viral replication in the gastrointestinal tract, they said. This has substantial implications for community spread in day care centers, schools, and in the home.

A great deal has been learned about COVID-19 in a short time, but there still is much to learn about the effect of the virus on children, the impact of children on viral spread, and about possible vertical transmission, they said.

“Widespread availability of testing will allow for us to more accurately describe the spectrum of illness and may result in adjustment of the apparent morbidity and mortality rate as fewer ill individuals are diagnosed,” Dr. Cruz and Dr. Zeichner wrote, adding that “rigorously gauging the impact of COVID-19 on children will be important to accurately model the pandemic and to ensure that appropriate resources are allocated to children requiring care.”

They noted that understanding differences in children versus adults with COVID-19 “can yield important insights into disease pathogenesis, informing management and the development of therapeutics.”

This study was partially supported by the Science and Technology Commission of Shanghai Municipality. The authors reported having no disclosures. Dr. Cruz and Dr. Zeichner are associate editors for Pediatrics. Dr. Cruz reported having no disclosures. Dr. Zeichner is an inventor of new technologies for the rapid production of vaccines, for which the University of Virginia has filed patent applications.

[email protected]

SOURCE: Dong Y et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0702; Cruz A and Zeichner S. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0834.