MDedge Pediatrics

The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.

Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).

In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.

The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.

Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.

The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.

Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”

The drug is currently under regulatory review for the same indication in Europe, the company said.

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

The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.

Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).

In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.

The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.

Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.

The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.

Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”

The drug is currently under regulatory review for the same indication in Europe, the company said.

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

The Food and Drug Administration has approved the fully human monoclonal antibody evinacumab-dgnb (Evkeeza, Regeneron Pharmaceuticals) for use on top of other cholesterol-modifying medication in patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), the agency and Regeneron have announced.

Evinacumab had received orphan drug designation and underwent priority regulatory review based primarily on the phase 3 ELIPSE trial, presented at a meeting in March 2020 and published in August 2020 in the New England Journal of Medicine (doi: 10.1056/NEJMoa2004215).

In the trial with 65 patients with HoFH on guideline-based lipid-modifying therapy, those who also received evinacumab 15 mg/kg intravenously every 4 weeks showed a nearly 50% drop in LDL cholesterol levels after 24 weeks, compared with patients given a placebo. Only 2% of patients in both groups discontinued therapy because of adverse reactions.

The drug blocks angiopoietin-like 3, itself an inhibitor of lipoprotein lipase and endothelial lipase. It therefore lowers LDL cholesterol levels by mechanisms that don’t directly involve the LDL receptor.

Regeneron estimates that about 1300 people in the United States have the homozygous genetic disorder, which can lead to LDL cholesterol levels of a 1,000 mg/dL or higher, advanced premature atherosclerosis, and extreme risk for cardiovascular events.

The drug’s average wholesale acquisition cost per patient in the United States is expected to be about $450,000 per year, the company said, adding that it has a financial support program to help qualified patients with out-of-pocket costs.

Regeneron’s announcement included a comment from dyslipidemia-therapy expert Daniel J. Rader, MD, University of Pennsylvania, Philadelphia, who called evinacumab “a potentially transformational new treatment for people with HoFH.”

The drug is currently under regulatory review for the same indication in Europe, the company said.

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

The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.

“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”

Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.

A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.

Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.

Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.

But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.

Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.

The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.

Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).

Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).

There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.

The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”

In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.

The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.

This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.

Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.

The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.

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

The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.

“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”

Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.

A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.

Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.

Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.

But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.

Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.

The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.

Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).

Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).

There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.

The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”

In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.

The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.

This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.

Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.

The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.

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

The combination of methylprednisolone and intravenous immunoglobulins works better than intravenous immunoglobulins alone for multisystem inflammatory syndrome in children (MIS-C), researchers say.

“I’m not sure it’s the best treatment because we have not studied every possible treatment,” François Angoulvant, MD, PhD, told this news organization, “but right now, it’s the standard of care.”

Dr. Angoulvant, a professor of pediatrics at University of Paris, and colleagues published a comparison of the two treatments in the Journal of the American Medical Association.

A small percentage of children infected with SARS-CoV-2 develop MIS-C about 2 to 4 weeks later. It is considered a separate disease entity from COVID-19 and is associated with persistent fever, digestive symptoms, rash, bilateral nonpurulent conjunctivitis, mucocutaneous inflammation signs, and frequent cardiovascular involvement. In more than 60% of cases, it leads to hemodynamic failure, with acute cardiac dysfunction.

Because MIS-C resembles Kawasaki disease, clinicians modeled their treatment on that condition and started with immunoglobulins alone, Dr. Angoulvant said.

Based on expert opinion, the National Health Service in the United Kingdom published a consensus statement in Sept. listing immunoglobulins alone as the first-line treatment.

But anecdotal reports have emerged that combining the immunoglobulins with a corticosteroid worked better. To investigate this possibility, Dr. Angoulvant and colleagues analyzed records of MIS-C cases in France, where physicians are required to report all suspected cases of MIS-C to the French National Public Health Agency.

Among the 181 cases they scrutinized, 111 fulfilled the World Health Organization criteria for MIS-C. Of these, the researchers were able to match 64 patients who had received immunoglobulins alone with 32 who had received the combined therapy and could be matched using propensity scores.

The researchers defined treatment failure as persistence of fever for 2 days after the start of therapy or recurrence of fever within a week. By this measure, the combination treatment failed in only 9% of cases while immunoglobulins alone failed in 38% of cases. The difference was statistically significant (P = .008). Most of those for whom these treatments failed received second-line treatments such as steroids or biological agents.

Patients treated with the combination therapy also had a lower risk of secondary acute left ventricular dysfunction (odds ratio, 0.20; 95% confidence interval, 0.06-0.66) and a lower risk of needing hemodynamic support (OR, 0.21; 95% CI, 0.06-0.76).

Those receiving the combination therapy spent a mean of 4 days in the pediatric intensive care unit compared with 6 days for those receiving immunoglobulins alone. (Difference in days, −2.4; 95% CI, −4.0 to −0.7; P = .005).

There are few drawbacks to the combination approach, Dr. Angoulvant said, as the side effects of corticosteroids are generally not severe and they can be anticipated because this class of medications has been used for many years.

The study raises the question of whether corticosteroids might work as well by themselves, but it could not be answered with this database as no one is using that approach in France, Dr. Angoulvant said. “I hope other teams around the world could bring us the answer.”

In the United States, most physicians appear to already be using the combination therapy, said David Teachey, MD, an associate professor of pediatrics at the Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia.

The reduction in time in pediatric intensive care and the reduced risk of cardiac dysfunction are important findings, he said.

This retrospective study falls short of the evidence provided by a randomized clinical trial, Dr. Teachey noted. But he acknowledged that few families would agree to participate in such a trial as they would have to take a chance that the sick children would receive a less effective therapy than what they would otherwise get. “It’s hard to [talk] about a therapy reduction,” he told this news organization.

Given that impediment, he agreed with Dr. Angoulvant that the current study and others like it may provide the best data available pointing to a treatment approach for MIS-C.

The study received an unrestricted grant from Pfizer. The French COVID-19 Paediatric Inflammation Consortium received an unrestricted grant from the Square Foundation (Grandir–Fonds de Solidarité pour L’Enfance). Dr. Angoulvant and Dr. Teachey have disclosed no relevant financial relationships.

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

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Critical care staff are less likely to acquire COVID-19 infection from ICU patients than they are from areas away from the bedside, a new study has found.

Courtesy NIAID

“Other staff, other areas of the hospital, and the wider community are more likely sources of infection,” said lead author Kate El Bouzidi, MRCP, South London Specialist Virology Centre, King’s College Hospital NHS Foundation Trust, London.

She noted that 60% of critical care staff were symptomatic during the first wave of the coronavirus pandemic and 20% were antibody positive, with 10% asymptomatic. “Staff acquisition peaked 3 weeks before the peak of COVID-19 ICU admission, and personal protective equipment (PPE) was effective at preventing transmission from patients.” Working in other areas of the hospital was associated with higher seroprevalence, Dr. El Bouzidi noted.

The findings were presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The novel coronavirus was spreading around the world, and when it reached northern Italy, medical authorities began to think in terms of how it might overwhelm the health care system in the United Kingdom, explained Dr. El Bouzidi.

“There was a lot of interest at this time about health care workers who were particularly vulnerable and also about the allocation of resources and rationing of care, particularly in intensive care,” she said. “And this only intensified when our prime minister was admitted to intensive care. About this time, antibody testing also became available.”

The goal of their study was to determine the SARS-CoV-2 seroprevalence in critical care staff, as well as look at the correlation between antibody status, prior swab testing, and COVID-19 symptoms.

The survey was conducted at Kings College Hospital in London, which is a tertiary-care teaching center. The critical care department is one of the largest in the United Kingdom. The authors estimate that more than 800 people worked in the critical care units, and between March and April 2020, more than 2,000 patients with COVID-19 were admitted, of whom 180 required care in the ICU.

“There was good PPE available in the ICU units right from the start,” she said, “and staff testing was available.”

All staff working in the critical care department participated in the study, which required serum samples and completion of a questionnaire. The samples were tested via six different assays to measure receptor-binding domain, nucleoprotein, and tri-spike, with one antibody result determined for each sample.

Of the 625 staff members, 384 (61.4%) had previously reported experiencing symptoms and 124 (19.8%) had sent a swab for testing. COVID-19 infection had been confirmed in 37 of those health care workers (29.8%).

Overall, 21% were positive for SARS-CoV-2 antibodies, of whom 9.9% had been asymptomatic.

“We were surprised to find that 61% of staff reported symptoms they felt could be consistent with COVID-19,” she said, noting that fatigue, headache, and cough were the most common symptoms reported. “Seroprevalence was reported in 31% of symptomatic staff and in 5% of those without symptoms.”

Seroprevalence differed by role in a critical care unit, although it did not significantly differ by factors such as age, sex, ethnicity, or underlying conditions. Consultants, who are senior physicians, were twice as likely to test positive, compared with junior doctors. The reason for this finding is not clear, but it may lie in the nature of their work responsibilities, such as performing more aerosol-generating procedures in the ICU or in other departments.

The investigators looked at the timing of infections and found that they preceded peak of patient admissions by 3 weeks, with peak onset of staff symptoms in early March. At this time, Dr. El Bouzidi noted, there were very few patients with COVID-19 in the hospital, and good PPE was available throughout this time period.

“Staff were unlikely to be infected by ICU patients, and therefore PPE was largely effective,” she said. “Other sources of infection were more likely to be the cause, such as interactions with other staff, meetings, or contact in break rooms. Routine mask-wearing throughout the hospital was only encouraged as of June 15.”

There were several limitations to the study, such as the cross-sectional design, reliance on response/recall, the fact that antibody tests are unlikely to detect all previous infections, and no genomic data were available to confirm infections. Even though the study had limitations, Dr. El Bouzidi concluded that ICU staff are unlikely to contract COVID-19 from patients but that other staff, other areas of the hospital, and the wider community are more likely sources of infection.

These findings, she added, demonstrate that PPE was effective at preventing transmission from patients and that protective measures need to be maintained when staff is away from the bedside.

In commenting on the study, Greg S. Martin, MD, professor of medicine in the division of pulmonary, allergy, critical care and sleep medicine, Emory University, Atlanta, noted that, even though the study was conducted almost a year ago, the results are still relevant with regard to the effectiveness of PPE.

“There was a huge amount of uncertainty about PPE – what was most effective, could we reuse it, how to sterilize it, what about surfaces, and so on,” he said. “Even for people who work in ICU and who are familiar with the environment and familiar with the patients, there was 1,000 times more uncertainty about everything they were doing.”

Dr. Martin believes that the situation has improved. “It’s not that we take COVID more lightly, but I think the staff is more comfortable dealing with it,” he said. “They now know what they need to do on an hourly and daily basis to stay safe. The PPE had become second nature to them now, with all the other precautions.”

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Science by press release and preprint has cooled clinician enthusiasm for the use of colchicine in nonhospitalized patients with COVID-19, despite a pressing need for early treatments.

Photo by Jimmy Hamelin

As previously reported by this news organization, a Jan. 22 press release announced that the massive ColCORONA study missed its primary endpoint of hospitalization or death among 4,488 newly diagnosed patients at increased risk for hospitalization.

But it also touted that use of the anti-inflammatory drug significantly reduced the primary endpoint in 4,159 of those patients with polymerase chain reaction–confirmed COVID and led to reductions of 25%, 50%, and 44%, respectively, for hospitalizations, ventilations, and death.

Lead investigator Jean-Claude Tardif, MD, director of the Montreal Heart Institute Research Centre, deemed the findings a “medical breakthrough.”

When the preprint released a few days later, however, newly revealed confidence intervals showed colchicine did not meaningfully reduce the need for mechanical ventilation (odds ratio, 0.50; 95% confidence interval, 0.23-1.07) or death alone (OR, 0.56; 95% CI, 0.19-1.66).

Further, the significant benefit on the primary outcome came at the cost of a fivefold increase in pulmonary embolism (11 vs. 2; P = .01), which was not mentioned in the press release.

“Whether this represents a real phenomenon or simply the play of chance is not known,” Dr. Tardif and colleagues noted later in the preprint.

“I read the preprint on colchicine and I have so many questions,” Aaron E. Glatt, MD, spokesperson for the Infectious Diseases Society of America and chief of infectious diseases, Mount Sinai South Nassau, Hewlett, N.Y., said in an interview. “I’ve been burned too many times with COVID and prefer to see better data.

“People sometimes say if you wait for perfect data, people are going to die,” he said. “Yeah, but we have no idea if people are going to die from getting this drug more than not getting it. That’s what concerns me. How many pulmonary emboli are going to be fatal versus the slight benefit that the study showed?”

The pushback to the non–peer-reviewed data on social media and via emails was so strong that Dr. Tardif posted a nearly 2,000-word letter responding to the many questions at play.

Chief among them was why the trial, originally planned for 6,000 patients, was stopped early by the investigators without consultation with the data safety monitoring board (DSMB).

The explanation in the letter that logistical issues like running the study call center, budget constraints, and a perceived need to quickly communicate the results left some calling foul that the study wasn’t allowed to finish and come to a more definitive conclusion.

“I can be a little bit sympathetic to their cause but at the same time the DSMB should have said no,” said David Boulware, MD, MPH, who led a recent hydroxychloroquine trial in COVID-19. “The problem is we’re sort of left in limbo, where some people kind of believe it and some say it’s not really a thing. So it’s not really moving the needle, as far as guidelines go.”

Indeed, a Twitter poll by cardiologist James Januzzi Jr., MD, captured the uncertainty, with 28% of respondents saying the trial was “neutral,” 58% saying “maybe but meh,” and 14% saying “colchicine for all.”

Another poll cheekily asked whether ColCORONA was the Gamestop/Reddit equivalent of COVID.

“The press release really didn’t help things because it very much oversold the effect. That, I think, poisoned the well,” said Dr. Boulware, professor of medicine in infectious diseases at the University of Minnesota, Minneapolis.

“The question I’m left with is not whether colchicine works, but who does it work in,” he said. “That’s really the fundamental question because it does seem that there are probably high-risk groups in their trial and others where they benefit, whereas other groups don’t benefit. In the subgroup analysis, there was absolutely no beneficial effect in women.”

According to the authors, the number needed to treat to prevent one death or hospitalization was 71 overall, but 29 for patients with diabetes, 31 for those aged 70 years and older, 53 for patients with respiratory disease, and 25 for those with coronary disease or heart failure.

Men are at higher risk overall for poor outcomes. But “the authors didn’t present a multivariable analysis, so it is unclear if another factor, such as a differential prevalence of smoking or cardiovascular risk factors, contributed to the differential benefit,” Rachel Bender Ignacio, MD, MPH, infectious disease specialist, University of Washington, Seattle, said in an interview.

Importantly, in this pragmatic study, duration and severity of symptoms were not reported, observed Dr. Bender Ignacio, who is also a STOP-COVID-2 investigator. “We don’t yet have data as to whether colchicine shortens duration or severity of symptoms or prevents long COVID, so we need more data on that.”

The overall risk for serious adverse events was lower in the colchicine group, but the difference in pulmonary embolism (PE) was striking, she said. This could be caused by a real biologic effect, or it’s possible that persons with shortness of breath and hypoxia, without evident viral pneumonia on chest x-ray after a positive COVID-19 test, were more likely to receive a CT-PE study.

The press release also failed to include information, later noted in the preprint, that the MHI has submitted two patents related to colchicine: “Methods of treating a coronavirus infection using colchicine” and “Early administration of low-dose colchicine after myocardial infarction.”

Reached for clarification, MHI communications adviser Camille Turbide said in an interview that the first patent “simply refers to the novel concept of preventing complications of COVID-19, such as admission to the hospital, with colchicine as tested in the ColCORONA study.”

The second patent, she said, refers to the “novel concept that administering colchicine early after a major adverse cardiovascular event is better than waiting several days,” as supported by the COLCOT study, which Dr. Tardif also led.

The patents are being reviewed by authorities and “Dr. Tardif has waived his rights in these patents and does not stand to benefit financially at all if colchicine becomes used as a treatment for COVID-19,” Ms. Turbide said.

Dr. Tardif did not respond to interview requests for this story. Dr. Glatt said conflicts of interest must be assessed and are “something that is of great concern in any scientific study.”

Cardiologist Steve Nissen, MD, of the Cleveland Clinic said in an interview that, “despite the negative results, the study does suggest that colchicine might have a benefit and should be studied in future trials. These findings are not sufficient evidence to suggest use of the drug in patients infected with COVID-19.”

He noted that adverse effects like diarrhea were expected but that the excess PE was unexpected and needs greater clarification.

“Stopping the trial for administrative reasons is puzzling and undermined the ability of the trial to give a reliable answer,” Dr. Nissen said. “This is a reasonable pilot study that should be viewed as hypothesis generating but inconclusive.”

Several sources said a new trial is unlikely, particularly given the cost and 28 trials already evaluating colchicine. Among these are RECOVERY and COLCOVID, testing whether colchicine can reduce the duration of hospitalization or death in hospitalized patients with COVID-19.

Because there are so many trials ongoing right now, including for antivirals and other immunomodulators, it’s important that, if colchicine comes to routine clinical use, it provides access to treatment for those not able or willing to access clinical trials, rather than impeding clinical trial enrollment, Dr. Bender Ignacio suggested.

“We have already learned the lesson in the pandemic that early adoption of potentially promising therapies can negatively impact our ability to study and develop other promising treatments,” she said.

The trial was coordinated by the Montreal Heart Institute and funded by the government of Quebec; the National Heart, Lung, and Blood Institute of the National Institutes of Health; Montreal philanthropist Sophie Desmarais, and the COVID-19 Therapeutics Accelerator launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard. CGI, Dacima, and Pharmascience of Montreal were also collaborators. Dr. Glatt reported no conflicts of interest. Dr. Boulware reported receiving $18 in food and beverages from Gilead Sciences in 2018.
 

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

Functional brain connectivity patterns are a stable biomarker of attention-deficit/hyperactivity disorder, new research suggests.

By applying a machine-learning approach to brain-imaging data, investigators were able to identify with 99% accuracy the adult study participants who had been diagnosed with ADHD in childhood.

“Even though the symptoms of ADHD may be less apparent in adulthood, the brain-wiring signature seems to be persistent,” study investigator Christopher McNorgan, PhD, of the department of psychology, State University of New York at Buffalo told this news organization.

The findings were published online Dec. 17, 2020, in Frontiers of Psychology.
 

Deep-learning neural networks

The researchers analyzed archived functional magnetic resonance imaging (fMRI) and behavioral data for 80 adults (mean age, 24 years; 64 male). Of these participants, 55 were diagnosed with ADHD in childhood and 25 were not.

The fMRI data were obtained during a response inhibition task that tested the individual’s ability to not respond automatically; for example, not saying “Simon Says” after someone else makes the comment.

The behavioral data included scores on the Iowa Gambling Task (IGT), which is used to measure impulsivity and risk taking.

“Usually, but not always, people with ADHD make riskier choices on this task,” Dr. McNorgan noted.

The investigators measured the amount of interconnectedness among different brain regions during the response inhibition task, which was repeated four times.

Patterns of interconnectivity were then fed into a deep-learning neural network that learned which patterns belonged to the ADHD group vs. those without ADHD (control group) and which patterns belonged to the high vs. low scorers on the IGT.
 

Caveats, cautionary notes

“The trained models are then tested on brain patterns they had never seen before, and we found the models would make the correct ADHD diagnosis and could tell apart the high and low scorers on the IGT 99% of the time,” Dr. McNorgan reported.

“The trained classifiers make predictions by calculating probabilities, and the neural networks learned how each of the brain connections contributes towards the final classification probability. We identified the set of brain connections that had the greatest influence on these probability calculations,” he noted.

Because the network classified both ADHD diagnosis and gambling task performance, the researchers were able to distinguish between connections that predicted ADHD when gambling performance was poor, as is typical for patients with ADHD, and those predicting ADHD when gambling performance was uncharacteristically good.

While more work is needed, the findings have potential clinical relevance, Dr. McNorgan said.

“ADHD can be difficult to diagnose reliably. If expense wasn’t an issue, fMRI may be able to help make diagnosis more reliable and objective,” he added.

Dr. McNorgan admitted that it might not be cost effective to use fMRI in this manner. However, because individuals with ADHD have different behavioral profiles, such as scoring atypically well on the IGT, additional studies using this approach may help identify brain networks “that are more or less active in those with ADHD that show a particular diagnostic trait,” he said.

“This could help inform what treatments might be more effective for those individuals,” Dr. McNorgan said.

Of course, he added, “clinicians’ diagnostic expertise is still required, as I would not base an ADHD diagnosis solely on the results of a single brain scan.”
 

No cross-validation

Commenting on the findings for this news organization, Vince Calhoun, PhD, neuroscientist and founding director of the Center for Translational Research in Neuroimaging and Data Science, Atlanta, a joint effort between Georgia State, Georgia Tech, and Emory University, noted some study limitations.

One cautionary note is that the investigators “appear to select relevant regions to include in the model based on activation to the task, then computed the predictions using the subset of regions that showed strong activation. The issue is this was done on the same data, so there was no cross-validation of this ‘feature selection’ step,” said Dr. Calhoun, who was not involved with the research. “This is a type of circularity which can lead to inflated accuracies,” he added.

Dr. Calhoun also noted that “multiple ADHD classification studies” have reported accuracies above 90%. In addition, there were only 80 participants in the current dataset.

“That’s relatively small for making strong claims about high accuracies as has been reported elsewhere,” he said.

Dr. McNorgan and Dr. Calhoun have reported no relevant financial relationships.

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

Functional brain connectivity patterns are a stable biomarker of attention-deficit/hyperactivity disorder, new research suggests.

By applying a machine-learning approach to brain-imaging data, investigators were able to identify with 99% accuracy the adult study participants who had been diagnosed with ADHD in childhood.

“Even though the symptoms of ADHD may be less apparent in adulthood, the brain-wiring signature seems to be persistent,” study investigator Christopher McNorgan, PhD, of the department of psychology, State University of New York at Buffalo told this news organization.

The findings were published online Dec. 17, 2020, in Frontiers of Psychology.
 

Deep-learning neural networks

The researchers analyzed archived functional magnetic resonance imaging (fMRI) and behavioral data for 80 adults (mean age, 24 years; 64 male). Of these participants, 55 were diagnosed with ADHD in childhood and 25 were not.

The fMRI data were obtained during a response inhibition task that tested the individual’s ability to not respond automatically; for example, not saying “Simon Says” after someone else makes the comment.

The behavioral data included scores on the Iowa Gambling Task (IGT), which is used to measure impulsivity and risk taking.

“Usually, but not always, people with ADHD make riskier choices on this task,” Dr. McNorgan noted.

The investigators measured the amount of interconnectedness among different brain regions during the response inhibition task, which was repeated four times.

Patterns of interconnectivity were then fed into a deep-learning neural network that learned which patterns belonged to the ADHD group vs. those without ADHD (control group) and which patterns belonged to the high vs. low scorers on the IGT.
 

Caveats, cautionary notes

“The trained models are then tested on brain patterns they had never seen before, and we found the models would make the correct ADHD diagnosis and could tell apart the high and low scorers on the IGT 99% of the time,” Dr. McNorgan reported.

“The trained classifiers make predictions by calculating probabilities, and the neural networks learned how each of the brain connections contributes towards the final classification probability. We identified the set of brain connections that had the greatest influence on these probability calculations,” he noted.

Because the network classified both ADHD diagnosis and gambling task performance, the researchers were able to distinguish between connections that predicted ADHD when gambling performance was poor, as is typical for patients with ADHD, and those predicting ADHD when gambling performance was uncharacteristically good.

While more work is needed, the findings have potential clinical relevance, Dr. McNorgan said.

“ADHD can be difficult to diagnose reliably. If expense wasn’t an issue, fMRI may be able to help make diagnosis more reliable and objective,” he added.

Dr. McNorgan admitted that it might not be cost effective to use fMRI in this manner. However, because individuals with ADHD have different behavioral profiles, such as scoring atypically well on the IGT, additional studies using this approach may help identify brain networks “that are more or less active in those with ADHD that show a particular diagnostic trait,” he said.

“This could help inform what treatments might be more effective for those individuals,” Dr. McNorgan said.

Of course, he added, “clinicians’ diagnostic expertise is still required, as I would not base an ADHD diagnosis solely on the results of a single brain scan.”
 

No cross-validation

Commenting on the findings for this news organization, Vince Calhoun, PhD, neuroscientist and founding director of the Center for Translational Research in Neuroimaging and Data Science, Atlanta, a joint effort between Georgia State, Georgia Tech, and Emory University, noted some study limitations.

One cautionary note is that the investigators “appear to select relevant regions to include in the model based on activation to the task, then computed the predictions using the subset of regions that showed strong activation. The issue is this was done on the same data, so there was no cross-validation of this ‘feature selection’ step,” said Dr. Calhoun, who was not involved with the research. “This is a type of circularity which can lead to inflated accuracies,” he added.

Dr. Calhoun also noted that “multiple ADHD classification studies” have reported accuracies above 90%. In addition, there were only 80 participants in the current dataset.

“That’s relatively small for making strong claims about high accuracies as has been reported elsewhere,” he said.

Dr. McNorgan and Dr. Calhoun have reported no relevant financial relationships.

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

Functional brain connectivity patterns are a stable biomarker of attention-deficit/hyperactivity disorder, new research suggests.

By applying a machine-learning approach to brain-imaging data, investigators were able to identify with 99% accuracy the adult study participants who had been diagnosed with ADHD in childhood.

“Even though the symptoms of ADHD may be less apparent in adulthood, the brain-wiring signature seems to be persistent,” study investigator Christopher McNorgan, PhD, of the department of psychology, State University of New York at Buffalo told this news organization.

The findings were published online Dec. 17, 2020, in Frontiers of Psychology.
 

Deep-learning neural networks

The researchers analyzed archived functional magnetic resonance imaging (fMRI) and behavioral data for 80 adults (mean age, 24 years; 64 male). Of these participants, 55 were diagnosed with ADHD in childhood and 25 were not.

The fMRI data were obtained during a response inhibition task that tested the individual’s ability to not respond automatically; for example, not saying “Simon Says” after someone else makes the comment.

The behavioral data included scores on the Iowa Gambling Task (IGT), which is used to measure impulsivity and risk taking.

“Usually, but not always, people with ADHD make riskier choices on this task,” Dr. McNorgan noted.

The investigators measured the amount of interconnectedness among different brain regions during the response inhibition task, which was repeated four times.

Patterns of interconnectivity were then fed into a deep-learning neural network that learned which patterns belonged to the ADHD group vs. those without ADHD (control group) and which patterns belonged to the high vs. low scorers on the IGT.
 

Caveats, cautionary notes

“The trained models are then tested on brain patterns they had never seen before, and we found the models would make the correct ADHD diagnosis and could tell apart the high and low scorers on the IGT 99% of the time,” Dr. McNorgan reported.

“The trained classifiers make predictions by calculating probabilities, and the neural networks learned how each of the brain connections contributes towards the final classification probability. We identified the set of brain connections that had the greatest influence on these probability calculations,” he noted.

Because the network classified both ADHD diagnosis and gambling task performance, the researchers were able to distinguish between connections that predicted ADHD when gambling performance was poor, as is typical for patients with ADHD, and those predicting ADHD when gambling performance was uncharacteristically good.

While more work is needed, the findings have potential clinical relevance, Dr. McNorgan said.

“ADHD can be difficult to diagnose reliably. If expense wasn’t an issue, fMRI may be able to help make diagnosis more reliable and objective,” he added.

Dr. McNorgan admitted that it might not be cost effective to use fMRI in this manner. However, because individuals with ADHD have different behavioral profiles, such as scoring atypically well on the IGT, additional studies using this approach may help identify brain networks “that are more or less active in those with ADHD that show a particular diagnostic trait,” he said.

“This could help inform what treatments might be more effective for those individuals,” Dr. McNorgan said.

Of course, he added, “clinicians’ diagnostic expertise is still required, as I would not base an ADHD diagnosis solely on the results of a single brain scan.”
 

No cross-validation

Commenting on the findings for this news organization, Vince Calhoun, PhD, neuroscientist and founding director of the Center for Translational Research in Neuroimaging and Data Science, Atlanta, a joint effort between Georgia State, Georgia Tech, and Emory University, noted some study limitations.

One cautionary note is that the investigators “appear to select relevant regions to include in the model based on activation to the task, then computed the predictions using the subset of regions that showed strong activation. The issue is this was done on the same data, so there was no cross-validation of this ‘feature selection’ step,” said Dr. Calhoun, who was not involved with the research. “This is a type of circularity which can lead to inflated accuracies,” he added.

Dr. Calhoun also noted that “multiple ADHD classification studies” have reported accuracies above 90%. In addition, there were only 80 participants in the current dataset.

“That’s relatively small for making strong claims about high accuracies as has been reported elsewhere,” he said.

Dr. McNorgan and Dr. Calhoun have reported no relevant financial relationships.

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

Developmental outcomes in the first 2 years of life improved in children whose mothers received the revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) while pregnant, based on data from approximately 1,200 women.

Maternal nutrition is essential to healthy fetal development, and the WIC was revised in 2009 to align with current dietary guidelines and to support the health of women and children in low-income households, wrote Alice Guan, MPH, of the University of California, San Francisco, and colleagues.

“However, no researchers, to our knowledge, have evaluated effects of this revision on downstream child health or development,” they said.

In a study published in Pediatrics, the researchers reviewed data from mothers and their children who participated in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) longitudinal cohort study conducted in Tennessee between 2006 and 2011. Their quasi-experimental analysis included 700 women who received WIC during pregnancy and 525 women who did not.

The researchers considered core developmental outcomes of child growth, cognitive development, and socioemotional development at age 12 months and 24 months, and age 4-6 years.

Overall, infants of women who received the WIC food package showed significant increases in length-for-age z scores at 12 months of age (.33, representing approximately one-fifth of a standard deviation), compared to infants of women who did not receive the revised WIC package.

In addition, the Bayley Scales of Infant Development cognitive composite score showed a 4.3-point increase at 24 months of age (approximately one-third of a standard deviation) compared to infants of women who did not receive the revised WIC package.

No effects on growth at age 24 months or on cognitive development at age 4-6 years were noted, which suggests that the impact of the WIC program during pregnancy may fade over time, the researchers said.

“The magnitude of the findings in this study represents clinically relevant effect sizes and provides evidence that one of the largest U.S. safety net policies improves developmental outcomes among low-income and marginalized children,” they noted.

The study findings were limited by several factors including the statistical, quasi-experimental design; the reliance on self-reports for information on income, receipt of WIC, and other variables; and a potential lack of generalizability to other states, the researchers noted. However, the results support findings from previous studies and were strengthened by the review of multiple outcomes and use of a longitudinal database, they said.

“These findings provide timely and critical evidence for the role that WIC plays in improving the health of the nation’s most vulnerable populations, suggesting meaningful impacts of the revised WIC food package on child development,” the researchers said. In addition, “considering the relatively modest scope of the 2009 revision, more substantial updates to the program based on up-to-date nutritional guidance may have substantial effects on improving the health of WIC recipients,” they concluded.
 

Findings support program’s value

“Pediatrics has always had a commitment to reducing disparities in health care, and we are the main clinicians to see many Medicaid patients on a regular basis,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“We all know that pregnant women eating nutritiously ought to help child outcomes, but the current study provides an evidence base for something that seems like common sense,” he noted.

Having such an evidence base is helpful to reinforce the value of the WIC program for its intended recipients, especially in the wake of the COVID-19 pandemic when many funding sources are stretched thin, Dr. Lessin said.

The WIC is intended to try to reduce racial and socioeconomic disparities in the most basic form possible, by helping people who are disadvantaged get enough high-quality food to eat, but results of the program’s impact have not been well studied, he said.

“Outcomes are fiendishly difficult to measure,” and the study is subject to the limitations of its statistical nature, he said. But the large sample size adds support to the findings, which are encouraging, Dr. Lessin noted.

Other potential areas for research include comparing the quality of WIC programs in different states, but such research is very difficult, Dr. Lessin noted. However, the findings might encourage states with less robust WIC programs to consider increasing support, he said.

The study was funded by the National Institutes of Health (National Heart, Lung, and Blood Institute); the National Institute on Aging; the University of California, San Francisco, National Center of Excellence in Women’s Health; and the Urban Child Institute. The researchers had no financial conflicts to disclose. Dr. Lessin serves on the editorial advisory board of Pediatric News and had no relevant financial conflicts to disclose.

pdnews@mdedge.com

Developmental outcomes in the first 2 years of life improved in children whose mothers received the revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) while pregnant, based on data from approximately 1,200 women.

Maternal nutrition is essential to healthy fetal development, and the WIC was revised in 2009 to align with current dietary guidelines and to support the health of women and children in low-income households, wrote Alice Guan, MPH, of the University of California, San Francisco, and colleagues.

“However, no researchers, to our knowledge, have evaluated effects of this revision on downstream child health or development,” they said.

In a study published in Pediatrics, the researchers reviewed data from mothers and their children who participated in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) longitudinal cohort study conducted in Tennessee between 2006 and 2011. Their quasi-experimental analysis included 700 women who received WIC during pregnancy and 525 women who did not.

The researchers considered core developmental outcomes of child growth, cognitive development, and socioemotional development at age 12 months and 24 months, and age 4-6 years.

Overall, infants of women who received the WIC food package showed significant increases in length-for-age z scores at 12 months of age (.33, representing approximately one-fifth of a standard deviation), compared to infants of women who did not receive the revised WIC package.

In addition, the Bayley Scales of Infant Development cognitive composite score showed a 4.3-point increase at 24 months of age (approximately one-third of a standard deviation) compared to infants of women who did not receive the revised WIC package.

No effects on growth at age 24 months or on cognitive development at age 4-6 years were noted, which suggests that the impact of the WIC program during pregnancy may fade over time, the researchers said.

“The magnitude of the findings in this study represents clinically relevant effect sizes and provides evidence that one of the largest U.S. safety net policies improves developmental outcomes among low-income and marginalized children,” they noted.

The study findings were limited by several factors including the statistical, quasi-experimental design; the reliance on self-reports for information on income, receipt of WIC, and other variables; and a potential lack of generalizability to other states, the researchers noted. However, the results support findings from previous studies and were strengthened by the review of multiple outcomes and use of a longitudinal database, they said.

“These findings provide timely and critical evidence for the role that WIC plays in improving the health of the nation’s most vulnerable populations, suggesting meaningful impacts of the revised WIC food package on child development,” the researchers said. In addition, “considering the relatively modest scope of the 2009 revision, more substantial updates to the program based on up-to-date nutritional guidance may have substantial effects on improving the health of WIC recipients,” they concluded.
 

Findings support program’s value

“Pediatrics has always had a commitment to reducing disparities in health care, and we are the main clinicians to see many Medicaid patients on a regular basis,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“We all know that pregnant women eating nutritiously ought to help child outcomes, but the current study provides an evidence base for something that seems like common sense,” he noted.

Having such an evidence base is helpful to reinforce the value of the WIC program for its intended recipients, especially in the wake of the COVID-19 pandemic when many funding sources are stretched thin, Dr. Lessin said.

The WIC is intended to try to reduce racial and socioeconomic disparities in the most basic form possible, by helping people who are disadvantaged get enough high-quality food to eat, but results of the program’s impact have not been well studied, he said.

“Outcomes are fiendishly difficult to measure,” and the study is subject to the limitations of its statistical nature, he said. But the large sample size adds support to the findings, which are encouraging, Dr. Lessin noted.

Other potential areas for research include comparing the quality of WIC programs in different states, but such research is very difficult, Dr. Lessin noted. However, the findings might encourage states with less robust WIC programs to consider increasing support, he said.

The study was funded by the National Institutes of Health (National Heart, Lung, and Blood Institute); the National Institute on Aging; the University of California, San Francisco, National Center of Excellence in Women’s Health; and the Urban Child Institute. The researchers had no financial conflicts to disclose. Dr. Lessin serves on the editorial advisory board of Pediatric News and had no relevant financial conflicts to disclose.

pdnews@mdedge.com

Developmental outcomes in the first 2 years of life improved in children whose mothers received the revised Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) while pregnant, based on data from approximately 1,200 women.

Maternal nutrition is essential to healthy fetal development, and the WIC was revised in 2009 to align with current dietary guidelines and to support the health of women and children in low-income households, wrote Alice Guan, MPH, of the University of California, San Francisco, and colleagues.

“However, no researchers, to our knowledge, have evaluated effects of this revision on downstream child health or development,” they said.

In a study published in Pediatrics, the researchers reviewed data from mothers and their children who participated in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) longitudinal cohort study conducted in Tennessee between 2006 and 2011. Their quasi-experimental analysis included 700 women who received WIC during pregnancy and 525 women who did not.

The researchers considered core developmental outcomes of child growth, cognitive development, and socioemotional development at age 12 months and 24 months, and age 4-6 years.

Overall, infants of women who received the WIC food package showed significant increases in length-for-age z scores at 12 months of age (.33, representing approximately one-fifth of a standard deviation), compared to infants of women who did not receive the revised WIC package.

In addition, the Bayley Scales of Infant Development cognitive composite score showed a 4.3-point increase at 24 months of age (approximately one-third of a standard deviation) compared to infants of women who did not receive the revised WIC package.

No effects on growth at age 24 months or on cognitive development at age 4-6 years were noted, which suggests that the impact of the WIC program during pregnancy may fade over time, the researchers said.

“The magnitude of the findings in this study represents clinically relevant effect sizes and provides evidence that one of the largest U.S. safety net policies improves developmental outcomes among low-income and marginalized children,” they noted.

The study findings were limited by several factors including the statistical, quasi-experimental design; the reliance on self-reports for information on income, receipt of WIC, and other variables; and a potential lack of generalizability to other states, the researchers noted. However, the results support findings from previous studies and were strengthened by the review of multiple outcomes and use of a longitudinal database, they said.

“These findings provide timely and critical evidence for the role that WIC plays in improving the health of the nation’s most vulnerable populations, suggesting meaningful impacts of the revised WIC food package on child development,” the researchers said. In addition, “considering the relatively modest scope of the 2009 revision, more substantial updates to the program based on up-to-date nutritional guidance may have substantial effects on improving the health of WIC recipients,” they concluded.
 

Findings support program’s value

“Pediatrics has always had a commitment to reducing disparities in health care, and we are the main clinicians to see many Medicaid patients on a regular basis,” Herschel Lessin, MD, of Children’s Medical Group, Poughkeepsie, N.Y., said in an interview.

“We all know that pregnant women eating nutritiously ought to help child outcomes, but the current study provides an evidence base for something that seems like common sense,” he noted.

Having such an evidence base is helpful to reinforce the value of the WIC program for its intended recipients, especially in the wake of the COVID-19 pandemic when many funding sources are stretched thin, Dr. Lessin said.

The WIC is intended to try to reduce racial and socioeconomic disparities in the most basic form possible, by helping people who are disadvantaged get enough high-quality food to eat, but results of the program’s impact have not been well studied, he said.

“Outcomes are fiendishly difficult to measure,” and the study is subject to the limitations of its statistical nature, he said. But the large sample size adds support to the findings, which are encouraging, Dr. Lessin noted.

Other potential areas for research include comparing the quality of WIC programs in different states, but such research is very difficult, Dr. Lessin noted. However, the findings might encourage states with less robust WIC programs to consider increasing support, he said.

The study was funded by the National Institutes of Health (National Heart, Lung, and Blood Institute); the National Institute on Aging; the University of California, San Francisco, National Center of Excellence in Women’s Health; and the Urban Child Institute. The researchers had no financial conflicts to disclose. Dr. Lessin serves on the editorial advisory board of Pediatric News and had no relevant financial conflicts to disclose.

pdnews@mdedge.com

Sixteen dysregulated genes strongly characterize hidradenitis suppurativa (HS), Andre da Costa, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

He presented highlights of a multicenter translational study, which utilized whole transcriptome analysis of lesional and nonlesional skin from patients with HS and normal controls along with quantitative real-time PCR and immunohistochemistry. The purpose was to further define the molecular taxonomy of this inflammatory disease. And while this objective was achieved, the results also underscored a truism regarding the painful and scarring disease: “HS is characterized by an ever-growing complexity, which translates into multiple potential mechanistic drivers,” observed Dr. da Costa, head of immunology precision medicine at AstraZeneca in Gothenburg, Sweden.

Indeed, the study identified a panel of immune-related drivers in HS that influence innate immunity and cell differentiation in follicular and epidermal keratinocytes. The research by Dr. da Costa and coinvestigators identified a broad array of promising novel therapeutic targets in HS.

“Our findings provide evidence of an inflammatory process coupled with impaired barrier function, altered epidermal cell differentiation, and possibly abnormal microbiome activity which can be seen at the follicular and epidermal keratinocytes and also to a minor degree at the level of the skin glands,” Dr. da Costa said.

There is a huge unmet need for new therapies for HS, since at present adalimumab (Humira) is the only approved medication for this debilitating inflammatory disease. Some good news that emerged from this translational study is that some of the novel molecular mediators implicated in HS are targeted by multiple Food and Drug Administration–approved therapies that have other indications. From a drug development standpoint, repurposing a commercially available drug for a novel indication is a much more efficient and less costly endeavor than is necessary to establish the safety and efficacy of an unproven new agent.

The translational work demonstrated that the proteins calgranulin-A and -B and serpin-B4 were strongly expressed in the hair root sheaths of patients with HS. Connexin-32 and koebnerisin were present in stratum granulosum, matrix metallopeptidase-9 was strongly expressed in resident monocytes, small prolin-rich protein 3 in apocrine sweat glands and ducts as well as in sebaceous glands and ducts, and transcobalamin-1 was prominent in stratum spinosum.

Of the 19 key molecular mediators of HS identified in the study, FDA-approved agents are already available that target 12 of them. For example, apremilast (Otezla) targets interferon-gamma and tumor necrosis factor–alpha. Gentamicin targets growth arrest-specific 6 (GAS6) and interleukin-17 (IL-17). Secukinumab (Cosentyx) and ixekizumab (Taltz) target IL-17A, and brodalumab (Siliq) more broadly targets IL-17A as well as all the other IL-17 receptors. Thalidomide targets hepatocyte growth factor (HGF) and TNF-alpha. Spironolactone targets androgen receptor (AR) and TNF-alpha. Colchicine targets tubulin. Anakinra (Kineret) homes in on the IL-1 receptor. And prednisone targets NFxB.

Other key molecular mediators of HS, which are targeted by commercially available drugs, include epidermal growth factor (EGF), macrophage colony-stimulating factor (MCSF), epiregulin (EREG), fibroblast growth factor 1 (FGF1), FGF2, insulin-like growth factor 2 (IGF2), and IL-6, according to Dr. da Costa.

In addition, clinical trials are underway in HS involving totally investigational agents, including several Janus kinase inhibitors and tyrosine kinase 2 inhibitors.

The work described by Dr. da Costa had multiple funding sources, including the European Hidradenitis Suppurativa Foundation, the University of Copenhagen, the Icahn School of Medicine at Mount Sinai, AstraZeneca, and the German Federal Ministry of Education and Research. Dr. da Costa is an employee of AstraZeneca, Gothenburg, Sweden.

bjancin@mdedge.com

Sixteen dysregulated genes strongly characterize hidradenitis suppurativa (HS), Andre da Costa, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

He presented highlights of a multicenter translational study, which utilized whole transcriptome analysis of lesional and nonlesional skin from patients with HS and normal controls along with quantitative real-time PCR and immunohistochemistry. The purpose was to further define the molecular taxonomy of this inflammatory disease. And while this objective was achieved, the results also underscored a truism regarding the painful and scarring disease: “HS is characterized by an ever-growing complexity, which translates into multiple potential mechanistic drivers,” observed Dr. da Costa, head of immunology precision medicine at AstraZeneca in Gothenburg, Sweden.

Indeed, the study identified a panel of immune-related drivers in HS that influence innate immunity and cell differentiation in follicular and epidermal keratinocytes. The research by Dr. da Costa and coinvestigators identified a broad array of promising novel therapeutic targets in HS.

“Our findings provide evidence of an inflammatory process coupled with impaired barrier function, altered epidermal cell differentiation, and possibly abnormal microbiome activity which can be seen at the follicular and epidermal keratinocytes and also to a minor degree at the level of the skin glands,” Dr. da Costa said.

There is a huge unmet need for new therapies for HS, since at present adalimumab (Humira) is the only approved medication for this debilitating inflammatory disease. Some good news that emerged from this translational study is that some of the novel molecular mediators implicated in HS are targeted by multiple Food and Drug Administration–approved therapies that have other indications. From a drug development standpoint, repurposing a commercially available drug for a novel indication is a much more efficient and less costly endeavor than is necessary to establish the safety and efficacy of an unproven new agent.

The translational work demonstrated that the proteins calgranulin-A and -B and serpin-B4 were strongly expressed in the hair root sheaths of patients with HS. Connexin-32 and koebnerisin were present in stratum granulosum, matrix metallopeptidase-9 was strongly expressed in resident monocytes, small prolin-rich protein 3 in apocrine sweat glands and ducts as well as in sebaceous glands and ducts, and transcobalamin-1 was prominent in stratum spinosum.

Of the 19 key molecular mediators of HS identified in the study, FDA-approved agents are already available that target 12 of them. For example, apremilast (Otezla) targets interferon-gamma and tumor necrosis factor–alpha. Gentamicin targets growth arrest-specific 6 (GAS6) and interleukin-17 (IL-17). Secukinumab (Cosentyx) and ixekizumab (Taltz) target IL-17A, and brodalumab (Siliq) more broadly targets IL-17A as well as all the other IL-17 receptors. Thalidomide targets hepatocyte growth factor (HGF) and TNF-alpha. Spironolactone targets androgen receptor (AR) and TNF-alpha. Colchicine targets tubulin. Anakinra (Kineret) homes in on the IL-1 receptor. And prednisone targets NFxB.

Other key molecular mediators of HS, which are targeted by commercially available drugs, include epidermal growth factor (EGF), macrophage colony-stimulating factor (MCSF), epiregulin (EREG), fibroblast growth factor 1 (FGF1), FGF2, insulin-like growth factor 2 (IGF2), and IL-6, according to Dr. da Costa.

In addition, clinical trials are underway in HS involving totally investigational agents, including several Janus kinase inhibitors and tyrosine kinase 2 inhibitors.

The work described by Dr. da Costa had multiple funding sources, including the European Hidradenitis Suppurativa Foundation, the University of Copenhagen, the Icahn School of Medicine at Mount Sinai, AstraZeneca, and the German Federal Ministry of Education and Research. Dr. da Costa is an employee of AstraZeneca, Gothenburg, Sweden.

bjancin@mdedge.com

Sixteen dysregulated genes strongly characterize hidradenitis suppurativa (HS), Andre da Costa, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

He presented highlights of a multicenter translational study, which utilized whole transcriptome analysis of lesional and nonlesional skin from patients with HS and normal controls along with quantitative real-time PCR and immunohistochemistry. The purpose was to further define the molecular taxonomy of this inflammatory disease. And while this objective was achieved, the results also underscored a truism regarding the painful and scarring disease: “HS is characterized by an ever-growing complexity, which translates into multiple potential mechanistic drivers,” observed Dr. da Costa, head of immunology precision medicine at AstraZeneca in Gothenburg, Sweden.

Indeed, the study identified a panel of immune-related drivers in HS that influence innate immunity and cell differentiation in follicular and epidermal keratinocytes. The research by Dr. da Costa and coinvestigators identified a broad array of promising novel therapeutic targets in HS.

“Our findings provide evidence of an inflammatory process coupled with impaired barrier function, altered epidermal cell differentiation, and possibly abnormal microbiome activity which can be seen at the follicular and epidermal keratinocytes and also to a minor degree at the level of the skin glands,” Dr. da Costa said.

There is a huge unmet need for new therapies for HS, since at present adalimumab (Humira) is the only approved medication for this debilitating inflammatory disease. Some good news that emerged from this translational study is that some of the novel molecular mediators implicated in HS are targeted by multiple Food and Drug Administration–approved therapies that have other indications. From a drug development standpoint, repurposing a commercially available drug for a novel indication is a much more efficient and less costly endeavor than is necessary to establish the safety and efficacy of an unproven new agent.

The translational work demonstrated that the proteins calgranulin-A and -B and serpin-B4 were strongly expressed in the hair root sheaths of patients with HS. Connexin-32 and koebnerisin were present in stratum granulosum, matrix metallopeptidase-9 was strongly expressed in resident monocytes, small prolin-rich protein 3 in apocrine sweat glands and ducts as well as in sebaceous glands and ducts, and transcobalamin-1 was prominent in stratum spinosum.

Of the 19 key molecular mediators of HS identified in the study, FDA-approved agents are already available that target 12 of them. For example, apremilast (Otezla) targets interferon-gamma and tumor necrosis factor–alpha. Gentamicin targets growth arrest-specific 6 (GAS6) and interleukin-17 (IL-17). Secukinumab (Cosentyx) and ixekizumab (Taltz) target IL-17A, and brodalumab (Siliq) more broadly targets IL-17A as well as all the other IL-17 receptors. Thalidomide targets hepatocyte growth factor (HGF) and TNF-alpha. Spironolactone targets androgen receptor (AR) and TNF-alpha. Colchicine targets tubulin. Anakinra (Kineret) homes in on the IL-1 receptor. And prednisone targets NFxB.

Other key molecular mediators of HS, which are targeted by commercially available drugs, include epidermal growth factor (EGF), macrophage colony-stimulating factor (MCSF), epiregulin (EREG), fibroblast growth factor 1 (FGF1), FGF2, insulin-like growth factor 2 (IGF2), and IL-6, according to Dr. da Costa.

In addition, clinical trials are underway in HS involving totally investigational agents, including several Janus kinase inhibitors and tyrosine kinase 2 inhibitors.

The work described by Dr. da Costa had multiple funding sources, including the European Hidradenitis Suppurativa Foundation, the University of Copenhagen, the Icahn School of Medicine at Mount Sinai, AstraZeneca, and the German Federal Ministry of Education and Research. Dr. da Costa is an employee of AstraZeneca, Gothenburg, Sweden.

bjancin@mdedge.com

The big news in the Wilkoff household is that Marilyn and I will be celebrating the arrival of a granddog into our nuclear family. Our younger daughter and her husband will be welcoming into their home a golden retriever puppy the first week in March. This may not seem like big news to some families and is certainly a step down on the priority list to the arrival of the four grandchildren that we already claim on our resume. But, you must understand that no one in our family has ever owned a dog.

Although my wife’s family had a dog, she apparently never really bonded with the canine. My pleas and occasional whining from our three children to get a dog were always met with my wife’s concerns about cleanliness and hygiene. We did have an antisocial cat who lived under a bed in the guest room or in the basement. His passing after 16 years when the kids were in college was not an event marked with any emotion beyond relief.

I think I harbored an unspoken concern about how I and our children might respond emotionally and psychologically to the inevitable death of what would likely have become our family’s best friend. Dispatching a belly-up goldfish after a month or two is small potatoes compared to putting down a tail-wagging, frisbee-catching, four-footed member of the family.

It turns out that my concerns about the mental health of our children may not have been unfounded. A recently published study from the Harvard Medical School and Massachusetts General Hospital found that children who had experienced the death of a loved pet were more likely to exhibit symptoms of psychopathology than were those who had loved a pet who was still alive (Crawford et al. Eur Child Adolesc Psychiatry. 2020 Sep 10. doi: 10.1007/s00787-020-01594-5). The observed effect of the loss was more pronounced in boys. There was also no statistical difference between the psychopathology symptoms of those children who had loved and lost and those children who had never loved a pet.

By the time I left for college I had grown up with five different dogs. I had endured the loss of sweet Mary, the boxer, when we moved to a small apartment and had to send her to a “farm.” I had watched 2-year-old Blackie experience a seizure that heralded his fatal bout with distemper. I shared the struggle with my parents as we made the decision to send my much loved inveterate car chasing “Butch” back to the pound.

However, I survived these losses and wonder whether they in some way prepared me for some of the emotional challenges that would come later in life. This study from Harvard sampled only children from birth to age 8 years. For those of us in primary care a more interesting study might be one that looked for any long-term associations between pet loss as a young child with adolescent and adult mental health. With the surge in pet ownership that has surfaced during the pandemic, there should be an abundance of clinical material to mine. The Harvard researchers’ findings should make us aware of the potential for psychopathology in a child who has suffered the loss of a pet. Each family must decide whether the plusses of pet ownership are worth the risk. However, I side with Tennyson who said it is better to have loved and lost than never to have loved at all.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

The big news in the Wilkoff household is that Marilyn and I will be celebrating the arrival of a granddog into our nuclear family. Our younger daughter and her husband will be welcoming into their home a golden retriever puppy the first week in March. This may not seem like big news to some families and is certainly a step down on the priority list to the arrival of the four grandchildren that we already claim on our resume. But, you must understand that no one in our family has ever owned a dog.

Although my wife’s family had a dog, she apparently never really bonded with the canine. My pleas and occasional whining from our three children to get a dog were always met with my wife’s concerns about cleanliness and hygiene. We did have an antisocial cat who lived under a bed in the guest room or in the basement. His passing after 16 years when the kids were in college was not an event marked with any emotion beyond relief.

I think I harbored an unspoken concern about how I and our children might respond emotionally and psychologically to the inevitable death of what would likely have become our family’s best friend. Dispatching a belly-up goldfish after a month or two is small potatoes compared to putting down a tail-wagging, frisbee-catching, four-footed member of the family.

It turns out that my concerns about the mental health of our children may not have been unfounded. A recently published study from the Harvard Medical School and Massachusetts General Hospital found that children who had experienced the death of a loved pet were more likely to exhibit symptoms of psychopathology than were those who had loved a pet who was still alive (Crawford et al. Eur Child Adolesc Psychiatry. 2020 Sep 10. doi: 10.1007/s00787-020-01594-5). The observed effect of the loss was more pronounced in boys. There was also no statistical difference between the psychopathology symptoms of those children who had loved and lost and those children who had never loved a pet.

By the time I left for college I had grown up with five different dogs. I had endured the loss of sweet Mary, the boxer, when we moved to a small apartment and had to send her to a “farm.” I had watched 2-year-old Blackie experience a seizure that heralded his fatal bout with distemper. I shared the struggle with my parents as we made the decision to send my much loved inveterate car chasing “Butch” back to the pound.

However, I survived these losses and wonder whether they in some way prepared me for some of the emotional challenges that would come later in life. This study from Harvard sampled only children from birth to age 8 years. For those of us in primary care a more interesting study might be one that looked for any long-term associations between pet loss as a young child with adolescent and adult mental health. With the surge in pet ownership that has surfaced during the pandemic, there should be an abundance of clinical material to mine. The Harvard researchers’ findings should make us aware of the potential for psychopathology in a child who has suffered the loss of a pet. Each family must decide whether the plusses of pet ownership are worth the risk. However, I side with Tennyson who said it is better to have loved and lost than never to have loved at all.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

The big news in the Wilkoff household is that Marilyn and I will be celebrating the arrival of a granddog into our nuclear family. Our younger daughter and her husband will be welcoming into their home a golden retriever puppy the first week in March. This may not seem like big news to some families and is certainly a step down on the priority list to the arrival of the four grandchildren that we already claim on our resume. But, you must understand that no one in our family has ever owned a dog.

Although my wife’s family had a dog, she apparently never really bonded with the canine. My pleas and occasional whining from our three children to get a dog were always met with my wife’s concerns about cleanliness and hygiene. We did have an antisocial cat who lived under a bed in the guest room or in the basement. His passing after 16 years when the kids were in college was not an event marked with any emotion beyond relief.

I think I harbored an unspoken concern about how I and our children might respond emotionally and psychologically to the inevitable death of what would likely have become our family’s best friend. Dispatching a belly-up goldfish after a month or two is small potatoes compared to putting down a tail-wagging, frisbee-catching, four-footed member of the family.

It turns out that my concerns about the mental health of our children may not have been unfounded. A recently published study from the Harvard Medical School and Massachusetts General Hospital found that children who had experienced the death of a loved pet were more likely to exhibit symptoms of psychopathology than were those who had loved a pet who was still alive (Crawford et al. Eur Child Adolesc Psychiatry. 2020 Sep 10. doi: 10.1007/s00787-020-01594-5). The observed effect of the loss was more pronounced in boys. There was also no statistical difference between the psychopathology symptoms of those children who had loved and lost and those children who had never loved a pet.

By the time I left for college I had grown up with five different dogs. I had endured the loss of sweet Mary, the boxer, when we moved to a small apartment and had to send her to a “farm.” I had watched 2-year-old Blackie experience a seizure that heralded his fatal bout with distemper. I shared the struggle with my parents as we made the decision to send my much loved inveterate car chasing “Butch” back to the pound.

However, I survived these losses and wonder whether they in some way prepared me for some of the emotional challenges that would come later in life. This study from Harvard sampled only children from birth to age 8 years. For those of us in primary care a more interesting study might be one that looked for any long-term associations between pet loss as a young child with adolescent and adult mental health. With the surge in pet ownership that has surfaced during the pandemic, there should be an abundance of clinical material to mine. The Harvard researchers’ findings should make us aware of the potential for psychopathology in a child who has suffered the loss of a pet. Each family must decide whether the plusses of pet ownership are worth the risk. However, I side with Tennyson who said it is better to have loved and lost than never to have loved at all.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

Large numbers of COVID-19 cases have been undetected and unreported, which has resulted in severe undercounting of the total number of people who have been infected during the pandemic, according to a new study published Monday in the journal PLOS ONE.

In the United States, the number of COVID-19 cases is likely three times that of reported cases. According to the study, more than 71 million Americans have contracted the virus during the pandemic, and 7 million were infected or potentially contagious last week.

Public health officials rely on case counts to guide decisions, so the undercounting should be considered while trying to end the pandemic.

“The estimates of actual infections reveal for the first time the true severity of COVID-19 across the U.S. and in countries worldwide,” Jungsik Noh, PhD, a bioinformatics professor at the University of Texas Southwestern Medical Center, said in a statement.

Dr. Noh and colleague Gaudenz Danuser created a computational model that uses machine-learning strategies to estimate the actual number of daily cases in the United States and the 50 most-infected countries.

The model pulls data from the Johns Hopkins University database and the COVID Tracking Project, as well as large-scale surveys conducted by the CDC and several states. The algorithm uses the number of reported deaths, which is thought to be more accurate than the number of lab-confirmed cases, as the basis for calculations.

In 25 of the 50 countries, the “actual” cumulative cases were estimated to be 5-20 times greater than the confirmed cases. In the United States, Belgium, and Brazil, about 10% of the population has contracted the coronavirus, according to the model. At the beginning of February, about 11% of the population in Pennsylvania had current infections, which was the highest rate of any state. About 0.15% of residents in Minnesota had infections, and about 2.5% of residents in New York and Texas had infections.

“Knowing the true severity in different regions will help us effectively fight against the virus spreading,” Dr. Noh said. “The currently infected population is the cause of future infections and deaths. Its actual size in a region is a crucial variable required when determining the severity of COVID-19 and building strategies against regional outbreaks.”

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

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.

In outpatients with COVID-19, peginterferon lambda has the potential to prevent clinical deterioration and shorten the duration of viral shedding, according to results of a double-blind, placebo-controlled trial (NCT04354259).

Reductions in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA were greater with peginterferon lambda than with placebo from day 3 onward in the phase 2 study led by Jordan J. Feld, MD, of the Toronto Centre for Liver Disease. The findings were reported in The Lancet Respiratory Medicine.
 

Fewer side effects

To date in randomized clinical trials, efficacy in treatment of COVID-19 has been shown only for remdesivir and dexamethasone in hospitalized patients, and in an interim analysis of accelerated viral clearance for a monoclonal antibody infusion in outpatients.

Activity against respiratory pathogens has been demonstrated for interferon lambda-1, a type III interferon shown to be involved in innate antiviral responses. Interferons, Dr. Feld and coauthors stated, drive induction of genes with antiviral, antiproliferative and immunoregulatory properties, and early treatment with interferons might halt clinical progression and shorten the duration of viral shedding with reduced onward transmission. In addition, interferon lambdas (type III) use a distinct receptor complex with high expression levels limited to epithelial cells in the lung, liver, and intestine, leading to fewer side effects than other interferons, including avoiding risk of promoting cytokine storm syndrome.

The researchers investigated peginterferon lambda safety and efficacy in treatment of patients with laboratory-confirmed, mild to moderate COVID-19. Sixty patients (median age 46 years, about 60% female, about 50% White) were recruited from outpatient testing centers at six institutions in Toronto, and referred to a single ambulatory site. Patients were randomly assigned 1:1 to a single subcutaneous injection of peginterferon lambda 180 mcg or placebo within 7 days of symptom onset or, if asymptomatic, of their first positive swab. Mean time from symptom onset to injection was about 4.5 days, and about 18.5% were asymptomatic. The primary outcome was the proportion of patients negative for SARS-CoV-2 RNA on day 7 after the injection.
 

Greater benefit with higher baseline load

A higher baseline SARS-CoV-2 RNA concentration found in the peginterferon lambda group was found to be significantly associated with day 7 clearance (odds ratio [OR] 0.69 [95% confidence interval 0.51-0.87]; P = ·001). In the peginterferon lambda group, also, the mean decline in SARS-CoV-2 RNA was significantly larger than in the placebo group across all time points (days 3, 5, 7, and14). While viral load decline was 0.81 log greater in the treatment group (P = .14) by day 3, viral load decline increased to 1.67 log copies per mL by day 5 (P = .013) and 2.42 log copies per mL by day 7 (P = .0041). At day 14, the viral decline was 1.77 log copies per mL larger in the peginterferon lambda group (P = .048). The investigators pointed out that the difference in viral load decline between groups was greater in patients with high baseline viral load (at or above 106 copies per mL). In the peginterferon lambda high baseline viral load group, the reduction was 7.17 log copies per mL, versus 4.92 log copies per mL in the placebo group (P = .004).
 

More patients SARS-CoV-2 RNA negative

By day 7, 80% of patients in the peginterferon lambda group were negative for SARS-CoV-2 RNA, compared with 63% in the placebo group (P = .15). After baseline load adjustment, however, the peginterferon lambda treatment was significantly associated with day 7 clearance (OR 4·12 [95% CI 1·15-16·73]; P = .029).
 

Respiratory symptoms improved faster

Most symptoms in both groups were mild to moderate, without difference in frequency or severity. While symptom improvement was generally similar over time for both groups, respiratory symptoms improved faster with peginterferon lambda, with the effect more pronounced in the high baseline viral load group (OR 5·88 (0·81-42·46; P =. 079).

Laboratory adverse events, similar for both groups, were mild.

“Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding,” the investigators concluded.

“This clinical trial is important” because it suggests that a single intravenous dose of peginterferon lambda administered to outpatients with a positive SARS-CoV-2 nasopharyngeal swab speeds reduction of SARS-CoV-2 viral load, David L. Bowton, MD, FCCP, professor emeritus, Wake Forest Baptist Health, Winston-Salem, N.C., said in an interview. He observed that the smaller viral load difference observed at day 14 likely reflects host immune responses.

Dr. Bowton also noted that two placebo group baseline characteristics (five placebo group patients with anti-SARS-CoV-2 S protein IgG antibodies; two times more undetectable SARS-CoV-2 RNA at baseline assessment) would tend to reduce differences between the peginterferon lambda and placebo groups. He added that the study findings were concordant with another phase 2 trial of hospitalized COVID-19 patients receiving inhaled interferon beta-1a.

“Thus, interferons may find a place in the treatment of COVID-19 and perhaps other severe viral illnesses,” Dr. Bowton said.

The study was funded by the Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

Dr. Bowton had no disclosures. Disclosures for Dr. Feld and coauthors are listed on the Lancet Respiratory Medicine website.