Dermatology News

The Food and Drug Administration has approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis, the manufacturers announced.

The new indication is for children “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable,” Regeneron and Sanofi said in a press release, which points out that this is the first biologic approved for AD in this age group.

For children aged 6-11, the two available dupilumab (Dupixent) doses in prefilled syringes are given based on weight – 300 mg every 4 weeks for children between 15 to 29 kg and 200 mg every 2 weeks for children 30 to 59 kg – following an initial loading dose.

In phase 3 trials, children with severe AD who received dupilumab and topical corticosteroids improved significantly in overall disease severity, skin clearance, and itch, compared with those getting steroids alone. Eczema Area and Severity Index-75, for example, was reached by 75% of patients on either dupilumab dose, compared with 28% and 26% , respectively, for those receiving steroids alone every 4 and every 2 weeks, the statement said.

Over the 16-week treatment period, overall rates of adverse events were 65% for those getting dupilumab every 4 weeks and 61% for every 2 weeks – compared with steroids alone (72% and 75%, respectively), the statement said.

The fully human monoclonal antibody inhibits signaling of the interleukin-4 and interleukin-13 proteins and is already approved as an add-on maintenance treatment in children aged 12 years and older with moderate to severe asthma (eosinophilic phenotype or oral-corticosteroid dependent) and in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis, according to the prescribing information.

[email protected]

The Food and Drug Administration has approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis, the manufacturers announced.

The new indication is for children “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable,” Regeneron and Sanofi said in a press release, which points out that this is the first biologic approved for AD in this age group.

For children aged 6-11, the two available dupilumab (Dupixent) doses in prefilled syringes are given based on weight – 300 mg every 4 weeks for children between 15 to 29 kg and 200 mg every 2 weeks for children 30 to 59 kg – following an initial loading dose.

In phase 3 trials, children with severe AD who received dupilumab and topical corticosteroids improved significantly in overall disease severity, skin clearance, and itch, compared with those getting steroids alone. Eczema Area and Severity Index-75, for example, was reached by 75% of patients on either dupilumab dose, compared with 28% and 26% , respectively, for those receiving steroids alone every 4 and every 2 weeks, the statement said.

Over the 16-week treatment period, overall rates of adverse events were 65% for those getting dupilumab every 4 weeks and 61% for every 2 weeks – compared with steroids alone (72% and 75%, respectively), the statement said.

The fully human monoclonal antibody inhibits signaling of the interleukin-4 and interleukin-13 proteins and is already approved as an add-on maintenance treatment in children aged 12 years and older with moderate to severe asthma (eosinophilic phenotype or oral-corticosteroid dependent) and in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis, according to the prescribing information.

[email protected]

The Food and Drug Administration has approved dupilumab for children aged 6-11 years with moderate to severe atopic dermatitis, the manufacturers announced.

The new indication is for children “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable,” Regeneron and Sanofi said in a press release, which points out that this is the first biologic approved for AD in this age group.

For children aged 6-11, the two available dupilumab (Dupixent) doses in prefilled syringes are given based on weight – 300 mg every 4 weeks for children between 15 to 29 kg and 200 mg every 2 weeks for children 30 to 59 kg – following an initial loading dose.

In phase 3 trials, children with severe AD who received dupilumab and topical corticosteroids improved significantly in overall disease severity, skin clearance, and itch, compared with those getting steroids alone. Eczema Area and Severity Index-75, for example, was reached by 75% of patients on either dupilumab dose, compared with 28% and 26% , respectively, for those receiving steroids alone every 4 and every 2 weeks, the statement said.

Over the 16-week treatment period, overall rates of adverse events were 65% for those getting dupilumab every 4 weeks and 61% for every 2 weeks – compared with steroids alone (72% and 75%, respectively), the statement said.

The fully human monoclonal antibody inhibits signaling of the interleukin-4 and interleukin-13 proteins and is already approved as an add-on maintenance treatment in children aged 12 years and older with moderate to severe asthma (eosinophilic phenotype or oral-corticosteroid dependent) and in adults with inadequately controlled chronic rhinosinusitis with nasal polyposis, according to the prescribing information.

[email protected]

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.

Bruce Jancin/MDedge News

In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.

Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.

Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.

“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
 

‘Inconclusive’ evidence

The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.

Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.

“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.

The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.

They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.

Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).

The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.

Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).

Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
 

Comorbidities and underlying conditions

The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.

“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.

No significant differences were found in distribution of demographics and comorbidities between the groups.
 

As good as it gets

“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.

Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.

After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.

Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).

“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.

“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.

“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.

“Let the science speak for itself”

Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”

Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”

Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.

He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”

Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”

Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”

The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.

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

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.

“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”

Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m² (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.

Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.

“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”

They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”

Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”

The researchers and Dr. Goldberg reported having no disclosures.

[email protected]

SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Here are the stories our MDedge editors across specialties think you need to know about today:

Remdesivir trial data published

Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.

FDA approves contraceptive gel

The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.

COVID-19 lessons from one cancer center

Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.

Convalescent plasma: Hope or hype?

There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.

New rosacea treatment guidelines

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.

For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.

Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.

zimmytws/Thinkstock

Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?

What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?

Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?

My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.

Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.

Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.

Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.

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.” Email him at [email protected].

Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.

zimmytws/Thinkstock

Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?

What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?

Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?

My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.

Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.

Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.

Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.

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.” Email him at [email protected].

Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.

zimmytws/Thinkstock

Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?

What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?

Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?

My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.

Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.

Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.

Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.

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.” Email him at [email protected].

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, instead of being assigned into artificially distinct subtype categories, as was previously practiced, according to an update on options for managing rosacea published in the Journal of the American Academy of Dermatology.

The update, by the National Rosacea Society Expert Committee, is based on a review of the evidence, and is a follow-up to the classification system for rosacea that was updated in 2017, which recommended classification of rosacea based on phenotype (Am Acad Dermatol. 2018;78:148-155).

The key take-away is “that patients shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” lead author of the management update, Diane Thiboutot, MD, professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey, said in an interview.

“There is an opportunity for physicians to recognize that the symptom complex of rosacea differs widely and treatments should be selected to address the symptoms experienced by the patient, particularly with regard to ocular rosacea,” she said.

Until there were updated guidelines on rosacea classification, published in 2018, relying primarily on diagnostic subtypes “tended to limit consideration of the full range of potential signs and symptoms as well as the frequent simultaneous occurrence of more than one subtype or the potential progression from one subtype to another,” Dr. Thiboutot and coauthors wrote in the management update (J Am Acad Dermatol 2020;82:1501-10).

“The more we learn, the more complex rosacea becomes,” she said in the interview. “The clinical manifestations of rosacea are so varied, ranging from skin erythema, eye findings, papules and pustules to rhinophyma, [that] it calls into question, if all of these are actually one disease (rosacea) or if they represent localized reaction patterns to a multitude of stimuli that vary among individuals.”

Etiology and impact

Dr. Thiboutot and colleagues summarized the management options and recommendations from a committee of 27 experts who assessed the data on rosacea therapies using the updated standard classification system. They also highlighted the suspected systemic nature of rosacea etiology and its psychosocial impact on those with the condition.

“Recent studies have found an association between rosacea and increased risk of a growing number of systemic disorders, including cardiovascular, gastrointestinal, neurologic, and autoimmune diseases as well as certain types of cancer,” the authors wrote. “These findings further elevate the clinical significance of rosacea as growing evidence of its potential link with systemic inflammation is increasingly understood.”

Dr. Thiboutot said that research has implicated both the innate and adaptive immune systems and the neuromuscular system in rosacea’s underpinnings.

“Many of the triggers associated with clinical exacerbation of rosacea are known to activate the immune system and/or the neurovasculature, such as demodex, sunlight, alcohol, and changes in temperature,” she said, adding that therapies targeting the neurovascular effects of rosacea are particularly needed.

More than 50% of patients with rosacea have ocular manifestations, with symptoms such as “dryness, burning and stinging, light sensitivity, blurred vision, and foreign body sensation,” the authors reported.
 

Diagnosis and management

Without definitive laboratory tests, it’s essential that the clinical diagnosis takes into account not only the physical examination findings, but also patient history, the authors stressed, since “some features may not be visually evident or present at the time of the patient’s visit.”

The authors also recommend taking into account patients’ perception and response to their appearance and its effects on their emotional, social, and professional lives when selecting interventions.

“Rosacea’s unsightly and conspicuous appearance often has significant emotional ramifications, potentially resulting in depression or anxiety, and frequently interferes with social and occupational interactions,” the authors wrote. “It may also be advisable to remind patients that normalization of skin tone and color is the goal rather than complete eradication of facial coloration, which can leave the face with a sallow appearance.”

Therapy will often require multiple agents, such as topical and oral agents for inflammatory papules/pustules of rosacea. If insufficient, adjunctive therapy with oral antibiotics or retinoids may be options, though the latter requires prevention of pregnancy during treatment. The authors also discussed pharmacological treatments for facial erythema and flushing, with all these drugs organized in tables according to symptoms and their levels of evidence and effectiveness.

Despite limited clinical evidence, the authors noted success with two types of laser therapy – pulsed-dye and potassium titanyl phosphate – for telangiectasia and erythema. They also noted the option of intense pulsed light for flushing, ocular symptoms, and meibomian gland dysfunction, and of ablative lasers for rhinophymatous nose. But they highlighted the importance of being cautious when using these therapies on darker skin.

In their discussion of ocular rosacea, the authors described the various manifestations and the two “mainstays” of treatment: “eyelash hygiene and oral [omega-3] supplementation, followed by topical azithromycin or calcineurin inhibitors.” In addition to pharmacological and light therapy options, attention to environmental contributors and conscientious skin care regimens can benefit patients with rosacea as well.

“Clinicians may advise patients to keep a daily diary of lifestyle and environmental factors that appear to affect their rosacea to help identify and avoid their personal triggers,” the authors wrote. “The most common factors are sun exposure, emotional stress, hot weather, wind, heavy exercise, alcohol consumption, hot baths, cold weather, spicy foods, humidity, indoor heat, certain skin-care products, heated beverages, certain medications, medical conditions, certain fruits, marinated meats, certain vegetables, and dairy products.”

The paper also emphasizes the importance of gentle skin care given the highly sensitive and easily irritated skin of patients with rosacea. Sunscreen use, particularly with mineral sunscreens that provide physical barriers and reflect ultraviolet light, should be a key aspect of patients’ skin care, and clinicians should advise patients to seek out gentle, nonirritating cleansers.

Funding was provided by the National Rosacea Society, which receives funding from patients and corporations that include Aclaris Therapeutics, Allergan, Bayer, Cutanea Life Sciences, and Galderma Laboratories. Dr. Thiboutot consults for Galderma. Six of the other nine coauthors have financial links to industry through advisory boards, consulting, or research funding.

SOURCE: Thiboutot D et al. J Am Acad Dermatol. 2020;82:1501-10.

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, instead of being assigned into artificially distinct subtype categories, as was previously practiced, according to an update on options for managing rosacea published in the Journal of the American Academy of Dermatology.

The update, by the National Rosacea Society Expert Committee, is based on a review of the evidence, and is a follow-up to the classification system for rosacea that was updated in 2017, which recommended classification of rosacea based on phenotype (Am Acad Dermatol. 2018;78:148-155).

The key take-away is “that patients shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” lead author of the management update, Diane Thiboutot, MD, professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey, said in an interview.

“There is an opportunity for physicians to recognize that the symptom complex of rosacea differs widely and treatments should be selected to address the symptoms experienced by the patient, particularly with regard to ocular rosacea,” she said.

Until there were updated guidelines on rosacea classification, published in 2018, relying primarily on diagnostic subtypes “tended to limit consideration of the full range of potential signs and symptoms as well as the frequent simultaneous occurrence of more than one subtype or the potential progression from one subtype to another,” Dr. Thiboutot and coauthors wrote in the management update (J Am Acad Dermatol 2020;82:1501-10).

“The more we learn, the more complex rosacea becomes,” she said in the interview. “The clinical manifestations of rosacea are so varied, ranging from skin erythema, eye findings, papules and pustules to rhinophyma, [that] it calls into question, if all of these are actually one disease (rosacea) or if they represent localized reaction patterns to a multitude of stimuli that vary among individuals.”

Etiology and impact

Dr. Thiboutot and colleagues summarized the management options and recommendations from a committee of 27 experts who assessed the data on rosacea therapies using the updated standard classification system. They also highlighted the suspected systemic nature of rosacea etiology and its psychosocial impact on those with the condition.

“Recent studies have found an association between rosacea and increased risk of a growing number of systemic disorders, including cardiovascular, gastrointestinal, neurologic, and autoimmune diseases as well as certain types of cancer,” the authors wrote. “These findings further elevate the clinical significance of rosacea as growing evidence of its potential link with systemic inflammation is increasingly understood.”

Dr. Thiboutot said that research has implicated both the innate and adaptive immune systems and the neuromuscular system in rosacea’s underpinnings.

“Many of the triggers associated with clinical exacerbation of rosacea are known to activate the immune system and/or the neurovasculature, such as demodex, sunlight, alcohol, and changes in temperature,” she said, adding that therapies targeting the neurovascular effects of rosacea are particularly needed.

More than 50% of patients with rosacea have ocular manifestations, with symptoms such as “dryness, burning and stinging, light sensitivity, blurred vision, and foreign body sensation,” the authors reported.
 

Diagnosis and management

Without definitive laboratory tests, it’s essential that the clinical diagnosis takes into account not only the physical examination findings, but also patient history, the authors stressed, since “some features may not be visually evident or present at the time of the patient’s visit.”

The authors also recommend taking into account patients’ perception and response to their appearance and its effects on their emotional, social, and professional lives when selecting interventions.

“Rosacea’s unsightly and conspicuous appearance often has significant emotional ramifications, potentially resulting in depression or anxiety, and frequently interferes with social and occupational interactions,” the authors wrote. “It may also be advisable to remind patients that normalization of skin tone and color is the goal rather than complete eradication of facial coloration, which can leave the face with a sallow appearance.”

Therapy will often require multiple agents, such as topical and oral agents for inflammatory papules/pustules of rosacea. If insufficient, adjunctive therapy with oral antibiotics or retinoids may be options, though the latter requires prevention of pregnancy during treatment. The authors also discussed pharmacological treatments for facial erythema and flushing, with all these drugs organized in tables according to symptoms and their levels of evidence and effectiveness.

Despite limited clinical evidence, the authors noted success with two types of laser therapy – pulsed-dye and potassium titanyl phosphate – for telangiectasia and erythema. They also noted the option of intense pulsed light for flushing, ocular symptoms, and meibomian gland dysfunction, and of ablative lasers for rhinophymatous nose. But they highlighted the importance of being cautious when using these therapies on darker skin.

In their discussion of ocular rosacea, the authors described the various manifestations and the two “mainstays” of treatment: “eyelash hygiene and oral [omega-3] supplementation, followed by topical azithromycin or calcineurin inhibitors.” In addition to pharmacological and light therapy options, attention to environmental contributors and conscientious skin care regimens can benefit patients with rosacea as well.

“Clinicians may advise patients to keep a daily diary of lifestyle and environmental factors that appear to affect their rosacea to help identify and avoid their personal triggers,” the authors wrote. “The most common factors are sun exposure, emotional stress, hot weather, wind, heavy exercise, alcohol consumption, hot baths, cold weather, spicy foods, humidity, indoor heat, certain skin-care products, heated beverages, certain medications, medical conditions, certain fruits, marinated meats, certain vegetables, and dairy products.”

The paper also emphasizes the importance of gentle skin care given the highly sensitive and easily irritated skin of patients with rosacea. Sunscreen use, particularly with mineral sunscreens that provide physical barriers and reflect ultraviolet light, should be a key aspect of patients’ skin care, and clinicians should advise patients to seek out gentle, nonirritating cleansers.

Funding was provided by the National Rosacea Society, which receives funding from patients and corporations that include Aclaris Therapeutics, Allergan, Bayer, Cutanea Life Sciences, and Galderma Laboratories. Dr. Thiboutot consults for Galderma. Six of the other nine coauthors have financial links to industry through advisory boards, consulting, or research funding.

SOURCE: Thiboutot D et al. J Am Acad Dermatol. 2020;82:1501-10.

Patients with rosacea should receive treatments based on their phenotype and specific symptoms, instead of being assigned into artificially distinct subtype categories, as was previously practiced, according to an update on options for managing rosacea published in the Journal of the American Academy of Dermatology.

The update, by the National Rosacea Society Expert Committee, is based on a review of the evidence, and is a follow-up to the classification system for rosacea that was updated in 2017, which recommended classification of rosacea based on phenotype (Am Acad Dermatol. 2018;78:148-155).

The key take-away is “that patients shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” lead author of the management update, Diane Thiboutot, MD, professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey, said in an interview.

“There is an opportunity for physicians to recognize that the symptom complex of rosacea differs widely and treatments should be selected to address the symptoms experienced by the patient, particularly with regard to ocular rosacea,” she said.

Until there were updated guidelines on rosacea classification, published in 2018, relying primarily on diagnostic subtypes “tended to limit consideration of the full range of potential signs and symptoms as well as the frequent simultaneous occurrence of more than one subtype or the potential progression from one subtype to another,” Dr. Thiboutot and coauthors wrote in the management update (J Am Acad Dermatol 2020;82:1501-10).

“The more we learn, the more complex rosacea becomes,” she said in the interview. “The clinical manifestations of rosacea are so varied, ranging from skin erythema, eye findings, papules and pustules to rhinophyma, [that] it calls into question, if all of these are actually one disease (rosacea) or if they represent localized reaction patterns to a multitude of stimuli that vary among individuals.”

Etiology and impact

Dr. Thiboutot and colleagues summarized the management options and recommendations from a committee of 27 experts who assessed the data on rosacea therapies using the updated standard classification system. They also highlighted the suspected systemic nature of rosacea etiology and its psychosocial impact on those with the condition.

“Recent studies have found an association between rosacea and increased risk of a growing number of systemic disorders, including cardiovascular, gastrointestinal, neurologic, and autoimmune diseases as well as certain types of cancer,” the authors wrote. “These findings further elevate the clinical significance of rosacea as growing evidence of its potential link with systemic inflammation is increasingly understood.”

Dr. Thiboutot said that research has implicated both the innate and adaptive immune systems and the neuromuscular system in rosacea’s underpinnings.

“Many of the triggers associated with clinical exacerbation of rosacea are known to activate the immune system and/or the neurovasculature, such as demodex, sunlight, alcohol, and changes in temperature,” she said, adding that therapies targeting the neurovascular effects of rosacea are particularly needed.

More than 50% of patients with rosacea have ocular manifestations, with symptoms such as “dryness, burning and stinging, light sensitivity, blurred vision, and foreign body sensation,” the authors reported.
 

Diagnosis and management

Without definitive laboratory tests, it’s essential that the clinical diagnosis takes into account not only the physical examination findings, but also patient history, the authors stressed, since “some features may not be visually evident or present at the time of the patient’s visit.”

The authors also recommend taking into account patients’ perception and response to their appearance and its effects on their emotional, social, and professional lives when selecting interventions.

“Rosacea’s unsightly and conspicuous appearance often has significant emotional ramifications, potentially resulting in depression or anxiety, and frequently interferes with social and occupational interactions,” the authors wrote. “It may also be advisable to remind patients that normalization of skin tone and color is the goal rather than complete eradication of facial coloration, which can leave the face with a sallow appearance.”

Therapy will often require multiple agents, such as topical and oral agents for inflammatory papules/pustules of rosacea. If insufficient, adjunctive therapy with oral antibiotics or retinoids may be options, though the latter requires prevention of pregnancy during treatment. The authors also discussed pharmacological treatments for facial erythema and flushing, with all these drugs organized in tables according to symptoms and their levels of evidence and effectiveness.

Despite limited clinical evidence, the authors noted success with two types of laser therapy – pulsed-dye and potassium titanyl phosphate – for telangiectasia and erythema. They also noted the option of intense pulsed light for flushing, ocular symptoms, and meibomian gland dysfunction, and of ablative lasers for rhinophymatous nose. But they highlighted the importance of being cautious when using these therapies on darker skin.

In their discussion of ocular rosacea, the authors described the various manifestations and the two “mainstays” of treatment: “eyelash hygiene and oral [omega-3] supplementation, followed by topical azithromycin or calcineurin inhibitors.” In addition to pharmacological and light therapy options, attention to environmental contributors and conscientious skin care regimens can benefit patients with rosacea as well.

“Clinicians may advise patients to keep a daily diary of lifestyle and environmental factors that appear to affect their rosacea to help identify and avoid their personal triggers,” the authors wrote. “The most common factors are sun exposure, emotional stress, hot weather, wind, heavy exercise, alcohol consumption, hot baths, cold weather, spicy foods, humidity, indoor heat, certain skin-care products, heated beverages, certain medications, medical conditions, certain fruits, marinated meats, certain vegetables, and dairy products.”

The paper also emphasizes the importance of gentle skin care given the highly sensitive and easily irritated skin of patients with rosacea. Sunscreen use, particularly with mineral sunscreens that provide physical barriers and reflect ultraviolet light, should be a key aspect of patients’ skin care, and clinicians should advise patients to seek out gentle, nonirritating cleansers.

Funding was provided by the National Rosacea Society, which receives funding from patients and corporations that include Aclaris Therapeutics, Allergan, Bayer, Cutanea Life Sciences, and Galderma Laboratories. Dr. Thiboutot consults for Galderma. Six of the other nine coauthors have financial links to industry through advisory boards, consulting, or research funding.

SOURCE: Thiboutot D et al. J Am Acad Dermatol. 2020;82:1501-10.

The Food and Drug Administration has approved Phexxi (lactic acid, citric acid and potassium bitartrate) to prevent pregnancy in women of reproductive potential.

Evofem Biosciences expects to release Phexxi – the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5 – in September 2020 alongside the Phexxi Concierge Experience, a comprehensive patient and health care provider telemedicine support system, according to the company’s press release. The service is designed to provide physicians with on-demand educational support, and to speed and simplify women’s access to Phexxi.

In an open-label multicenter trial, women aged 18-35 with regular menstrual cycles intravaginally administered a 5-gram dose of Phexxi vaginal gel up to 1 hour prior to intercourse; they did so for up to seven cycles. There were 101 pregnancies in 1,183 subjects during 4,769 cycles. The 7-cycle cumulative pregnancy rate was 14% (95% confidence interval: 10.0%, 17.5%).

The most common adverse events associated with Phexxi were vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, bacterial vaginosis, vaginal discharge, dysuria, and vulvovaginal pain.

[email protected]

The Food and Drug Administration has approved Phexxi (lactic acid, citric acid and potassium bitartrate) to prevent pregnancy in women of reproductive potential.

Evofem Biosciences expects to release Phexxi – the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5 – in September 2020 alongside the Phexxi Concierge Experience, a comprehensive patient and health care provider telemedicine support system, according to the company’s press release. The service is designed to provide physicians with on-demand educational support, and to speed and simplify women’s access to Phexxi.

In an open-label multicenter trial, women aged 18-35 with regular menstrual cycles intravaginally administered a 5-gram dose of Phexxi vaginal gel up to 1 hour prior to intercourse; they did so for up to seven cycles. There were 101 pregnancies in 1,183 subjects during 4,769 cycles. The 7-cycle cumulative pregnancy rate was 14% (95% confidence interval: 10.0%, 17.5%).

The most common adverse events associated with Phexxi were vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, bacterial vaginosis, vaginal discharge, dysuria, and vulvovaginal pain.

[email protected]

The Food and Drug Administration has approved Phexxi (lactic acid, citric acid and potassium bitartrate) to prevent pregnancy in women of reproductive potential.

Evofem Biosciences expects to release Phexxi – the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5 – in September 2020 alongside the Phexxi Concierge Experience, a comprehensive patient and health care provider telemedicine support system, according to the company’s press release. The service is designed to provide physicians with on-demand educational support, and to speed and simplify women’s access to Phexxi.

In an open-label multicenter trial, women aged 18-35 with regular menstrual cycles intravaginally administered a 5-gram dose of Phexxi vaginal gel up to 1 hour prior to intercourse; they did so for up to seven cycles. There were 101 pregnancies in 1,183 subjects during 4,769 cycles. The 7-cycle cumulative pregnancy rate was 14% (95% confidence interval: 10.0%, 17.5%).

The most common adverse events associated with Phexxi were vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, bacterial vaginosis, vaginal discharge, dysuria, and vulvovaginal pain.

[email protected]

On March 31, soon after the Food and Drug Administration authorized emergency use of antibody-packed plasma from recovered patients with COVID-19, Marisa Leuzzi became the first donor at an American Red Cross center. She hoped it could help her aunt, Renee Bannister, who was failing after 3 weeks on a ventilator at Virtua Hospital in Voorhees, N.J.

It may have worked; 11 days after receiving the plasma, Ms. Bannister was weaned off the ventilator and she is now awake and speaking, said Red Cross spokesperson Stephanie Rendon.

This kind of anecdote is fueling demand for the therapy, which can be provided through an expanded access program led by the Mayo Clinic, backed by the FDA, and the plasma paid for by the U.S. Department of Health & Human Services. But while this program is collecting safety and outcomes data, it’s not a randomized, controlled trial.

Others, however, are pursuing that data. At least a dozen researchers are investigating the potential of plasma – both as a treatment and whether it could act as a stand-in for a vaccine until one is developed.

“One of the things I don’t want this to be is the flavor of the month,” Shmuel Shoham, MD, associate professor of medicine at Johns Hopkins University, said in an interview.

Dr. Shoham, principal investigator for a study evaluating convalescent plasma to prevent the infection in high-risk individuals, said some clinicians, desperate for any treatment, have tried potential therapies such as hydroxychloroquine and remdesivir without evidence of safety or efficacy in COVID-19.

The National Institutes of Health recently said something similar for convalescent plasma, that “there are insufficient clinical data to recommend either for or against” its use for COVID-19.

But plasma has promise, according to a Johns Hopkins School of Medicine’s Bloomberg Distinguished Professor, Arturo Casadevall, MD, PhD, in Baltimore, and Liise-anne Pirofski, MD, a professor at Albert Einstein College of Medicine, New York. They lay out the case for convalescent plasma in an article published online March 13 in the Journal of Clinical Investigation. Passive antibody therapy, they wrote, has been used to stem polio, measles, mumps, and influenza, and more recently has shown some success against SARS-CoV-1 and Middle East respiratory syndrome (MERS).

“The special attraction of this modality of treatment is that, unlike vaccines or newly developed drugs, it could, in principle, be made available very rapidly,” said researchers with the National COVID-19 Convalescent Plasma Project, which includes physicians and scientists from 57 institutions in 46 states. But where principle veers from reality is in availability of the plasma itself, and donors are in short supply.
 

Aiming to prevent infection

So far, the FDA has approved 12 plasma trials – including Dr. Shoham’s – and the NIH’s clinicaltrials.gov lists more than two dozen convalescent plasma studies in the United States and elsewhere.

Most are single-arm trials to determine if one infusion can decrease the need for intubation or help those on a ventilator improve. Two others, one at Johns Hopkins and one at Stanford (Calif.) Hospital are investigating whether convalescent plasma might be used before severe disease sets in.

“A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease,” Dr. Casadevall and Dr. Pirofski wrote.

Stanford’s randomized, double-blind study will evaluate regular versus convalescent plasma in ED patients who are not sick enough to require hospitalization.

The Johns Hopkins trial, which aims to protect against infection in the first place, will begin at Johns Hopkins, Baltimore, and at Hopkins-affiliated hospitals throughout Maryland, Dr. Shoham said. He hopes it will expand nationwide eventually, and said that they expect to enroll the first patients soon.

To start, the prevention study will enroll only 150 patients, each of whom must have had close contact with someone who has COVID-19 within the previous 120 hours and be asymptomatic. The number of subjects is small, compared with the trial size of other potential therapies, and an issue, Shoham said, “that keeps me up at night.” But finding thousands of enrollees for plasma studies is hard, in part because it’s so difficult to recruit donors.

Participants will receive normal plasma (which will act as a placebo) or convalescent plasma.

The primary endpoint is cumulative incidence of COVID-19, defined as symptoms and a polymerase chain reaction–positive test; participants will be tracked for 90 days. Hospitals and health care workers could then decide if they want to use the therapy, he said.

The study will not answer whether participants will continue to have antibodies beyond the 90 days. Convalescent plasma is given as a rapid response to an emergent pathogen – a short-term boost of immunity rather than a long-term therapeutic.
 

What can we learn from expanded access?

Meanwhile, some 2,200 hospitals are participating in the expanded access program being led by the Mayo Clinic nationwide; more than 9,000 patients had received infusions at press time.

One participant is Northwell Health, a 23-hospital system that sprawls across the U.S. COVID epicenter: four of the five boroughs of New York City and Long Island.

Convalescent plasma is an in-demand therapy, said Christina Brennan, MD, vice president of clinical research at Northwell. “We get patients, family members, they say my family member is at X hospital – if it’s not being offered there, can you have them transferred?” she said in an interview.

When Northwell – through the New York Blood Bank – opened up donor registration, 800 people signed up in the first 24 hours, Dr. Brennan said. As of mid-May, 527 patients had received a transfusion.
 

Who’s the best donor and when should donation occur?

The Red Cross, hospitals, and independent blood banks are all soliciting donors, who can sign up at the Red Cross website. The FDA recommends that donors have a history of COVID-19 as confirmed by molecular or antibody testing, be symptom free for 14 days, have a negative follow-up molecular test, and be virus free at the time of collection. The FDA also suggests measuring a donor’s SARS-CoV-2 neutralizing antibody titers, if available, with a recommendation of at least 1:160.

But questions remain, such as whether there is a theoretical risk for antibody-dependent enhancement (ADE) of infection with SARS-CoV-2. “Antibodies to one type of coronavirus could enhance infection to another viral strain,” of coronavirus, Dr. Casadevall wrote. ADE has been observed in both severe acute respiratory syndrome (SARS) and MERS.

The other risk is that donors may still be shedding active virus. While the FDA suggests that donors are unlikely to still be infectious 14 days after infection, that is as of yet unproven. Both COVID-19 diagnostics and antibody tests have high rates of false negatives, which raises the specter that infection could be spread via the plasma donation.

Daniele Focosi, MD, PhD, from Pisa (Italy) University Hospital and colleagues raise that concern in a preprint review on convalescent plasma in COVID-19. “Although the recipient is already infected, theoretically transmission of more infectious particles could worsen clinical conditions,” they wrote, noting that “such a concern can be somewhat reduced by treatment with modern pathogen inactivation techniques.”

No evidence exists that SARS-CoV-2 can be transmitted through blood, but “we don’t know for sure,” Dr. Shoham said in an interview. A reassuring point: Even those with severe infection do not have viral RNA in their blood, he said, adding, “We don’t think there’s going to be viral transmission of this particular virus with transfusion.”

For another highly infectious pathogen, the Ebola virus, the World Health Organization recommended in 2014 that potential plasma donors wait at least 28 days after infection.

It’s also not known how long SARS-CoV-2 antibodies persist in the blood; longer viability could mean a longer donation window. Dr. Focosi noted that a previous Chinese study had shown that SARS-specific antibodies in people infected with the first SARS virus, SARS-CoV-1, persisted for 2 years.

Dr. Casadevall and Dr. Pirofski have disclosed no relevant financial relationships. Shoham has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

On March 31, soon after the Food and Drug Administration authorized emergency use of antibody-packed plasma from recovered patients with COVID-19, Marisa Leuzzi became the first donor at an American Red Cross center. She hoped it could help her aunt, Renee Bannister, who was failing after 3 weeks on a ventilator at Virtua Hospital in Voorhees, N.J.

It may have worked; 11 days after receiving the plasma, Ms. Bannister was weaned off the ventilator and she is now awake and speaking, said Red Cross spokesperson Stephanie Rendon.

This kind of anecdote is fueling demand for the therapy, which can be provided through an expanded access program led by the Mayo Clinic, backed by the FDA, and the plasma paid for by the U.S. Department of Health & Human Services. But while this program is collecting safety and outcomes data, it’s not a randomized, controlled trial.

Others, however, are pursuing that data. At least a dozen researchers are investigating the potential of plasma – both as a treatment and whether it could act as a stand-in for a vaccine until one is developed.

“One of the things I don’t want this to be is the flavor of the month,” Shmuel Shoham, MD, associate professor of medicine at Johns Hopkins University, said in an interview.

Dr. Shoham, principal investigator for a study evaluating convalescent plasma to prevent the infection in high-risk individuals, said some clinicians, desperate for any treatment, have tried potential therapies such as hydroxychloroquine and remdesivir without evidence of safety or efficacy in COVID-19.

The National Institutes of Health recently said something similar for convalescent plasma, that “there are insufficient clinical data to recommend either for or against” its use for COVID-19.

But plasma has promise, according to a Johns Hopkins School of Medicine’s Bloomberg Distinguished Professor, Arturo Casadevall, MD, PhD, in Baltimore, and Liise-anne Pirofski, MD, a professor at Albert Einstein College of Medicine, New York. They lay out the case for convalescent plasma in an article published online March 13 in the Journal of Clinical Investigation. Passive antibody therapy, they wrote, has been used to stem polio, measles, mumps, and influenza, and more recently has shown some success against SARS-CoV-1 and Middle East respiratory syndrome (MERS).

“The special attraction of this modality of treatment is that, unlike vaccines or newly developed drugs, it could, in principle, be made available very rapidly,” said researchers with the National COVID-19 Convalescent Plasma Project, which includes physicians and scientists from 57 institutions in 46 states. But where principle veers from reality is in availability of the plasma itself, and donors are in short supply.
 

Aiming to prevent infection

So far, the FDA has approved 12 plasma trials – including Dr. Shoham’s – and the NIH’s clinicaltrials.gov lists more than two dozen convalescent plasma studies in the United States and elsewhere.

Most are single-arm trials to determine if one infusion can decrease the need for intubation or help those on a ventilator improve. Two others, one at Johns Hopkins and one at Stanford (Calif.) Hospital are investigating whether convalescent plasma might be used before severe disease sets in.

“A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease,” Dr. Casadevall and Dr. Pirofski wrote.

Stanford’s randomized, double-blind study will evaluate regular versus convalescent plasma in ED patients who are not sick enough to require hospitalization.

The Johns Hopkins trial, which aims to protect against infection in the first place, will begin at Johns Hopkins, Baltimore, and at Hopkins-affiliated hospitals throughout Maryland, Dr. Shoham said. He hopes it will expand nationwide eventually, and said that they expect to enroll the first patients soon.

To start, the prevention study will enroll only 150 patients, each of whom must have had close contact with someone who has COVID-19 within the previous 120 hours and be asymptomatic. The number of subjects is small, compared with the trial size of other potential therapies, and an issue, Shoham said, “that keeps me up at night.” But finding thousands of enrollees for plasma studies is hard, in part because it’s so difficult to recruit donors.

Participants will receive normal plasma (which will act as a placebo) or convalescent plasma.

The primary endpoint is cumulative incidence of COVID-19, defined as symptoms and a polymerase chain reaction–positive test; participants will be tracked for 90 days. Hospitals and health care workers could then decide if they want to use the therapy, he said.

The study will not answer whether participants will continue to have antibodies beyond the 90 days. Convalescent plasma is given as a rapid response to an emergent pathogen – a short-term boost of immunity rather than a long-term therapeutic.
 

What can we learn from expanded access?

Meanwhile, some 2,200 hospitals are participating in the expanded access program being led by the Mayo Clinic nationwide; more than 9,000 patients had received infusions at press time.

One participant is Northwell Health, a 23-hospital system that sprawls across the U.S. COVID epicenter: four of the five boroughs of New York City and Long Island.

Convalescent plasma is an in-demand therapy, said Christina Brennan, MD, vice president of clinical research at Northwell. “We get patients, family members, they say my family member is at X hospital – if it’s not being offered there, can you have them transferred?” she said in an interview.

When Northwell – through the New York Blood Bank – opened up donor registration, 800 people signed up in the first 24 hours, Dr. Brennan said. As of mid-May, 527 patients had received a transfusion.
 

Who’s the best donor and when should donation occur?

The Red Cross, hospitals, and independent blood banks are all soliciting donors, who can sign up at the Red Cross website. The FDA recommends that donors have a history of COVID-19 as confirmed by molecular or antibody testing, be symptom free for 14 days, have a negative follow-up molecular test, and be virus free at the time of collection. The FDA also suggests measuring a donor’s SARS-CoV-2 neutralizing antibody titers, if available, with a recommendation of at least 1:160.

But questions remain, such as whether there is a theoretical risk for antibody-dependent enhancement (ADE) of infection with SARS-CoV-2. “Antibodies to one type of coronavirus could enhance infection to another viral strain,” of coronavirus, Dr. Casadevall wrote. ADE has been observed in both severe acute respiratory syndrome (SARS) and MERS.

The other risk is that donors may still be shedding active virus. While the FDA suggests that donors are unlikely to still be infectious 14 days after infection, that is as of yet unproven. Both COVID-19 diagnostics and antibody tests have high rates of false negatives, which raises the specter that infection could be spread via the plasma donation.

Daniele Focosi, MD, PhD, from Pisa (Italy) University Hospital and colleagues raise that concern in a preprint review on convalescent plasma in COVID-19. “Although the recipient is already infected, theoretically transmission of more infectious particles could worsen clinical conditions,” they wrote, noting that “such a concern can be somewhat reduced by treatment with modern pathogen inactivation techniques.”

No evidence exists that SARS-CoV-2 can be transmitted through blood, but “we don’t know for sure,” Dr. Shoham said in an interview. A reassuring point: Even those with severe infection do not have viral RNA in their blood, he said, adding, “We don’t think there’s going to be viral transmission of this particular virus with transfusion.”

For another highly infectious pathogen, the Ebola virus, the World Health Organization recommended in 2014 that potential plasma donors wait at least 28 days after infection.

It’s also not known how long SARS-CoV-2 antibodies persist in the blood; longer viability could mean a longer donation window. Dr. Focosi noted that a previous Chinese study had shown that SARS-specific antibodies in people infected with the first SARS virus, SARS-CoV-1, persisted for 2 years.

Dr. Casadevall and Dr. Pirofski have disclosed no relevant financial relationships. Shoham has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

On March 31, soon after the Food and Drug Administration authorized emergency use of antibody-packed plasma from recovered patients with COVID-19, Marisa Leuzzi became the first donor at an American Red Cross center. She hoped it could help her aunt, Renee Bannister, who was failing after 3 weeks on a ventilator at Virtua Hospital in Voorhees, N.J.

It may have worked; 11 days after receiving the plasma, Ms. Bannister was weaned off the ventilator and she is now awake and speaking, said Red Cross spokesperson Stephanie Rendon.

This kind of anecdote is fueling demand for the therapy, which can be provided through an expanded access program led by the Mayo Clinic, backed by the FDA, and the plasma paid for by the U.S. Department of Health & Human Services. But while this program is collecting safety and outcomes data, it’s not a randomized, controlled trial.

Others, however, are pursuing that data. At least a dozen researchers are investigating the potential of plasma – both as a treatment and whether it could act as a stand-in for a vaccine until one is developed.

“One of the things I don’t want this to be is the flavor of the month,” Shmuel Shoham, MD, associate professor of medicine at Johns Hopkins University, said in an interview.

Dr. Shoham, principal investigator for a study evaluating convalescent plasma to prevent the infection in high-risk individuals, said some clinicians, desperate for any treatment, have tried potential therapies such as hydroxychloroquine and remdesivir without evidence of safety or efficacy in COVID-19.

The National Institutes of Health recently said something similar for convalescent plasma, that “there are insufficient clinical data to recommend either for or against” its use for COVID-19.

But plasma has promise, according to a Johns Hopkins School of Medicine’s Bloomberg Distinguished Professor, Arturo Casadevall, MD, PhD, in Baltimore, and Liise-anne Pirofski, MD, a professor at Albert Einstein College of Medicine, New York. They lay out the case for convalescent plasma in an article published online March 13 in the Journal of Clinical Investigation. Passive antibody therapy, they wrote, has been used to stem polio, measles, mumps, and influenza, and more recently has shown some success against SARS-CoV-1 and Middle East respiratory syndrome (MERS).

“The special attraction of this modality of treatment is that, unlike vaccines or newly developed drugs, it could, in principle, be made available very rapidly,” said researchers with the National COVID-19 Convalescent Plasma Project, which includes physicians and scientists from 57 institutions in 46 states. But where principle veers from reality is in availability of the plasma itself, and donors are in short supply.
 

Aiming to prevent infection

So far, the FDA has approved 12 plasma trials – including Dr. Shoham’s – and the NIH’s clinicaltrials.gov lists more than two dozen convalescent plasma studies in the United States and elsewhere.

Most are single-arm trials to determine if one infusion can decrease the need for intubation or help those on a ventilator improve. Two others, one at Johns Hopkins and one at Stanford (Calif.) Hospital are investigating whether convalescent plasma might be used before severe disease sets in.

“A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease,” Dr. Casadevall and Dr. Pirofski wrote.

Stanford’s randomized, double-blind study will evaluate regular versus convalescent plasma in ED patients who are not sick enough to require hospitalization.

The Johns Hopkins trial, which aims to protect against infection in the first place, will begin at Johns Hopkins, Baltimore, and at Hopkins-affiliated hospitals throughout Maryland, Dr. Shoham said. He hopes it will expand nationwide eventually, and said that they expect to enroll the first patients soon.

To start, the prevention study will enroll only 150 patients, each of whom must have had close contact with someone who has COVID-19 within the previous 120 hours and be asymptomatic. The number of subjects is small, compared with the trial size of other potential therapies, and an issue, Shoham said, “that keeps me up at night.” But finding thousands of enrollees for plasma studies is hard, in part because it’s so difficult to recruit donors.

Participants will receive normal plasma (which will act as a placebo) or convalescent plasma.

The primary endpoint is cumulative incidence of COVID-19, defined as symptoms and a polymerase chain reaction–positive test; participants will be tracked for 90 days. Hospitals and health care workers could then decide if they want to use the therapy, he said.

The study will not answer whether participants will continue to have antibodies beyond the 90 days. Convalescent plasma is given as a rapid response to an emergent pathogen – a short-term boost of immunity rather than a long-term therapeutic.
 

What can we learn from expanded access?

Meanwhile, some 2,200 hospitals are participating in the expanded access program being led by the Mayo Clinic nationwide; more than 9,000 patients had received infusions at press time.

One participant is Northwell Health, a 23-hospital system that sprawls across the U.S. COVID epicenter: four of the five boroughs of New York City and Long Island.

Convalescent plasma is an in-demand therapy, said Christina Brennan, MD, vice president of clinical research at Northwell. “We get patients, family members, they say my family member is at X hospital – if it’s not being offered there, can you have them transferred?” she said in an interview.

When Northwell – through the New York Blood Bank – opened up donor registration, 800 people signed up in the first 24 hours, Dr. Brennan said. As of mid-May, 527 patients had received a transfusion.
 

Who’s the best donor and when should donation occur?

The Red Cross, hospitals, and independent blood banks are all soliciting donors, who can sign up at the Red Cross website. The FDA recommends that donors have a history of COVID-19 as confirmed by molecular or antibody testing, be symptom free for 14 days, have a negative follow-up molecular test, and be virus free at the time of collection. The FDA also suggests measuring a donor’s SARS-CoV-2 neutralizing antibody titers, if available, with a recommendation of at least 1:160.

But questions remain, such as whether there is a theoretical risk for antibody-dependent enhancement (ADE) of infection with SARS-CoV-2. “Antibodies to one type of coronavirus could enhance infection to another viral strain,” of coronavirus, Dr. Casadevall wrote. ADE has been observed in both severe acute respiratory syndrome (SARS) and MERS.

The other risk is that donors may still be shedding active virus. While the FDA suggests that donors are unlikely to still be infectious 14 days after infection, that is as of yet unproven. Both COVID-19 diagnostics and antibody tests have high rates of false negatives, which raises the specter that infection could be spread via the plasma donation.

Daniele Focosi, MD, PhD, from Pisa (Italy) University Hospital and colleagues raise that concern in a preprint review on convalescent plasma in COVID-19. “Although the recipient is already infected, theoretically transmission of more infectious particles could worsen clinical conditions,” they wrote, noting that “such a concern can be somewhat reduced by treatment with modern pathogen inactivation techniques.”

No evidence exists that SARS-CoV-2 can be transmitted through blood, but “we don’t know for sure,” Dr. Shoham said in an interview. A reassuring point: Even those with severe infection do not have viral RNA in their blood, he said, adding, “We don’t think there’s going to be viral transmission of this particular virus with transfusion.”

For another highly infectious pathogen, the Ebola virus, the World Health Organization recommended in 2014 that potential plasma donors wait at least 28 days after infection.

It’s also not known how long SARS-CoV-2 antibodies persist in the blood; longer viability could mean a longer donation window. Dr. Focosi noted that a previous Chinese study had shown that SARS-specific antibodies in people infected with the first SARS virus, SARS-CoV-1, persisted for 2 years.

Dr. Casadevall and Dr. Pirofski have disclosed no relevant financial relationships. Shoham has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Much-anticipated results from the National Institute of Allergy and Infectious Diseases’ clinical trial of remdesivir in COVID-19 patients published in the New England Journal of Medicine suggest remdesivir shortens the disease course for hospitalized COVID-19 patients.

The agency reported initial promising results from the study earlier this month, which prompted the Food and Drug Administration to issue an emergency use authorization (EUA) for the drug, but the full data and results have not been widely available until now.

In the study of 1,063 patients, the researchers found patients who received a 10-day course of remdesivir had a reduced recovery time of 11 days, compared with 15 days to recovery in the group that received a placebo. The findings also suggest remdesivir should be started, if possible, before patients have such severe pulmonary disease that they require mechanical ventilation, according to the study authors.

The published results are “completely consistent” with the NIAID’s earlier announcement, H. Clifford Lane, MD, deputy director for clinical research and special projects at the NIAID, said in an interview. “The benefit appeared to be the greatest for the patients who are hospitalized with severe disease who require supplemental oxygen.”

Given the limited supply of remdesivir, physicians have been eager to see the full data to ensure they use the drug most effectively, Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said in an interview. Hospitals in states across the country, including New York, Michigan, and Washington, have received limited supplies of the drug in the last couple of weeks since the FDA’s authorization.

“I am losing my patience waiting for #remdesivir data. I was willing to give them a week to verify the numbers, triple proof the tables, cautiously frame conclusions. But it’s gone on too long. We are rationing with no rationale. We are floating on whisps [sic] of data, adrift,” Kate Stephenson, MD, an infectious diseases specialist at the Center for Virology and Vaccine Research at Harvard Medical School, Boston, wrote on Twitter May 18. After reading the paper, she tweeted Friday evening that she was “relieved to see convincing benefit – I was starting to worry!”

In the midst of a public health crisis, however, it is not unusual to make an announcement about trial results before the full dataset has been analyzed, said Dr. Lane. The NIAID followed a similar playbook for the PALM trial evaluating possible Ebola treatments in the Democratic Republic of Congo, with the independent monitoring board recommending the trial be terminated early in response to positive results from two of the four candidate drugs.

“When you have a result you think is of public health importance, you don’t wait for it to be published in a peer-reviewed journal,” said Dr. Lane, a coauthor of the study. The lag time from announcement to study publication was a result of the time it took to write up the paper for publication and go through peer review, Dr. Lane added. He also noted that the FDA had access to the data when the agency wrote its guidance for physicians administering the drug to patients under the EUA.

The authors opted not to publish the initial findings on a preprint server because they felt it was important to undergo peer review, said Dr. Lane. “The last thing you want for something this critical is for incomplete data to be out there, or you don’t have everything audited to the level that you want.”

 

Trial details

In the ACTT-1 randomized, placebo-controlled, double-blinded trial, researchers enrolled 1,063 patients from Feb. 21 to April 19, 2020, at 60 trial sites and 13 subsites worldwide (45 sites in the United States). The remdesivir group had 541 patients, and the placebo group had 522. A small number of patients (49 in the remdesivir group and 53 in the placebo group) discontinued treatment before day 10 because of an adverse event or withdrawn consent. When data collection for this preliminary analysis ended in late April, 301 patients had not recovered and had not completed their final follow-up visit.

Most of the patients had one (27%) or more (52.1%) preexisting conditions, including hypertension (49.6%), obesity (37%), and type 2 diabetes mellitus (29.7%). Mean patient age was 58.9 years, and the majority of patients were men (64.3%). The median number of days from symptom onset to randomization was 9, and 53.6% of the patients were white, 20.6% were black, 12.6% were Asian, 23.4% were Hispanic or Latino, and the ethnicity of 13.6% were not reported or reported as other.

Patients received one 200-mg loading dose on the first day of the trial, and then one 100-mg maintenance dose every day for days 2 through 10, or until discharge or death. Patients in the control group of the study received a matching placebo on the same schedule and volume. The clinical status of each patient was assessed every day, from day 1 through day 29 of his or her hospital stay, according to an eight-category ordinal scale.

Time to recovery was defined as the first day during the 28-day enrollment period that a patient’s clinical status met a 1 (not hospitalization, no activity limitations), 2 (not hospitalized, activity limitation, oxygen requirement or both), or 3 (hospitalized, not requiring supplemental oxygen or medical care if hospitalization was extended for infection-control reasons) on the eight-category scale. A score of 4 indicated a patient was hospitalized and needed ongoing medical care, but did not require supplemental oxygen; a score of 8 signified death.

The analysis found remdesivir patients had a median time to recovery of 11 days, compared with the median 15 days for patients on the placebo (rate ratio for recovery, 1.32; 95% confidence interval, 1.12-1.55; P < .001). Mortality was also lower in the remdesivir group (hazard ratio for death, 0.70; 95% CI, 0.47-1.04), but the result was not statistically significant. By 14 days, the Kaplan-Meier estimate of mortality was 7.1 % in the remdesivir group and 11.9% in the placebo group.

Patients receiving oxygen, but not yet requiring high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation, seemed to fare best from treatment with remdesivir (these patients had a baseline ordinal score of 5). That may be a result of the larger sample size of these patients, the researchers note in the study. The study authors were unable to estimate the recovery time for the most severely ill patients (category 7), possibly because the follow-up time was too short to fully evaluate this subgroup.

“There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Dr. Kaul, who was not involved in the study, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.”

Dr. Kaul said there is still the possibility that remdesivir could benefit patients on mechanical ventilation, but “clinicians will have to determine if the evidence suggesting no benefit in those who are intubated is strong enough to justify using this currently scarce resource in that population versus limiting use to those requiring oxygen but not on mechanical ventilation.”

Site investigators estimated that just four serious adverse events (two in each group) in enrolled patients were related to remdesivir or placebo. No deaths were attributed to the treatments, although acute respiratory failure, hypotension, acute kidney injury, and viral pneumonia were slightly more common in patients receiving the placebo than those receiving remdesivir.

The researchers plan to publish a follow-up study in the coming weeks or months, after the full cohort has completed 28 days of follow-up, Dr. Lane said. In future studies, the agency will likely focus on comparing remdesivir with combinations of remdesivir with other treatments, like the anti-inflammatory baricitinib.

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

Much-anticipated results from the National Institute of Allergy and Infectious Diseases’ clinical trial of remdesivir in COVID-19 patients published in the New England Journal of Medicine suggest remdesivir shortens the disease course for hospitalized COVID-19 patients.

The agency reported initial promising results from the study earlier this month, which prompted the Food and Drug Administration to issue an emergency use authorization (EUA) for the drug, but the full data and results have not been widely available until now.

In the study of 1,063 patients, the researchers found patients who received a 10-day course of remdesivir had a reduced recovery time of 11 days, compared with 15 days to recovery in the group that received a placebo. The findings also suggest remdesivir should be started, if possible, before patients have such severe pulmonary disease that they require mechanical ventilation, according to the study authors.

The published results are “completely consistent” with the NIAID’s earlier announcement, H. Clifford Lane, MD, deputy director for clinical research and special projects at the NIAID, said in an interview. “The benefit appeared to be the greatest for the patients who are hospitalized with severe disease who require supplemental oxygen.”

Given the limited supply of remdesivir, physicians have been eager to see the full data to ensure they use the drug most effectively, Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said in an interview. Hospitals in states across the country, including New York, Michigan, and Washington, have received limited supplies of the drug in the last couple of weeks since the FDA’s authorization.

“I am losing my patience waiting for #remdesivir data. I was willing to give them a week to verify the numbers, triple proof the tables, cautiously frame conclusions. But it’s gone on too long. We are rationing with no rationale. We are floating on whisps [sic] of data, adrift,” Kate Stephenson, MD, an infectious diseases specialist at the Center for Virology and Vaccine Research at Harvard Medical School, Boston, wrote on Twitter May 18. After reading the paper, she tweeted Friday evening that she was “relieved to see convincing benefit – I was starting to worry!”

In the midst of a public health crisis, however, it is not unusual to make an announcement about trial results before the full dataset has been analyzed, said Dr. Lane. The NIAID followed a similar playbook for the PALM trial evaluating possible Ebola treatments in the Democratic Republic of Congo, with the independent monitoring board recommending the trial be terminated early in response to positive results from two of the four candidate drugs.

“When you have a result you think is of public health importance, you don’t wait for it to be published in a peer-reviewed journal,” said Dr. Lane, a coauthor of the study. The lag time from announcement to study publication was a result of the time it took to write up the paper for publication and go through peer review, Dr. Lane added. He also noted that the FDA had access to the data when the agency wrote its guidance for physicians administering the drug to patients under the EUA.

The authors opted not to publish the initial findings on a preprint server because they felt it was important to undergo peer review, said Dr. Lane. “The last thing you want for something this critical is for incomplete data to be out there, or you don’t have everything audited to the level that you want.”

 

Trial details

In the ACTT-1 randomized, placebo-controlled, double-blinded trial, researchers enrolled 1,063 patients from Feb. 21 to April 19, 2020, at 60 trial sites and 13 subsites worldwide (45 sites in the United States). The remdesivir group had 541 patients, and the placebo group had 522. A small number of patients (49 in the remdesivir group and 53 in the placebo group) discontinued treatment before day 10 because of an adverse event or withdrawn consent. When data collection for this preliminary analysis ended in late April, 301 patients had not recovered and had not completed their final follow-up visit.

Most of the patients had one (27%) or more (52.1%) preexisting conditions, including hypertension (49.6%), obesity (37%), and type 2 diabetes mellitus (29.7%). Mean patient age was 58.9 years, and the majority of patients were men (64.3%). The median number of days from symptom onset to randomization was 9, and 53.6% of the patients were white, 20.6% were black, 12.6% were Asian, 23.4% were Hispanic or Latino, and the ethnicity of 13.6% were not reported or reported as other.

Patients received one 200-mg loading dose on the first day of the trial, and then one 100-mg maintenance dose every day for days 2 through 10, or until discharge or death. Patients in the control group of the study received a matching placebo on the same schedule and volume. The clinical status of each patient was assessed every day, from day 1 through day 29 of his or her hospital stay, according to an eight-category ordinal scale.

Time to recovery was defined as the first day during the 28-day enrollment period that a patient’s clinical status met a 1 (not hospitalization, no activity limitations), 2 (not hospitalized, activity limitation, oxygen requirement or both), or 3 (hospitalized, not requiring supplemental oxygen or medical care if hospitalization was extended for infection-control reasons) on the eight-category scale. A score of 4 indicated a patient was hospitalized and needed ongoing medical care, but did not require supplemental oxygen; a score of 8 signified death.

The analysis found remdesivir patients had a median time to recovery of 11 days, compared with the median 15 days for patients on the placebo (rate ratio for recovery, 1.32; 95% confidence interval, 1.12-1.55; P < .001). Mortality was also lower in the remdesivir group (hazard ratio for death, 0.70; 95% CI, 0.47-1.04), but the result was not statistically significant. By 14 days, the Kaplan-Meier estimate of mortality was 7.1 % in the remdesivir group and 11.9% in the placebo group.

Patients receiving oxygen, but not yet requiring high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation, seemed to fare best from treatment with remdesivir (these patients had a baseline ordinal score of 5). That may be a result of the larger sample size of these patients, the researchers note in the study. The study authors were unable to estimate the recovery time for the most severely ill patients (category 7), possibly because the follow-up time was too short to fully evaluate this subgroup.

“There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Dr. Kaul, who was not involved in the study, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.”

Dr. Kaul said there is still the possibility that remdesivir could benefit patients on mechanical ventilation, but “clinicians will have to determine if the evidence suggesting no benefit in those who are intubated is strong enough to justify using this currently scarce resource in that population versus limiting use to those requiring oxygen but not on mechanical ventilation.”

Site investigators estimated that just four serious adverse events (two in each group) in enrolled patients were related to remdesivir or placebo. No deaths were attributed to the treatments, although acute respiratory failure, hypotension, acute kidney injury, and viral pneumonia were slightly more common in patients receiving the placebo than those receiving remdesivir.

The researchers plan to publish a follow-up study in the coming weeks or months, after the full cohort has completed 28 days of follow-up, Dr. Lane said. In future studies, the agency will likely focus on comparing remdesivir with combinations of remdesivir with other treatments, like the anti-inflammatory baricitinib.

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

Much-anticipated results from the National Institute of Allergy and Infectious Diseases’ clinical trial of remdesivir in COVID-19 patients published in the New England Journal of Medicine suggest remdesivir shortens the disease course for hospitalized COVID-19 patients.

The agency reported initial promising results from the study earlier this month, which prompted the Food and Drug Administration to issue an emergency use authorization (EUA) for the drug, but the full data and results have not been widely available until now.

In the study of 1,063 patients, the researchers found patients who received a 10-day course of remdesivir had a reduced recovery time of 11 days, compared with 15 days to recovery in the group that received a placebo. The findings also suggest remdesivir should be started, if possible, before patients have such severe pulmonary disease that they require mechanical ventilation, according to the study authors.

The published results are “completely consistent” with the NIAID’s earlier announcement, H. Clifford Lane, MD, deputy director for clinical research and special projects at the NIAID, said in an interview. “The benefit appeared to be the greatest for the patients who are hospitalized with severe disease who require supplemental oxygen.”

Given the limited supply of remdesivir, physicians have been eager to see the full data to ensure they use the drug most effectively, Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said in an interview. Hospitals in states across the country, including New York, Michigan, and Washington, have received limited supplies of the drug in the last couple of weeks since the FDA’s authorization.

“I am losing my patience waiting for #remdesivir data. I was willing to give them a week to verify the numbers, triple proof the tables, cautiously frame conclusions. But it’s gone on too long. We are rationing with no rationale. We are floating on whisps [sic] of data, adrift,” Kate Stephenson, MD, an infectious diseases specialist at the Center for Virology and Vaccine Research at Harvard Medical School, Boston, wrote on Twitter May 18. After reading the paper, she tweeted Friday evening that she was “relieved to see convincing benefit – I was starting to worry!”

In the midst of a public health crisis, however, it is not unusual to make an announcement about trial results before the full dataset has been analyzed, said Dr. Lane. The NIAID followed a similar playbook for the PALM trial evaluating possible Ebola treatments in the Democratic Republic of Congo, with the independent monitoring board recommending the trial be terminated early in response to positive results from two of the four candidate drugs.

“When you have a result you think is of public health importance, you don’t wait for it to be published in a peer-reviewed journal,” said Dr. Lane, a coauthor of the study. The lag time from announcement to study publication was a result of the time it took to write up the paper for publication and go through peer review, Dr. Lane added. He also noted that the FDA had access to the data when the agency wrote its guidance for physicians administering the drug to patients under the EUA.

The authors opted not to publish the initial findings on a preprint server because they felt it was important to undergo peer review, said Dr. Lane. “The last thing you want for something this critical is for incomplete data to be out there, or you don’t have everything audited to the level that you want.”

 

Trial details

In the ACTT-1 randomized, placebo-controlled, double-blinded trial, researchers enrolled 1,063 patients from Feb. 21 to April 19, 2020, at 60 trial sites and 13 subsites worldwide (45 sites in the United States). The remdesivir group had 541 patients, and the placebo group had 522. A small number of patients (49 in the remdesivir group and 53 in the placebo group) discontinued treatment before day 10 because of an adverse event or withdrawn consent. When data collection for this preliminary analysis ended in late April, 301 patients had not recovered and had not completed their final follow-up visit.

Most of the patients had one (27%) or more (52.1%) preexisting conditions, including hypertension (49.6%), obesity (37%), and type 2 diabetes mellitus (29.7%). Mean patient age was 58.9 years, and the majority of patients were men (64.3%). The median number of days from symptom onset to randomization was 9, and 53.6% of the patients were white, 20.6% were black, 12.6% were Asian, 23.4% were Hispanic or Latino, and the ethnicity of 13.6% were not reported or reported as other.

Patients received one 200-mg loading dose on the first day of the trial, and then one 100-mg maintenance dose every day for days 2 through 10, or until discharge or death. Patients in the control group of the study received a matching placebo on the same schedule and volume. The clinical status of each patient was assessed every day, from day 1 through day 29 of his or her hospital stay, according to an eight-category ordinal scale.

Time to recovery was defined as the first day during the 28-day enrollment period that a patient’s clinical status met a 1 (not hospitalization, no activity limitations), 2 (not hospitalized, activity limitation, oxygen requirement or both), or 3 (hospitalized, not requiring supplemental oxygen or medical care if hospitalization was extended for infection-control reasons) on the eight-category scale. A score of 4 indicated a patient was hospitalized and needed ongoing medical care, but did not require supplemental oxygen; a score of 8 signified death.

The analysis found remdesivir patients had a median time to recovery of 11 days, compared with the median 15 days for patients on the placebo (rate ratio for recovery, 1.32; 95% confidence interval, 1.12-1.55; P < .001). Mortality was also lower in the remdesivir group (hazard ratio for death, 0.70; 95% CI, 0.47-1.04), but the result was not statistically significant. By 14 days, the Kaplan-Meier estimate of mortality was 7.1 % in the remdesivir group and 11.9% in the placebo group.

Patients receiving oxygen, but not yet requiring high-flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation, seemed to fare best from treatment with remdesivir (these patients had a baseline ordinal score of 5). That may be a result of the larger sample size of these patients, the researchers note in the study. The study authors were unable to estimate the recovery time for the most severely ill patients (category 7), possibly because the follow-up time was too short to fully evaluate this subgroup.

“There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Dr. Kaul, who was not involved in the study, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.”

Dr. Kaul said there is still the possibility that remdesivir could benefit patients on mechanical ventilation, but “clinicians will have to determine if the evidence suggesting no benefit in those who are intubated is strong enough to justify using this currently scarce resource in that population versus limiting use to those requiring oxygen but not on mechanical ventilation.”

Site investigators estimated that just four serious adverse events (two in each group) in enrolled patients were related to remdesivir or placebo. No deaths were attributed to the treatments, although acute respiratory failure, hypotension, acute kidney injury, and viral pneumonia were slightly more common in patients receiving the placebo than those receiving remdesivir.

The researchers plan to publish a follow-up study in the coming weeks or months, after the full cohort has completed 28 days of follow-up, Dr. Lane said. In future studies, the agency will likely focus on comparing remdesivir with combinations of remdesivir with other treatments, like the anti-inflammatory baricitinib.

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

Real epidemiologists are out knocking on doors, chasing down contacts, or hunched over their computers trying to make sense out of screens full of data and maps. A few are trying valiantly to talk some sense into our elected officials.

konradlew/Thinkstock

This leaves the rest of us with time on our hands to fabricate our own less-than-scientific explanations for the behavior of the SARS-CoV-2 virus. So I have decided to put on hold my current mental challenge of choosing which pasta shape to pair with the sauce I’ve prepared from an online recipe. Here is my educated guess based on what I can glean from media sources that may have been filtered through a variety politically biased lenses. Remember, I did go to medical school; however, when I was in college the DNA helix was still just theoretical.

From those halcyon days of mid-February when our attention was focused on the Diamond Princess quarantined in Yokohama Harbor, it didn’t take a board-certified epidemiologist to suspect that the virus was spreading through the ventilating system in the ship’s tight quarters. Subsequent outbreaks on U.S. and French military ships suggests a similar explanation.

While still not proven, it sounds like SARS-CoV-2 jumped to humans from bats. It should not surprise us that having evolved in a dense population of mammals it would thrive in other high-density populations such as New York and nursing homes. Because we have lacked a robust testing capability, it has been less obvious until recently that, while it is easily transmitted, the virus has infected many who are asymptomatic (“Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable,” Gretchen Vogel, Science, April 21, 2020). Subsequent surveys seem to confirm this higher level carrier state; it suggests that the virus is far less deadly than was previously suggested. However, it seems to be a crafty little bug attacking just about any organ system it lands on.

I don’t think any of us are surprised that the elderly population with weakened immune systems, particularly those in congregate housing, has been much more vulnerable. However, many of the deaths among younger apparently healthy people have defied explanation. The anecdotal observations that physicians, particularly those who practice in-your-face medicine (e.g., ophthalmologists and otolaryngologists) may be more vulnerable raises the issue of viral load. It may be that, although it can be extremely contagious, the virus is not terribly dangerous for most people until the inoculum dose of the virus reaches a certain level. To my knowledge this dose is unknown.

A published survey of more than 300 outbreaks from 120 Chinese cities also may support my suspicion that viral load is of critical importance. The researchers found that all the “identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk” (Huan Qian et al. “Indoor transmission of SARS-CoV-2,” MedRxiv. 2020 Apr 7. doi: 10.1101/2020.04.04.20053058). Again, this data shouldn’t surprise us when we look back at what little we know about the outbreaks in the confined spaces on cruise ships and in nursing homes.

I’m not sure that we have any data that helps us determine whether wearing a mask in an outdoor space has any more than symbolic value when we are talking about this particular virus. We may read that the virus in a droplet can survive on the surface it lands on for 8 minutes, and we can see those slow motion videos of the impressive plume of snot spray released by a sneeze. It would seem obvious that even outside someone within 10 feet of the sneeze has a good chance of being infected. However, how much of a threat is the asymptomatic carrier who passes within three feet of you while you are out on lovely summer day stroll? This armchair epidemiologist suspects that, when we are talking about an outside space, the 6-foot guideline for small groups of a dozen or less is overly restrictive. But until we know, I’m staying put in my armchair ... outside on the porch overlooking Casco Bay.
 

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.” He has no disclosures. Email him at [email protected].

Real epidemiologists are out knocking on doors, chasing down contacts, or hunched over their computers trying to make sense out of screens full of data and maps. A few are trying valiantly to talk some sense into our elected officials.

konradlew/Thinkstock

This leaves the rest of us with time on our hands to fabricate our own less-than-scientific explanations for the behavior of the SARS-CoV-2 virus. So I have decided to put on hold my current mental challenge of choosing which pasta shape to pair with the sauce I’ve prepared from an online recipe. Here is my educated guess based on what I can glean from media sources that may have been filtered through a variety politically biased lenses. Remember, I did go to medical school; however, when I was in college the DNA helix was still just theoretical.

From those halcyon days of mid-February when our attention was focused on the Diamond Princess quarantined in Yokohama Harbor, it didn’t take a board-certified epidemiologist to suspect that the virus was spreading through the ventilating system in the ship’s tight quarters. Subsequent outbreaks on U.S. and French military ships suggests a similar explanation.

While still not proven, it sounds like SARS-CoV-2 jumped to humans from bats. It should not surprise us that having evolved in a dense population of mammals it would thrive in other high-density populations such as New York and nursing homes. Because we have lacked a robust testing capability, it has been less obvious until recently that, while it is easily transmitted, the virus has infected many who are asymptomatic (“Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable,” Gretchen Vogel, Science, April 21, 2020). Subsequent surveys seem to confirm this higher level carrier state; it suggests that the virus is far less deadly than was previously suggested. However, it seems to be a crafty little bug attacking just about any organ system it lands on.

I don’t think any of us are surprised that the elderly population with weakened immune systems, particularly those in congregate housing, has been much more vulnerable. However, many of the deaths among younger apparently healthy people have defied explanation. The anecdotal observations that physicians, particularly those who practice in-your-face medicine (e.g., ophthalmologists and otolaryngologists) may be more vulnerable raises the issue of viral load. It may be that, although it can be extremely contagious, the virus is not terribly dangerous for most people until the inoculum dose of the virus reaches a certain level. To my knowledge this dose is unknown.

A published survey of more than 300 outbreaks from 120 Chinese cities also may support my suspicion that viral load is of critical importance. The researchers found that all the “identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk” (Huan Qian et al. “Indoor transmission of SARS-CoV-2,” MedRxiv. 2020 Apr 7. doi: 10.1101/2020.04.04.20053058). Again, this data shouldn’t surprise us when we look back at what little we know about the outbreaks in the confined spaces on cruise ships and in nursing homes.

I’m not sure that we have any data that helps us determine whether wearing a mask in an outdoor space has any more than symbolic value when we are talking about this particular virus. We may read that the virus in a droplet can survive on the surface it lands on for 8 minutes, and we can see those slow motion videos of the impressive plume of snot spray released by a sneeze. It would seem obvious that even outside someone within 10 feet of the sneeze has a good chance of being infected. However, how much of a threat is the asymptomatic carrier who passes within three feet of you while you are out on lovely summer day stroll? This armchair epidemiologist suspects that, when we are talking about an outside space, the 6-foot guideline for small groups of a dozen or less is overly restrictive. But until we know, I’m staying put in my armchair ... outside on the porch overlooking Casco Bay.
 

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.” He has no disclosures. Email him at [email protected].

Real epidemiologists are out knocking on doors, chasing down contacts, or hunched over their computers trying to make sense out of screens full of data and maps. A few are trying valiantly to talk some sense into our elected officials.

konradlew/Thinkstock

This leaves the rest of us with time on our hands to fabricate our own less-than-scientific explanations for the behavior of the SARS-CoV-2 virus. So I have decided to put on hold my current mental challenge of choosing which pasta shape to pair with the sauce I’ve prepared from an online recipe. Here is my educated guess based on what I can glean from media sources that may have been filtered through a variety politically biased lenses. Remember, I did go to medical school; however, when I was in college the DNA helix was still just theoretical.

From those halcyon days of mid-February when our attention was focused on the Diamond Princess quarantined in Yokohama Harbor, it didn’t take a board-certified epidemiologist to suspect that the virus was spreading through the ventilating system in the ship’s tight quarters. Subsequent outbreaks on U.S. and French military ships suggests a similar explanation.

While still not proven, it sounds like SARS-CoV-2 jumped to humans from bats. It should not surprise us that having evolved in a dense population of mammals it would thrive in other high-density populations such as New York and nursing homes. Because we have lacked a robust testing capability, it has been less obvious until recently that, while it is easily transmitted, the virus has infected many who are asymptomatic (“Antibody surveys suggesting vast undercount of coronavirus infections may be unreliable,” Gretchen Vogel, Science, April 21, 2020). Subsequent surveys seem to confirm this higher level carrier state; it suggests that the virus is far less deadly than was previously suggested. However, it seems to be a crafty little bug attacking just about any organ system it lands on.

I don’t think any of us are surprised that the elderly population with weakened immune systems, particularly those in congregate housing, has been much more vulnerable. However, many of the deaths among younger apparently healthy people have defied explanation. The anecdotal observations that physicians, particularly those who practice in-your-face medicine (e.g., ophthalmologists and otolaryngologists) may be more vulnerable raises the issue of viral load. It may be that, although it can be extremely contagious, the virus is not terribly dangerous for most people until the inoculum dose of the virus reaches a certain level. To my knowledge this dose is unknown.

A published survey of more than 300 outbreaks from 120 Chinese cities also may support my suspicion that viral load is of critical importance. The researchers found that all the “identified outbreaks of three or more cases occurred in an indoor environment, which confirms that sharing indoor space is a major SARS-CoV-2 infection risk” (Huan Qian et al. “Indoor transmission of SARS-CoV-2,” MedRxiv. 2020 Apr 7. doi: 10.1101/2020.04.04.20053058). Again, this data shouldn’t surprise us when we look back at what little we know about the outbreaks in the confined spaces on cruise ships and in nursing homes.

I’m not sure that we have any data that helps us determine whether wearing a mask in an outdoor space has any more than symbolic value when we are talking about this particular virus. We may read that the virus in a droplet can survive on the surface it lands on for 8 minutes, and we can see those slow motion videos of the impressive plume of snot spray released by a sneeze. It would seem obvious that even outside someone within 10 feet of the sneeze has a good chance of being infected. However, how much of a threat is the asymptomatic carrier who passes within three feet of you while you are out on lovely summer day stroll? This armchair epidemiologist suspects that, when we are talking about an outside space, the 6-foot guideline for small groups of a dozen or less is overly restrictive. But until we know, I’m staying put in my armchair ... outside on the porch overlooking Casco Bay.
 

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.” He has no disclosures. Email him at [email protected].