MDedge Infectious Disease

About 2% of highly allergic individuals had a reaction to the Pfizer-BioNTech COVID-19 vaccine in a study from Israel published Aug. 31, 2021, in JAMA Network Open. Symptoms resolved in a few hours with medication, and no patients required hospitalization.

Risk for allergic reaction has been one of several obstacles in global vaccination efforts, the authors, led by Nancy Agmon-Levin, MD, of the Sheba Medical Center, Ramat Gan, Israel, wrote. Clinical trials for the Moderna and Pfizer-BioNTech COVID-19 vaccines excluded individuals with allergies to any component of the vaccine or with previous allergies to other vaccines. Early reports of anaphylaxis in reaction to the vaccines caused concern among patients and practitioners. Soon after, the Centers for Disease Control and Prevention and other authorities released guidance on preparing for allergic reactions. “Despite these recommendations, uncertainty remains, particularly among patients with a history of anaphylaxis and/or multiple allergies,” the authors added.

In response to early concerns, the Sheba Medical Center opened a COVID-19 referral center to address safety questions and to conduct assessments of allergy risk for the Pfizer-BioNTech vaccine, the first COVID-19 vaccine approved in Israel. From Dec. 27, 2020, to Feb. 22, 2021, the referral center assessed 8,102 patients with allergies. Those who were not clearly at low risk filled out a questionnaire about prior allergic or anaphylactic reactions to drugs or vaccines, other allergies, and other relevant medical history. Patients were considered to be at high risk for allergic reactions if they met at least one of the following criteria: previous anaphylactic reaction to any drug or vaccine, multiple drug allergies, multiple other allergies, and mast cell disorders. Individuals were also classified as high risk if their health care practitioner deferred vaccination because of allergy concerns.

Nearly 95% of the cohort (7,668 individuals) were classified as low risk and received both Pfizer vaccine doses at standard immunization sites and underwent 30 minutes of observation after immunization. Although the study did not follow these lower-risk patients, “no serious allergic reactions were reported back to our referral center by patients or their general practitioner after immunization in the regular settings,” the authors wrote.

Five patients were considered ineligible for immunization because of known sensitivity to polyethylene glycol or multiple anaphylactic reactions to different injectable drugs, following recommendations from the Ministry of Health of Israel at the time. The remaining 429 individuals were deemed high risk and underwent observation for 2 hours from a dedicated allergy team after immunization. For these high-risk patients, both vaccine doses were administered in the same setting. Patients also reported any adverse reactions in the 21 days between the first and second dose.

Women made up most of the high-risk cohort (70.9%). The average age of participants was 52 years. Of the high-risk individuals, 63.2% reported prior anaphylaxis, 32.9% had multiple drug allergies, and 30.3% had multiple other allergies.

During the first 2 hours following immunization, nine individuals (2.1%), all women, experienced allergic reactions. Six individuals (1.4%) experienced minor reactions, including skin flushing, tongue or uvula swelling, or a cough that resolved with antihistamine treatment during the observation period. Three patients (0.7%) had anaphylactic reactions that occurred 10 to 20 minutes after injection. All three patients experienced significant bronchospasm, skin eruption, itching, and shortness of breath. Two patients experienced angioedema, and one patient had gastrointestinal symptoms. They were treated with adrenaline, antihistamines, and an inhaled bronchodilator. All symptoms resolved within 2-6 hours, and no patient required hospitalization.

In the days following vaccination, patients commonly reported pain at the injection site, fatigue, muscle pain, and headache; 14.7% of patients reported skin eruption, itching, or urticaria.

As of Feb. 22, 2021, 218 patients from this highly allergic cohort received their second dose of the vaccine. Four patients (1.8%) had mild allergic reactions. All four developed flushing, and one patient also developed a cough that resolved with antihistamine treatment. Three of these patients had experienced mild allergic reactions to the first dose and were premedicated for the second dose. One patient only reacted to the second dose.

The findings should be “very reassuring” to individuals hesitant to receive the vaccine, Elizabeth Phillips, MD, the director of the Center for Drug Safety and Immunology at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. She was not involved with the research and wrote an invited commentary on the study. “The rates of anaphylaxis and allergic reactions are truly quite low,” she said. Although about 2% of the high-risk group developed allergic reactions to immunization, the overall percentage for the entire cohort would be much lower.

The study did not investigate specific risk factors for and mechanisms of allergic reactions to COVID-19 vaccines, Dr. Phillips said, which is a study limitation that the authors also acknowledge. The National Institute for Allergy and Infectious Diseases is currently trying to answer some of these questions with a multisite, randomized, double-blinded study. The study is intended to help understand why people have these allergic reactions, Dr. Phillips added. Vanderbilt is one of the sites for the study.

While researchers continue to hunt for answers, the algorithm developed by the authors provides “a great strategy to get people that are at higher risk vaccinated in a monitored setting,” she said. The results show that “people should not be avoiding vaccination because of a history of anaphylaxis.”

Dr. Phillips has received institutional grants from the National Institutes of Health and the National Health and Medical Research Council; royalties from UpToDate and Lexicomp; and consulting fees from Janssen, Vertex, Biocryst, and Regeneron.

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

About 2% of highly allergic individuals had a reaction to the Pfizer-BioNTech COVID-19 vaccine in a study from Israel published Aug. 31, 2021, in JAMA Network Open. Symptoms resolved in a few hours with medication, and no patients required hospitalization.

Risk for allergic reaction has been one of several obstacles in global vaccination efforts, the authors, led by Nancy Agmon-Levin, MD, of the Sheba Medical Center, Ramat Gan, Israel, wrote. Clinical trials for the Moderna and Pfizer-BioNTech COVID-19 vaccines excluded individuals with allergies to any component of the vaccine or with previous allergies to other vaccines. Early reports of anaphylaxis in reaction to the vaccines caused concern among patients and practitioners. Soon after, the Centers for Disease Control and Prevention and other authorities released guidance on preparing for allergic reactions. “Despite these recommendations, uncertainty remains, particularly among patients with a history of anaphylaxis and/or multiple allergies,” the authors added.

In response to early concerns, the Sheba Medical Center opened a COVID-19 referral center to address safety questions and to conduct assessments of allergy risk for the Pfizer-BioNTech vaccine, the first COVID-19 vaccine approved in Israel. From Dec. 27, 2020, to Feb. 22, 2021, the referral center assessed 8,102 patients with allergies. Those who were not clearly at low risk filled out a questionnaire about prior allergic or anaphylactic reactions to drugs or vaccines, other allergies, and other relevant medical history. Patients were considered to be at high risk for allergic reactions if they met at least one of the following criteria: previous anaphylactic reaction to any drug or vaccine, multiple drug allergies, multiple other allergies, and mast cell disorders. Individuals were also classified as high risk if their health care practitioner deferred vaccination because of allergy concerns.

Nearly 95% of the cohort (7,668 individuals) were classified as low risk and received both Pfizer vaccine doses at standard immunization sites and underwent 30 minutes of observation after immunization. Although the study did not follow these lower-risk patients, “no serious allergic reactions were reported back to our referral center by patients or their general practitioner after immunization in the regular settings,” the authors wrote.

Five patients were considered ineligible for immunization because of known sensitivity to polyethylene glycol or multiple anaphylactic reactions to different injectable drugs, following recommendations from the Ministry of Health of Israel at the time. The remaining 429 individuals were deemed high risk and underwent observation for 2 hours from a dedicated allergy team after immunization. For these high-risk patients, both vaccine doses were administered in the same setting. Patients also reported any adverse reactions in the 21 days between the first and second dose.

Women made up most of the high-risk cohort (70.9%). The average age of participants was 52 years. Of the high-risk individuals, 63.2% reported prior anaphylaxis, 32.9% had multiple drug allergies, and 30.3% had multiple other allergies.

During the first 2 hours following immunization, nine individuals (2.1%), all women, experienced allergic reactions. Six individuals (1.4%) experienced minor reactions, including skin flushing, tongue or uvula swelling, or a cough that resolved with antihistamine treatment during the observation period. Three patients (0.7%) had anaphylactic reactions that occurred 10 to 20 minutes after injection. All three patients experienced significant bronchospasm, skin eruption, itching, and shortness of breath. Two patients experienced angioedema, and one patient had gastrointestinal symptoms. They were treated with adrenaline, antihistamines, and an inhaled bronchodilator. All symptoms resolved within 2-6 hours, and no patient required hospitalization.

In the days following vaccination, patients commonly reported pain at the injection site, fatigue, muscle pain, and headache; 14.7% of patients reported skin eruption, itching, or urticaria.

As of Feb. 22, 2021, 218 patients from this highly allergic cohort received their second dose of the vaccine. Four patients (1.8%) had mild allergic reactions. All four developed flushing, and one patient also developed a cough that resolved with antihistamine treatment. Three of these patients had experienced mild allergic reactions to the first dose and were premedicated for the second dose. One patient only reacted to the second dose.

The findings should be “very reassuring” to individuals hesitant to receive the vaccine, Elizabeth Phillips, MD, the director of the Center for Drug Safety and Immunology at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. She was not involved with the research and wrote an invited commentary on the study. “The rates of anaphylaxis and allergic reactions are truly quite low,” she said. Although about 2% of the high-risk group developed allergic reactions to immunization, the overall percentage for the entire cohort would be much lower.

The study did not investigate specific risk factors for and mechanisms of allergic reactions to COVID-19 vaccines, Dr. Phillips said, which is a study limitation that the authors also acknowledge. The National Institute for Allergy and Infectious Diseases is currently trying to answer some of these questions with a multisite, randomized, double-blinded study. The study is intended to help understand why people have these allergic reactions, Dr. Phillips added. Vanderbilt is one of the sites for the study.

While researchers continue to hunt for answers, the algorithm developed by the authors provides “a great strategy to get people that are at higher risk vaccinated in a monitored setting,” she said. The results show that “people should not be avoiding vaccination because of a history of anaphylaxis.”

Dr. Phillips has received institutional grants from the National Institutes of Health and the National Health and Medical Research Council; royalties from UpToDate and Lexicomp; and consulting fees from Janssen, Vertex, Biocryst, and Regeneron.

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

About 2% of highly allergic individuals had a reaction to the Pfizer-BioNTech COVID-19 vaccine in a study from Israel published Aug. 31, 2021, in JAMA Network Open. Symptoms resolved in a few hours with medication, and no patients required hospitalization.

Risk for allergic reaction has been one of several obstacles in global vaccination efforts, the authors, led by Nancy Agmon-Levin, MD, of the Sheba Medical Center, Ramat Gan, Israel, wrote. Clinical trials for the Moderna and Pfizer-BioNTech COVID-19 vaccines excluded individuals with allergies to any component of the vaccine or with previous allergies to other vaccines. Early reports of anaphylaxis in reaction to the vaccines caused concern among patients and practitioners. Soon after, the Centers for Disease Control and Prevention and other authorities released guidance on preparing for allergic reactions. “Despite these recommendations, uncertainty remains, particularly among patients with a history of anaphylaxis and/or multiple allergies,” the authors added.

In response to early concerns, the Sheba Medical Center opened a COVID-19 referral center to address safety questions and to conduct assessments of allergy risk for the Pfizer-BioNTech vaccine, the first COVID-19 vaccine approved in Israel. From Dec. 27, 2020, to Feb. 22, 2021, the referral center assessed 8,102 patients with allergies. Those who were not clearly at low risk filled out a questionnaire about prior allergic or anaphylactic reactions to drugs or vaccines, other allergies, and other relevant medical history. Patients were considered to be at high risk for allergic reactions if they met at least one of the following criteria: previous anaphylactic reaction to any drug or vaccine, multiple drug allergies, multiple other allergies, and mast cell disorders. Individuals were also classified as high risk if their health care practitioner deferred vaccination because of allergy concerns.

Nearly 95% of the cohort (7,668 individuals) were classified as low risk and received both Pfizer vaccine doses at standard immunization sites and underwent 30 minutes of observation after immunization. Although the study did not follow these lower-risk patients, “no serious allergic reactions were reported back to our referral center by patients or their general practitioner after immunization in the regular settings,” the authors wrote.

Five patients were considered ineligible for immunization because of known sensitivity to polyethylene glycol or multiple anaphylactic reactions to different injectable drugs, following recommendations from the Ministry of Health of Israel at the time. The remaining 429 individuals were deemed high risk and underwent observation for 2 hours from a dedicated allergy team after immunization. For these high-risk patients, both vaccine doses were administered in the same setting. Patients also reported any adverse reactions in the 21 days between the first and second dose.

Women made up most of the high-risk cohort (70.9%). The average age of participants was 52 years. Of the high-risk individuals, 63.2% reported prior anaphylaxis, 32.9% had multiple drug allergies, and 30.3% had multiple other allergies.

During the first 2 hours following immunization, nine individuals (2.1%), all women, experienced allergic reactions. Six individuals (1.4%) experienced minor reactions, including skin flushing, tongue or uvula swelling, or a cough that resolved with antihistamine treatment during the observation period. Three patients (0.7%) had anaphylactic reactions that occurred 10 to 20 minutes after injection. All three patients experienced significant bronchospasm, skin eruption, itching, and shortness of breath. Two patients experienced angioedema, and one patient had gastrointestinal symptoms. They were treated with adrenaline, antihistamines, and an inhaled bronchodilator. All symptoms resolved within 2-6 hours, and no patient required hospitalization.

In the days following vaccination, patients commonly reported pain at the injection site, fatigue, muscle pain, and headache; 14.7% of patients reported skin eruption, itching, or urticaria.

As of Feb. 22, 2021, 218 patients from this highly allergic cohort received their second dose of the vaccine. Four patients (1.8%) had mild allergic reactions. All four developed flushing, and one patient also developed a cough that resolved with antihistamine treatment. Three of these patients had experienced mild allergic reactions to the first dose and were premedicated for the second dose. One patient only reacted to the second dose.

The findings should be “very reassuring” to individuals hesitant to receive the vaccine, Elizabeth Phillips, MD, the director of the Center for Drug Safety and Immunology at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. She was not involved with the research and wrote an invited commentary on the study. “The rates of anaphylaxis and allergic reactions are truly quite low,” she said. Although about 2% of the high-risk group developed allergic reactions to immunization, the overall percentage for the entire cohort would be much lower.

The study did not investigate specific risk factors for and mechanisms of allergic reactions to COVID-19 vaccines, Dr. Phillips said, which is a study limitation that the authors also acknowledge. The National Institute for Allergy and Infectious Diseases is currently trying to answer some of these questions with a multisite, randomized, double-blinded study. The study is intended to help understand why people have these allergic reactions, Dr. Phillips added. Vanderbilt is one of the sites for the study.

While researchers continue to hunt for answers, the algorithm developed by the authors provides “a great strategy to get people that are at higher risk vaccinated in a monitored setting,” she said. The results show that “people should not be avoiding vaccination because of a history of anaphylaxis.”

Dr. Phillips has received institutional grants from the National Institutes of Health and the National Health and Medical Research Council; royalties from UpToDate and Lexicomp; and consulting fees from Janssen, Vertex, Biocryst, and Regeneron.

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

A new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

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

A new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

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

A new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

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

Another case, another state, another judge ordering a hospital to give a patient a controversial horse deworming drug to treat a severe case of COVID-19.

This time, a judge in Ohio has ordered West Chester Hospital, part of the University of Cincinnati network, to provide Jeffrey Smith, 51, with ivermectin, according to the Ohio Capital Journal. Judge Gregory Howard’s ruling comes after Mr. Smith’s wife sued to force the hospital to provide the controversial drug to her husband, who has been hospitalized since July 15.

Julie Smith has gotten Fred Wagshul, MD, to agree to administer ivermectin to her husband. Dr. Wagshul is known as a member of a group of doctors who say the Centers for Disease Control and Prevention and the Food and Drug Administration are lying about ivermectin’s usefulness in fighting COVID-19. Both agencies have warned against using the drug to treat COVID-19, saying there is no evidence it works and that it can be dangerous in large amounts.

According to the Ohio Capital Journal, Dr. Wagshul accused the CDC and FDA of engaging in a “conspiracy” to prevent ivermectin’s use.

But Arthur L. Caplan, MD, professor of bioethics at New York University’s Langone Medical Center, said, “it is absurd that this order was issued,” according to an interview in Ars Technica. “If I were these doctors, I simply wouldn’t do it.”

It is not the first time a judge has ordered ivermectin’s use against a hospital’s wishes.

A 68-year-old woman with COVID-19 in an Illinois hospital started receiving the controversial drug in May after her family sued the hospital to have someone administer it.

Nurije Fype’s daughter, Desareta, filed suit against Elmhurst Hospital, part of Edward-Elmhurst Health, asking that her mother receive the treatment, which is approved as an antiparasitic drug but not approved for the treatment of COVID-19. Desareta Fype was granted temporary guardianship of her mother.

The FDA has published guidance titled “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19” on its website. The National Institutes of Health said there is not enough data to recommend either for or against its use in treating COVID-19.

But DuPage County Judge James Orel ruled Ms. Fype should be allowed to get the treatment.

Three days later, according to the Daily Herald, the lawyer for the hospital, Joseph Monahan, argued the hospital could not find a hospital-affiliated doctor to administer the ivermectin.

The Herald reported the judge told the hospital to “get out of the way” and allow any board-certified doctor to administer the drug.

When Ms. Fype’s doctor was unable to administer it, the legal team found another doctor, Alan Bain, DO, to do it. Mr. Monahan said Dr. Bain was granted credentials to work at the hospital so he could administer it.

Judge Orel denied a request from Desareta Fype’s lawyer to order the hospital’s nurses to administer further doses. The judge also denied a request to hold the hospital in contempt of court.

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

Another case, another state, another judge ordering a hospital to give a patient a controversial horse deworming drug to treat a severe case of COVID-19.

This time, a judge in Ohio has ordered West Chester Hospital, part of the University of Cincinnati network, to provide Jeffrey Smith, 51, with ivermectin, according to the Ohio Capital Journal. Judge Gregory Howard’s ruling comes after Mr. Smith’s wife sued to force the hospital to provide the controversial drug to her husband, who has been hospitalized since July 15.

Julie Smith has gotten Fred Wagshul, MD, to agree to administer ivermectin to her husband. Dr. Wagshul is known as a member of a group of doctors who say the Centers for Disease Control and Prevention and the Food and Drug Administration are lying about ivermectin’s usefulness in fighting COVID-19. Both agencies have warned against using the drug to treat COVID-19, saying there is no evidence it works and that it can be dangerous in large amounts.

According to the Ohio Capital Journal, Dr. Wagshul accused the CDC and FDA of engaging in a “conspiracy” to prevent ivermectin’s use.

But Arthur L. Caplan, MD, professor of bioethics at New York University’s Langone Medical Center, said, “it is absurd that this order was issued,” according to an interview in Ars Technica. “If I were these doctors, I simply wouldn’t do it.”

It is not the first time a judge has ordered ivermectin’s use against a hospital’s wishes.

A 68-year-old woman with COVID-19 in an Illinois hospital started receiving the controversial drug in May after her family sued the hospital to have someone administer it.

Nurije Fype’s daughter, Desareta, filed suit against Elmhurst Hospital, part of Edward-Elmhurst Health, asking that her mother receive the treatment, which is approved as an antiparasitic drug but not approved for the treatment of COVID-19. Desareta Fype was granted temporary guardianship of her mother.

The FDA has published guidance titled “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19” on its website. The National Institutes of Health said there is not enough data to recommend either for or against its use in treating COVID-19.

But DuPage County Judge James Orel ruled Ms. Fype should be allowed to get the treatment.

Three days later, according to the Daily Herald, the lawyer for the hospital, Joseph Monahan, argued the hospital could not find a hospital-affiliated doctor to administer the ivermectin.

The Herald reported the judge told the hospital to “get out of the way” and allow any board-certified doctor to administer the drug.

When Ms. Fype’s doctor was unable to administer it, the legal team found another doctor, Alan Bain, DO, to do it. Mr. Monahan said Dr. Bain was granted credentials to work at the hospital so he could administer it.

Judge Orel denied a request from Desareta Fype’s lawyer to order the hospital’s nurses to administer further doses. The judge also denied a request to hold the hospital in contempt of court.

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

Another case, another state, another judge ordering a hospital to give a patient a controversial horse deworming drug to treat a severe case of COVID-19.

This time, a judge in Ohio has ordered West Chester Hospital, part of the University of Cincinnati network, to provide Jeffrey Smith, 51, with ivermectin, according to the Ohio Capital Journal. Judge Gregory Howard’s ruling comes after Mr. Smith’s wife sued to force the hospital to provide the controversial drug to her husband, who has been hospitalized since July 15.

Julie Smith has gotten Fred Wagshul, MD, to agree to administer ivermectin to her husband. Dr. Wagshul is known as a member of a group of doctors who say the Centers for Disease Control and Prevention and the Food and Drug Administration are lying about ivermectin’s usefulness in fighting COVID-19. Both agencies have warned against using the drug to treat COVID-19, saying there is no evidence it works and that it can be dangerous in large amounts.

According to the Ohio Capital Journal, Dr. Wagshul accused the CDC and FDA of engaging in a “conspiracy” to prevent ivermectin’s use.

But Arthur L. Caplan, MD, professor of bioethics at New York University’s Langone Medical Center, said, “it is absurd that this order was issued,” according to an interview in Ars Technica. “If I were these doctors, I simply wouldn’t do it.”

It is not the first time a judge has ordered ivermectin’s use against a hospital’s wishes.

A 68-year-old woman with COVID-19 in an Illinois hospital started receiving the controversial drug in May after her family sued the hospital to have someone administer it.

Nurije Fype’s daughter, Desareta, filed suit against Elmhurst Hospital, part of Edward-Elmhurst Health, asking that her mother receive the treatment, which is approved as an antiparasitic drug but not approved for the treatment of COVID-19. Desareta Fype was granted temporary guardianship of her mother.

The FDA has published guidance titled “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19” on its website. The National Institutes of Health said there is not enough data to recommend either for or against its use in treating COVID-19.

But DuPage County Judge James Orel ruled Ms. Fype should be allowed to get the treatment.

Three days later, according to the Daily Herald, the lawyer for the hospital, Joseph Monahan, argued the hospital could not find a hospital-affiliated doctor to administer the ivermectin.

The Herald reported the judge told the hospital to “get out of the way” and allow any board-certified doctor to administer the drug.

When Ms. Fype’s doctor was unable to administer it, the legal team found another doctor, Alan Bain, DO, to do it. Mr. Monahan said Dr. Bain was granted credentials to work at the hospital so he could administer it.

Judge Orel denied a request from Desareta Fype’s lawyer to order the hospital’s nurses to administer further doses. The judge also denied a request to hold the hospital in contempt of court.

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

Jessica Gosnell, MD, 41, from Portland, Oregon, lives daily with the knowledge that her rare disease — a form of hereditary angioedema — could cause a sudden, severe swelling in her throat that could require quick intubation and land her in an intensive care unit (ICU) for days.

“I’ve been hospitalized for throat swells three times in the last year,” she said in an interview.

Dr. Gosnell no longer practices medicine because of a combination of illnesses, but lives with her husband, Andrew, and two young children, and said they are all “terrified” she will have to go to the hospital amid a COVID-19 surge that had shrunk the number of available ICU beds to 152 from 780 in Oregon as of Aug. 30. Thirty percent of the beds are in use for patients with COVID-19.

She said her life depends on being near hospitals that have ICUs and having access to highly specialized medications, one of which can cost up to $50,000 for the rescue dose.

Her fear has her “literally living bedbound.” In addition to hereditary angioedema, she has Ehlers-Danlos syndrome, which weakens connective tissue. She wears a cervical collar 24/7 to keep from tearing tissues, as any tissue injury can trigger a swell.
 

Patients worry there won’t be room

As ICU beds in most states are filling with COVID-19 patients as the Delta variant spreads, fears are rising among people like Dr. Gosnell, who have chronic conditions and diseases with unpredictable emergency visits, who worry that if they need emergency care there won’t be room.

As of Aug. 30, in the United States, 79% of ICU beds nationally were in use, 30% of them for COVID-19 patients, according to the U.S. Department of Health and Human Services.

In individual states, the picture is dire. Alabama has fewer than 10% of its ICU beds open across the entire state. In Florida, 93% of ICU beds are filled, 53% of them with COVID patients. In Louisiana, 87% of beds were already in use, 45% of them with COVID patients, just as category 4 hurricane Ida smashed into the coastline on Aug. 29.

News reports have told of people transported and airlifted as hospitals reach capacity.

In Bellville, Tex., U.S. Army veteran Daniel Wilkinson needed advanced care for gallstone pancreatitis that normally would take 30 minutes to treat, his Bellville doctor, Hasan Kakli, MD, told CBS News.

Mr. Wilkinson’s house was three doors from Bellville Hospital, but the hospital was not equipped to treat the condition. Calls to other hospitals found the same answer: no empty ICU beds. After a 7-hour wait on a stretcher, he was airlifted to a Veterans Affairs hospital in Houston, but it was too late. He died on August 22 at age 46.

Dr. Kakli said, “I’ve never lost a patient with this diagnosis. Ever. I’m scared that the next patient I see is someone that I can’t get to where they need to get to. We are playing musical chairs with 100 people and 10 chairs. When the music stops, what happens?”

Also in Texas in August, Joe Valdez, who was shot six times as an unlucky bystander in a domestic dispute, waited for more than a week for surgery at Ben Taub Hospital in Houston, which was over capacity with COVID patients, the Washington Post reported.

Others with chronic diseases fear needing emergency services or even entering a hospital for regular care with the COVID surge.

Nicole Seefeldt, 44, from Easton, Penn., who had a double-lung transplant in 2016, said that she hasn’t been able to see her lung transplant specialists in Philadelphia — an hour-and-a-half drive — for almost 2 years because of fear of contracting COVID. Before the pandemic, she made the trip almost weekly.

“I protect my lungs like they’re children,” she said. 

She relies on her local hospital for care, but has put off some needed care, such as a colonoscopy, and has relied on telemedicine because she wants to limit her hospital exposure.

Ms. Seefeldt now faces an eventual kidney transplant, as her kidney function has been reduced to 20%. In the meantime, she worries she will need emergency care for either her lungs or kidneys.

“For those of us who are chronically ill or disabled, what if we have an emergency that is not COVID-related? Are we going to be able to get a bed? Are we going to be able to get treatment? It’s not just COVID patients who come to the [emergency room],” she said.
 

A pandemic problem

Paul E. Casey, MD, MBA, chief medical officer at Rush University Medical Center in Chicago, said that high vaccination rates in Chicago have helped Rush continue to accommodate both non-COVID and COVID patients in the emergency department.

Though the hospital treated a large volume of COVID patients, “The vast majority of people we see and did see through the pandemic were non-COVID patents,” he said.

Dr. Casey said that in the first wave the hospital noticed a concerning drop in patients coming in for strokes and heart attacks — “things we knew hadn’t gone away.”

And the data backs it up. Over the course of the pandemic, the Centers for Disease Control and Prevention’s National Health Interview Survey found that the percentage of Americans who reported seeing a doctor or health professional fell from 85% at the end of 2019 to about 80% in the first three months of 2021. The survey did not differentiate between in-person visits and telehealth appointments.

Medical practices and patients themselves postponed elective procedures and delayed routine visits during the early months of the crisis.

Patients also reported staying away from hospitals’ emergency departments throughout the pandemic. At the end of 2019, 22% of respondents reported visiting an emergency department in the past year. That dropped to 17% by the end of 2020, and was at 17.7% in the first 3 months of 2021.

Dr. Casey said that, in his hospital’s case, clear messaging became very important to assure patients it was safe to come back. And the message is still critical.

“We want to be loud and clear that patients should continue to seek care for those conditions,” Dr. Casey said. “Deferring healthcare only comes with the long-term sequelae of disease left untreated so we want people to be as proactive in seeking care as they always would be.”

In some cases, fears of entering emergency rooms because of excess patients and risk for infection are keeping some patients from seeking necessary care for minor injuries.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health in Bloomington, said that some of his patients have expressed fears of coming into the hospital for fractures.

Some patients, particularly elderly patients, he said, are having falls and fractures and wearing slings or braces at home rather than going into the hospital for injuries that need immediate attention.

Bones start healing incorrectly, Dr. Rickert said, and the correction becomes much more difficult.
 

Plea for vaccinations

Dr. Gosnell made a plea posted on her neighborhood news forum for people to get COVID vaccinations.

“It seems to me it’s easy for other people who are not in bodies like mine to take health for granted,” she said. “But there are a lot of us who live in very fragile bodies and our entire life is at the intersection of us and getting healthcare treatment. Small complications to getting treatment can be life altering.”

Dr. Gosnell, Ms. Seefeldt, Dr. Casey, and Dr. Rickert reported no relevant financial relationships.

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

Jessica Gosnell, MD, 41, from Portland, Oregon, lives daily with the knowledge that her rare disease — a form of hereditary angioedema — could cause a sudden, severe swelling in her throat that could require quick intubation and land her in an intensive care unit (ICU) for days.

“I’ve been hospitalized for throat swells three times in the last year,” she said in an interview.

Dr. Gosnell no longer practices medicine because of a combination of illnesses, but lives with her husband, Andrew, and two young children, and said they are all “terrified” she will have to go to the hospital amid a COVID-19 surge that had shrunk the number of available ICU beds to 152 from 780 in Oregon as of Aug. 30. Thirty percent of the beds are in use for patients with COVID-19.

She said her life depends on being near hospitals that have ICUs and having access to highly specialized medications, one of which can cost up to $50,000 for the rescue dose.

Her fear has her “literally living bedbound.” In addition to hereditary angioedema, she has Ehlers-Danlos syndrome, which weakens connective tissue. She wears a cervical collar 24/7 to keep from tearing tissues, as any tissue injury can trigger a swell.
 

Patients worry there won’t be room

As ICU beds in most states are filling with COVID-19 patients as the Delta variant spreads, fears are rising among people like Dr. Gosnell, who have chronic conditions and diseases with unpredictable emergency visits, who worry that if they need emergency care there won’t be room.

As of Aug. 30, in the United States, 79% of ICU beds nationally were in use, 30% of them for COVID-19 patients, according to the U.S. Department of Health and Human Services.

In individual states, the picture is dire. Alabama has fewer than 10% of its ICU beds open across the entire state. In Florida, 93% of ICU beds are filled, 53% of them with COVID patients. In Louisiana, 87% of beds were already in use, 45% of them with COVID patients, just as category 4 hurricane Ida smashed into the coastline on Aug. 29.

News reports have told of people transported and airlifted as hospitals reach capacity.

In Bellville, Tex., U.S. Army veteran Daniel Wilkinson needed advanced care for gallstone pancreatitis that normally would take 30 minutes to treat, his Bellville doctor, Hasan Kakli, MD, told CBS News.

Mr. Wilkinson’s house was three doors from Bellville Hospital, but the hospital was not equipped to treat the condition. Calls to other hospitals found the same answer: no empty ICU beds. After a 7-hour wait on a stretcher, he was airlifted to a Veterans Affairs hospital in Houston, but it was too late. He died on August 22 at age 46.

Dr. Kakli said, “I’ve never lost a patient with this diagnosis. Ever. I’m scared that the next patient I see is someone that I can’t get to where they need to get to. We are playing musical chairs with 100 people and 10 chairs. When the music stops, what happens?”

Also in Texas in August, Joe Valdez, who was shot six times as an unlucky bystander in a domestic dispute, waited for more than a week for surgery at Ben Taub Hospital in Houston, which was over capacity with COVID patients, the Washington Post reported.

Others with chronic diseases fear needing emergency services or even entering a hospital for regular care with the COVID surge.

Nicole Seefeldt, 44, from Easton, Penn., who had a double-lung transplant in 2016, said that she hasn’t been able to see her lung transplant specialists in Philadelphia — an hour-and-a-half drive — for almost 2 years because of fear of contracting COVID. Before the pandemic, she made the trip almost weekly.

“I protect my lungs like they’re children,” she said. 

She relies on her local hospital for care, but has put off some needed care, such as a colonoscopy, and has relied on telemedicine because she wants to limit her hospital exposure.

Ms. Seefeldt now faces an eventual kidney transplant, as her kidney function has been reduced to 20%. In the meantime, she worries she will need emergency care for either her lungs or kidneys.

“For those of us who are chronically ill or disabled, what if we have an emergency that is not COVID-related? Are we going to be able to get a bed? Are we going to be able to get treatment? It’s not just COVID patients who come to the [emergency room],” she said.
 

A pandemic problem

Paul E. Casey, MD, MBA, chief medical officer at Rush University Medical Center in Chicago, said that high vaccination rates in Chicago have helped Rush continue to accommodate both non-COVID and COVID patients in the emergency department.

Though the hospital treated a large volume of COVID patients, “The vast majority of people we see and did see through the pandemic were non-COVID patents,” he said.

Dr. Casey said that in the first wave the hospital noticed a concerning drop in patients coming in for strokes and heart attacks — “things we knew hadn’t gone away.”

And the data backs it up. Over the course of the pandemic, the Centers for Disease Control and Prevention’s National Health Interview Survey found that the percentage of Americans who reported seeing a doctor or health professional fell from 85% at the end of 2019 to about 80% in the first three months of 2021. The survey did not differentiate between in-person visits and telehealth appointments.

Medical practices and patients themselves postponed elective procedures and delayed routine visits during the early months of the crisis.

Patients also reported staying away from hospitals’ emergency departments throughout the pandemic. At the end of 2019, 22% of respondents reported visiting an emergency department in the past year. That dropped to 17% by the end of 2020, and was at 17.7% in the first 3 months of 2021.

Dr. Casey said that, in his hospital’s case, clear messaging became very important to assure patients it was safe to come back. And the message is still critical.

“We want to be loud and clear that patients should continue to seek care for those conditions,” Dr. Casey said. “Deferring healthcare only comes with the long-term sequelae of disease left untreated so we want people to be as proactive in seeking care as they always would be.”

In some cases, fears of entering emergency rooms because of excess patients and risk for infection are keeping some patients from seeking necessary care for minor injuries.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health in Bloomington, said that some of his patients have expressed fears of coming into the hospital for fractures.

Some patients, particularly elderly patients, he said, are having falls and fractures and wearing slings or braces at home rather than going into the hospital for injuries that need immediate attention.

Bones start healing incorrectly, Dr. Rickert said, and the correction becomes much more difficult.
 

Plea for vaccinations

Dr. Gosnell made a plea posted on her neighborhood news forum for people to get COVID vaccinations.

“It seems to me it’s easy for other people who are not in bodies like mine to take health for granted,” she said. “But there are a lot of us who live in very fragile bodies and our entire life is at the intersection of us and getting healthcare treatment. Small complications to getting treatment can be life altering.”

Dr. Gosnell, Ms. Seefeldt, Dr. Casey, and Dr. Rickert reported no relevant financial relationships.

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

Jessica Gosnell, MD, 41, from Portland, Oregon, lives daily with the knowledge that her rare disease — a form of hereditary angioedema — could cause a sudden, severe swelling in her throat that could require quick intubation and land her in an intensive care unit (ICU) for days.

“I’ve been hospitalized for throat swells three times in the last year,” she said in an interview.

Dr. Gosnell no longer practices medicine because of a combination of illnesses, but lives with her husband, Andrew, and two young children, and said they are all “terrified” she will have to go to the hospital amid a COVID-19 surge that had shrunk the number of available ICU beds to 152 from 780 in Oregon as of Aug. 30. Thirty percent of the beds are in use for patients with COVID-19.

She said her life depends on being near hospitals that have ICUs and having access to highly specialized medications, one of which can cost up to $50,000 for the rescue dose.

Her fear has her “literally living bedbound.” In addition to hereditary angioedema, she has Ehlers-Danlos syndrome, which weakens connective tissue. She wears a cervical collar 24/7 to keep from tearing tissues, as any tissue injury can trigger a swell.
 

Patients worry there won’t be room

As ICU beds in most states are filling with COVID-19 patients as the Delta variant spreads, fears are rising among people like Dr. Gosnell, who have chronic conditions and diseases with unpredictable emergency visits, who worry that if they need emergency care there won’t be room.

As of Aug. 30, in the United States, 79% of ICU beds nationally were in use, 30% of them for COVID-19 patients, according to the U.S. Department of Health and Human Services.

In individual states, the picture is dire. Alabama has fewer than 10% of its ICU beds open across the entire state. In Florida, 93% of ICU beds are filled, 53% of them with COVID patients. In Louisiana, 87% of beds were already in use, 45% of them with COVID patients, just as category 4 hurricane Ida smashed into the coastline on Aug. 29.

News reports have told of people transported and airlifted as hospitals reach capacity.

In Bellville, Tex., U.S. Army veteran Daniel Wilkinson needed advanced care for gallstone pancreatitis that normally would take 30 minutes to treat, his Bellville doctor, Hasan Kakli, MD, told CBS News.

Mr. Wilkinson’s house was three doors from Bellville Hospital, but the hospital was not equipped to treat the condition. Calls to other hospitals found the same answer: no empty ICU beds. After a 7-hour wait on a stretcher, he was airlifted to a Veterans Affairs hospital in Houston, but it was too late. He died on August 22 at age 46.

Dr. Kakli said, “I’ve never lost a patient with this diagnosis. Ever. I’m scared that the next patient I see is someone that I can’t get to where they need to get to. We are playing musical chairs with 100 people and 10 chairs. When the music stops, what happens?”

Also in Texas in August, Joe Valdez, who was shot six times as an unlucky bystander in a domestic dispute, waited for more than a week for surgery at Ben Taub Hospital in Houston, which was over capacity with COVID patients, the Washington Post reported.

Others with chronic diseases fear needing emergency services or even entering a hospital for regular care with the COVID surge.

Nicole Seefeldt, 44, from Easton, Penn., who had a double-lung transplant in 2016, said that she hasn’t been able to see her lung transplant specialists in Philadelphia — an hour-and-a-half drive — for almost 2 years because of fear of contracting COVID. Before the pandemic, she made the trip almost weekly.

“I protect my lungs like they’re children,” she said. 

She relies on her local hospital for care, but has put off some needed care, such as a colonoscopy, and has relied on telemedicine because she wants to limit her hospital exposure.

Ms. Seefeldt now faces an eventual kidney transplant, as her kidney function has been reduced to 20%. In the meantime, she worries she will need emergency care for either her lungs or kidneys.

“For those of us who are chronically ill or disabled, what if we have an emergency that is not COVID-related? Are we going to be able to get a bed? Are we going to be able to get treatment? It’s not just COVID patients who come to the [emergency room],” she said.
 

A pandemic problem

Paul E. Casey, MD, MBA, chief medical officer at Rush University Medical Center in Chicago, said that high vaccination rates in Chicago have helped Rush continue to accommodate both non-COVID and COVID patients in the emergency department.

Though the hospital treated a large volume of COVID patients, “The vast majority of people we see and did see through the pandemic were non-COVID patents,” he said.

Dr. Casey said that in the first wave the hospital noticed a concerning drop in patients coming in for strokes and heart attacks — “things we knew hadn’t gone away.”

And the data backs it up. Over the course of the pandemic, the Centers for Disease Control and Prevention’s National Health Interview Survey found that the percentage of Americans who reported seeing a doctor or health professional fell from 85% at the end of 2019 to about 80% in the first three months of 2021. The survey did not differentiate between in-person visits and telehealth appointments.

Medical practices and patients themselves postponed elective procedures and delayed routine visits during the early months of the crisis.

Patients also reported staying away from hospitals’ emergency departments throughout the pandemic. At the end of 2019, 22% of respondents reported visiting an emergency department in the past year. That dropped to 17% by the end of 2020, and was at 17.7% in the first 3 months of 2021.

Dr. Casey said that, in his hospital’s case, clear messaging became very important to assure patients it was safe to come back. And the message is still critical.

“We want to be loud and clear that patients should continue to seek care for those conditions,” Dr. Casey said. “Deferring healthcare only comes with the long-term sequelae of disease left untreated so we want people to be as proactive in seeking care as they always would be.”

In some cases, fears of entering emergency rooms because of excess patients and risk for infection are keeping some patients from seeking necessary care for minor injuries.

Jim Rickert, MD, an orthopedic surgeon with Indiana University Health in Bloomington, said that some of his patients have expressed fears of coming into the hospital for fractures.

Some patients, particularly elderly patients, he said, are having falls and fractures and wearing slings or braces at home rather than going into the hospital for injuries that need immediate attention.

Bones start healing incorrectly, Dr. Rickert said, and the correction becomes much more difficult.
 

Plea for vaccinations

Dr. Gosnell made a plea posted on her neighborhood news forum for people to get COVID vaccinations.

“It seems to me it’s easy for other people who are not in bodies like mine to take health for granted,” she said. “But there are a lot of us who live in very fragile bodies and our entire life is at the intersection of us and getting healthcare treatment. Small complications to getting treatment can be life altering.”

Dr. Gosnell, Ms. Seefeldt, Dr. Casey, and Dr. Rickert reported no relevant financial relationships.

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

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.

Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

rfranki@mdedge.com

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.

Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

rfranki@mdedge.com

Weekly pediatric cases of COVID-19 exceeded 200,000 for just the second time during the pandemic, while new vaccinations in children continued to decline.

There were almost 204,000 new cases reported in children during the week of Aug. 20-26, the highest 1-week total since the peak of 211,000 in mid-January. The weekly count has now increased for 9 consecutive weeks, during which time it has risen by over 2,300%, the American Academy of Pediatrics and the Children’s Hospital Association said in their weekly COVID-19 report. Total cases in children number almost 4.8 million since the pandemic started.

Vaccinations in children are following a different trend. Vaccine initiation has dropped 3 weeks in a row for both of the eligible age groups: First doses administered were down by 29% among 12- to 15-year-olds over that span and by 32% in 16- to 17-year-olds, according to data from the Centers for Disease Control and Prevention.

Since vaccination for children aged 12-15 years started in May, 49% had received at least one dose, and just over 36% were fully vaccinated as of Aug. 30. Among children aged 16-17 years, who have been eligible since December, 57.5% had gotten at least one dose of the vaccine and 46% have completed the two-dose regimen. The total number of children with at least one dose, including those under age 12 who are involved in clinical trials, was about 12 million, the CDC said on its COVID Data Tracker.
 

Hospitalizations are higher than ever

The recent rise in new child cases has been accompanied by an unprecedented increase in hospitalizations. The daily rate in children aged 0-17 years, which did not surpass 0.30 new admissions per 100,000 population during the worst of the winter surge, had risen to 0.45 per 100,000 by Aug. 26. Since July 4, when the new-admission rate was at its low point of 0.07 per 100,000, hospitalizations in children have jumped by 543%, based on data reported to the CDC by 5,251 hospitals.

A total of 52,245 children were admitted with confirmed COVID-19 from Aug. 1, 2020, when the CDC dataset begins, to Aug. 28, 2021. Those children represent 1.9% of all COVID admissions (2.7 million) in the United States over that period, the CDC said.

Total COVID-related deaths in children are up to 425 in the 48 jurisdictions (45 states, New York City, Puerto Rico, and Guam) that provide mortality data by age, the AAP and the CHA said.

Record-high numbers for the previous 2 reporting weeks – 23 deaths during Aug. 20-26 and 24 deaths during Aug. 13-19, when the previous weekly high was 16 – at least partially reflect the recent addition of South Carolina and New Mexico to the AAP/CHA database, as the two states just started reporting age-related data.

rfranki@mdedge.com

Most children who develop multisystemic inflammatory syndrome (MIS-C) after infection with SARS-CoV-2 recover relatively quickly and without significant sequelae, according to a research letter published online in JAMA Pediatrics.

“The results of this research letter offer some reassurance as has been the case with other longitudinal reports, that children with MIS-C largely recover from the illness with minimal sequelae,” said Kanwal M. Farooqi, MD, a pediatric cardiologist from Columbia University Irving Medical Center, New York.

“This is despite the severity of the initial clinical presentation, which can be quite significant with signs of systemic inflammation, hypotension, and need for ICU-level care,” continued Dr. Farooqi, who was not involved in the study.

Given that little is known about the medium- and long-term effects of MIS-C following infection with COVID-19, Patrick Davies, MRCPCH, Nottingham (England) University Hospitals NHS Trust, and colleagues reviewed data from one of the earliest multicenter national cohorts of children in the United Kingdom. The cohort included children admitted to the hospital prior to May 10, 2020, and the analysis was based on data from 68 of 76 (89%) patients of the initial surviving cohort. Information regarding critical care readmissions and outpatient follow-up visits up to April 1, 2021 (1-year post admission), was included in the analysis.

Overall laboratory results appeared normal for most children at 50 days post admission, including neutrophils, platelets, ferritin, creatinine, and alanine transaminase. Just 3% (2/65 test results) of children showed elevated levels of C-reactive protein, 3% (2/59 test results) for D-dimer, and 2% (1/60 test results) for troponin.

Based on echocardiographic data, 14 of the 19 patients who presented with aneurysms had resolution. Nine of 10 patients who presented with “bright” coronary arteries had resolution and only one progressed to having unresolved coronary artery aneurysms with the latest follow-up at 86 days post admission. All of the 38 patients who presented with impaired function without aneurysm had recovered by day 74.

Of the six patients with ongoing echocardiographic abnormalities, all had aneurysmal changes noted on echocardiograms performed between 86 and 336 days post admission. The authors were surprised to find that troponin levels in this group were lower when compared with others in the cohort (0.06 ng/mL [interquartile range, 0.02-0.418 ng/mL] vs. 0.157 ng/mL [0.033-0.81 ng/mL]; P = .02).

These six patients ranged in age from 0 to 13 years (median age, 8.75 years); five were Afro Caribbean boys and one was a White girl.

The researchers acknowledged that, despite coming from a nationwide data set, the interpretation of this data is limited given the small size of the cohort and the lack of standardized follow-up protocol available at the time.

When asked how this data might inform follow-up guidance for children post COVID infection, Dr. Farooqi said, “although it appears from the data that we have seen in the last few months that the patients recover relatively quickly from MIS-C, I believe it is reasonable to evaluate them at 6-month intervals for the second year until we have more information regarding longer-term outcomes.”

The study authors and Dr. Farooqi disclosed no relevant financial relationships.

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

Most children who develop multisystemic inflammatory syndrome (MIS-C) after infection with SARS-CoV-2 recover relatively quickly and without significant sequelae, according to a research letter published online in JAMA Pediatrics.

“The results of this research letter offer some reassurance as has been the case with other longitudinal reports, that children with MIS-C largely recover from the illness with minimal sequelae,” said Kanwal M. Farooqi, MD, a pediatric cardiologist from Columbia University Irving Medical Center, New York.

“This is despite the severity of the initial clinical presentation, which can be quite significant with signs of systemic inflammation, hypotension, and need for ICU-level care,” continued Dr. Farooqi, who was not involved in the study.

Given that little is known about the medium- and long-term effects of MIS-C following infection with COVID-19, Patrick Davies, MRCPCH, Nottingham (England) University Hospitals NHS Trust, and colleagues reviewed data from one of the earliest multicenter national cohorts of children in the United Kingdom. The cohort included children admitted to the hospital prior to May 10, 2020, and the analysis was based on data from 68 of 76 (89%) patients of the initial surviving cohort. Information regarding critical care readmissions and outpatient follow-up visits up to April 1, 2021 (1-year post admission), was included in the analysis.

Overall laboratory results appeared normal for most children at 50 days post admission, including neutrophils, platelets, ferritin, creatinine, and alanine transaminase. Just 3% (2/65 test results) of children showed elevated levels of C-reactive protein, 3% (2/59 test results) for D-dimer, and 2% (1/60 test results) for troponin.

Based on echocardiographic data, 14 of the 19 patients who presented with aneurysms had resolution. Nine of 10 patients who presented with “bright” coronary arteries had resolution and only one progressed to having unresolved coronary artery aneurysms with the latest follow-up at 86 days post admission. All of the 38 patients who presented with impaired function without aneurysm had recovered by day 74.

Of the six patients with ongoing echocardiographic abnormalities, all had aneurysmal changes noted on echocardiograms performed between 86 and 336 days post admission. The authors were surprised to find that troponin levels in this group were lower when compared with others in the cohort (0.06 ng/mL [interquartile range, 0.02-0.418 ng/mL] vs. 0.157 ng/mL [0.033-0.81 ng/mL]; P = .02).

These six patients ranged in age from 0 to 13 years (median age, 8.75 years); five were Afro Caribbean boys and one was a White girl.

The researchers acknowledged that, despite coming from a nationwide data set, the interpretation of this data is limited given the small size of the cohort and the lack of standardized follow-up protocol available at the time.

When asked how this data might inform follow-up guidance for children post COVID infection, Dr. Farooqi said, “although it appears from the data that we have seen in the last few months that the patients recover relatively quickly from MIS-C, I believe it is reasonable to evaluate them at 6-month intervals for the second year until we have more information regarding longer-term outcomes.”

The study authors and Dr. Farooqi disclosed no relevant financial relationships.

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

Most children who develop multisystemic inflammatory syndrome (MIS-C) after infection with SARS-CoV-2 recover relatively quickly and without significant sequelae, according to a research letter published online in JAMA Pediatrics.

“The results of this research letter offer some reassurance as has been the case with other longitudinal reports, that children with MIS-C largely recover from the illness with minimal sequelae,” said Kanwal M. Farooqi, MD, a pediatric cardiologist from Columbia University Irving Medical Center, New York.

“This is despite the severity of the initial clinical presentation, which can be quite significant with signs of systemic inflammation, hypotension, and need for ICU-level care,” continued Dr. Farooqi, who was not involved in the study.

Given that little is known about the medium- and long-term effects of MIS-C following infection with COVID-19, Patrick Davies, MRCPCH, Nottingham (England) University Hospitals NHS Trust, and colleagues reviewed data from one of the earliest multicenter national cohorts of children in the United Kingdom. The cohort included children admitted to the hospital prior to May 10, 2020, and the analysis was based on data from 68 of 76 (89%) patients of the initial surviving cohort. Information regarding critical care readmissions and outpatient follow-up visits up to April 1, 2021 (1-year post admission), was included in the analysis.

Overall laboratory results appeared normal for most children at 50 days post admission, including neutrophils, platelets, ferritin, creatinine, and alanine transaminase. Just 3% (2/65 test results) of children showed elevated levels of C-reactive protein, 3% (2/59 test results) for D-dimer, and 2% (1/60 test results) for troponin.

Based on echocardiographic data, 14 of the 19 patients who presented with aneurysms had resolution. Nine of 10 patients who presented with “bright” coronary arteries had resolution and only one progressed to having unresolved coronary artery aneurysms with the latest follow-up at 86 days post admission. All of the 38 patients who presented with impaired function without aneurysm had recovered by day 74.

Of the six patients with ongoing echocardiographic abnormalities, all had aneurysmal changes noted on echocardiograms performed between 86 and 336 days post admission. The authors were surprised to find that troponin levels in this group were lower when compared with others in the cohort (0.06 ng/mL [interquartile range, 0.02-0.418 ng/mL] vs. 0.157 ng/mL [0.033-0.81 ng/mL]; P = .02).

These six patients ranged in age from 0 to 13 years (median age, 8.75 years); five were Afro Caribbean boys and one was a White girl.

The researchers acknowledged that, despite coming from a nationwide data set, the interpretation of this data is limited given the small size of the cohort and the lack of standardized follow-up protocol available at the time.

When asked how this data might inform follow-up guidance for children post COVID infection, Dr. Farooqi said, “although it appears from the data that we have seen in the last few months that the patients recover relatively quickly from MIS-C, I believe it is reasonable to evaluate them at 6-month intervals for the second year until we have more information regarding longer-term outcomes.”

The study authors and Dr. Farooqi disclosed no relevant financial relationships.

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

Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.

The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.

Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report. 

The study was published online Aug. 28 in The Lancet.

“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.

“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.

“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.

“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
 

Study details

Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.

Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.

Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.

Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.

Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).

At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.

Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients. 

Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.

Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.

Mental health hit

Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.

Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.

As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).

Compared with men, women were twice as likely to report anxiety or depression.

“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.

“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.

The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).

The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”

“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.

“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.

The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.

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

Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.

The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.

Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report. 

The study was published online Aug. 28 in The Lancet.

“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.

“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.

“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.

“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
 

Study details

Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.

Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.

Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.

Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.

Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).

At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.

Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients. 

Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.

Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.

Mental health hit

Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.

Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.

As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).

Compared with men, women were twice as likely to report anxiety or depression.

“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.

“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.

The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).

The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”

“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.

“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.

The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.

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

Nearly half of people who are hospitalized with COVID-19 suffer at least one lingering symptom 1 year after discharge, according to the largest study yet to assess the dynamic recovery of a group of COVID-19 survivors 12 months after the illness.

The most common lingering symptoms are fatigue and muscle weakness. One-third continue to have shortness of breath.

Overall, at 12 months, COVID-19 survivors had more problems with mobility, pain or discomfort, and anxiety or depression, and had lower self-assessment scores of quality of life than matched COVID-free peers, the investigators report. 

The study was published online Aug. 28 in The Lancet.

“While most had made a good recovery, health problems persisted in some patients, especially those who had been critically ill during their hospital stay,” Bin Cao, MD, from the National Center for Respiratory Medicine at the China-Japan Friendship Hospital and Capital Medical University, both in Beijing, said in a Lancet news release.

“Our findings suggest that recovery for some patients will take longer than 1 year, and this should be taken into account when planning delivery of health care services post pandemic,” Dr. Cao said.

“As the COVID-19 pandemic continues, the need to understand and respond to long COVID is increasingly pressing,” says a Lancet editorial.

“Symptoms such as persistent fatigue, breathlessness, brain fog, and depression could debilitate many millions of people globally. Long COVID is a modern medical challenge of the first order,” it reads.
 

Study details

Dr. Cao and colleagues studied 1,276 COVID-19 patients (median age 59; 53% men) discharged from a hospital in Wuhan, China, between Jan. 7 and May 29, 2020. The patients were assessed at 6 and 12 months from the date they first experienced COVID-19 symptoms.

Many symptoms resolved over time, regardless of the severity of illness. Yet 49% of patients still had at least one symptom 12 months after their acute illness, down from 68% at the 6-month mark, the authors report.

Fatigue and muscle weakness were the most commonly reported symptoms seen in 52% of patients at 6 months and 20% at 12 months. Compared with men, women were 1.4 times more likely to report fatigue or muscle weakness.

Patients treated with corticosteroids during the acute phase of COVID-19 were 1.5 times as likely to experience fatigue or muscle weakness after 12 months, compared with those who had not received corticosteroids.

Thirty percent of patients reported dyspnea at 12 months, slightly more than at 6 months (26%). Dyspnea was more common in the most severely ill patients needing a ventilator during their hospital stay (39%), compared with those who did not need oxygen treatment (25%).

At the 6-month check, 349 study participants underwent pulmonary function tests and 244 of those patients completed the same test at 12 months.

Spirometric and lung volume parameters of most of these patients were within normal limits at 12 months. But lung diffusion impairment was observed in about 20%-30% of patients who had been moderately ill with COVID-19 and as high as 54% in critically ill patients. 

Compared with men, women were almost three times as likely to have lung diffusion impairment after 12 months.

Of 186 patients with abnormal lung CT scan at 6 months, 118 patients had a repeat CT scan at 12 months. The lung imaging abnormality gradually recovered during follow-up, yet 76% of the most critically ill patients still had ground glass opacity at 12 months.

Mental health hit

Among those patients who had been employed full- or part-time before catching COVID, the majority had returned to their original job (88%) and most had returned to their pre-COVID-19 level of work (76%) within 12 months.

Among those who did not return to their original work, 32% cited decreased physical function, 25% were unwilling to do their previous job, and 18% were unemployed.

As shown in multiple other studies, COVID-19 can take a toll on mental health. In this cohort, slightly more patients reported anxiety or depression at 12 months than at 6 months (23% vs. 26%), and the proportion was much greater than in matched community-dwelling adults without COVID-19 (5%).

Compared with men, women were twice as likely to report anxiety or depression.

“We do not yet fully understand why psychiatric symptoms are slightly more common at 1 year than at 6 months in COVID-19 survivors,” study author Xiaoying Gu, PhD, from the Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, said in the news release.

“These could be caused by a biological process linked to the virus infection itself, or the body’s immune response to it. Or they could be linked to reduced social contact, loneliness, incomplete recovery of physical health, or loss of employment associated with illness. Large, long-term studies of COVID-19 survivors are needed so that we can better understand the long-term physical and mental health consequences of COVID-19,” Dr. Gu said.

The authors caution that the findings represent a group of patients from a single hospital in China and the cohort included only a small number of patients who had been admitted to intensive care (94 of 1,276; 7.4%).

The Lancet editorial urges the scientific and medical community to “collaborate to explore the mechanism and pathogenesis of long COVID, estimate the global and regional disease burdens, better delineate who is most at risk, understand how vaccines might affect the condition, and find effective treatments via randomized controlled trials.”

“At the same time, health care providers must acknowledge and validate the toll of the persistent symptoms of long COVID on patients, and health systems need to be prepared to meet individualized, patient-oriented goals, with an appropriately trained workforce involving physical, cognitive, social, and occupational elements,” the editorial states.

“Answering these research questions while providing compassionate and multidisciplinary care will require the full breadth of scientific and medical ingenuity. It is a challenge to which the whole health community must rise,” the editorialists conclude.

The study was funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, the National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, the China Evergrande Group, the Jack Ma Foundation, Sino Biopharmaceutical, the Ping An Insurance (Group), and the New Sunshine Charity Foundation. The full list of author disclosures is available with the original article.

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

An independent expert panel within the Centers for Disease Control and Prevention (CDC) has studied the potential benefits and risks of the Pfizer-BioNTech COVID-19 vaccine and voted unanimously to recommend the shots for all Americans ages 16 and older.

All 14 members of the Advisory Committee on Immunization Practices (ACIP) voted ‘yes’ to recommend the vaccine for Americans ages 16 and up. The vaccine was fully approved by the U.S. Food and Drug Administration (FDA) last week.

The inoculation is still available to teens ages 12 to 15 under an emergency use authorization from the FDA.

ACIP now sends its recommendation to the CDC Director Rochelle Walensky, MD, for her sign off.

After reviewing the evidence behind the vaccine, panel member Sarah Long, MD, a professor of pediatrics at Drexel University College of Medicine, Philadelphia, said she couldn’t recall another instance where panelists had so much data on which to base their recommendation.

“This vaccine is worthy of the trust of the American people,” she said.

Doctors across the country use vaccines in line with the recommendations made by the ACIP. Their approval typically means that private and government insurers will cover the cost of the shots. In the case of the COVID-19 vaccines, the government is already picking up the tab.

Few surprises

The panel’s independent review of the vaccine’s effectiveness from nine studies held few surprises. 

They found the Pfizer vaccine prevented a COVID infection with symptoms about 90%–92% of the time, at least for the first 4 months after the second shot. Protection against hospitalization and death was even higher.

The vaccine was about 89% effective at preventing a COVID infection without symptoms, according to a pooled estimate of five studies.

The data included in the review was updated only through March 13 of this year, however, and does not reflect the impact of further waning of immunity or the impact of the Delta variant.

In making their recommendation, the panel got an update on the safety of the vaccines, which have now been used in the United States for about 9 months.

The rate of anaphylaxis has settled at around five cases for every million shots given, according to the ACIP’s review of the evidence. 

Cases of myocarditis and pericarditis were more common after getting a Pfizer-BioNTech vaccine than would be expected to happen naturally in the general population, but the risk was still very rare, and elevated primarily for men younger than age 30. 

Out of 17 million second doses of Pfizer-BioNTech vaccines in the United States, there have been 327 confirmed cases of myocarditis reported to the Vaccine Adverse Event Reporting System in people who are younger than age 30. The average hospital stay for a myocarditis cases is 1 to 2 days. 

So far, no one in the United States diagnosed with myocarditis after vaccination has died.

What’s more, the risk of myocarditis after vaccination was dwarfed by the risk of myocarditis after a COVID infection. The risk of myocarditis after a COVID infection was 6 to 34 times higher than the risk after receiving an mRNA vaccine.

About 11% of people who get the vaccine experience a serious reaction to the shot, compared with about 3% in the placebo group. Serious reactions were defined as pain; swelling or redness at the injection site that interferes with activity; needing to visit the hospital or ER for pain; tissue necrosis, or having skin slough off; high fever; vomiting that requires hydration; persistent diarrhea; severe headache;  or muscle pain/severe joint pain.

“Safe and effective”

After hearing a presentation on the state of the pandemic in the US, some panel members were struck and shaken that 38% of Americans who are eligible are still not fully vaccinated.

Pablo Sanchez, MD, a pediatrician at Nationwide Children’s Hospital in Columbus, Ohio, said, “We’re doing an abysmal job vaccinating the American people. The message has to go out that the vaccines are safe and effective.”



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

An independent expert panel within the Centers for Disease Control and Prevention (CDC) has studied the potential benefits and risks of the Pfizer-BioNTech COVID-19 vaccine and voted unanimously to recommend the shots for all Americans ages 16 and older.

All 14 members of the Advisory Committee on Immunization Practices (ACIP) voted ‘yes’ to recommend the vaccine for Americans ages 16 and up. The vaccine was fully approved by the U.S. Food and Drug Administration (FDA) last week.

The inoculation is still available to teens ages 12 to 15 under an emergency use authorization from the FDA.

ACIP now sends its recommendation to the CDC Director Rochelle Walensky, MD, for her sign off.

After reviewing the evidence behind the vaccine, panel member Sarah Long, MD, a professor of pediatrics at Drexel University College of Medicine, Philadelphia, said she couldn’t recall another instance where panelists had so much data on which to base their recommendation.

“This vaccine is worthy of the trust of the American people,” she said.

Doctors across the country use vaccines in line with the recommendations made by the ACIP. Their approval typically means that private and government insurers will cover the cost of the shots. In the case of the COVID-19 vaccines, the government is already picking up the tab.

Few surprises

The panel’s independent review of the vaccine’s effectiveness from nine studies held few surprises. 

They found the Pfizer vaccine prevented a COVID infection with symptoms about 90%–92% of the time, at least for the first 4 months after the second shot. Protection against hospitalization and death was even higher.

The vaccine was about 89% effective at preventing a COVID infection without symptoms, according to a pooled estimate of five studies.

The data included in the review was updated only through March 13 of this year, however, and does not reflect the impact of further waning of immunity or the impact of the Delta variant.

In making their recommendation, the panel got an update on the safety of the vaccines, which have now been used in the United States for about 9 months.

The rate of anaphylaxis has settled at around five cases for every million shots given, according to the ACIP’s review of the evidence. 

Cases of myocarditis and pericarditis were more common after getting a Pfizer-BioNTech vaccine than would be expected to happen naturally in the general population, but the risk was still very rare, and elevated primarily for men younger than age 30. 

Out of 17 million second doses of Pfizer-BioNTech vaccines in the United States, there have been 327 confirmed cases of myocarditis reported to the Vaccine Adverse Event Reporting System in people who are younger than age 30. The average hospital stay for a myocarditis cases is 1 to 2 days. 

So far, no one in the United States diagnosed with myocarditis after vaccination has died.

What’s more, the risk of myocarditis after vaccination was dwarfed by the risk of myocarditis after a COVID infection. The risk of myocarditis after a COVID infection was 6 to 34 times higher than the risk after receiving an mRNA vaccine.

About 11% of people who get the vaccine experience a serious reaction to the shot, compared with about 3% in the placebo group. Serious reactions were defined as pain; swelling or redness at the injection site that interferes with activity; needing to visit the hospital or ER for pain; tissue necrosis, or having skin slough off; high fever; vomiting that requires hydration; persistent diarrhea; severe headache;  or muscle pain/severe joint pain.

“Safe and effective”

After hearing a presentation on the state of the pandemic in the US, some panel members were struck and shaken that 38% of Americans who are eligible are still not fully vaccinated.

Pablo Sanchez, MD, a pediatrician at Nationwide Children’s Hospital in Columbus, Ohio, said, “We’re doing an abysmal job vaccinating the American people. The message has to go out that the vaccines are safe and effective.”



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

An independent expert panel within the Centers for Disease Control and Prevention (CDC) has studied the potential benefits and risks of the Pfizer-BioNTech COVID-19 vaccine and voted unanimously to recommend the shots for all Americans ages 16 and older.

All 14 members of the Advisory Committee on Immunization Practices (ACIP) voted ‘yes’ to recommend the vaccine for Americans ages 16 and up. The vaccine was fully approved by the U.S. Food and Drug Administration (FDA) last week.

The inoculation is still available to teens ages 12 to 15 under an emergency use authorization from the FDA.

ACIP now sends its recommendation to the CDC Director Rochelle Walensky, MD, for her sign off.

After reviewing the evidence behind the vaccine, panel member Sarah Long, MD, a professor of pediatrics at Drexel University College of Medicine, Philadelphia, said she couldn’t recall another instance where panelists had so much data on which to base their recommendation.

“This vaccine is worthy of the trust of the American people,” she said.

Doctors across the country use vaccines in line with the recommendations made by the ACIP. Their approval typically means that private and government insurers will cover the cost of the shots. In the case of the COVID-19 vaccines, the government is already picking up the tab.

Few surprises

The panel’s independent review of the vaccine’s effectiveness from nine studies held few surprises. 

They found the Pfizer vaccine prevented a COVID infection with symptoms about 90%–92% of the time, at least for the first 4 months after the second shot. Protection against hospitalization and death was even higher.

The vaccine was about 89% effective at preventing a COVID infection without symptoms, according to a pooled estimate of five studies.

The data included in the review was updated only through March 13 of this year, however, and does not reflect the impact of further waning of immunity or the impact of the Delta variant.

In making their recommendation, the panel got an update on the safety of the vaccines, which have now been used in the United States for about 9 months.

The rate of anaphylaxis has settled at around five cases for every million shots given, according to the ACIP’s review of the evidence. 

Cases of myocarditis and pericarditis were more common after getting a Pfizer-BioNTech vaccine than would be expected to happen naturally in the general population, but the risk was still very rare, and elevated primarily for men younger than age 30. 

Out of 17 million second doses of Pfizer-BioNTech vaccines in the United States, there have been 327 confirmed cases of myocarditis reported to the Vaccine Adverse Event Reporting System in people who are younger than age 30. The average hospital stay for a myocarditis cases is 1 to 2 days. 

So far, no one in the United States diagnosed with myocarditis after vaccination has died.

What’s more, the risk of myocarditis after vaccination was dwarfed by the risk of myocarditis after a COVID infection. The risk of myocarditis after a COVID infection was 6 to 34 times higher than the risk after receiving an mRNA vaccine.

About 11% of people who get the vaccine experience a serious reaction to the shot, compared with about 3% in the placebo group. Serious reactions were defined as pain; swelling or redness at the injection site that interferes with activity; needing to visit the hospital or ER for pain; tissue necrosis, or having skin slough off; high fever; vomiting that requires hydration; persistent diarrhea; severe headache;  or muscle pain/severe joint pain.

“Safe and effective”

After hearing a presentation on the state of the pandemic in the US, some panel members were struck and shaken that 38% of Americans who are eligible are still not fully vaccinated.

Pablo Sanchez, MD, a pediatrician at Nationwide Children’s Hospital in Columbus, Ohio, said, “We’re doing an abysmal job vaccinating the American people. The message has to go out that the vaccines are safe and effective.”



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

Epithelial and immune cells of the upper airways of children are preactivated and primed to detect SARS-CoV-2 infection, which may contribute to stronger early immune responses to SARS-CoV-2 infection than adults, new research suggests.

The findings may help to explain why children have a lower risk of developing severe COVID-19 illness or becoming infected with SARS-CoV-2 in the first place, the researchers say.

The study was published online Aug. 18 in Nature Biotechnology.
 

Primed for action

Children appear to be better able than adults to control SARS-CoV-2 infection, but, until now, the exact molecular mechanisms have been unclear.

A team of investigators from Germany did an in-depth analysis of nasal swab samples obtained from 24 children and 21 adults who tested positive for SARS-CoV-2, as well as a control group of 18 children and 23 adults who tested negative for SARS-CoV-2.

“We wanted to understand why viral defense appears to work so much better in children than in adults,” Irina Lehmann, PhD, head of the molecular epidemiology unit at the Berlin Institute of Health Charité – Universitätsmedizin Berlin, explained in a news release. 

Single-cell sequencing showed that children had higher baseline levels of certain RNA-sensing receptors that are relevant to SARS-CoV-2 detection, such as MDA5 and RIG-I, in the epithelial and immune cells of their noses.

This differential expression led to stronger early immune responses to SARS-CoV-2 infection in children than in adults.

Children were also more likely than adults to have distinct immune cell subpopulations, including KLRC1+ cytotoxic T cells, involved in fighting infection, and memory CD8+ T cells, associated with the development of long-lasting immunity.
 

‘Clear evidence’

The study provides “clear evidence” that upper-airway immune cells of children are “primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults,” the investigators say.

Primed virus sensing and a preactivated innate immune response in children leads to efficient early production of interferons (IFNs) in the infected airways, likely mediating substantial antiviral effects, they note.

Ultimately, this may lead to lower viral replication and faster clearance in children. In fact, several studies have already shown that children eliminate the virus more quickly than adults, consistent with the concept that they shut down viral replication earlier, the study team says.

Weighing in on the findings for this news organization, John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, said this “interesting study highlights potential differences in innate immunity and possibly geographic immunity in the upper respiratory tract in children versus adults.”

“We know there are differences in innate immunity over a lifespan, but exactly how these differences might relate to viral infection remains unclear,” said Dr. Wherry, who was not involved in the study.

“Children, of course, often have more respiratory infections than adults [but] whether this is due to exposure [i.e., daycare, schools, etc.] or susceptibility [lack of accumulated adaptive immunity over a greater number of years of exposure] is unclear,” Dr. Wherry noted.

“These data may help reveal what kinds of innate immune responses in the upper respiratory tract might help restrain SARS-CoV-2 and [perhaps partially] explain why children typically have milder COVID-19 disease,” he added.

The study was supported by the Berlin Institute of Health COVID-19 research program and fightCOVID@DKFZ initiative, European Commission, German Federal Ministry for Education and Research (BMBF), and German Research Foundation. Dr. Lehmann and Dr. Wherry have reported no relevant financial relationships.

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

Epithelial and immune cells of the upper airways of children are preactivated and primed to detect SARS-CoV-2 infection, which may contribute to stronger early immune responses to SARS-CoV-2 infection than adults, new research suggests.

The findings may help to explain why children have a lower risk of developing severe COVID-19 illness or becoming infected with SARS-CoV-2 in the first place, the researchers say.

The study was published online Aug. 18 in Nature Biotechnology.
 

Primed for action

Children appear to be better able than adults to control SARS-CoV-2 infection, but, until now, the exact molecular mechanisms have been unclear.

A team of investigators from Germany did an in-depth analysis of nasal swab samples obtained from 24 children and 21 adults who tested positive for SARS-CoV-2, as well as a control group of 18 children and 23 adults who tested negative for SARS-CoV-2.

“We wanted to understand why viral defense appears to work so much better in children than in adults,” Irina Lehmann, PhD, head of the molecular epidemiology unit at the Berlin Institute of Health Charité – Universitätsmedizin Berlin, explained in a news release. 

Single-cell sequencing showed that children had higher baseline levels of certain RNA-sensing receptors that are relevant to SARS-CoV-2 detection, such as MDA5 and RIG-I, in the epithelial and immune cells of their noses.

This differential expression led to stronger early immune responses to SARS-CoV-2 infection in children than in adults.

Children were also more likely than adults to have distinct immune cell subpopulations, including KLRC1+ cytotoxic T cells, involved in fighting infection, and memory CD8+ T cells, associated with the development of long-lasting immunity.
 

‘Clear evidence’

The study provides “clear evidence” that upper-airway immune cells of children are “primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults,” the investigators say.

Primed virus sensing and a preactivated innate immune response in children leads to efficient early production of interferons (IFNs) in the infected airways, likely mediating substantial antiviral effects, they note.

Ultimately, this may lead to lower viral replication and faster clearance in children. In fact, several studies have already shown that children eliminate the virus more quickly than adults, consistent with the concept that they shut down viral replication earlier, the study team says.

Weighing in on the findings for this news organization, John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, said this “interesting study highlights potential differences in innate immunity and possibly geographic immunity in the upper respiratory tract in children versus adults.”

“We know there are differences in innate immunity over a lifespan, but exactly how these differences might relate to viral infection remains unclear,” said Dr. Wherry, who was not involved in the study.

“Children, of course, often have more respiratory infections than adults [but] whether this is due to exposure [i.e., daycare, schools, etc.] or susceptibility [lack of accumulated adaptive immunity over a greater number of years of exposure] is unclear,” Dr. Wherry noted.

“These data may help reveal what kinds of innate immune responses in the upper respiratory tract might help restrain SARS-CoV-2 and [perhaps partially] explain why children typically have milder COVID-19 disease,” he added.

The study was supported by the Berlin Institute of Health COVID-19 research program and fightCOVID@DKFZ initiative, European Commission, German Federal Ministry for Education and Research (BMBF), and German Research Foundation. Dr. Lehmann and Dr. Wherry have reported no relevant financial relationships.

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

Epithelial and immune cells of the upper airways of children are preactivated and primed to detect SARS-CoV-2 infection, which may contribute to stronger early immune responses to SARS-CoV-2 infection than adults, new research suggests.

The findings may help to explain why children have a lower risk of developing severe COVID-19 illness or becoming infected with SARS-CoV-2 in the first place, the researchers say.

The study was published online Aug. 18 in Nature Biotechnology.
 

Primed for action

Children appear to be better able than adults to control SARS-CoV-2 infection, but, until now, the exact molecular mechanisms have been unclear.

A team of investigators from Germany did an in-depth analysis of nasal swab samples obtained from 24 children and 21 adults who tested positive for SARS-CoV-2, as well as a control group of 18 children and 23 adults who tested negative for SARS-CoV-2.

“We wanted to understand why viral defense appears to work so much better in children than in adults,” Irina Lehmann, PhD, head of the molecular epidemiology unit at the Berlin Institute of Health Charité – Universitätsmedizin Berlin, explained in a news release. 

Single-cell sequencing showed that children had higher baseline levels of certain RNA-sensing receptors that are relevant to SARS-CoV-2 detection, such as MDA5 and RIG-I, in the epithelial and immune cells of their noses.

This differential expression led to stronger early immune responses to SARS-CoV-2 infection in children than in adults.

Children were also more likely than adults to have distinct immune cell subpopulations, including KLRC1+ cytotoxic T cells, involved in fighting infection, and memory CD8+ T cells, associated with the development of long-lasting immunity.
 

‘Clear evidence’

The study provides “clear evidence” that upper-airway immune cells of children are “primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults,” the investigators say.

Primed virus sensing and a preactivated innate immune response in children leads to efficient early production of interferons (IFNs) in the infected airways, likely mediating substantial antiviral effects, they note.

Ultimately, this may lead to lower viral replication and faster clearance in children. In fact, several studies have already shown that children eliminate the virus more quickly than adults, consistent with the concept that they shut down viral replication earlier, the study team says.

Weighing in on the findings for this news organization, John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, said this “interesting study highlights potential differences in innate immunity and possibly geographic immunity in the upper respiratory tract in children versus adults.”

“We know there are differences in innate immunity over a lifespan, but exactly how these differences might relate to viral infection remains unclear,” said Dr. Wherry, who was not involved in the study.

“Children, of course, often have more respiratory infections than adults [but] whether this is due to exposure [i.e., daycare, schools, etc.] or susceptibility [lack of accumulated adaptive immunity over a greater number of years of exposure] is unclear,” Dr. Wherry noted.

“These data may help reveal what kinds of innate immune responses in the upper respiratory tract might help restrain SARS-CoV-2 and [perhaps partially] explain why children typically have milder COVID-19 disease,” he added.

The study was supported by the Berlin Institute of Health COVID-19 research program and fightCOVID@DKFZ initiative, European Commission, German Federal Ministry for Education and Research (BMBF), and German Research Foundation. Dr. Lehmann and Dr. Wherry have reported no relevant financial relationships.

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

A handful of studies have suggested that for newly infected COVID-19 patients, risk for serious illness may be reduced with a short course of fluvoxamine (Luvox), a decades-old pill typically prescribed for depression or obsessive-compulsive disorder (OCD). But those were small studies involving just a few hundred people.

This week, researchers reported promising data from a large, randomized phase 3 trial that enrolled COVID-19 patients from 11 sites in Brazil. In this study, in which 1,472 people were assigned to receive either a 10-day course of fluvoxamine or placebo pills, the antidepressant cut emergency department and hospital admissions by 29%.

Findings from the new study, which have not yet been peer reviewed, were published August 23 in MedRxiv.

Around the globe, particularly in countries without access to vaccines, “treatment options that are cheap and available and supported by good-quality evidence are the only hope we’ve got to reduce mortality within high-risk populations,” said Edward Mills, PhD, professor in the department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont.

The new findings came from TOGETHER, a large platform trial coordinated by Dr. Mills and colleagues to evaluate the use of fluvoxamine and other repurposed drug candidates for symptomatic, high-risk, adult outpatients with confirmed cases of COVID-19.

The trial’s adaptive format allows multiple agents to be added and tested alongside placebo in a single master protocol – similar to the United Kingdom’s Recovery trial, which found that the common steroid dexamethasone could reduce deaths among hospitalized COVID-19 patients.

In platform trials, treatment arms can be dropped for futility, as was the case with hydroxychloroquine and lopinavir-ritonavir, neither of which did better than placebo at preventing hospitalization in an earlier TOGETHER trial analysis.
 

Study details

In the newly reported analysis, patients were randomly assigned to receive fluvoxamine or placebo between January and August 2021. Participants took fluvoxamine 100 mg twice daily for 10 days. By comparison, the U.S. Food and Drug Administration recommends a maximum daily dose of 300 mg of fluvoxamine for patients with OCD; full psychiatric benefits occur after 6 weeks.

For the primary outcome, the investigators assessed whether the conditions of patients with COVID worsened over a 28-day period so as to require either hospitalization or observation in the emergency department for more than 6 hours. In the placebo group, 108 of 733 patients’ conditions deteriorated to this extent (14.7%); by contrast, only 77 of 739 patients in the fluvoxamine group (10.4%) met these primary criteria – a relative risk reduction of 29%.

The treatment effect was greater (34%) in the per protocol analysis of participants who completed their course of pills.

The investigators also collected data on vital signs, including temperature and oxygen saturation, as well as adverse events reported at clinic visits or through video conferencing, phone calls, or social media applications. Side effects were mild, most commonly nausea and fatigue, and did not differ significantly between active treatment and control groups, Dr. Mills said in an interview.

Amid scores of studies evaluating repurposed drugs for COVID-19, the data on fluvoxamine are “looking much more favorable than anyone could have guessed – at least anyone in infectious disease,” said Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

The new TOGETHER trial results augment supportive data published in JAMA last November from a phase 2 randomized trial that was small but “very well done,” Dr. Sax told this news organization.

Those results got a boost from a subsequent study of 65 racetrack workers who chose to take fluvoxamine during a COVID-19 outbreak in the San Francisco Bay area. Forty-eight persons opted against taking the drug. In this small, nonrandomized study, “the people who chose to be treated with fluvoxamine were sicker [at baseline] than the people who didn’t go on it, and yet the [treated group] ended up better,” said Dr. Sax, who discussed accumulating data on the use of fluvoxamine for COVID-19 in a recent New England Journal of Medicine blog post.
 

Anti-inflammatory effect?

After reviewing the new findings, Frank Domino, MD, professor of family medicine and community health at the University of Massachusetts, Worcester, said he would encourage patients with high-risk COVID-19 to consider taking fluvoxamine to lower their risk of being hospitalized. “But I would make it clear this was not a ‘cure,’ “ he said, “and we are unsure how it helps.”

At this point, U.S. treatment guidelines do not recommend fluvoxamine as the standard of care for nonhospitalized COVID-19 patients, but the National Institutes of Health is “very aware of the data,” Dr. Sax told this news organization.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) – a class of drugs that includes the more commonly prescribed antidepressant fluoxetine (Prozac). If prescribed off-label to COVID-19 patients, fluvoxamine should not be used within 2 weeks of starting treatment with other SSRI or monoamine oxidase inhibitor antidepressants and should be used with caution with other QT-interval prolonging medications, Dr. Sax said.

In addition, fluvoxamine can enhance the effect of antiplatelet and anticoagulant drugs, potentially triggering bleeding.

On the basis of in vitro and mouse studies of fluvoxamine, “we think it has an anti-inflammatory effect,” said child psychiatrist Angela Reiersen, MD, of Washington University, St. Louis, who came up with the idea for testing fluvoxamine in last year’s phase 2 trial and coauthored a recent article describing the drug’s potential mechanisms of action in COVID-19.

She and other researchers believe fluvoxamine’s anti-inflammatory effects derive from the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, which regulates cellular responses to stress and infection.

Fluvoxamine also inhibits the activation of platelets. “In COVID-19, there does seem to be a problem with hyperactivation of platelets and excessive blood clots forming, so it is possible this could be another mechanism where it might be helping,” Dr. Reiersen said.

If sigma-1 activation turns out to be the main mechanism underlying fluvoxamine’s benefits in COVID-19, other sigma-1 agonists, such as fluoxetine, may also help. In a retrospective analysis of thousands of adults hospitalized for COVID-19 in France early in the pandemic, those who were taking antidepressants had a 44% lower risk for intubation or death.

And in a study under review, researchers at Stanford (Calif.) University and the University of California, San Francisco, analyzed electronic health records to explore a potential link between fluoxetine use and COVID outcomes among more than 80,000 patients from over 80 institutions across the United States. Other research suggests that antipsychotics could also have protective effects for patients with COVID-19.
 

Long COVID, long-term challenges

On the basis of its potential mechanisms of action, fluvoxamine may be able to prevent or treat long COVID, Dr. Reiersen said. That possibility will be assessed among other secondary endpoints in two ongoing studies of repurposed drugs: the NIH’s ACTIV-6, and the University of Minnesota’s COVID-OUT, an at-home trial of ivermectin, metformin, and fluvoxamine.

Dr. Reiersen and Washington University colleagues are also analyzing longer-term outcomes of participants in their own phase 3 trial of fluvoxamine (Stop COVID 2), which was discontinued when enrollment slowed to a trickle during the U.S. vaccine rollout. Logistical hurdles and scant funding have greatly hampered efforts to test the use of off-patent drugs for COVID-19 outpatients during the pandemic.

U.S. efforts face other obstacles as well. Elsewhere in the world – including Brazil, where the TOGETHER trial was run – vaccines are scarce, and there are no monoclonal antibodies.

“People have a great sense of community duty, and they’re participating in the trials,” Dr. Mills said. “You’re in a much more political environment in the U.S. on these outpatient trials.”

The TOGETHER trial was funded by Fast Grants and the Rainwater Foundation. Dr. Reiersen is an inventor on a patent application related to methods of treating COVID-19, which was filed by Washington University, St. Louis. Dr. Mills, Dr. Domino, and Dr. Sax report no relevant financial relationships.

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

A handful of studies have suggested that for newly infected COVID-19 patients, risk for serious illness may be reduced with a short course of fluvoxamine (Luvox), a decades-old pill typically prescribed for depression or obsessive-compulsive disorder (OCD). But those were small studies involving just a few hundred people.

This week, researchers reported promising data from a large, randomized phase 3 trial that enrolled COVID-19 patients from 11 sites in Brazil. In this study, in which 1,472 people were assigned to receive either a 10-day course of fluvoxamine or placebo pills, the antidepressant cut emergency department and hospital admissions by 29%.

Findings from the new study, which have not yet been peer reviewed, were published August 23 in MedRxiv.

Around the globe, particularly in countries without access to vaccines, “treatment options that are cheap and available and supported by good-quality evidence are the only hope we’ve got to reduce mortality within high-risk populations,” said Edward Mills, PhD, professor in the department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont.

The new findings came from TOGETHER, a large platform trial coordinated by Dr. Mills and colleagues to evaluate the use of fluvoxamine and other repurposed drug candidates for symptomatic, high-risk, adult outpatients with confirmed cases of COVID-19.

The trial’s adaptive format allows multiple agents to be added and tested alongside placebo in a single master protocol – similar to the United Kingdom’s Recovery trial, which found that the common steroid dexamethasone could reduce deaths among hospitalized COVID-19 patients.

In platform trials, treatment arms can be dropped for futility, as was the case with hydroxychloroquine and lopinavir-ritonavir, neither of which did better than placebo at preventing hospitalization in an earlier TOGETHER trial analysis.
 

Study details

In the newly reported analysis, patients were randomly assigned to receive fluvoxamine or placebo between January and August 2021. Participants took fluvoxamine 100 mg twice daily for 10 days. By comparison, the U.S. Food and Drug Administration recommends a maximum daily dose of 300 mg of fluvoxamine for patients with OCD; full psychiatric benefits occur after 6 weeks.

For the primary outcome, the investigators assessed whether the conditions of patients with COVID worsened over a 28-day period so as to require either hospitalization or observation in the emergency department for more than 6 hours. In the placebo group, 108 of 733 patients’ conditions deteriorated to this extent (14.7%); by contrast, only 77 of 739 patients in the fluvoxamine group (10.4%) met these primary criteria – a relative risk reduction of 29%.

The treatment effect was greater (34%) in the per protocol analysis of participants who completed their course of pills.

The investigators also collected data on vital signs, including temperature and oxygen saturation, as well as adverse events reported at clinic visits or through video conferencing, phone calls, or social media applications. Side effects were mild, most commonly nausea and fatigue, and did not differ significantly between active treatment and control groups, Dr. Mills said in an interview.

Amid scores of studies evaluating repurposed drugs for COVID-19, the data on fluvoxamine are “looking much more favorable than anyone could have guessed – at least anyone in infectious disease,” said Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

The new TOGETHER trial results augment supportive data published in JAMA last November from a phase 2 randomized trial that was small but “very well done,” Dr. Sax told this news organization.

Those results got a boost from a subsequent study of 65 racetrack workers who chose to take fluvoxamine during a COVID-19 outbreak in the San Francisco Bay area. Forty-eight persons opted against taking the drug. In this small, nonrandomized study, “the people who chose to be treated with fluvoxamine were sicker [at baseline] than the people who didn’t go on it, and yet the [treated group] ended up better,” said Dr. Sax, who discussed accumulating data on the use of fluvoxamine for COVID-19 in a recent New England Journal of Medicine blog post.
 

Anti-inflammatory effect?

After reviewing the new findings, Frank Domino, MD, professor of family medicine and community health at the University of Massachusetts, Worcester, said he would encourage patients with high-risk COVID-19 to consider taking fluvoxamine to lower their risk of being hospitalized. “But I would make it clear this was not a ‘cure,’ “ he said, “and we are unsure how it helps.”

At this point, U.S. treatment guidelines do not recommend fluvoxamine as the standard of care for nonhospitalized COVID-19 patients, but the National Institutes of Health is “very aware of the data,” Dr. Sax told this news organization.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) – a class of drugs that includes the more commonly prescribed antidepressant fluoxetine (Prozac). If prescribed off-label to COVID-19 patients, fluvoxamine should not be used within 2 weeks of starting treatment with other SSRI or monoamine oxidase inhibitor antidepressants and should be used with caution with other QT-interval prolonging medications, Dr. Sax said.

In addition, fluvoxamine can enhance the effect of antiplatelet and anticoagulant drugs, potentially triggering bleeding.

On the basis of in vitro and mouse studies of fluvoxamine, “we think it has an anti-inflammatory effect,” said child psychiatrist Angela Reiersen, MD, of Washington University, St. Louis, who came up with the idea for testing fluvoxamine in last year’s phase 2 trial and coauthored a recent article describing the drug’s potential mechanisms of action in COVID-19.

She and other researchers believe fluvoxamine’s anti-inflammatory effects derive from the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, which regulates cellular responses to stress and infection.

Fluvoxamine also inhibits the activation of platelets. “In COVID-19, there does seem to be a problem with hyperactivation of platelets and excessive blood clots forming, so it is possible this could be another mechanism where it might be helping,” Dr. Reiersen said.

If sigma-1 activation turns out to be the main mechanism underlying fluvoxamine’s benefits in COVID-19, other sigma-1 agonists, such as fluoxetine, may also help. In a retrospective analysis of thousands of adults hospitalized for COVID-19 in France early in the pandemic, those who were taking antidepressants had a 44% lower risk for intubation or death.

And in a study under review, researchers at Stanford (Calif.) University and the University of California, San Francisco, analyzed electronic health records to explore a potential link between fluoxetine use and COVID outcomes among more than 80,000 patients from over 80 institutions across the United States. Other research suggests that antipsychotics could also have protective effects for patients with COVID-19.
 

Long COVID, long-term challenges

On the basis of its potential mechanisms of action, fluvoxamine may be able to prevent or treat long COVID, Dr. Reiersen said. That possibility will be assessed among other secondary endpoints in two ongoing studies of repurposed drugs: the NIH’s ACTIV-6, and the University of Minnesota’s COVID-OUT, an at-home trial of ivermectin, metformin, and fluvoxamine.

Dr. Reiersen and Washington University colleagues are also analyzing longer-term outcomes of participants in their own phase 3 trial of fluvoxamine (Stop COVID 2), which was discontinued when enrollment slowed to a trickle during the U.S. vaccine rollout. Logistical hurdles and scant funding have greatly hampered efforts to test the use of off-patent drugs for COVID-19 outpatients during the pandemic.

U.S. efforts face other obstacles as well. Elsewhere in the world – including Brazil, where the TOGETHER trial was run – vaccines are scarce, and there are no monoclonal antibodies.

“People have a great sense of community duty, and they’re participating in the trials,” Dr. Mills said. “You’re in a much more political environment in the U.S. on these outpatient trials.”

The TOGETHER trial was funded by Fast Grants and the Rainwater Foundation. Dr. Reiersen is an inventor on a patent application related to methods of treating COVID-19, which was filed by Washington University, St. Louis. Dr. Mills, Dr. Domino, and Dr. Sax report no relevant financial relationships.

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

A handful of studies have suggested that for newly infected COVID-19 patients, risk for serious illness may be reduced with a short course of fluvoxamine (Luvox), a decades-old pill typically prescribed for depression or obsessive-compulsive disorder (OCD). But those were small studies involving just a few hundred people.

This week, researchers reported promising data from a large, randomized phase 3 trial that enrolled COVID-19 patients from 11 sites in Brazil. In this study, in which 1,472 people were assigned to receive either a 10-day course of fluvoxamine or placebo pills, the antidepressant cut emergency department and hospital admissions by 29%.

Findings from the new study, which have not yet been peer reviewed, were published August 23 in MedRxiv.

Around the globe, particularly in countries without access to vaccines, “treatment options that are cheap and available and supported by good-quality evidence are the only hope we’ve got to reduce mortality within high-risk populations,” said Edward Mills, PhD, professor in the department of health research methods, evidence, and impact, McMaster University, Hamilton, Ont.

The new findings came from TOGETHER, a large platform trial coordinated by Dr. Mills and colleagues to evaluate the use of fluvoxamine and other repurposed drug candidates for symptomatic, high-risk, adult outpatients with confirmed cases of COVID-19.

The trial’s adaptive format allows multiple agents to be added and tested alongside placebo in a single master protocol – similar to the United Kingdom’s Recovery trial, which found that the common steroid dexamethasone could reduce deaths among hospitalized COVID-19 patients.

In platform trials, treatment arms can be dropped for futility, as was the case with hydroxychloroquine and lopinavir-ritonavir, neither of which did better than placebo at preventing hospitalization in an earlier TOGETHER trial analysis.
 

Study details

In the newly reported analysis, patients were randomly assigned to receive fluvoxamine or placebo between January and August 2021. Participants took fluvoxamine 100 mg twice daily for 10 days. By comparison, the U.S. Food and Drug Administration recommends a maximum daily dose of 300 mg of fluvoxamine for patients with OCD; full psychiatric benefits occur after 6 weeks.

For the primary outcome, the investigators assessed whether the conditions of patients with COVID worsened over a 28-day period so as to require either hospitalization or observation in the emergency department for more than 6 hours. In the placebo group, 108 of 733 patients’ conditions deteriorated to this extent (14.7%); by contrast, only 77 of 739 patients in the fluvoxamine group (10.4%) met these primary criteria – a relative risk reduction of 29%.

The treatment effect was greater (34%) in the per protocol analysis of participants who completed their course of pills.

The investigators also collected data on vital signs, including temperature and oxygen saturation, as well as adverse events reported at clinic visits or through video conferencing, phone calls, or social media applications. Side effects were mild, most commonly nausea and fatigue, and did not differ significantly between active treatment and control groups, Dr. Mills said in an interview.

Amid scores of studies evaluating repurposed drugs for COVID-19, the data on fluvoxamine are “looking much more favorable than anyone could have guessed – at least anyone in infectious disease,” said Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston.

The new TOGETHER trial results augment supportive data published in JAMA last November from a phase 2 randomized trial that was small but “very well done,” Dr. Sax told this news organization.

Those results got a boost from a subsequent study of 65 racetrack workers who chose to take fluvoxamine during a COVID-19 outbreak in the San Francisco Bay area. Forty-eight persons opted against taking the drug. In this small, nonrandomized study, “the people who chose to be treated with fluvoxamine were sicker [at baseline] than the people who didn’t go on it, and yet the [treated group] ended up better,” said Dr. Sax, who discussed accumulating data on the use of fluvoxamine for COVID-19 in a recent New England Journal of Medicine blog post.
 

Anti-inflammatory effect?

After reviewing the new findings, Frank Domino, MD, professor of family medicine and community health at the University of Massachusetts, Worcester, said he would encourage patients with high-risk COVID-19 to consider taking fluvoxamine to lower their risk of being hospitalized. “But I would make it clear this was not a ‘cure,’ “ he said, “and we are unsure how it helps.”

At this point, U.S. treatment guidelines do not recommend fluvoxamine as the standard of care for nonhospitalized COVID-19 patients, but the National Institutes of Health is “very aware of the data,” Dr. Sax told this news organization.

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) – a class of drugs that includes the more commonly prescribed antidepressant fluoxetine (Prozac). If prescribed off-label to COVID-19 patients, fluvoxamine should not be used within 2 weeks of starting treatment with other SSRI or monoamine oxidase inhibitor antidepressants and should be used with caution with other QT-interval prolonging medications, Dr. Sax said.

In addition, fluvoxamine can enhance the effect of antiplatelet and anticoagulant drugs, potentially triggering bleeding.

On the basis of in vitro and mouse studies of fluvoxamine, “we think it has an anti-inflammatory effect,” said child psychiatrist Angela Reiersen, MD, of Washington University, St. Louis, who came up with the idea for testing fluvoxamine in last year’s phase 2 trial and coauthored a recent article describing the drug’s potential mechanisms of action in COVID-19.

She and other researchers believe fluvoxamine’s anti-inflammatory effects derive from the molecule’s binding to the sigma-1 receptor in the endoplasmic reticulum, which regulates cellular responses to stress and infection.

Fluvoxamine also inhibits the activation of platelets. “In COVID-19, there does seem to be a problem with hyperactivation of platelets and excessive blood clots forming, so it is possible this could be another mechanism where it might be helping,” Dr. Reiersen said.

If sigma-1 activation turns out to be the main mechanism underlying fluvoxamine’s benefits in COVID-19, other sigma-1 agonists, such as fluoxetine, may also help. In a retrospective analysis of thousands of adults hospitalized for COVID-19 in France early in the pandemic, those who were taking antidepressants had a 44% lower risk for intubation or death.

And in a study under review, researchers at Stanford (Calif.) University and the University of California, San Francisco, analyzed electronic health records to explore a potential link between fluoxetine use and COVID outcomes among more than 80,000 patients from over 80 institutions across the United States. Other research suggests that antipsychotics could also have protective effects for patients with COVID-19.
 

Long COVID, long-term challenges

On the basis of its potential mechanisms of action, fluvoxamine may be able to prevent or treat long COVID, Dr. Reiersen said. That possibility will be assessed among other secondary endpoints in two ongoing studies of repurposed drugs: the NIH’s ACTIV-6, and the University of Minnesota’s COVID-OUT, an at-home trial of ivermectin, metformin, and fluvoxamine.

Dr. Reiersen and Washington University colleagues are also analyzing longer-term outcomes of participants in their own phase 3 trial of fluvoxamine (Stop COVID 2), which was discontinued when enrollment slowed to a trickle during the U.S. vaccine rollout. Logistical hurdles and scant funding have greatly hampered efforts to test the use of off-patent drugs for COVID-19 outpatients during the pandemic.

U.S. efforts face other obstacles as well. Elsewhere in the world – including Brazil, where the TOGETHER trial was run – vaccines are scarce, and there are no monoclonal antibodies.

“People have a great sense of community duty, and they’re participating in the trials,” Dr. Mills said. “You’re in a much more political environment in the U.S. on these outpatient trials.”

The TOGETHER trial was funded by Fast Grants and the Rainwater Foundation. Dr. Reiersen is an inventor on a patent application related to methods of treating COVID-19, which was filed by Washington University, St. Louis. Dr. Mills, Dr. Domino, and Dr. Sax report no relevant financial relationships.

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