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Damian McNamara is a journalist for Medscape Medical News and MDedge. He worked full-time for MDedge as the Miami Bureau covering a dozen medical specialties during 2001-2012, then as a freelancer for Medscape and MDedge, before being hired on staff by Medscape in 2018. Now the two companies are one. He uses what he learned in school – Damian has a BS in chemistry and an MS in science, health and environmental reporting/journalism. He works out of a home office in Miami, with a 100-pound chocolate lab known to snore under his desk during work hours.
COVID-19 vaccination linked to less mechanical ventilation
new evidence reveals.
Compared with residents younger than 50 – so far vaccinated at lower rates than those of the higher-risk older people – Israelis 70 and older were 67% less likely to require mechanical ventilation for SARS-CoV-2 infection in February 2021 compared with October-December 2020.
“This study provides preliminary evidence at the population level for the reduction in risk for severe COVID-19, as manifested by need for mechanical ventilation, after vaccination with the Pfizer-BioNTech COVID-19 vaccine,” wrote lead author Ehud Rinott, department of public health, faculty of health sciences, Ben-Gurion University of the Negev in Beer-Sheva, Israel, and colleagues.
The study was published online Feb. 26, 2021, in Morbidity and Mortality Weekly Report.
The progress of COVID-19 vaccination across Israel presents researchers with a unique opportunity to study effectiveness on a population level. In this study, 84% of residents 70 and older received two-dose vaccinations. In contrast, only 10% of people in Israel younger than 50 received the same vaccine coverage.
Along with senior author Yair Lewis, MD, PhD, and coauthor Ilan Youngster, MD, Mr. Rinott compared mechanical ventilation rates between Oct. 2, 2020, and Feb. 9, 2021. They found that the ratio of people 70 and older compared with those younger than 50 requiring mechanical ventilation changed from 5.8:1 to 1.9:1 between these periods. This translates to the 67% decrease.
The study offers a “real-world” look at vaccination effectiveness, adding to more controlled evidence from clinical trials. “Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality,” the researchers wrote.
Israel started a national vaccination program on Dec. 20, 2020, targeting high-risk residents including people 60 and older, health care workers, and those with relevant comorbidities. At the same time, in addition to immunization, Israel has used strategies like stay-at-home orders, school closures, mask mandates, and more.
Potential limitations include a limited ability to account for the effect of the stay-at-home orders, spread of virus variants, and other concomitant factors; a potential for a delayed reporting of cases; and variability in mitigation measures by age group.
Dr. Youngster reported receipt of consulting fees from MyBiotix Ltd.
A version of this article first appeared on Medscape.com.
new evidence reveals.
Compared with residents younger than 50 – so far vaccinated at lower rates than those of the higher-risk older people – Israelis 70 and older were 67% less likely to require mechanical ventilation for SARS-CoV-2 infection in February 2021 compared with October-December 2020.
“This study provides preliminary evidence at the population level for the reduction in risk for severe COVID-19, as manifested by need for mechanical ventilation, after vaccination with the Pfizer-BioNTech COVID-19 vaccine,” wrote lead author Ehud Rinott, department of public health, faculty of health sciences, Ben-Gurion University of the Negev in Beer-Sheva, Israel, and colleagues.
The study was published online Feb. 26, 2021, in Morbidity and Mortality Weekly Report.
The progress of COVID-19 vaccination across Israel presents researchers with a unique opportunity to study effectiveness on a population level. In this study, 84% of residents 70 and older received two-dose vaccinations. In contrast, only 10% of people in Israel younger than 50 received the same vaccine coverage.
Along with senior author Yair Lewis, MD, PhD, and coauthor Ilan Youngster, MD, Mr. Rinott compared mechanical ventilation rates between Oct. 2, 2020, and Feb. 9, 2021. They found that the ratio of people 70 and older compared with those younger than 50 requiring mechanical ventilation changed from 5.8:1 to 1.9:1 between these periods. This translates to the 67% decrease.
The study offers a “real-world” look at vaccination effectiveness, adding to more controlled evidence from clinical trials. “Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality,” the researchers wrote.
Israel started a national vaccination program on Dec. 20, 2020, targeting high-risk residents including people 60 and older, health care workers, and those with relevant comorbidities. At the same time, in addition to immunization, Israel has used strategies like stay-at-home orders, school closures, mask mandates, and more.
Potential limitations include a limited ability to account for the effect of the stay-at-home orders, spread of virus variants, and other concomitant factors; a potential for a delayed reporting of cases; and variability in mitigation measures by age group.
Dr. Youngster reported receipt of consulting fees from MyBiotix Ltd.
A version of this article first appeared on Medscape.com.
new evidence reveals.
Compared with residents younger than 50 – so far vaccinated at lower rates than those of the higher-risk older people – Israelis 70 and older were 67% less likely to require mechanical ventilation for SARS-CoV-2 infection in February 2021 compared with October-December 2020.
“This study provides preliminary evidence at the population level for the reduction in risk for severe COVID-19, as manifested by need for mechanical ventilation, after vaccination with the Pfizer-BioNTech COVID-19 vaccine,” wrote lead author Ehud Rinott, department of public health, faculty of health sciences, Ben-Gurion University of the Negev in Beer-Sheva, Israel, and colleagues.
The study was published online Feb. 26, 2021, in Morbidity and Mortality Weekly Report.
The progress of COVID-19 vaccination across Israel presents researchers with a unique opportunity to study effectiveness on a population level. In this study, 84% of residents 70 and older received two-dose vaccinations. In contrast, only 10% of people in Israel younger than 50 received the same vaccine coverage.
Along with senior author Yair Lewis, MD, PhD, and coauthor Ilan Youngster, MD, Mr. Rinott compared mechanical ventilation rates between Oct. 2, 2020, and Feb. 9, 2021. They found that the ratio of people 70 and older compared with those younger than 50 requiring mechanical ventilation changed from 5.8:1 to 1.9:1 between these periods. This translates to the 67% decrease.
The study offers a “real-world” look at vaccination effectiveness, adding to more controlled evidence from clinical trials. “Achieving high vaccination coverage through intensive vaccination campaigns has the potential to substantially reduce COVID-19-associated morbidity and mortality,” the researchers wrote.
Israel started a national vaccination program on Dec. 20, 2020, targeting high-risk residents including people 60 and older, health care workers, and those with relevant comorbidities. At the same time, in addition to immunization, Israel has used strategies like stay-at-home orders, school closures, mask mandates, and more.
Potential limitations include a limited ability to account for the effect of the stay-at-home orders, spread of virus variants, and other concomitant factors; a potential for a delayed reporting of cases; and variability in mitigation measures by age group.
Dr. Youngster reported receipt of consulting fees from MyBiotix Ltd.
A version of this article first appeared on Medscape.com.
FDA grants emergency use authorization to Johnson & Johnson COVID-19 vaccine
And then there were three.
More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.
Initial reactions to the EUA for the J&J vaccine have been positive.
“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.
“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”
“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.
The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.
One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.
The more the merrier
The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.
“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”
Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.
On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.
One and done?
Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.
“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”
This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”
Looking beyond the numbers
The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.
However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.
“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”
“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.
More work to do
“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.
“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”
Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.
A version of this article first appeared on Medscape.com.
And then there were three.
More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.
Initial reactions to the EUA for the J&J vaccine have been positive.
“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.
“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”
“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.
The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.
One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.
The more the merrier
The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.
“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”
Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.
On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.
One and done?
Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.
“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”
This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”
Looking beyond the numbers
The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.
However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.
“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”
“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.
More work to do
“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.
“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”
Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.
A version of this article first appeared on Medscape.com.
And then there were three.
More vaccine availability at a time of high demand and limited supply could help officials vaccinate more Americans, more quickly. In addition, the J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.
Initial reactions to the EUA for the J&J vaccine have been positive.
“The advantages of having a third vaccine, especially one that is a single shot and can be stored without special refrigeration requirements, will be a major contribution in getting the general public vaccinated sooner, both in the U.S. and around the world,” Phyllis Tien, MD, professor of medicine in the division of infectious diseases at the University of California, San Francisco, told Medscape Medical News.
“It’s great news. We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID,” said Paul Goepfert, MD. It’s a “tremendous boon for our country and other countries as well.”
“This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa,” added Dr. Goepfert, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama at Birmingham.
The EUA “is indeed exciting news,” Colleen Kraft, MD, associate chief medical officer at Emory University Hospital and associate professor at Emory University School of Medicine in Atlanta, said during a February 25 media briefing.
One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.
The more the merrier
The scope and urgency of the COVID-19 pandemic necessitates as many protective measures as possible, said Raj Shah, MD, geriatrician, and associate professor of family medicine and codirector of the Center for Community Health Equity at Rush University in Chicago.
“Trying to vaccinate as many individuals living in the United States to prevent the spread of COVID is such a big project that no one company or one vaccine was going to be able to ramp up fast enough on its own,” Dr. Shah told Medscape Medical News.“This has been the hope for us,” he added, “to get to multiple vaccines with slightly different properties that will provide more options.”
Experience with the J&J vaccine so far suggests reactions are less severe. “The nice thing about the Johnson and Johnson [vaccine] is that it definitely has less side effects,” Dr. Kraft said.
On the other hand, low-grade fever, chills, or fatigue after vaccination can be considered a positive because they can reflect how well the immune system is responding, she added.
One and done?
Single-dose administration could be more than a convenience — it could also help clinicians vaccinate members of underserved communities and rural locations, where returning for a second dose could be more difficult for some people.
“In a controlled setting, in a clinical trial, we do a lot to make sure people get all the treatment they need,” Dr. Shah said. “We’re not seeing it right now, but we’re always worried when we have more than one dose that has to be administered, that some people will drop off and not come back for the second vaccine.”
This group could include the needle-phobic, he added. “For them, having it done once alleviates a lot of the anxiety.”
Looking beyond the numbers
The phase 3 ENSEMBLE study of the J&J vaccine revealed a 72% efficacy for preventing moderate-to-severe COVID-19 among U.S. participants. In contrast, researchers reported 94% to 95% efficacy for the Pfizer/BioNTech and Moderna vaccines.
However, experts agreed that focusing solely on these numbers can miss more important points. For example, no participants who received the J&J vaccine in the phase 3 trial died from COVID-19-related illness. There were five such deaths in the placebo cohort.
“One of the things that these vaccines do very well is they minimize severe disease,” Dr. Kraft said. “As somebody that has spent an inordinate time in the hospital taking care of patients with severe disease from COVID, this is very much a welcome addition to our armamentarium to fight this virus.”
“If you can give something that prevents people from dying, that is a true path to normalcy,” Dr. Goepfert added.
More work to do
“The demand is strong from all groups right now. We just have to work on getting more vaccines out there,” Dr. Shah said.
“We are at a point in this country where we are getting better with the distribution of the vaccine,” he added, “but we are nowhere close to achieving that distribution of vaccines to get to everybody.”
Dr. Goepfert, Dr. Shah, and Dr. Kraft disclosed no relevant financial relationships. Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the San Francisco VA Health Care System.
A version of this article first appeared on Medscape.com.
Janssen/J&J COVID-19 vaccine cuts transmission, new data show
The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.
“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.
“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.
“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”
The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.
The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.
The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.
In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.
If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.
Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.
“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.
“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.
“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”
The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.
The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.
The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.
In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.
If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.
Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The single-dose vaccine reduces the risk of asymptomatic transmission by 74% at 71 days, compared with placebo, according to documents released today by the U.S. Food and Drug Administration.
“The decrease in asymptomatic transmission is very welcome news too in curbing the spread of the virus,” Phyllis Tien, MD, told this news organization.
“While the earlier press release reported that the vaccine was effective against preventing severe COVID-19 disease, as well as hospitalizations and death, this new data shows that the vaccine can also decrease transmission, which is very important on a public health level,” said Dr. Tien, professor of medicine in the division of infectious diseases at the University of California, San Francisco.
“It is extremely important in terms of getting to herd immunity,” Paul Goepfert, MD, director of the Alabama Vaccine Research Clinic and infectious disease specialist at the University of Alabama, Birmingham, said in an interview. “It means that this vaccine is likely preventing subsequent transmission after a single dose, which could have huge implications once we get the majority of folks vaccinated.”
The FDA cautioned that the numbers of participants included in the study are relatively small and need to be verified. However, the Johnson & Johnson vaccine might not be the only product offering this advantage. Early data suggest that the Pfizer/BioNTech vaccine also decreases transmission, providing further evidence that the protection offered by immunization goes beyond the individual.
The new analyses were provided by the FDA in advance of its review of the Janssen/Johnson & Johnson vaccine. The agency plans to fully address the Ad26.COV2.S vaccine at its Vaccines and Related Biological Products Advisory Committee Meeting on Friday, including evaluating its safety and efficacy.
The agency’s decision on whether or not to grant emergency use authorization (EUA) to the Johnson & Johnson vaccine could come as early as Friday evening or Saturday.
In addition to the newly released data, officials are likely to discuss phase 3 data, released Jan. 29, that reveal an 85% efficacy for the vaccine against severe COVID-19 illness globally, including data from South America, South Africa, and the United States. When the analysis was restricted to data from U.S. participants, the trial showed a 73% efficacy against moderate to severe COVID-19.
If and when the FDA grants an EUA, it remains unclear how much of the new vaccine will be immediately available. Initially, Johnson & Johnson predicted 18 million doses would be ready by the end of February, but others stated the figure will be closer to 2-4 million. The manufacturer’s contract with the U.S. government stipulates production of 100-million doses by the end of June.
Dr. Tien received support from Johnson & Johnson to conduct the J&J COVID-19 vaccine trial in the SF VA HealthCare System. Dr. Goepfert has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Infectious diseases ‘giant’ John Bartlett: His ‘impact will endure’
The cause of death was not immediately disclosed.
Dr. Bartlett is remembered by colleagues for his wide range of infectious disease expertise, an ability to repeatedly predict emerging issues in the field, and for inspiring students and trainees to choose the same specialty.
“What I consistently found so extraordinary about John was his excitement for ID – the whole field. He had a wonderful sixth sense about what was going to be the next ‘big thing,’” Paul Edward Sax, MD, clinical director of the Infectious Disease Clinic at Brigham and Women’s Hospital in Boston, told this news organization.
“He thoroughly absorbed the emerging research on the topic and then provided the most wonderful clinical summaries,” Dr. Sax said. “His range of expert content areas was unbelievably broad.” Dr. Bartlett was “a true ID polymath.”
Dr. Bartlett was “a giant in the field of infectious diseases,” David Lee Thomas, MD, MPH, said in an interview. He agreed that Dr. Bartlett was a visionary who could anticipate the most exciting developments in the specialty.
Dr. Bartlett also “led the efforts to combat the foes, from HIV to antimicrobial resistance,” said Dr. Thomas, director of the division of infectious diseases and professor of medicine at Johns Hopkins University.
A pioneer in HIV research and care
Dr. Bartlett’s early research focused on anaerobic pulmonary and other infections, Bacteroides fragilis pathogenesis, and colitis caused by Clostridioides difficile.
Shortly after joining Johns Hopkins in 1980, he focused on HIV/AIDS research and caring for people with HIV. Dr. Bartlett led clinical trials of new treatments and developed years of HIV clinical treatment guidelines.
“Back when most hospitals, university medical centers, and ID divisions were running away from the AIDS epidemic, John took it on, both as a scientific priority and a moral imperative,” Dr. Sax writes in a blog post for NEJM Journal Watch. “With the help of Frank Polk and the Hopkins president, he established an outpatient AIDS clinic and an inpatient AIDS ward – both of which were way ahead of their time.”
In the same post, Dr. Sax points out that Dr. Bartlett was an expert in multiple areas – any one of which could be a sole career focus. “How many ID doctors are true experts in all of the following distinct topics? HIV, Clostridium difficile, respiratory tract infections, antimicrobial resistance, and anaerobic pulmonary infections.” Dr. Sax writes.
Expertise that defined an era
In a piece reviewing the long history of infectious disease medicine at Johns Hopkins published in Clinical Infectious Diseases in 2014, Paul Auwaerter, MD, and colleagues describe his tenure at the institution from 1980 to 2006 as “The Bartlett Era,” notable for the many advances he spearheaded.
“It is nearly impossible to find someone trained in infectious diseases in the past 30 years who has not been impacted by John Bartlett,” Dr. Auwaerter and colleagues note. “His tireless devotion to scholarship, teaching, and patient care remains an inspiration to his faculty members at Johns Hopkins, his colleagues, and coworkers around the world.”
Dr. Bartlett was not only a faculty member in the division of infectious diseases, he also helped establish it. When he joined Johns Hopkins, the infectious disease department featured just three faculty members with a research budget of less than $285,000. By the time he left 26 years later, the division had 44 faculty members on tenure track and a research budget exceeding $40 million.
Sharing memories via social media
Reactions to Dr. Bartlett’s passing on Twitter were swift.
“We have lost one of the greatest physicians I have ever met or had the privilege to learn from. Saddened to hear of Dr. John G. Bartlett’s passing. He inspired so many, including me, to choose the field of infectious diseases,” David Fisk, MD, infectious disease specialist in Santa Barbara, Calif., wrote on Twitter.
“John Bartlett just died – a true visionary and the classic ‘Renaissance’ person in clinical ID. Such a nice guy, too! His IDSA/IDWeek literature summaries (among other things) were amazing. We’ll miss him!” Dr. Sax tweeted on Jan. 19.
A colleague at Johns Hopkins, transplant infectious disease specialist Shmuel Shoham, MD, shared an anecdote about Dr. Bartlett on Twitter: “Year ago. My office is across from his. I ask him what he is doing. He tells me he is reviewing a file from the Vatican to adjudicate whether a miracle happened. True story.”
Infectious disease specialist Graeme Forrest, MBBS, also shared a story about Dr. Bartlett via Twitter. “He described to me in 2001 how the U.S. model of health care would not cope with a pandemic or serious bioterror attack as it’s not connected to disseminate information. How prescient from 20 years ago.”
Dr. Bartlett shared his expertise at many national and international infectious disease conferences over the years. He also authored 470 articles, 282 book chapters, and 61 editions of 14 books.
Dr. Bartlett was also a regular contributor to this news organization. For example, he shared his expertise in perspective pieces that addressed priorities in antibiotic stewardship, upcoming infectious disease predictions, and critical infectious disease topics in a three-part series.
Dr. Bartlett’s education includes a bachelor’s degree from Dartmouth College in Hanover, N.H., in 1959 and an MD from Upstate Medical Center in Syracuse, N.Y., in 1963. He did his first 2 years of residency at Brigham and Women’s Hospital.
He also served as an Army captain from 1965 to 1967, treating patients in fever wards in Vietnam. He then returned to the United States to finish his internal medicine training at the University of Alabama in 1968.
Dr. Bartlett completed his fellowship in infectious diseases at the University of California, Los Angeles. In 1975, he joined the faculty at Tufts University, Boston.
Leaving a legacy
Dr. Bartlett’s influence will likely live on in many ways at Johns Hopkins.
“John is a larger-than-life legend whose impact will endure and after whom we are so proud to have named our clinical service, The Bartlett Specialty Practice,” Dr. Thomas said.
The specialty practice clinic named for him has 23 exam rooms and features multidisciplinary care for people with HIV, hepatitis, bone infections, general infectious diseases, and more. Furthermore, friends, family, and colleagues joined forces to create the “Dr. John G. Bartlett HIV/AIDS Fund.”
They note that it is “only appropriate that we honor him by creating an endowment that will provide support for young trainees and junior faculty in the division, helping them transition to their independent careers.”
In addition to all his professional accomplishments, “He was also a genuinely nice person, approachable and humble,” Dr. Sax said. “We really lost a great one!”
A version of this article first appeared on Medscape.com.
The cause of death was not immediately disclosed.
Dr. Bartlett is remembered by colleagues for his wide range of infectious disease expertise, an ability to repeatedly predict emerging issues in the field, and for inspiring students and trainees to choose the same specialty.
“What I consistently found so extraordinary about John was his excitement for ID – the whole field. He had a wonderful sixth sense about what was going to be the next ‘big thing,’” Paul Edward Sax, MD, clinical director of the Infectious Disease Clinic at Brigham and Women’s Hospital in Boston, told this news organization.
“He thoroughly absorbed the emerging research on the topic and then provided the most wonderful clinical summaries,” Dr. Sax said. “His range of expert content areas was unbelievably broad.” Dr. Bartlett was “a true ID polymath.”
Dr. Bartlett was “a giant in the field of infectious diseases,” David Lee Thomas, MD, MPH, said in an interview. He agreed that Dr. Bartlett was a visionary who could anticipate the most exciting developments in the specialty.
Dr. Bartlett also “led the efforts to combat the foes, from HIV to antimicrobial resistance,” said Dr. Thomas, director of the division of infectious diseases and professor of medicine at Johns Hopkins University.
A pioneer in HIV research and care
Dr. Bartlett’s early research focused on anaerobic pulmonary and other infections, Bacteroides fragilis pathogenesis, and colitis caused by Clostridioides difficile.
Shortly after joining Johns Hopkins in 1980, he focused on HIV/AIDS research and caring for people with HIV. Dr. Bartlett led clinical trials of new treatments and developed years of HIV clinical treatment guidelines.
“Back when most hospitals, university medical centers, and ID divisions were running away from the AIDS epidemic, John took it on, both as a scientific priority and a moral imperative,” Dr. Sax writes in a blog post for NEJM Journal Watch. “With the help of Frank Polk and the Hopkins president, he established an outpatient AIDS clinic and an inpatient AIDS ward – both of which were way ahead of their time.”
In the same post, Dr. Sax points out that Dr. Bartlett was an expert in multiple areas – any one of which could be a sole career focus. “How many ID doctors are true experts in all of the following distinct topics? HIV, Clostridium difficile, respiratory tract infections, antimicrobial resistance, and anaerobic pulmonary infections.” Dr. Sax writes.
Expertise that defined an era
In a piece reviewing the long history of infectious disease medicine at Johns Hopkins published in Clinical Infectious Diseases in 2014, Paul Auwaerter, MD, and colleagues describe his tenure at the institution from 1980 to 2006 as “The Bartlett Era,” notable for the many advances he spearheaded.
“It is nearly impossible to find someone trained in infectious diseases in the past 30 years who has not been impacted by John Bartlett,” Dr. Auwaerter and colleagues note. “His tireless devotion to scholarship, teaching, and patient care remains an inspiration to his faculty members at Johns Hopkins, his colleagues, and coworkers around the world.”
Dr. Bartlett was not only a faculty member in the division of infectious diseases, he also helped establish it. When he joined Johns Hopkins, the infectious disease department featured just three faculty members with a research budget of less than $285,000. By the time he left 26 years later, the division had 44 faculty members on tenure track and a research budget exceeding $40 million.
Sharing memories via social media
Reactions to Dr. Bartlett’s passing on Twitter were swift.
“We have lost one of the greatest physicians I have ever met or had the privilege to learn from. Saddened to hear of Dr. John G. Bartlett’s passing. He inspired so many, including me, to choose the field of infectious diseases,” David Fisk, MD, infectious disease specialist in Santa Barbara, Calif., wrote on Twitter.
“John Bartlett just died – a true visionary and the classic ‘Renaissance’ person in clinical ID. Such a nice guy, too! His IDSA/IDWeek literature summaries (among other things) were amazing. We’ll miss him!” Dr. Sax tweeted on Jan. 19.
A colleague at Johns Hopkins, transplant infectious disease specialist Shmuel Shoham, MD, shared an anecdote about Dr. Bartlett on Twitter: “Year ago. My office is across from his. I ask him what he is doing. He tells me he is reviewing a file from the Vatican to adjudicate whether a miracle happened. True story.”
Infectious disease specialist Graeme Forrest, MBBS, also shared a story about Dr. Bartlett via Twitter. “He described to me in 2001 how the U.S. model of health care would not cope with a pandemic or serious bioterror attack as it’s not connected to disseminate information. How prescient from 20 years ago.”
Dr. Bartlett shared his expertise at many national and international infectious disease conferences over the years. He also authored 470 articles, 282 book chapters, and 61 editions of 14 books.
Dr. Bartlett was also a regular contributor to this news organization. For example, he shared his expertise in perspective pieces that addressed priorities in antibiotic stewardship, upcoming infectious disease predictions, and critical infectious disease topics in a three-part series.
Dr. Bartlett’s education includes a bachelor’s degree from Dartmouth College in Hanover, N.H., in 1959 and an MD from Upstate Medical Center in Syracuse, N.Y., in 1963. He did his first 2 years of residency at Brigham and Women’s Hospital.
He also served as an Army captain from 1965 to 1967, treating patients in fever wards in Vietnam. He then returned to the United States to finish his internal medicine training at the University of Alabama in 1968.
Dr. Bartlett completed his fellowship in infectious diseases at the University of California, Los Angeles. In 1975, he joined the faculty at Tufts University, Boston.
Leaving a legacy
Dr. Bartlett’s influence will likely live on in many ways at Johns Hopkins.
“John is a larger-than-life legend whose impact will endure and after whom we are so proud to have named our clinical service, The Bartlett Specialty Practice,” Dr. Thomas said.
The specialty practice clinic named for him has 23 exam rooms and features multidisciplinary care for people with HIV, hepatitis, bone infections, general infectious diseases, and more. Furthermore, friends, family, and colleagues joined forces to create the “Dr. John G. Bartlett HIV/AIDS Fund.”
They note that it is “only appropriate that we honor him by creating an endowment that will provide support for young trainees and junior faculty in the division, helping them transition to their independent careers.”
In addition to all his professional accomplishments, “He was also a genuinely nice person, approachable and humble,” Dr. Sax said. “We really lost a great one!”
A version of this article first appeared on Medscape.com.
The cause of death was not immediately disclosed.
Dr. Bartlett is remembered by colleagues for his wide range of infectious disease expertise, an ability to repeatedly predict emerging issues in the field, and for inspiring students and trainees to choose the same specialty.
“What I consistently found so extraordinary about John was his excitement for ID – the whole field. He had a wonderful sixth sense about what was going to be the next ‘big thing,’” Paul Edward Sax, MD, clinical director of the Infectious Disease Clinic at Brigham and Women’s Hospital in Boston, told this news organization.
“He thoroughly absorbed the emerging research on the topic and then provided the most wonderful clinical summaries,” Dr. Sax said. “His range of expert content areas was unbelievably broad.” Dr. Bartlett was “a true ID polymath.”
Dr. Bartlett was “a giant in the field of infectious diseases,” David Lee Thomas, MD, MPH, said in an interview. He agreed that Dr. Bartlett was a visionary who could anticipate the most exciting developments in the specialty.
Dr. Bartlett also “led the efforts to combat the foes, from HIV to antimicrobial resistance,” said Dr. Thomas, director of the division of infectious diseases and professor of medicine at Johns Hopkins University.
A pioneer in HIV research and care
Dr. Bartlett’s early research focused on anaerobic pulmonary and other infections, Bacteroides fragilis pathogenesis, and colitis caused by Clostridioides difficile.
Shortly after joining Johns Hopkins in 1980, he focused on HIV/AIDS research and caring for people with HIV. Dr. Bartlett led clinical trials of new treatments and developed years of HIV clinical treatment guidelines.
“Back when most hospitals, university medical centers, and ID divisions were running away from the AIDS epidemic, John took it on, both as a scientific priority and a moral imperative,” Dr. Sax writes in a blog post for NEJM Journal Watch. “With the help of Frank Polk and the Hopkins president, he established an outpatient AIDS clinic and an inpatient AIDS ward – both of which were way ahead of their time.”
In the same post, Dr. Sax points out that Dr. Bartlett was an expert in multiple areas – any one of which could be a sole career focus. “How many ID doctors are true experts in all of the following distinct topics? HIV, Clostridium difficile, respiratory tract infections, antimicrobial resistance, and anaerobic pulmonary infections.” Dr. Sax writes.
Expertise that defined an era
In a piece reviewing the long history of infectious disease medicine at Johns Hopkins published in Clinical Infectious Diseases in 2014, Paul Auwaerter, MD, and colleagues describe his tenure at the institution from 1980 to 2006 as “The Bartlett Era,” notable for the many advances he spearheaded.
“It is nearly impossible to find someone trained in infectious diseases in the past 30 years who has not been impacted by John Bartlett,” Dr. Auwaerter and colleagues note. “His tireless devotion to scholarship, teaching, and patient care remains an inspiration to his faculty members at Johns Hopkins, his colleagues, and coworkers around the world.”
Dr. Bartlett was not only a faculty member in the division of infectious diseases, he also helped establish it. When he joined Johns Hopkins, the infectious disease department featured just three faculty members with a research budget of less than $285,000. By the time he left 26 years later, the division had 44 faculty members on tenure track and a research budget exceeding $40 million.
Sharing memories via social media
Reactions to Dr. Bartlett’s passing on Twitter were swift.
“We have lost one of the greatest physicians I have ever met or had the privilege to learn from. Saddened to hear of Dr. John G. Bartlett’s passing. He inspired so many, including me, to choose the field of infectious diseases,” David Fisk, MD, infectious disease specialist in Santa Barbara, Calif., wrote on Twitter.
“John Bartlett just died – a true visionary and the classic ‘Renaissance’ person in clinical ID. Such a nice guy, too! His IDSA/IDWeek literature summaries (among other things) were amazing. We’ll miss him!” Dr. Sax tweeted on Jan. 19.
A colleague at Johns Hopkins, transplant infectious disease specialist Shmuel Shoham, MD, shared an anecdote about Dr. Bartlett on Twitter: “Year ago. My office is across from his. I ask him what he is doing. He tells me he is reviewing a file from the Vatican to adjudicate whether a miracle happened. True story.”
Infectious disease specialist Graeme Forrest, MBBS, also shared a story about Dr. Bartlett via Twitter. “He described to me in 2001 how the U.S. model of health care would not cope with a pandemic or serious bioterror attack as it’s not connected to disseminate information. How prescient from 20 years ago.”
Dr. Bartlett shared his expertise at many national and international infectious disease conferences over the years. He also authored 470 articles, 282 book chapters, and 61 editions of 14 books.
Dr. Bartlett was also a regular contributor to this news organization. For example, he shared his expertise in perspective pieces that addressed priorities in antibiotic stewardship, upcoming infectious disease predictions, and critical infectious disease topics in a three-part series.
Dr. Bartlett’s education includes a bachelor’s degree from Dartmouth College in Hanover, N.H., in 1959 and an MD from Upstate Medical Center in Syracuse, N.Y., in 1963. He did his first 2 years of residency at Brigham and Women’s Hospital.
He also served as an Army captain from 1965 to 1967, treating patients in fever wards in Vietnam. He then returned to the United States to finish his internal medicine training at the University of Alabama in 1968.
Dr. Bartlett completed his fellowship in infectious diseases at the University of California, Los Angeles. In 1975, he joined the faculty at Tufts University, Boston.
Leaving a legacy
Dr. Bartlett’s influence will likely live on in many ways at Johns Hopkins.
“John is a larger-than-life legend whose impact will endure and after whom we are so proud to have named our clinical service, The Bartlett Specialty Practice,” Dr. Thomas said.
The specialty practice clinic named for him has 23 exam rooms and features multidisciplinary care for people with HIV, hepatitis, bone infections, general infectious diseases, and more. Furthermore, friends, family, and colleagues joined forces to create the “Dr. John G. Bartlett HIV/AIDS Fund.”
They note that it is “only appropriate that we honor him by creating an endowment that will provide support for young trainees and junior faculty in the division, helping them transition to their independent careers.”
In addition to all his professional accomplishments, “He was also a genuinely nice person, approachable and humble,” Dr. Sax said. “We really lost a great one!”
A version of this article first appeared on Medscape.com.
J&J vaccine 85% efficacious against severe COVID globally
The Janssen/Johnson & Johnson single-dose adenovirus vaccine provides 85% efficacy globally against severe COVID-19 illness, according to the highly anticipated interim phase 3 results announced this morning.
The efficacy against severe disease provided by the Janssen/J&J vaccine held true regardless of age, race/ethnicity, absence or presence of comorbidities, and geography. The 44,000-participant ENSEMBLE study was conducted in the United States, South America, and South Africa.
“The team is very diligently monitoring all the variants that come up, and there are literally thousands of these. We are acting in anticipation of a variant being a potential problem. The South African variant we too acted on right away. So we too are preparing that antigen for testing.
“With data today, we do see that not a single South African, after 28 days post vaccination, ended up needing to go to the hospital, no South African died who was vaccinated.
“We do see that 85%-plus protection in South African against severe disease. That is one of the most exciting results in the dataset today,” said Mathai Mammen, MD, PhD, global head of Janssen Research & Development.
The overall efficacy was 66% globally, 72% in the United States, 66% in Latin America, and 57% in South Africa against moderate to severe SARS-CoV-2 28 days post vaccination, officials from the National Institutes of Health and Janssen reported during a media briefing.
But the J&J vaccine has potential advantages over the existing two-dose Pfizer/BioNTech and Moderna mRNA vaccines because it’s single dose and has less stringent storage requirements – only regular refrigeration is needed versus a need to freeze the two-dose Pfizer/BioNTech and Moderna COVID-19 vaccines. The J&J vaccine can be refrigerated for up to 3 months at 36°-46° F (2°-8° C).
But the difference between these just-released efficacy figures and the 94%-95% efficacy provided by the existing Pfizer/BioNTech and Moderna mRNA vaccines generated many questions during the briefing.
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the focus should not just be on the overall numbers. “The most important thing from a public health standpoint domestically is to keep people out of the hospital and prevent them from getting severe illness,” he said. “Many in the general public might look at a number and want to know if they get symptomatic disease or not.”
“More important than preventing someone from getting some aches and a sore throat is to prevent people – particularly people who have underlying conditions and the elderly, the ones most susceptible to a severe outcome – [from getting] severe disease,” Dr. Fauci added. Prevention of severe outcomes in a high percentage of individuals “will alleviate so much of the stress, human suffering, and death.”
Dr. Fauci acknowledged that many people will naturally focus on the distinction between 72% efficacy and 94%-95% efficacy. “This could be a messaging challenge [but] you have to make sure people understand the implications.”
It is more complex, he added, than just asking people: “If you go to the door on the left, you get 94% or 95%. If you go to the door to the right, you get 72%. What door do you want to go to?”
Instead, the messaging should be that “this and the other vaccines we have are actually preventing severe disease to a very substantial degree.”
Company defends numbers
Janssen defended their efficacy findings, pointing out that it is not a fair comparison.
“The vaccine programs that went a couple of months ago, they ran their studies during different times, when the pandemic was less complex. There were not these variants, and there was not the same level of incidence, which puts pressure on vaccine efficacy,” said Mathai Mammen, MD, PhD, global head of research and development for Janssen.
“So the numbers cannot really be compared, and that does pose a messaging challenge,” he said. “But the reality is, if one was to run the same studies [for the Pfizer and Moderna vaccines] today you would likely see different results.”
Asked if the efficacy figures could affect vaccine hesitancy, National Institutes of Health Director Francis Collins, MD, PhD, said at the announcement that most reluctance among people to get vaccinated against SARS-CoV-2 stems from concerns about safety. “The safety record is extremely good for this vaccine, as it is for the others that have received emergency use authorization.”
Janssen/J&J plans to submit for emergency use authorization from the U.S. Food and Drug Administration next week, at which point the company plans to release more information on side effects, deaths, and patient subpopulation efficacy, and more from the ENSEMBLE trial.
Janssen is aiming to provide 1 billion doses by the end of this year.
A version of this article first appeared on Medscape.com.
The Janssen/Johnson & Johnson single-dose adenovirus vaccine provides 85% efficacy globally against severe COVID-19 illness, according to the highly anticipated interim phase 3 results announced this morning.
The efficacy against severe disease provided by the Janssen/J&J vaccine held true regardless of age, race/ethnicity, absence or presence of comorbidities, and geography. The 44,000-participant ENSEMBLE study was conducted in the United States, South America, and South Africa.
“The team is very diligently monitoring all the variants that come up, and there are literally thousands of these. We are acting in anticipation of a variant being a potential problem. The South African variant we too acted on right away. So we too are preparing that antigen for testing.
“With data today, we do see that not a single South African, after 28 days post vaccination, ended up needing to go to the hospital, no South African died who was vaccinated.
“We do see that 85%-plus protection in South African against severe disease. That is one of the most exciting results in the dataset today,” said Mathai Mammen, MD, PhD, global head of Janssen Research & Development.
The overall efficacy was 66% globally, 72% in the United States, 66% in Latin America, and 57% in South Africa against moderate to severe SARS-CoV-2 28 days post vaccination, officials from the National Institutes of Health and Janssen reported during a media briefing.
But the J&J vaccine has potential advantages over the existing two-dose Pfizer/BioNTech and Moderna mRNA vaccines because it’s single dose and has less stringent storage requirements – only regular refrigeration is needed versus a need to freeze the two-dose Pfizer/BioNTech and Moderna COVID-19 vaccines. The J&J vaccine can be refrigerated for up to 3 months at 36°-46° F (2°-8° C).
But the difference between these just-released efficacy figures and the 94%-95% efficacy provided by the existing Pfizer/BioNTech and Moderna mRNA vaccines generated many questions during the briefing.
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the focus should not just be on the overall numbers. “The most important thing from a public health standpoint domestically is to keep people out of the hospital and prevent them from getting severe illness,” he said. “Many in the general public might look at a number and want to know if they get symptomatic disease or not.”
“More important than preventing someone from getting some aches and a sore throat is to prevent people – particularly people who have underlying conditions and the elderly, the ones most susceptible to a severe outcome – [from getting] severe disease,” Dr. Fauci added. Prevention of severe outcomes in a high percentage of individuals “will alleviate so much of the stress, human suffering, and death.”
Dr. Fauci acknowledged that many people will naturally focus on the distinction between 72% efficacy and 94%-95% efficacy. “This could be a messaging challenge [but] you have to make sure people understand the implications.”
It is more complex, he added, than just asking people: “If you go to the door on the left, you get 94% or 95%. If you go to the door to the right, you get 72%. What door do you want to go to?”
Instead, the messaging should be that “this and the other vaccines we have are actually preventing severe disease to a very substantial degree.”
Company defends numbers
Janssen defended their efficacy findings, pointing out that it is not a fair comparison.
“The vaccine programs that went a couple of months ago, they ran their studies during different times, when the pandemic was less complex. There were not these variants, and there was not the same level of incidence, which puts pressure on vaccine efficacy,” said Mathai Mammen, MD, PhD, global head of research and development for Janssen.
“So the numbers cannot really be compared, and that does pose a messaging challenge,” he said. “But the reality is, if one was to run the same studies [for the Pfizer and Moderna vaccines] today you would likely see different results.”
Asked if the efficacy figures could affect vaccine hesitancy, National Institutes of Health Director Francis Collins, MD, PhD, said at the announcement that most reluctance among people to get vaccinated against SARS-CoV-2 stems from concerns about safety. “The safety record is extremely good for this vaccine, as it is for the others that have received emergency use authorization.”
Janssen/J&J plans to submit for emergency use authorization from the U.S. Food and Drug Administration next week, at which point the company plans to release more information on side effects, deaths, and patient subpopulation efficacy, and more from the ENSEMBLE trial.
Janssen is aiming to provide 1 billion doses by the end of this year.
A version of this article first appeared on Medscape.com.
The Janssen/Johnson & Johnson single-dose adenovirus vaccine provides 85% efficacy globally against severe COVID-19 illness, according to the highly anticipated interim phase 3 results announced this morning.
The efficacy against severe disease provided by the Janssen/J&J vaccine held true regardless of age, race/ethnicity, absence or presence of comorbidities, and geography. The 44,000-participant ENSEMBLE study was conducted in the United States, South America, and South Africa.
“The team is very diligently monitoring all the variants that come up, and there are literally thousands of these. We are acting in anticipation of a variant being a potential problem. The South African variant we too acted on right away. So we too are preparing that antigen for testing.
“With data today, we do see that not a single South African, after 28 days post vaccination, ended up needing to go to the hospital, no South African died who was vaccinated.
“We do see that 85%-plus protection in South African against severe disease. That is one of the most exciting results in the dataset today,” said Mathai Mammen, MD, PhD, global head of Janssen Research & Development.
The overall efficacy was 66% globally, 72% in the United States, 66% in Latin America, and 57% in South Africa against moderate to severe SARS-CoV-2 28 days post vaccination, officials from the National Institutes of Health and Janssen reported during a media briefing.
But the J&J vaccine has potential advantages over the existing two-dose Pfizer/BioNTech and Moderna mRNA vaccines because it’s single dose and has less stringent storage requirements – only regular refrigeration is needed versus a need to freeze the two-dose Pfizer/BioNTech and Moderna COVID-19 vaccines. The J&J vaccine can be refrigerated for up to 3 months at 36°-46° F (2°-8° C).
But the difference between these just-released efficacy figures and the 94%-95% efficacy provided by the existing Pfizer/BioNTech and Moderna mRNA vaccines generated many questions during the briefing.
Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the focus should not just be on the overall numbers. “The most important thing from a public health standpoint domestically is to keep people out of the hospital and prevent them from getting severe illness,” he said. “Many in the general public might look at a number and want to know if they get symptomatic disease or not.”
“More important than preventing someone from getting some aches and a sore throat is to prevent people – particularly people who have underlying conditions and the elderly, the ones most susceptible to a severe outcome – [from getting] severe disease,” Dr. Fauci added. Prevention of severe outcomes in a high percentage of individuals “will alleviate so much of the stress, human suffering, and death.”
Dr. Fauci acknowledged that many people will naturally focus on the distinction between 72% efficacy and 94%-95% efficacy. “This could be a messaging challenge [but] you have to make sure people understand the implications.”
It is more complex, he added, than just asking people: “If you go to the door on the left, you get 94% or 95%. If you go to the door to the right, you get 72%. What door do you want to go to?”
Instead, the messaging should be that “this and the other vaccines we have are actually preventing severe disease to a very substantial degree.”
Company defends numbers
Janssen defended their efficacy findings, pointing out that it is not a fair comparison.
“The vaccine programs that went a couple of months ago, they ran their studies during different times, when the pandemic was less complex. There were not these variants, and there was not the same level of incidence, which puts pressure on vaccine efficacy,” said Mathai Mammen, MD, PhD, global head of research and development for Janssen.
“So the numbers cannot really be compared, and that does pose a messaging challenge,” he said. “But the reality is, if one was to run the same studies [for the Pfizer and Moderna vaccines] today you would likely see different results.”
Asked if the efficacy figures could affect vaccine hesitancy, National Institutes of Health Director Francis Collins, MD, PhD, said at the announcement that most reluctance among people to get vaccinated against SARS-CoV-2 stems from concerns about safety. “The safety record is extremely good for this vaccine, as it is for the others that have received emergency use authorization.”
Janssen/J&J plans to submit for emergency use authorization from the U.S. Food and Drug Administration next week, at which point the company plans to release more information on side effects, deaths, and patient subpopulation efficacy, and more from the ENSEMBLE trial.
Janssen is aiming to provide 1 billion doses by the end of this year.
A version of this article first appeared on Medscape.com.
More than one-third of COVID-19 infections are asymptomatic: Review
A systematic review suggests at least one-third of SARS-CoV-2 infections occur in people who never develop symptoms, providing strong evidence for the prevalence of asymptomatic infections.
The finding that nearly one in three infected people remain symptom free suggests testing should be changed, the investigators noted.
“To reduce transmission from people who are presymptomatic or asymptomatic, we need to shift our testing focus to at-home screening,” lead author Daniel Oran, AM, said in an interview. “Inexpensive rapid antigen tests, provided to millions of people for frequent use, could help us significantly reduce the spread of the virus.”
The systematic review was published online Jan. 22 in Annals of Internal Medicine.
The findings come at a dire time when the official number of COVID-19 cases in the United States exceeds 25 million for the first time. Public health officials have raised concerns about more transmissible, and possibly more deadly, variants of SARS-CoV-2, while a new presidential administration tries to meet the challenge of improving vaccine distribution and acceptance rates.
The results also build on earlier findings from the same research team – Mr. Oran and senior author Eric Topol, MD – that published a review article looking at asymptomatic COVID-19 cases. Even though initial data were more limited, they likewise suggested a broader scope of testing is warranted, pointing out that asymptomatic individuals can transmit SARS-CoV-2 for up to 14 days. Dr. Topol is also editor in chief of Medscape.
In the current systematic review, the highest-quality evidence comes from large studies in England and Spain. The nationally representative evidence included serologic surveys from more than 365,000 people in England and more than 61,000 in Spain. When analyzed separately, about the same proportion of asymptomatic cases emerged: 32.4% in England and 33% in Spain.
“It was really remarkable to find that nationwide antibody testing studies in England and Spain – including hundreds of thousands of people – produced nearly identical results: About one-third of the SARS-CoV-2 infections were completely asymptomatic,” said Mr. Oran, a researcher at Scripps Research Translational Institute in La Jolla, Calif.
The systematic review included 43 studies with PCR testing for active SARS-CoV-2 infection and another 18 with antibody results that indicated present or previous infection. The studies were published up until Nov. 17, 2020.
An appreciation for asymptomatic transmission of SARS-CoV-2 infection has come a long way from initial dismissals about its importance, Dr. Topol noted via Twitter. “When Dr. @camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and disparaged. She was later named a TIME 100 Person of the Year.”
Not symptomatic vs. never symptomatic
The term “asymptomatic” could be misleading because some people in this group do progress to develop signs of infection. This “presymptomatic” group of patients is likely a minority, the authors noted. Longitudinal studies indicate that about three-quarters of people who are asymptomatic with SARS-CoV-2 remain so.
Dr. Topol anticipated the one-third asymptomatic finding could draw some feedback about distinguishing asymptomatic from presymptomatic individuals. He tweeted, “Some will argue that there is admixture with presymptomatic cases, but review of all the data supports this estimate as being a conservative one.”
The heterogeneity of the settings, populations and other features of the studies prevented the authors from performing a meta-analysis of the findings.
Home is where the test is
Based on their findings, Mr. Oran and Dr. Topol believe “that COVID-19 control strategies must be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.” They suggested frequent use of inexpensive, rapid home tests to identify people who are asymptomatic or presymptomatic, along with programs and housing provided by the government to offer financial assistance and allow this group of people to isolate themselves.
Further research is warranted to determine if and how well vaccines for SARS-CoV-2 prevent asymptomatic infection.
Dr. Topol and Mr. Oran created a short video to highlight the findings from their systematic review.
The study was supported by a grant from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
A systematic review suggests at least one-third of SARS-CoV-2 infections occur in people who never develop symptoms, providing strong evidence for the prevalence of asymptomatic infections.
The finding that nearly one in three infected people remain symptom free suggests testing should be changed, the investigators noted.
“To reduce transmission from people who are presymptomatic or asymptomatic, we need to shift our testing focus to at-home screening,” lead author Daniel Oran, AM, said in an interview. “Inexpensive rapid antigen tests, provided to millions of people for frequent use, could help us significantly reduce the spread of the virus.”
The systematic review was published online Jan. 22 in Annals of Internal Medicine.
The findings come at a dire time when the official number of COVID-19 cases in the United States exceeds 25 million for the first time. Public health officials have raised concerns about more transmissible, and possibly more deadly, variants of SARS-CoV-2, while a new presidential administration tries to meet the challenge of improving vaccine distribution and acceptance rates.
The results also build on earlier findings from the same research team – Mr. Oran and senior author Eric Topol, MD – that published a review article looking at asymptomatic COVID-19 cases. Even though initial data were more limited, they likewise suggested a broader scope of testing is warranted, pointing out that asymptomatic individuals can transmit SARS-CoV-2 for up to 14 days. Dr. Topol is also editor in chief of Medscape.
In the current systematic review, the highest-quality evidence comes from large studies in England and Spain. The nationally representative evidence included serologic surveys from more than 365,000 people in England and more than 61,000 in Spain. When analyzed separately, about the same proportion of asymptomatic cases emerged: 32.4% in England and 33% in Spain.
“It was really remarkable to find that nationwide antibody testing studies in England and Spain – including hundreds of thousands of people – produced nearly identical results: About one-third of the SARS-CoV-2 infections were completely asymptomatic,” said Mr. Oran, a researcher at Scripps Research Translational Institute in La Jolla, Calif.
The systematic review included 43 studies with PCR testing for active SARS-CoV-2 infection and another 18 with antibody results that indicated present or previous infection. The studies were published up until Nov. 17, 2020.
An appreciation for asymptomatic transmission of SARS-CoV-2 infection has come a long way from initial dismissals about its importance, Dr. Topol noted via Twitter. “When Dr. @camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and disparaged. She was later named a TIME 100 Person of the Year.”
Not symptomatic vs. never symptomatic
The term “asymptomatic” could be misleading because some people in this group do progress to develop signs of infection. This “presymptomatic” group of patients is likely a minority, the authors noted. Longitudinal studies indicate that about three-quarters of people who are asymptomatic with SARS-CoV-2 remain so.
Dr. Topol anticipated the one-third asymptomatic finding could draw some feedback about distinguishing asymptomatic from presymptomatic individuals. He tweeted, “Some will argue that there is admixture with presymptomatic cases, but review of all the data supports this estimate as being a conservative one.”
The heterogeneity of the settings, populations and other features of the studies prevented the authors from performing a meta-analysis of the findings.
Home is where the test is
Based on their findings, Mr. Oran and Dr. Topol believe “that COVID-19 control strategies must be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.” They suggested frequent use of inexpensive, rapid home tests to identify people who are asymptomatic or presymptomatic, along with programs and housing provided by the government to offer financial assistance and allow this group of people to isolate themselves.
Further research is warranted to determine if and how well vaccines for SARS-CoV-2 prevent asymptomatic infection.
Dr. Topol and Mr. Oran created a short video to highlight the findings from their systematic review.
The study was supported by a grant from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
A systematic review suggests at least one-third of SARS-CoV-2 infections occur in people who never develop symptoms, providing strong evidence for the prevalence of asymptomatic infections.
The finding that nearly one in three infected people remain symptom free suggests testing should be changed, the investigators noted.
“To reduce transmission from people who are presymptomatic or asymptomatic, we need to shift our testing focus to at-home screening,” lead author Daniel Oran, AM, said in an interview. “Inexpensive rapid antigen tests, provided to millions of people for frequent use, could help us significantly reduce the spread of the virus.”
The systematic review was published online Jan. 22 in Annals of Internal Medicine.
The findings come at a dire time when the official number of COVID-19 cases in the United States exceeds 25 million for the first time. Public health officials have raised concerns about more transmissible, and possibly more deadly, variants of SARS-CoV-2, while a new presidential administration tries to meet the challenge of improving vaccine distribution and acceptance rates.
The results also build on earlier findings from the same research team – Mr. Oran and senior author Eric Topol, MD – that published a review article looking at asymptomatic COVID-19 cases. Even though initial data were more limited, they likewise suggested a broader scope of testing is warranted, pointing out that asymptomatic individuals can transmit SARS-CoV-2 for up to 14 days. Dr. Topol is also editor in chief of Medscape.
In the current systematic review, the highest-quality evidence comes from large studies in England and Spain. The nationally representative evidence included serologic surveys from more than 365,000 people in England and more than 61,000 in Spain. When analyzed separately, about the same proportion of asymptomatic cases emerged: 32.4% in England and 33% in Spain.
“It was really remarkable to find that nationwide antibody testing studies in England and Spain – including hundreds of thousands of people – produced nearly identical results: About one-third of the SARS-CoV-2 infections were completely asymptomatic,” said Mr. Oran, a researcher at Scripps Research Translational Institute in La Jolla, Calif.
The systematic review included 43 studies with PCR testing for active SARS-CoV-2 infection and another 18 with antibody results that indicated present or previous infection. The studies were published up until Nov. 17, 2020.
An appreciation for asymptomatic transmission of SARS-CoV-2 infection has come a long way from initial dismissals about its importance, Dr. Topol noted via Twitter. “When Dr. @camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and disparaged. She was later named a TIME 100 Person of the Year.”
Not symptomatic vs. never symptomatic
The term “asymptomatic” could be misleading because some people in this group do progress to develop signs of infection. This “presymptomatic” group of patients is likely a minority, the authors noted. Longitudinal studies indicate that about three-quarters of people who are asymptomatic with SARS-CoV-2 remain so.
Dr. Topol anticipated the one-third asymptomatic finding could draw some feedback about distinguishing asymptomatic from presymptomatic individuals. He tweeted, “Some will argue that there is admixture with presymptomatic cases, but review of all the data supports this estimate as being a conservative one.”
The heterogeneity of the settings, populations and other features of the studies prevented the authors from performing a meta-analysis of the findings.
Home is where the test is
Based on their findings, Mr. Oran and Dr. Topol believe “that COVID-19 control strategies must be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.” They suggested frequent use of inexpensive, rapid home tests to identify people who are asymptomatic or presymptomatic, along with programs and housing provided by the government to offer financial assistance and allow this group of people to isolate themselves.
Further research is warranted to determine if and how well vaccines for SARS-CoV-2 prevent asymptomatic infection.
Dr. Topol and Mr. Oran created a short video to highlight the findings from their systematic review.
The study was supported by a grant from the National Institutes of Health.
A version of this article first appeared on Medscape.com.
What we know and don’t know about virus variants and vaccines
About 20 states across the country have detected the more transmissible B.1.1.7 SARS-CoV-2 variant to date. Given the unknowns of the emerging situation, experts with the Infectious Diseases Society of America addressed vaccine effectiveness, how well equipped the United States is to track new mutations, and shared their impressions of President Joe Biden’s COVID-19 executive orders.
One of the major concerns remains the ability of COVID-19 vaccines to work on new strains. “All of our vaccines target the spike protein and try to elicit neutralizing antibodies that bind to that protein,” Mirella Salvatore, MD, assistant professor of medicine and population health sciences at Weill Cornell Medicine, New York, said during an IDSA press briefing on Thursday.
The B.1.1.7 mutation occurs in the “very important” spike protein, a component of the SARS-CoV-2 virus necessary for binding, which allows the virus to enter cells, added Dr. Salvatore, an IDSA fellow.
The evidence suggests that SARS-CoV-2 should be capable of producing one or two mutations per month. However, the B.1.1.7 variant surprised investigators in the United Kingdom when they first discovered the strain had 17 mutations, Dr. Salvatore said.
It’s still unknown why this particular strain is more transmissible, but Dr. Salvatore speculated that the mutation gives the virus an advantage and increases binding, allowing it to enter cells more easily. She added that the mutations might have arisen among immunocompromised people infected with SARS-CoV-2, but “that is just a hypothesis.”
On a positive note, Kathryn M. Edwards, MD, another IDSA fellow, explained at the briefing that the existing vaccines target more than one location on the virus’ spike protein. Therefore, “if there is a mutation that changes one structure of the spike protein, there will be other areas where the binding can occur.”
This polyclonal response “is why the vaccine can still be effective against this virus,” added Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program and professor of pediatrics at Vanderbilt University, Nashville, Tenn.
Dr. Salvatore emphasized that, although the new variant is more transmissible, it doesn’t appear to be more lethal. “This might affect overall mortality but not for the individual who gets the infection.”
Staying one step ahead
When asked for assurance that COVID-19 vaccines will work against emerging variants, Dr. Edwards said, “It may be we will have to change the vaccine so it is more responsive to new variants, but at this point that does not seem to be the case.”
Should the vaccines require an update, the messenger RNA vaccines have an advantage – researchers can rapidly revise them. “All you need to do is put all the little nucleotides together,” Dr. Edwards said.
“A number of us are looking at how this will work, and we look to influenza,” she added. Dr. Edwards drew an analogy to choosing – and sometimes updating – the influenza strains each year for the annual flu vaccine. With appropriate funding, the same system could be replicated to address any evolving changes to SARS-CoV-2.
On funding, Dr. Salvatore said more money would be required to optimize the surveillance system for emerging strains in the United States.
“We actually have this system – there is a wonderful network that sequences the influenza strains,” she said. “The structure exists, we just need the funding.”
“The CDC is getting the system tooled up to get more viruses to be sequenced,” Dr. Edwards said.
Both experts praised the CDC for its website with up-to-date surveillance information on emerging strains of SARS-CoV-2.
President Biden’s backing of science
A reporter asked each infectious disease expert to share their impression of President Biden’s newly signed COVID-19 executive orders.
“The biggest takeaway is the role of science and the lessons we’ve learned from masks, handwashing, and distancing,” Dr. Edwards said. “We need to heed the advice ... [especially] with a variant that is more contagious.
“It is encouraging that science will be listened to – that is the overall message,” she added.
Dr. Salvatore agreed, saying that the orders give “the feeling that we can now act by following science.”
“We have plenty of papers that show the effectiveness of masking,” for example, she said. Dr. Salvatore acknowledged that there are “a lot of contrasting ideas about masking” across the United States but stressed their importance.
“We should follow measures that we know work,” she said.
Both experts said more research is needed to stay ahead of this evolving scenario. “We still need a lot of basic science showing how this virus replicates in the cell,” Dr. Salvatore said. “We need to really characterize all these mutations and their functions.”
“We need to be concerned, do follow-up studies,” she added, “but we don’t need to panic.”
This article was based on an Infectious Diseases Society of America Media Briefing on Jan. 21, 2021. Dr. Salvatore disclosed that she is a site principal investigator on a study from Verily Life Sciences/Brin Foundation on Predictors of Severe COVID-19 Outcomes and principal investigator for an investigator-initiated study sponsored by Genentech on combination therapy in influenza. Dr. Edwards disclosed National Institutes of Health and Centers for Disease Control and Prevention grants; consulting for Bionet and IBM; and being a member of data safety and monitoring committees for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, and Merck.
A version of this article first appeared on Medscape.com.
About 20 states across the country have detected the more transmissible B.1.1.7 SARS-CoV-2 variant to date. Given the unknowns of the emerging situation, experts with the Infectious Diseases Society of America addressed vaccine effectiveness, how well equipped the United States is to track new mutations, and shared their impressions of President Joe Biden’s COVID-19 executive orders.
One of the major concerns remains the ability of COVID-19 vaccines to work on new strains. “All of our vaccines target the spike protein and try to elicit neutralizing antibodies that bind to that protein,” Mirella Salvatore, MD, assistant professor of medicine and population health sciences at Weill Cornell Medicine, New York, said during an IDSA press briefing on Thursday.
The B.1.1.7 mutation occurs in the “very important” spike protein, a component of the SARS-CoV-2 virus necessary for binding, which allows the virus to enter cells, added Dr. Salvatore, an IDSA fellow.
The evidence suggests that SARS-CoV-2 should be capable of producing one or two mutations per month. However, the B.1.1.7 variant surprised investigators in the United Kingdom when they first discovered the strain had 17 mutations, Dr. Salvatore said.
It’s still unknown why this particular strain is more transmissible, but Dr. Salvatore speculated that the mutation gives the virus an advantage and increases binding, allowing it to enter cells more easily. She added that the mutations might have arisen among immunocompromised people infected with SARS-CoV-2, but “that is just a hypothesis.”
On a positive note, Kathryn M. Edwards, MD, another IDSA fellow, explained at the briefing that the existing vaccines target more than one location on the virus’ spike protein. Therefore, “if there is a mutation that changes one structure of the spike protein, there will be other areas where the binding can occur.”
This polyclonal response “is why the vaccine can still be effective against this virus,” added Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program and professor of pediatrics at Vanderbilt University, Nashville, Tenn.
Dr. Salvatore emphasized that, although the new variant is more transmissible, it doesn’t appear to be more lethal. “This might affect overall mortality but not for the individual who gets the infection.”
Staying one step ahead
When asked for assurance that COVID-19 vaccines will work against emerging variants, Dr. Edwards said, “It may be we will have to change the vaccine so it is more responsive to new variants, but at this point that does not seem to be the case.”
Should the vaccines require an update, the messenger RNA vaccines have an advantage – researchers can rapidly revise them. “All you need to do is put all the little nucleotides together,” Dr. Edwards said.
“A number of us are looking at how this will work, and we look to influenza,” she added. Dr. Edwards drew an analogy to choosing – and sometimes updating – the influenza strains each year for the annual flu vaccine. With appropriate funding, the same system could be replicated to address any evolving changes to SARS-CoV-2.
On funding, Dr. Salvatore said more money would be required to optimize the surveillance system for emerging strains in the United States.
“We actually have this system – there is a wonderful network that sequences the influenza strains,” she said. “The structure exists, we just need the funding.”
“The CDC is getting the system tooled up to get more viruses to be sequenced,” Dr. Edwards said.
Both experts praised the CDC for its website with up-to-date surveillance information on emerging strains of SARS-CoV-2.
President Biden’s backing of science
A reporter asked each infectious disease expert to share their impression of President Biden’s newly signed COVID-19 executive orders.
“The biggest takeaway is the role of science and the lessons we’ve learned from masks, handwashing, and distancing,” Dr. Edwards said. “We need to heed the advice ... [especially] with a variant that is more contagious.
“It is encouraging that science will be listened to – that is the overall message,” she added.
Dr. Salvatore agreed, saying that the orders give “the feeling that we can now act by following science.”
“We have plenty of papers that show the effectiveness of masking,” for example, she said. Dr. Salvatore acknowledged that there are “a lot of contrasting ideas about masking” across the United States but stressed their importance.
“We should follow measures that we know work,” she said.
Both experts said more research is needed to stay ahead of this evolving scenario. “We still need a lot of basic science showing how this virus replicates in the cell,” Dr. Salvatore said. “We need to really characterize all these mutations and their functions.”
“We need to be concerned, do follow-up studies,” she added, “but we don’t need to panic.”
This article was based on an Infectious Diseases Society of America Media Briefing on Jan. 21, 2021. Dr. Salvatore disclosed that she is a site principal investigator on a study from Verily Life Sciences/Brin Foundation on Predictors of Severe COVID-19 Outcomes and principal investigator for an investigator-initiated study sponsored by Genentech on combination therapy in influenza. Dr. Edwards disclosed National Institutes of Health and Centers for Disease Control and Prevention grants; consulting for Bionet and IBM; and being a member of data safety and monitoring committees for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, and Merck.
A version of this article first appeared on Medscape.com.
About 20 states across the country have detected the more transmissible B.1.1.7 SARS-CoV-2 variant to date. Given the unknowns of the emerging situation, experts with the Infectious Diseases Society of America addressed vaccine effectiveness, how well equipped the United States is to track new mutations, and shared their impressions of President Joe Biden’s COVID-19 executive orders.
One of the major concerns remains the ability of COVID-19 vaccines to work on new strains. “All of our vaccines target the spike protein and try to elicit neutralizing antibodies that bind to that protein,” Mirella Salvatore, MD, assistant professor of medicine and population health sciences at Weill Cornell Medicine, New York, said during an IDSA press briefing on Thursday.
The B.1.1.7 mutation occurs in the “very important” spike protein, a component of the SARS-CoV-2 virus necessary for binding, which allows the virus to enter cells, added Dr. Salvatore, an IDSA fellow.
The evidence suggests that SARS-CoV-2 should be capable of producing one or two mutations per month. However, the B.1.1.7 variant surprised investigators in the United Kingdom when they first discovered the strain had 17 mutations, Dr. Salvatore said.
It’s still unknown why this particular strain is more transmissible, but Dr. Salvatore speculated that the mutation gives the virus an advantage and increases binding, allowing it to enter cells more easily. She added that the mutations might have arisen among immunocompromised people infected with SARS-CoV-2, but “that is just a hypothesis.”
On a positive note, Kathryn M. Edwards, MD, another IDSA fellow, explained at the briefing that the existing vaccines target more than one location on the virus’ spike protein. Therefore, “if there is a mutation that changes one structure of the spike protein, there will be other areas where the binding can occur.”
This polyclonal response “is why the vaccine can still be effective against this virus,” added Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program and professor of pediatrics at Vanderbilt University, Nashville, Tenn.
Dr. Salvatore emphasized that, although the new variant is more transmissible, it doesn’t appear to be more lethal. “This might affect overall mortality but not for the individual who gets the infection.”
Staying one step ahead
When asked for assurance that COVID-19 vaccines will work against emerging variants, Dr. Edwards said, “It may be we will have to change the vaccine so it is more responsive to new variants, but at this point that does not seem to be the case.”
Should the vaccines require an update, the messenger RNA vaccines have an advantage – researchers can rapidly revise them. “All you need to do is put all the little nucleotides together,” Dr. Edwards said.
“A number of us are looking at how this will work, and we look to influenza,” she added. Dr. Edwards drew an analogy to choosing – and sometimes updating – the influenza strains each year for the annual flu vaccine. With appropriate funding, the same system could be replicated to address any evolving changes to SARS-CoV-2.
On funding, Dr. Salvatore said more money would be required to optimize the surveillance system for emerging strains in the United States.
“We actually have this system – there is a wonderful network that sequences the influenza strains,” she said. “The structure exists, we just need the funding.”
“The CDC is getting the system tooled up to get more viruses to be sequenced,” Dr. Edwards said.
Both experts praised the CDC for its website with up-to-date surveillance information on emerging strains of SARS-CoV-2.
President Biden’s backing of science
A reporter asked each infectious disease expert to share their impression of President Biden’s newly signed COVID-19 executive orders.
“The biggest takeaway is the role of science and the lessons we’ve learned from masks, handwashing, and distancing,” Dr. Edwards said. “We need to heed the advice ... [especially] with a variant that is more contagious.
“It is encouraging that science will be listened to – that is the overall message,” she added.
Dr. Salvatore agreed, saying that the orders give “the feeling that we can now act by following science.”
“We have plenty of papers that show the effectiveness of masking,” for example, she said. Dr. Salvatore acknowledged that there are “a lot of contrasting ideas about masking” across the United States but stressed their importance.
“We should follow measures that we know work,” she said.
Both experts said more research is needed to stay ahead of this evolving scenario. “We still need a lot of basic science showing how this virus replicates in the cell,” Dr. Salvatore said. “We need to really characterize all these mutations and their functions.”
“We need to be concerned, do follow-up studies,” she added, “but we don’t need to panic.”
This article was based on an Infectious Diseases Society of America Media Briefing on Jan. 21, 2021. Dr. Salvatore disclosed that she is a site principal investigator on a study from Verily Life Sciences/Brin Foundation on Predictors of Severe COVID-19 Outcomes and principal investigator for an investigator-initiated study sponsored by Genentech on combination therapy in influenza. Dr. Edwards disclosed National Institutes of Health and Centers for Disease Control and Prevention grants; consulting for Bionet and IBM; and being a member of data safety and monitoring committees for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, and Merck.
A version of this article first appeared on Medscape.com.
Arthritis drugs ‘impressive’ for severe COVID but not ‘magic cure’
New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.
Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.
However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.
The results were published online Jan. 7 in MedRxiv.
Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.
“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent story by Reuters.
Consider the big picture
“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.
One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”
“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
Interim findings
The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.
Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).
“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
Cautious optimism?
“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”
In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.
“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.
Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”
Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”
Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.
The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.
Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
Backing from the British
Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.
Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.
“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”
Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.
Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.
“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).
Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”
Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”
“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.
Awaiting peer review
“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.
“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”
“We need to make sure these findings, as outlined, hold up,” he said.
In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”
The REMAP-CAP study is ongoing and updated results will be provided online.
Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.
A version of this article first appeared on Medscape.com.
New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.
Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.
However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.
The results were published online Jan. 7 in MedRxiv.
Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.
“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent story by Reuters.
Consider the big picture
“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.
One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”
“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
Interim findings
The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.
Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).
“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
Cautious optimism?
“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”
In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.
“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.
Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”
Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”
Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.
The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.
Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
Backing from the British
Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.
Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.
“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”
Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.
Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.
“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).
Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”
Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”
“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.
Awaiting peer review
“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.
“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”
“We need to make sure these findings, as outlined, hold up,” he said.
In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”
The REMAP-CAP study is ongoing and updated results will be provided online.
Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.
A version of this article first appeared on Medscape.com.
New findings suggest that monoclonal antibodies used to treat RA could improve severe COVID-19 outcomes, including risk for death.
Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.
However, the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial comes with a caveat. The preprint findings have not yet been peer reviewed and “should not be used to guide clinical practice,” the authors stated.
The results were published online Jan. 7 in MedRxiv.
Nevertheless, the trial also revealed a mortality benefit associated with the two interleukin-6 antagonists. The hospital mortality rate was 22% with sarilumab, 28% with tocilizumab, and almost 36% with usual care.
“That’s a big change in survival. They are both lifesaving drugs,” lead coinvestigator Anthony Gordon, an Imperial College London professor of anesthesia and critical care, commented in a recent story by Reuters.
Consider the big picture
“What I think is important is ... this is one of many trials,” Paul Auwaerter, MD, MBA, said in an interview. Many other studies looking at monoclonal antibody therapy for people with COVID-19 were halted because they did not show improvement.
One exception is the EMPACTA trial, which suggested that tocilizumab was effective if given before a person becomes ill enough to be placed on a ventilator, said Dr. Auwaerter, clinical director of the division of infectious diseases at Johns Hopkins Medicine and a contributor to this news organization. “It appeared to reduce the need for mechanical ventilation or death.”
“These two trials are the first randomized, prospective trials that show a benefit on a background of others which have not,” Dr. Auwaerter added.
Interim findings
The REMAP-CAP investigators randomly assigned adults within 24 hours of critical care for COVID-19 to 8 mg/kg tocilizumab, 400 mg sarilumab, or usual care at 113 sites in six countries. There were 353 participants in the tocilizumab arm, 48 in the sarilumab group, and 402 in the control group.
Compared with the control group, the 10 days free of organ support in the tocilizumab cohort was associated with an adjusted odds ratio of 1.64 (95% confidence interval, 1.25-2.14). The 11 days free of organ support in the sarilumab cohort was likewise superior to control (adjusted odds ratio, 1.76; 95% CI, 1.17-2.91).
“All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists,” the authors note. These endpoints included 90-day survival, time to intensive care unit discharge, and hospital discharge.
Cautious optimism?
“The results were quite impressive – having 10 or 11 fewer days in the ICU, compared to standard of care,” Deepa Gotur, MD, said in an interview. “Choosing the right patient population and providing the anti-IL-6 treatment at the right time would be the key here.”
In addition to not yet receiving peer review, an open-label design, a relatively short follow-up of 21 days, and steroids becoming standard of care about halfway through the trial are potential limitations, said Dr. Gotur, an intensivist at Houston Methodist Hospital and associate professor of clinical medicine at Weill Cornell Medicine, New York.
“This is an interesting study,” Carl J. Fichtenbaum, MD, professor of clinical medicine at the University of Cincinnati, said in a comment.
Additional detail on how many participants in each group received steroids is warranted, Dr. Fichtenbaum said. “The analysis did not carefully adjust for the use of steroids that might have influenced outcomes.”
Dr. Fichtenbaum said it’s important to look at what is distinctive about REMAP-CAP because “there are several other studies showing opposite results.”
Dr. Gotur was an investigator on a previous study evaluating tocilizumab for patients already on mechanical ventilation. “One of the key differences between this and other studies is that they included more of the ICU population,” she said. “They also included patients within 24 hours of requiring organ support, cardiac, as well as respiratory support.” Some other research included less-acute patients, including all comers into the ED who required oxygen and received tocilizumab.
The prior studies also evaluated cytokine or inflammatory markers. In contrast, REMAP-CAP researchers “looked at organ failure itself ... which I think makes sense,” Dr. Gotur said.
Cytokine release syndrome can cause organ damage or organ failure, she added, “but these markers are all over the place. I’ve seen patients who are very, very sick despite having a low [C-reactive protein] or IL-6 level.”
Backing from the British
Citing the combined 24% decrease in the risk for death associated with these agents in the REMAP-CAP trial, the U.K. government announced Jan. 7 it will work to make tocilizumab and sarilumab available to citizens with severe COVID-19.
Experts in the United Kingdom shared their perspectives on the REMAP-CAP interim findings through the U.K. Science Media Centre.
“There are few treatments for severe COVID-19,” said Robin Ferner, MD, honorary professor of clinical pharmacology at the University of Birmingham (England) and honorary consultant physician at City Hospital Birmingham. “If the published data from REMAP-CAP are supported by further studies, this suggests that two IL-6 receptor antagonists can reduce the death rate in the most severely ill patients.”
Dr. Ferner added that the findings are not a “magic cure,” however. He pointed out that of 401 patients given the drugs, 109 died, and with standard treatment, 144 out of 402 died.
Peter Horby, MD, PhD, was more optimistic. “It is great to see a positive result at a time that we really need good news and more tools to fight COVID. This is great achievement for REMAP-CAP,” he said.
“We hope to soon have results from RECOVERY on the effect of tocilizumab in less severely ill patients in the hospital,” said Dr. Horby, cochief investigator of the RECOVERY trial and professor of emerging infectious diseases at the Centre for Tropical Medicine and Global Health at the University of Oxford (England).
Stephen Evans, BA, MSc, FRCP, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said, “This is a high-quality trial, and although published as a preprint, is of much higher quality than many non–peer-reviewed papers.”
Dr. Evans also noted the addition of steroid therapy for many participants. “Partway through the trial, the RECOVERY trial findings showed that the corticosteroid drug dexamethasone had notable mortality benefits. Consequently, quite a number of the patients in this trial had also received a corticosteroid.”
“It does look as though these drugs give some additional benefit beyond that given by dexamethasone,” he added.
Awaiting peer review
“We need to wait for the final results and ensure it was adequately powered with enough observations to make us confident in the results,” Dr. Fichtenbaum said.
“We in the United States have to step back and look at the entire set of studies and also, for this particular one, REMAP-CAP, to be in a peer-reviewed publication,” Dr. Auwaerter said. Preprints are often released “in the setting of the pandemic, where there may be important findings, especially if they impact mortality or severity of illness.”
“We need to make sure these findings, as outlined, hold up,” he said.
In the meantime, Dr. Auwaerter added, “Exactly how this will fit in is unclear. But it’s important to me as another potential drug that can help our critically ill patients.”
The REMAP-CAP study is ongoing and updated results will be provided online.
Dr. Auwaerter disclosed that he is a consultant for EMD Serono and a member of the data monitoring safety board for Humanigen. Dr. Gotur, Dr. Fichtenbaum, Dr. Ferner, and Dr. Evans disclosed no relevant financial relationships. Dr. Horby reported that Oxford University receives funding for the RECOVERY trial from U.K. Research and Innovation and the National Institute for Health Research. Roche Products and Sanofi supported REMAP-CAP through provision of tocilizumab and sarilumab in the United Kingdom.
A version of this article first appeared on Medscape.com.
The next likely COVID-19 vaccine has its advantages
Among the multiple vaccine candidates around the globe, next up in the arsenal against COVID-19 is likely the single-dose Ad26.COV2.S vaccine in development from Johnson & Johnson/Janssen, infectious disease experts predict.
And it got closer with promising interim phase 1/2a trial results, published online Jan. 13 in The New England Journal of Medicine.
A single Ad26.COV2.S dose was associated with S-binding and neutralizing antibodies in more than 90% of the participants. The finding was observed in both adults aged 18-55 years and participants 65 and older, as well as for participants given low-dose or high-dose vaccinations.
The results also suggest a durable vaccine response. “The take-home message [includes] a high neutralizing antibody responder rate to a single dose of our Ad26.COV2.S COVID-19 vaccine candidate. In addition, we see that these responses and antibody titers are stable for at least 71 days,” senior study author Hanneke Schuitemaker, PhD, global head of viral vaccine discovery and translational medicine at Johnson & Johnson in Leiden, the Netherlands, said in an interview.
If the single-dose Johnson & Johnson product gains Food and Drug Administration emergency use authorization (EUA), it could significantly boost the number of overall immunizations available. Less stringent storage requirements – only regular refrigeration vs. a need to freeze the Pfizer/BioNTech and Moderna COVID-19 vaccines – is another potential advantage. The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 36°-46 °F (2°-8 °C).
“Phase 1-2 trial data on the J&J vaccine: If it works as well as the mRNA options, it will have substantial advantages,” Jeremy Faust, MD, an emergency room physician affiliated with Brigham & Women’s Hospital and Harvard Medical School, Boston, tweeted on Jan. 13.
Unlike the Pfizer/BioNTech and Moderna messenger RNA vaccines, the Johnson & Johnson product is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.
Phase 3 efficacy/safety results pending
Under normal circumstances, phase 3 trial results would not be anticipated within weeks of phase 1/2a trial findings. However, the urgency of the COVID-19 pandemic accelerated the vaccine development process, so preclinical trials were conducted simultaneously and not sequentially. For this reason, phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and a company executive told Reuters that the rollout is on track for March.
“We hope to report data from our first phase 3 study, ENSEMBLE, in which we are testing the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February,” Dr. Schuitemaker said.
In the meantime, the phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results have drawn positive reactions.
“Data is highly encouraging and supports the single inoculation approach that makes this vaccine unique,” Carlos del Rio, executive associate dean for Emory University at Grady in Atlanta, wrote in a tweet on Jan. 13.
“Encouraging COVID vaccine data from J&J published [Jan. 13]. Solid antibody, CD4 T cell, and CD8 T cell responses – a nice trifecta of vaccine immune responses to see! And safe!” tweeted Shane Crotty, PhD, vaccine scientist and professor at the La Jolla (Calif.) Institute for Immunology.
First results in 800+ participants
At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.
A total of 402 people in the younger age cohort and 403 in the 65 and older group received a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose 56 days later for a separate trial, ENSEMBLE2, designed to compare safety and efficacy between single- and double-dose regimens. Results of that trial are still pending.
Safety profile
A single dose was associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. They also found that grade 3 adverse events decreased with increasing age.
Injection site pain on the day of immunization or the next day was the most common local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% of the low-dose vaccine group and 39% of the high-dose cohort. Fatigue, headache, and myalgia were the most common grade 1 or 2 solicited systemic adverse events reported.
Five serious adverse events were reported, including four that investigators deemed unrelated to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that resulted in hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours.
“These data confirm our previous experience with vaccine candidates based on our Ad26 viral vector platform in the younger age group. The almost similar performance in older adults is promising,” Dr. Schuitemaker said.
A potential limitation of the phase 1/2a trial is “the lack of representation of minority groups,” the researchers noted. Johnson & Johnson is working on improving the diversity of study participants “with respect to groups that seem to be affected most by the COVID-19 pandemic.”
AstraZeneca/Oxford vaccine status
The AstraZeneca/Oxford AZD1222 vaccine in development received approval for use in the United Kingdom on Dec. 30. The approval came after Public Health England said the country was facing “unprecedented” levels of infections, the BBC reported. AstraZeneca applied for European Medical Agency approval earlier in the week of Jan. 10, which could lead to more widespread use across Europe.
The status of the vaccine remains uncertain in the United States. A phase 3 trial that started in August was paused for about 6 weeks in September and October after an adverse event in a British volunteer halted studies worldwide. On Oct. 23, the FDA permitted researchers to continue the trial with approximately 40,000 participants.
There was some suggestion in the clinical trials that a half dose of the AstraZeneca vaccine was more effective than a full dose, 90% vs. 62%, but some irregularities in the research require further investigation.
Although the AstraZeneca vaccine is delivered to cells by an adenovirus – as with the Johnson & Johnson product – it is designed to be delivered in two doses 28 days apart, like the administration schedule of the Moderna mRNA vaccine.
A need for speed, and more doses
Regardless of which vaccine product is next to gain an EUA in the United States, many experts agree the COVID-19 vaccine rollouts so far have been problematic, at a time when cases are climbing to record-breaking levels, and likely more related to logistics over administration of the vaccine than production of the doses.
“Lots of doses being manufactured. In December 20 million, January 40 million, February 80 million and J&J hopefully soon to add to the count. The shortage is the number arms not getting vaccinated. Freezers do not get COVID. They do not need all those vaccines,” Daniel Griffin, MD, PhD, an infectious disease expert in Port Washington, N.Y., tweeted on Jan. 12.
“Unfortunately, the rollout has not gone smoothly, partly due to a lack of resources for this distribution phase we’re in,” Andrew T. Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah, Salt Lake City, said during a media briefing Jan. 14 sponsored by the Infectious Diseases Society of America (IDSA).
“We’re concerned about the mismatch between the number of people who are being told they are eligible and the amount of vaccine that is being distributed,” he said.
Complicating the rollout is a directive from U.S. Health and Human Services Secretary Alex Azar that states should start vaccinating everyone 65 and older as well as those with underlying conditions.
Expanding distribution to the 15% of Americans in just this age group is a big challenge, Dr. Pavia said. “We have enough vaccine maybe to vaccinate 40 million by the end of this month. There is a huge disconnect, and that creates a lot of problems.”
“One of the biggest problems is we are trying to do this mass vaccination program in the middle of the biggest surge we’ve ever seen,” Julie Vaishampayan, MD, MPH, chair of the IDSA Public Health Committee, said during the briefing. Without sufficient time for public health officials to plan for vaccinating a larger population, “people will come and stand in extremely long lines.”
Trying to expand immunization access without a proportionate increase in available doses prompted Dr. Vaishampayan to share an analogy from a colleague: “We are trying to fill a lake with a garden hose. Rather than making the lake bigger, what we really need is more water.”
Dr. Pavia emphasized that infectious disease experts “know the measures that work.” Not using masks, physical distancing, and hand hygiene, he said, “is a bit like knowing that really good shark repellents will be available in summer, so I’m going to jump into the ocean covered in blood while the great whites are swimming around.”
An official at the World Health Organization agreed. “Vaccines are coming online and I do believe vaccines will make a huge difference. But they are not here yet in enough quantities and in enough people to make that difference,” Michael Ryan, MB, WHO executive director of health emergencies, said during an online media briefing Jan. 13, held in conjunction with Emory University.
Dr. Ryan predicted that “we’ve got weeks if not months ahead of us in which our weapon is our knowledge ... what we know about this virus, its transmission, and stopping that transmission.
“And as the vaccines roll in, we can hopefully end this horrific pandemic.”
Dr. Schuitemaker reports grants from BARDA during the conduct of the study; personal fees and other from Janssen Vaccines and Prevention, a J&J company, outside the submitted work. Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services funded the phase 1/2a study.
A version of this article first appeared on Medscape.com.
Among the multiple vaccine candidates around the globe, next up in the arsenal against COVID-19 is likely the single-dose Ad26.COV2.S vaccine in development from Johnson & Johnson/Janssen, infectious disease experts predict.
And it got closer with promising interim phase 1/2a trial results, published online Jan. 13 in The New England Journal of Medicine.
A single Ad26.COV2.S dose was associated with S-binding and neutralizing antibodies in more than 90% of the participants. The finding was observed in both adults aged 18-55 years and participants 65 and older, as well as for participants given low-dose or high-dose vaccinations.
The results also suggest a durable vaccine response. “The take-home message [includes] a high neutralizing antibody responder rate to a single dose of our Ad26.COV2.S COVID-19 vaccine candidate. In addition, we see that these responses and antibody titers are stable for at least 71 days,” senior study author Hanneke Schuitemaker, PhD, global head of viral vaccine discovery and translational medicine at Johnson & Johnson in Leiden, the Netherlands, said in an interview.
If the single-dose Johnson & Johnson product gains Food and Drug Administration emergency use authorization (EUA), it could significantly boost the number of overall immunizations available. Less stringent storage requirements – only regular refrigeration vs. a need to freeze the Pfizer/BioNTech and Moderna COVID-19 vaccines – is another potential advantage. The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 36°-46 °F (2°-8 °C).
“Phase 1-2 trial data on the J&J vaccine: If it works as well as the mRNA options, it will have substantial advantages,” Jeremy Faust, MD, an emergency room physician affiliated with Brigham & Women’s Hospital and Harvard Medical School, Boston, tweeted on Jan. 13.
Unlike the Pfizer/BioNTech and Moderna messenger RNA vaccines, the Johnson & Johnson product is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.
Phase 3 efficacy/safety results pending
Under normal circumstances, phase 3 trial results would not be anticipated within weeks of phase 1/2a trial findings. However, the urgency of the COVID-19 pandemic accelerated the vaccine development process, so preclinical trials were conducted simultaneously and not sequentially. For this reason, phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and a company executive told Reuters that the rollout is on track for March.
“We hope to report data from our first phase 3 study, ENSEMBLE, in which we are testing the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February,” Dr. Schuitemaker said.
In the meantime, the phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results have drawn positive reactions.
“Data is highly encouraging and supports the single inoculation approach that makes this vaccine unique,” Carlos del Rio, executive associate dean for Emory University at Grady in Atlanta, wrote in a tweet on Jan. 13.
“Encouraging COVID vaccine data from J&J published [Jan. 13]. Solid antibody, CD4 T cell, and CD8 T cell responses – a nice trifecta of vaccine immune responses to see! And safe!” tweeted Shane Crotty, PhD, vaccine scientist and professor at the La Jolla (Calif.) Institute for Immunology.
First results in 800+ participants
At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.
A total of 402 people in the younger age cohort and 403 in the 65 and older group received a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose 56 days later for a separate trial, ENSEMBLE2, designed to compare safety and efficacy between single- and double-dose regimens. Results of that trial are still pending.
Safety profile
A single dose was associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. They also found that grade 3 adverse events decreased with increasing age.
Injection site pain on the day of immunization or the next day was the most common local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% of the low-dose vaccine group and 39% of the high-dose cohort. Fatigue, headache, and myalgia were the most common grade 1 or 2 solicited systemic adverse events reported.
Five serious adverse events were reported, including four that investigators deemed unrelated to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that resulted in hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours.
“These data confirm our previous experience with vaccine candidates based on our Ad26 viral vector platform in the younger age group. The almost similar performance in older adults is promising,” Dr. Schuitemaker said.
A potential limitation of the phase 1/2a trial is “the lack of representation of minority groups,” the researchers noted. Johnson & Johnson is working on improving the diversity of study participants “with respect to groups that seem to be affected most by the COVID-19 pandemic.”
AstraZeneca/Oxford vaccine status
The AstraZeneca/Oxford AZD1222 vaccine in development received approval for use in the United Kingdom on Dec. 30. The approval came after Public Health England said the country was facing “unprecedented” levels of infections, the BBC reported. AstraZeneca applied for European Medical Agency approval earlier in the week of Jan. 10, which could lead to more widespread use across Europe.
The status of the vaccine remains uncertain in the United States. A phase 3 trial that started in August was paused for about 6 weeks in September and October after an adverse event in a British volunteer halted studies worldwide. On Oct. 23, the FDA permitted researchers to continue the trial with approximately 40,000 participants.
There was some suggestion in the clinical trials that a half dose of the AstraZeneca vaccine was more effective than a full dose, 90% vs. 62%, but some irregularities in the research require further investigation.
Although the AstraZeneca vaccine is delivered to cells by an adenovirus – as with the Johnson & Johnson product – it is designed to be delivered in two doses 28 days apart, like the administration schedule of the Moderna mRNA vaccine.
A need for speed, and more doses
Regardless of which vaccine product is next to gain an EUA in the United States, many experts agree the COVID-19 vaccine rollouts so far have been problematic, at a time when cases are climbing to record-breaking levels, and likely more related to logistics over administration of the vaccine than production of the doses.
“Lots of doses being manufactured. In December 20 million, January 40 million, February 80 million and J&J hopefully soon to add to the count. The shortage is the number arms not getting vaccinated. Freezers do not get COVID. They do not need all those vaccines,” Daniel Griffin, MD, PhD, an infectious disease expert in Port Washington, N.Y., tweeted on Jan. 12.
“Unfortunately, the rollout has not gone smoothly, partly due to a lack of resources for this distribution phase we’re in,” Andrew T. Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah, Salt Lake City, said during a media briefing Jan. 14 sponsored by the Infectious Diseases Society of America (IDSA).
“We’re concerned about the mismatch between the number of people who are being told they are eligible and the amount of vaccine that is being distributed,” he said.
Complicating the rollout is a directive from U.S. Health and Human Services Secretary Alex Azar that states should start vaccinating everyone 65 and older as well as those with underlying conditions.
Expanding distribution to the 15% of Americans in just this age group is a big challenge, Dr. Pavia said. “We have enough vaccine maybe to vaccinate 40 million by the end of this month. There is a huge disconnect, and that creates a lot of problems.”
“One of the biggest problems is we are trying to do this mass vaccination program in the middle of the biggest surge we’ve ever seen,” Julie Vaishampayan, MD, MPH, chair of the IDSA Public Health Committee, said during the briefing. Without sufficient time for public health officials to plan for vaccinating a larger population, “people will come and stand in extremely long lines.”
Trying to expand immunization access without a proportionate increase in available doses prompted Dr. Vaishampayan to share an analogy from a colleague: “We are trying to fill a lake with a garden hose. Rather than making the lake bigger, what we really need is more water.”
Dr. Pavia emphasized that infectious disease experts “know the measures that work.” Not using masks, physical distancing, and hand hygiene, he said, “is a bit like knowing that really good shark repellents will be available in summer, so I’m going to jump into the ocean covered in blood while the great whites are swimming around.”
An official at the World Health Organization agreed. “Vaccines are coming online and I do believe vaccines will make a huge difference. But they are not here yet in enough quantities and in enough people to make that difference,” Michael Ryan, MB, WHO executive director of health emergencies, said during an online media briefing Jan. 13, held in conjunction with Emory University.
Dr. Ryan predicted that “we’ve got weeks if not months ahead of us in which our weapon is our knowledge ... what we know about this virus, its transmission, and stopping that transmission.
“And as the vaccines roll in, we can hopefully end this horrific pandemic.”
Dr. Schuitemaker reports grants from BARDA during the conduct of the study; personal fees and other from Janssen Vaccines and Prevention, a J&J company, outside the submitted work. Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services funded the phase 1/2a study.
A version of this article first appeared on Medscape.com.
Among the multiple vaccine candidates around the globe, next up in the arsenal against COVID-19 is likely the single-dose Ad26.COV2.S vaccine in development from Johnson & Johnson/Janssen, infectious disease experts predict.
And it got closer with promising interim phase 1/2a trial results, published online Jan. 13 in The New England Journal of Medicine.
A single Ad26.COV2.S dose was associated with S-binding and neutralizing antibodies in more than 90% of the participants. The finding was observed in both adults aged 18-55 years and participants 65 and older, as well as for participants given low-dose or high-dose vaccinations.
The results also suggest a durable vaccine response. “The take-home message [includes] a high neutralizing antibody responder rate to a single dose of our Ad26.COV2.S COVID-19 vaccine candidate. In addition, we see that these responses and antibody titers are stable for at least 71 days,” senior study author Hanneke Schuitemaker, PhD, global head of viral vaccine discovery and translational medicine at Johnson & Johnson in Leiden, the Netherlands, said in an interview.
If the single-dose Johnson & Johnson product gains Food and Drug Administration emergency use authorization (EUA), it could significantly boost the number of overall immunizations available. Less stringent storage requirements – only regular refrigeration vs. a need to freeze the Pfizer/BioNTech and Moderna COVID-19 vaccines – is another potential advantage. The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 36°-46 °F (2°-8 °C).
“Phase 1-2 trial data on the J&J vaccine: If it works as well as the mRNA options, it will have substantial advantages,” Jeremy Faust, MD, an emergency room physician affiliated with Brigham & Women’s Hospital and Harvard Medical School, Boston, tweeted on Jan. 13.
Unlike the Pfizer/BioNTech and Moderna messenger RNA vaccines, the Johnson & Johnson product is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.
Phase 3 efficacy/safety results pending
Under normal circumstances, phase 3 trial results would not be anticipated within weeks of phase 1/2a trial findings. However, the urgency of the COVID-19 pandemic accelerated the vaccine development process, so preclinical trials were conducted simultaneously and not sequentially. For this reason, phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and a company executive told Reuters that the rollout is on track for March.
“We hope to report data from our first phase 3 study, ENSEMBLE, in which we are testing the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February,” Dr. Schuitemaker said.
In the meantime, the phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results have drawn positive reactions.
“Data is highly encouraging and supports the single inoculation approach that makes this vaccine unique,” Carlos del Rio, executive associate dean for Emory University at Grady in Atlanta, wrote in a tweet on Jan. 13.
“Encouraging COVID vaccine data from J&J published [Jan. 13]. Solid antibody, CD4 T cell, and CD8 T cell responses – a nice trifecta of vaccine immune responses to see! And safe!” tweeted Shane Crotty, PhD, vaccine scientist and professor at the La Jolla (Calif.) Institute for Immunology.
First results in 800+ participants
At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.
A total of 402 people in the younger age cohort and 403 in the 65 and older group received a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose 56 days later for a separate trial, ENSEMBLE2, designed to compare safety and efficacy between single- and double-dose regimens. Results of that trial are still pending.
Safety profile
A single dose was associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. They also found that grade 3 adverse events decreased with increasing age.
Injection site pain on the day of immunization or the next day was the most common local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% of the low-dose vaccine group and 39% of the high-dose cohort. Fatigue, headache, and myalgia were the most common grade 1 or 2 solicited systemic adverse events reported.
Five serious adverse events were reported, including four that investigators deemed unrelated to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that resulted in hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours.
“These data confirm our previous experience with vaccine candidates based on our Ad26 viral vector platform in the younger age group. The almost similar performance in older adults is promising,” Dr. Schuitemaker said.
A potential limitation of the phase 1/2a trial is “the lack of representation of minority groups,” the researchers noted. Johnson & Johnson is working on improving the diversity of study participants “with respect to groups that seem to be affected most by the COVID-19 pandemic.”
AstraZeneca/Oxford vaccine status
The AstraZeneca/Oxford AZD1222 vaccine in development received approval for use in the United Kingdom on Dec. 30. The approval came after Public Health England said the country was facing “unprecedented” levels of infections, the BBC reported. AstraZeneca applied for European Medical Agency approval earlier in the week of Jan. 10, which could lead to more widespread use across Europe.
The status of the vaccine remains uncertain in the United States. A phase 3 trial that started in August was paused for about 6 weeks in September and October after an adverse event in a British volunteer halted studies worldwide. On Oct. 23, the FDA permitted researchers to continue the trial with approximately 40,000 participants.
There was some suggestion in the clinical trials that a half dose of the AstraZeneca vaccine was more effective than a full dose, 90% vs. 62%, but some irregularities in the research require further investigation.
Although the AstraZeneca vaccine is delivered to cells by an adenovirus – as with the Johnson & Johnson product – it is designed to be delivered in two doses 28 days apart, like the administration schedule of the Moderna mRNA vaccine.
A need for speed, and more doses
Regardless of which vaccine product is next to gain an EUA in the United States, many experts agree the COVID-19 vaccine rollouts so far have been problematic, at a time when cases are climbing to record-breaking levels, and likely more related to logistics over administration of the vaccine than production of the doses.
“Lots of doses being manufactured. In December 20 million, January 40 million, February 80 million and J&J hopefully soon to add to the count. The shortage is the number arms not getting vaccinated. Freezers do not get COVID. They do not need all those vaccines,” Daniel Griffin, MD, PhD, an infectious disease expert in Port Washington, N.Y., tweeted on Jan. 12.
“Unfortunately, the rollout has not gone smoothly, partly due to a lack of resources for this distribution phase we’re in,” Andrew T. Pavia, MD, chief of the division of pediatric infectious diseases at the University of Utah, Salt Lake City, said during a media briefing Jan. 14 sponsored by the Infectious Diseases Society of America (IDSA).
“We’re concerned about the mismatch between the number of people who are being told they are eligible and the amount of vaccine that is being distributed,” he said.
Complicating the rollout is a directive from U.S. Health and Human Services Secretary Alex Azar that states should start vaccinating everyone 65 and older as well as those with underlying conditions.
Expanding distribution to the 15% of Americans in just this age group is a big challenge, Dr. Pavia said. “We have enough vaccine maybe to vaccinate 40 million by the end of this month. There is a huge disconnect, and that creates a lot of problems.”
“One of the biggest problems is we are trying to do this mass vaccination program in the middle of the biggest surge we’ve ever seen,” Julie Vaishampayan, MD, MPH, chair of the IDSA Public Health Committee, said during the briefing. Without sufficient time for public health officials to plan for vaccinating a larger population, “people will come and stand in extremely long lines.”
Trying to expand immunization access without a proportionate increase in available doses prompted Dr. Vaishampayan to share an analogy from a colleague: “We are trying to fill a lake with a garden hose. Rather than making the lake bigger, what we really need is more water.”
Dr. Pavia emphasized that infectious disease experts “know the measures that work.” Not using masks, physical distancing, and hand hygiene, he said, “is a bit like knowing that really good shark repellents will be available in summer, so I’m going to jump into the ocean covered in blood while the great whites are swimming around.”
An official at the World Health Organization agreed. “Vaccines are coming online and I do believe vaccines will make a huge difference. But they are not here yet in enough quantities and in enough people to make that difference,” Michael Ryan, MB, WHO executive director of health emergencies, said during an online media briefing Jan. 13, held in conjunction with Emory University.
Dr. Ryan predicted that “we’ve got weeks if not months ahead of us in which our weapon is our knowledge ... what we know about this virus, its transmission, and stopping that transmission.
“And as the vaccines roll in, we can hopefully end this horrific pandemic.”
Dr. Schuitemaker reports grants from BARDA during the conduct of the study; personal fees and other from Janssen Vaccines and Prevention, a J&J company, outside the submitted work. Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services funded the phase 1/2a study.
A version of this article first appeared on Medscape.com.
Early use of high-titer plasma may prevent severe COVID-19
Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.
In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.
“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.
“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.
The study was published online Jan. 6 in The New England Journal of Medicine.
“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.
Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.
“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.
Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.
Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”
A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.
“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.
However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”
A search for clear answers
Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”
To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.
In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).
The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).
Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.
The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.
“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.
The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.
Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”
Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
An inexpensive therapy with global potential?
“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”
Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”
Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”
Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.
“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.
“We are glad it worked,” he said.
The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.
A version of this article first appeared on Medscape.com.
Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.
In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.
“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.
“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.
The study was published online Jan. 6 in The New England Journal of Medicine.
“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.
Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.
“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.
Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.
Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”
A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.
“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.
However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”
A search for clear answers
Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”
To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.
In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).
The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).
Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.
The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.
“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.
The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.
Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”
Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
An inexpensive therapy with global potential?
“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”
Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”
Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”
Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.
“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.
“We are glad it worked,” he said.
The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.
A version of this article first appeared on Medscape.com.
Administering convalescent plasma that has high levels of antibodies against SARS-CoV-2 within the first 3 days of symptoms was associated with significantly lower chances of progression to severe COVID-19, new evidence demonstrates.
In a trial of 160 older adults with COVID-19, half of whom were randomly assigned to receive plasma and half to receive placebo infusion, treatment with high-titer plasma lowered the relative risk for severe disease by 48% in an intent-to-treat analysis.
“We now have evidence, in the context of a small but well-designed study, that convalescent plasma with high titers of antibody against SARS-CoV-2 administered in the first 3 days of mild symptoms to infected elderly reduces progression of illness and the rate of severe presentations,” senior author Fernando Polack, MD, said in an interview.
“Not any plasma, not any time,” added Dr. Polack, an infectious disease specialist and scientific director at Fundacion INFANT and professor of pediatrics at the University of Buenos Aires. The key, he said, is to select plasma in the upper 28th percentile of IgG antibody concentrations and to administer therapy prior to disease progression.
The study was published online Jan. 6 in The New England Journal of Medicine.
“It’s a very good study and approaches a different population from the PlasmAr study,” Ventura Simonovich, MD, chief of the clinical pharmacology section, Medical Clinic Service, Hospital Italiano de Buenos Aires, said in an interview. “This is the first published randomized controlled trial that shows real benefit in this [older adult] population, the most vulnerable in this disease,” he said.
Dr. Simonovich, who was not affiliated with the current study, was lead author of the PlasmAr trial, which was published in The New England Journal of Medicine Nov. 24, 2020. In that trial, the researchers evaluated adults aged 18 years and older and found no significant benefit with convalescent plasma treatment over placebo for patients with COVID-19 and severe pneumonia.
“We know antibodies work best when given early and in high dose. This is one of the rare reports that validates it in the outpatient setting,” David Sullivan, MD, professor of molecular biology and immunology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview when asked to comment.
Dr. Sullivan pointed out that most previous studies on convalescent plasma focused on patients with COVID-19 who had severe cases late in the disease course.
Regarding the current study, he said, “The striking thing is treating people within 3 days of illness.”
A more cautious interpretation may be warranted, one expert said. “The study demonstrates the benefit of early intervention. There was a dose-dependent effect, with higher titers providing a greater benefit,” Manoj Menon, MD, MPH, a hematologist and oncologist at the University of Washington, Seattle, said in an interview.
“Taken together, the findings have biologic plausibility and produce more data on the role of convalescent plasma to a relevant age cohort,” he added.
However, Dr. Menon said: “Given the limited sample size, I do not think this study, although well conducted, definitively addresses the role of convalescent plasma for COVID-19. But it does merit additional study.”
A search for clear answers
Treatments that target the early stages of COVID-19 “remain elusive. Few strategies provide benefit, several have failed, and others are being evaluated,” the researchers noted. “In hospitalized patients with COVID-19, the infusion of convalescent plasma against SARS-CoV-2 late in the course of illness has not shown clear benefits and, consequently, the most appropriate antibody concentrations for effective treatment are unclear.”
To learn more, Dr. Polack and colleagues included patients with PCR-confirmed COVID-19 who were aged 75 years or older, regardless of comorbidities. They also included patients aged 65-74 years who had at least one underlying condition. Participants were enrolled at clinical sites or geriatric units in Argentina. The mean age was 77 years, and 62% were women.
In an intent-to-treat analysis, the primary outcome – severe respiratory disease – occurred in 16% of the plasma recipients, vs. 31% of the group that received placebo. The relative risk was 0.52 (95% confidence interval, 0.29-0.94; P = .03).
The number needed to treat to avoid a severe respiratory disease episode was 7 (95% CI, 4-50).
Life-threatening respiratory disease, a secondary outcome, occurred in four people in the plasma group, compared with 10 in the placebo group. Two patients in the treatment group and four patients in the placebo group died.
The researchers also ran a modified intent-to-treat analysis that excluded six participants who experienced severe respiratory disease prior to receiving plasma or placebo. In this analysis, efficacy of plasma therapy increased to 60%.
“Again, this finding suggests that early intervention is critical for efficacy,” the investigators noted.
The investigators, who are based in Argentina, defined their primary endpoint as a respiratory rate of 30 or more breaths per minute and/or an oxygen saturation of less than 93% while breathing ambient air.
Dr. Sullivan pointed out that this is equivalent to the threshold commonly used for hospitalizing people with COVID-19 in the United States. “So it’s equivalent to avoiding hospitalizations. The take-home is high-titer plasma prevents respiratory distress, which equals hospitalization for us.”
Dr. Sullivan is conducting similar research in the United States regarding the use of plasma for treatment or prevention. He and colleagues are evaluating adults aged 18-90 years, “not just the ones at highest risk for going to the hospital,” he said. Enrollment is ongoing.
An inexpensive therapy with global potential?
“Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary endpoints,” the researchers wrote. “Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection.”
Dr. Polack said, “This is an inexpensive solution to mitigate the burden of severe illness in the population most vulnerable to the virus: the elderly. And it has the attraction of being applicable not only in industrialized countries but in many areas of the developing world.”
Convalescent plasma “is a potentially inexpensive alternative to monoclonal antibodies,” the researchers added. Furthermore, “early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.”
Dr. Polack said the study findings did not surprise him. “We always thought that, as it has been the case in the past with many therapeutic strategies against respiratory and other viral infections, the earlier you treat, the better.
“We just hoped that within 72 hours of symptoms we would be treating early enough – remember that there is a 4- to 5-day incubation period that the virus leverages before the first symptom – and with enough antibody,” he added.
“We are glad it worked,” he said.
The study was supported by the Bill and Melinda Gates Foundation and by the Fundación INFANT Pandemic Fund. Dr. Polack, Dr. Simonovich, and Dr. Sullivan have disclosed various financial relationships industry.
A version of this article first appeared on Medscape.com.