MDedge Rheumatology

As the first American health care workers rolled up their sleeves for a COVID-19 vaccine, the images were instantly frozen in history, marking the triumph of scientific know-how and ingenuity. Cameras captured the first trucks pulling out of a warehouse in Portage, Mich., to the applause of workers and area residents. A day later, Boston Medical Center employees – some dressed in scrubs and wearing masks, face shields, and protective gowns – literally danced on the sidewalk when doses arrived. Some have photographed themselves getting the vaccine and posted it on social media, tagging it #MyCOVIDVax.

But the real story of the debut of COVID-19 vaccination is more methodical than monumental, a celebration of teamwork rather than of conquest. As hospitals waited for their first allotment, they reviewed their carefully drafted plans. They relied on each other, reaching across the usual divisions of competition and working collaboratively to share the limited supply. Their priority lists for the first vaccinations included environmental services workers who clean patient rooms and the critical care physicians who work to save lives.

“Health care workers have pulled together throughout this pandemic,” said Melanie Swift, MD, cochair of the COVID-19 Vaccine Allocation and Distribution Work Group at Mayo Clinic in Rochester, Minn. “We’ve gone through the darkest of years relying so heavily on each other,” she said. “Now we’re pulling together to get out of it.”

Still, a rollout of this magnitude has hitches. Stanford issued an apology Dec. 18 after its medical residents protested a vaccine distribution plan that left out nearly all of its residents and fellows, many of whom regularly treat patients with COVID-19.

There have already been more than 287,000 COVID-19 cases and 953 deaths among health care workers, according to the Centers for Disease Control and Prevention. In its guidance, the agency pointed out that the “continued protection of them at work, at home, and in the community remains a national priority.” That means vaccinating a workforce of about 21 million people, often the largest group of employees in a community.

“It collectively takes all of us to vaccinate our teams to maintain that stability in our health care infrastructure across the metro Atlanta area,” Christy Norman, PharmD, vice president of pharmacy services at Emory Healthcare, told reporters in a briefing as the health system awaited its first delivery.
 

Don’t waste a dose

One overriding imperative prevails: Hospitals don’t want to waste any doses. The storage requirements of the Pfizer vaccine make that tricky.

Once vials are removed from the pizza-box-shaped containers in ultracold storage and placed in a refrigerator, they must be used within 5 days. Thawed five-dose vials must be brought to room temperature before they are diluted, and they can remain at room temperature for no more than 2 hours. Once they are diluted with 1.8 mL of a 0.9% sodium chloride injection, the vials must be used within 6 hours.

COVID-19 precautions require employees to stay physically distant while they wait their turn for vaccination, which means the process can’t mirror typical large-scale flu immunization programs.

To prioritize groups, the vaccination planners at Mayo conducted a thorough risk stratification, considering each employee’s duties. Do they work in a dedicated COVID-19 unit? Do they handle lab tests or collect swabs? Do they work in the ICU or emergency department?

“We have applied some principles to make sure that as we roll it out, we prioritize people who are at greatest risk of ongoing exposure and who are really critical to maintaining the COVID response and other essential health services,” said Dr. Swift, associate medical director of Mayo’s occupational health service.

Mayo employees who are eligible for the first doses can sign up for appointments through the medical record system. If it seems likely that some doses will be left over at the end of the vaccination period – perhaps because of missed appointments – supervisors in high-risk areas can refer other health care workers. Mayo gave its first vaccines on Dec. 18, but the vaccination program began in earnest the following week. With the pleasant surprise that each five-dose vial actually provides six doses, 474 vials will allow for the vaccination of 2,844 employees in the top-priority group. “It’s going to expand each week or few days as we get more and more vaccine,” Dr. Swift said.
 

Sharing vials with small rural hospitals

Minnesota is using a hub-and-spoke system to give small rural hospitals access to the Pfizer vaccine, even though they lack ultracold storage and can’t use a minimum order of 975 doses. Large hospitals, acting as hubs, are sharing their orders. (The minimum order for Moderna is 100 doses.)

In south-central Minnesota, for example, two hub hospitals each have six spoke hospitals. Five of the 14 hospitals are independent, and the rest are part of large hospital systems, but affiliation doesn’t matter, said Eric Weller, regional health care preparedness coordinator for the South Central Healthcare Coalition. “We are all working together. It doesn’t matter what system you’re from,” he said. “We’re working for the good of the community.”

Each hospital designed a process to provide vaccine education, prioritize groups, allocate appointments, register people for vaccination, obtain signed consent forms, administer vaccines in a COVID-safe way, and provide follow-up appointments for the second dose. “We’re using some of the lessons we learned during H1N1,” said Mr. Weller, referring to immunization during the 2009 influenza pandemic. “The difference is that during H1N1, you could have lines of people.”

Coordinating the appointments will be more important than ever. “One of the vaccination strategies is to get people in groups of five, so you use one vial on those five people and don’t waste it,” he said.

Logistics are somewhat different for the Moderna vaccine, which will come in 10-dose vials that can be refrigerated for up to 30 days.

Both vaccines may produce mild flulike symptoms, such as fatigue, headache, or muscle pain, particularly after the second dose. That’s a sign that the immune system is reacting to the vaccine, but it’s also another consideration in the vaccination plans, because health care workers might take a day or two off work. “We’re not going to vaccinate a whole department at one time. It will be staggered,” said Kevin Smith, MD, medical director of the occupational medicine program at ProMedica, a health care system based in Toledo, Ohio.

Dr. Smith said he plans to encourage employees to use V-Safe, an app created by the CDC to track adverse effects in people who receive the vaccine. He pointed out that a day or two of achiness will be better than coping with the symptoms of COVID-19. Some employees who recovered from the infection still feel fatigued or haven’t regained their sense of taste and smell. “We are still monitoring quite a few employees to make sure they get back to 100%,” he said.
 

Hope for ending the pandemic

Public health officials have worried about vaccine hesitancy, even among health care workers, but so far, that concern seems overshadowed by enthusiasm. Dr. Smith said his department has been fielding calls from employees who want to know when they will be able to get the vaccine. “I think everyone feels relief,” he said. “We’re at the beginning of the end.”

At Mayo, Dr. Swift is surveying staff to gauge the willingness to get the vaccine, but she already senses excitement among employees. “No doubt there are still people who are hesitant, but I’m feeling a shift,” she said. “I’m feeling this momentum building of health care workers coming on board and wanting to take this vaccine, which is good, because they will set an example for their patients.”

For Colleen Kelley, MD, an infectious disease physician at Emory University in Atlanta who was principal investigator for an Emory-affiliated Moderna clinical trial site, it has been an emotional time. “Things were looking very bleak and dark for a time, and then we started to get these efficacy results that were greater than anyone imagined,” she said.

Dr. Kelley spends time talking to journalists and educating physician colleagues and hospital employees about how the vaccine was developed so quickly and how it works. “Everyone asks me, ‘Should I get it? Are you going to get it?’ My answer is ‘yes’ and ‘yes,’ “ she said. “I am 1,000% confident that the benefits of widespread vaccination outweigh the risks of continued COVID and a continued pandemic.”

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

As the first American health care workers rolled up their sleeves for a COVID-19 vaccine, the images were instantly frozen in history, marking the triumph of scientific know-how and ingenuity. Cameras captured the first trucks pulling out of a warehouse in Portage, Mich., to the applause of workers and area residents. A day later, Boston Medical Center employees – some dressed in scrubs and wearing masks, face shields, and protective gowns – literally danced on the sidewalk when doses arrived. Some have photographed themselves getting the vaccine and posted it on social media, tagging it #MyCOVIDVax.

But the real story of the debut of COVID-19 vaccination is more methodical than monumental, a celebration of teamwork rather than of conquest. As hospitals waited for their first allotment, they reviewed their carefully drafted plans. They relied on each other, reaching across the usual divisions of competition and working collaboratively to share the limited supply. Their priority lists for the first vaccinations included environmental services workers who clean patient rooms and the critical care physicians who work to save lives.

“Health care workers have pulled together throughout this pandemic,” said Melanie Swift, MD, cochair of the COVID-19 Vaccine Allocation and Distribution Work Group at Mayo Clinic in Rochester, Minn. “We’ve gone through the darkest of years relying so heavily on each other,” she said. “Now we’re pulling together to get out of it.”

Still, a rollout of this magnitude has hitches. Stanford issued an apology Dec. 18 after its medical residents protested a vaccine distribution plan that left out nearly all of its residents and fellows, many of whom regularly treat patients with COVID-19.

There have already been more than 287,000 COVID-19 cases and 953 deaths among health care workers, according to the Centers for Disease Control and Prevention. In its guidance, the agency pointed out that the “continued protection of them at work, at home, and in the community remains a national priority.” That means vaccinating a workforce of about 21 million people, often the largest group of employees in a community.

“It collectively takes all of us to vaccinate our teams to maintain that stability in our health care infrastructure across the metro Atlanta area,” Christy Norman, PharmD, vice president of pharmacy services at Emory Healthcare, told reporters in a briefing as the health system awaited its first delivery.
 

Don’t waste a dose

One overriding imperative prevails: Hospitals don’t want to waste any doses. The storage requirements of the Pfizer vaccine make that tricky.

Once vials are removed from the pizza-box-shaped containers in ultracold storage and placed in a refrigerator, they must be used within 5 days. Thawed five-dose vials must be brought to room temperature before they are diluted, and they can remain at room temperature for no more than 2 hours. Once they are diluted with 1.8 mL of a 0.9% sodium chloride injection, the vials must be used within 6 hours.

COVID-19 precautions require employees to stay physically distant while they wait their turn for vaccination, which means the process can’t mirror typical large-scale flu immunization programs.

To prioritize groups, the vaccination planners at Mayo conducted a thorough risk stratification, considering each employee’s duties. Do they work in a dedicated COVID-19 unit? Do they handle lab tests or collect swabs? Do they work in the ICU or emergency department?

“We have applied some principles to make sure that as we roll it out, we prioritize people who are at greatest risk of ongoing exposure and who are really critical to maintaining the COVID response and other essential health services,” said Dr. Swift, associate medical director of Mayo’s occupational health service.

Mayo employees who are eligible for the first doses can sign up for appointments through the medical record system. If it seems likely that some doses will be left over at the end of the vaccination period – perhaps because of missed appointments – supervisors in high-risk areas can refer other health care workers. Mayo gave its first vaccines on Dec. 18, but the vaccination program began in earnest the following week. With the pleasant surprise that each five-dose vial actually provides six doses, 474 vials will allow for the vaccination of 2,844 employees in the top-priority group. “It’s going to expand each week or few days as we get more and more vaccine,” Dr. Swift said.
 

Sharing vials with small rural hospitals

Minnesota is using a hub-and-spoke system to give small rural hospitals access to the Pfizer vaccine, even though they lack ultracold storage and can’t use a minimum order of 975 doses. Large hospitals, acting as hubs, are sharing their orders. (The minimum order for Moderna is 100 doses.)

In south-central Minnesota, for example, two hub hospitals each have six spoke hospitals. Five of the 14 hospitals are independent, and the rest are part of large hospital systems, but affiliation doesn’t matter, said Eric Weller, regional health care preparedness coordinator for the South Central Healthcare Coalition. “We are all working together. It doesn’t matter what system you’re from,” he said. “We’re working for the good of the community.”

Each hospital designed a process to provide vaccine education, prioritize groups, allocate appointments, register people for vaccination, obtain signed consent forms, administer vaccines in a COVID-safe way, and provide follow-up appointments for the second dose. “We’re using some of the lessons we learned during H1N1,” said Mr. Weller, referring to immunization during the 2009 influenza pandemic. “The difference is that during H1N1, you could have lines of people.”

Coordinating the appointments will be more important than ever. “One of the vaccination strategies is to get people in groups of five, so you use one vial on those five people and don’t waste it,” he said.

Logistics are somewhat different for the Moderna vaccine, which will come in 10-dose vials that can be refrigerated for up to 30 days.

Both vaccines may produce mild flulike symptoms, such as fatigue, headache, or muscle pain, particularly after the second dose. That’s a sign that the immune system is reacting to the vaccine, but it’s also another consideration in the vaccination plans, because health care workers might take a day or two off work. “We’re not going to vaccinate a whole department at one time. It will be staggered,” said Kevin Smith, MD, medical director of the occupational medicine program at ProMedica, a health care system based in Toledo, Ohio.

Dr. Smith said he plans to encourage employees to use V-Safe, an app created by the CDC to track adverse effects in people who receive the vaccine. He pointed out that a day or two of achiness will be better than coping with the symptoms of COVID-19. Some employees who recovered from the infection still feel fatigued or haven’t regained their sense of taste and smell. “We are still monitoring quite a few employees to make sure they get back to 100%,” he said.
 

Hope for ending the pandemic

Public health officials have worried about vaccine hesitancy, even among health care workers, but so far, that concern seems overshadowed by enthusiasm. Dr. Smith said his department has been fielding calls from employees who want to know when they will be able to get the vaccine. “I think everyone feels relief,” he said. “We’re at the beginning of the end.”

At Mayo, Dr. Swift is surveying staff to gauge the willingness to get the vaccine, but she already senses excitement among employees. “No doubt there are still people who are hesitant, but I’m feeling a shift,” she said. “I’m feeling this momentum building of health care workers coming on board and wanting to take this vaccine, which is good, because they will set an example for their patients.”

For Colleen Kelley, MD, an infectious disease physician at Emory University in Atlanta who was principal investigator for an Emory-affiliated Moderna clinical trial site, it has been an emotional time. “Things were looking very bleak and dark for a time, and then we started to get these efficacy results that were greater than anyone imagined,” she said.

Dr. Kelley spends time talking to journalists and educating physician colleagues and hospital employees about how the vaccine was developed so quickly and how it works. “Everyone asks me, ‘Should I get it? Are you going to get it?’ My answer is ‘yes’ and ‘yes,’ “ she said. “I am 1,000% confident that the benefits of widespread vaccination outweigh the risks of continued COVID and a continued pandemic.”

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

As the first American health care workers rolled up their sleeves for a COVID-19 vaccine, the images were instantly frozen in history, marking the triumph of scientific know-how and ingenuity. Cameras captured the first trucks pulling out of a warehouse in Portage, Mich., to the applause of workers and area residents. A day later, Boston Medical Center employees – some dressed in scrubs and wearing masks, face shields, and protective gowns – literally danced on the sidewalk when doses arrived. Some have photographed themselves getting the vaccine and posted it on social media, tagging it #MyCOVIDVax.

But the real story of the debut of COVID-19 vaccination is more methodical than monumental, a celebration of teamwork rather than of conquest. As hospitals waited for their first allotment, they reviewed their carefully drafted plans. They relied on each other, reaching across the usual divisions of competition and working collaboratively to share the limited supply. Their priority lists for the first vaccinations included environmental services workers who clean patient rooms and the critical care physicians who work to save lives.

“Health care workers have pulled together throughout this pandemic,” said Melanie Swift, MD, cochair of the COVID-19 Vaccine Allocation and Distribution Work Group at Mayo Clinic in Rochester, Minn. “We’ve gone through the darkest of years relying so heavily on each other,” she said. “Now we’re pulling together to get out of it.”

Still, a rollout of this magnitude has hitches. Stanford issued an apology Dec. 18 after its medical residents protested a vaccine distribution plan that left out nearly all of its residents and fellows, many of whom regularly treat patients with COVID-19.

There have already been more than 287,000 COVID-19 cases and 953 deaths among health care workers, according to the Centers for Disease Control and Prevention. In its guidance, the agency pointed out that the “continued protection of them at work, at home, and in the community remains a national priority.” That means vaccinating a workforce of about 21 million people, often the largest group of employees in a community.

“It collectively takes all of us to vaccinate our teams to maintain that stability in our health care infrastructure across the metro Atlanta area,” Christy Norman, PharmD, vice president of pharmacy services at Emory Healthcare, told reporters in a briefing as the health system awaited its first delivery.
 

Don’t waste a dose

One overriding imperative prevails: Hospitals don’t want to waste any doses. The storage requirements of the Pfizer vaccine make that tricky.

Once vials are removed from the pizza-box-shaped containers in ultracold storage and placed in a refrigerator, they must be used within 5 days. Thawed five-dose vials must be brought to room temperature before they are diluted, and they can remain at room temperature for no more than 2 hours. Once they are diluted with 1.8 mL of a 0.9% sodium chloride injection, the vials must be used within 6 hours.

COVID-19 precautions require employees to stay physically distant while they wait their turn for vaccination, which means the process can’t mirror typical large-scale flu immunization programs.

To prioritize groups, the vaccination planners at Mayo conducted a thorough risk stratification, considering each employee’s duties. Do they work in a dedicated COVID-19 unit? Do they handle lab tests or collect swabs? Do they work in the ICU or emergency department?

“We have applied some principles to make sure that as we roll it out, we prioritize people who are at greatest risk of ongoing exposure and who are really critical to maintaining the COVID response and other essential health services,” said Dr. Swift, associate medical director of Mayo’s occupational health service.

Mayo employees who are eligible for the first doses can sign up for appointments through the medical record system. If it seems likely that some doses will be left over at the end of the vaccination period – perhaps because of missed appointments – supervisors in high-risk areas can refer other health care workers. Mayo gave its first vaccines on Dec. 18, but the vaccination program began in earnest the following week. With the pleasant surprise that each five-dose vial actually provides six doses, 474 vials will allow for the vaccination of 2,844 employees in the top-priority group. “It’s going to expand each week or few days as we get more and more vaccine,” Dr. Swift said.
 

Sharing vials with small rural hospitals

Minnesota is using a hub-and-spoke system to give small rural hospitals access to the Pfizer vaccine, even though they lack ultracold storage and can’t use a minimum order of 975 doses. Large hospitals, acting as hubs, are sharing their orders. (The minimum order for Moderna is 100 doses.)

In south-central Minnesota, for example, two hub hospitals each have six spoke hospitals. Five of the 14 hospitals are independent, and the rest are part of large hospital systems, but affiliation doesn’t matter, said Eric Weller, regional health care preparedness coordinator for the South Central Healthcare Coalition. “We are all working together. It doesn’t matter what system you’re from,” he said. “We’re working for the good of the community.”

Each hospital designed a process to provide vaccine education, prioritize groups, allocate appointments, register people for vaccination, obtain signed consent forms, administer vaccines in a COVID-safe way, and provide follow-up appointments for the second dose. “We’re using some of the lessons we learned during H1N1,” said Mr. Weller, referring to immunization during the 2009 influenza pandemic. “The difference is that during H1N1, you could have lines of people.”

Coordinating the appointments will be more important than ever. “One of the vaccination strategies is to get people in groups of five, so you use one vial on those five people and don’t waste it,” he said.

Logistics are somewhat different for the Moderna vaccine, which will come in 10-dose vials that can be refrigerated for up to 30 days.

Both vaccines may produce mild flulike symptoms, such as fatigue, headache, or muscle pain, particularly after the second dose. That’s a sign that the immune system is reacting to the vaccine, but it’s also another consideration in the vaccination plans, because health care workers might take a day or two off work. “We’re not going to vaccinate a whole department at one time. It will be staggered,” said Kevin Smith, MD, medical director of the occupational medicine program at ProMedica, a health care system based in Toledo, Ohio.

Dr. Smith said he plans to encourage employees to use V-Safe, an app created by the CDC to track adverse effects in people who receive the vaccine. He pointed out that a day or two of achiness will be better than coping with the symptoms of COVID-19. Some employees who recovered from the infection still feel fatigued or haven’t regained their sense of taste and smell. “We are still monitoring quite a few employees to make sure they get back to 100%,” he said.
 

Hope for ending the pandemic

Public health officials have worried about vaccine hesitancy, even among health care workers, but so far, that concern seems overshadowed by enthusiasm. Dr. Smith said his department has been fielding calls from employees who want to know when they will be able to get the vaccine. “I think everyone feels relief,” he said. “We’re at the beginning of the end.”

At Mayo, Dr. Swift is surveying staff to gauge the willingness to get the vaccine, but she already senses excitement among employees. “No doubt there are still people who are hesitant, but I’m feeling a shift,” she said. “I’m feeling this momentum building of health care workers coming on board and wanting to take this vaccine, which is good, because they will set an example for their patients.”

For Colleen Kelley, MD, an infectious disease physician at Emory University in Atlanta who was principal investigator for an Emory-affiliated Moderna clinical trial site, it has been an emotional time. “Things were looking very bleak and dark for a time, and then we started to get these efficacy results that were greater than anyone imagined,” she said.

Dr. Kelley spends time talking to journalists and educating physician colleagues and hospital employees about how the vaccine was developed so quickly and how it works. “Everyone asks me, ‘Should I get it? Are you going to get it?’ My answer is ‘yes’ and ‘yes,’ “ she said. “I am 1,000% confident that the benefits of widespread vaccination outweigh the risks of continued COVID and a continued pandemic.”

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

Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been “paused” because of futility and safety concerns, a statement from the U.S. National Heart, Lung, and Blood Institute (NHLBI) confirms.

The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.

All three trials have paused enrollment of critically ill COVID-19 patients requiring intensive care unit support for whom therapeutic doses of anticoagulation drugs did not reduce the need for organ support, the NHLBI statement notes.

The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.   

The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs. lower prophylactic doses in COVID-19 patients.

Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. 

Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes.  

“Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question,” the NHLBI statement says.

Patients who require full dose anticoagulants for another medical indication are not included in these trials.

The statement explains that COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, myocardial infarction, and stroke. 

The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC).

The trials, which span four continents, have the common goal of assessing the benefit of full doses of anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.

In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.  

The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).

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

Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been “paused” because of futility and safety concerns, a statement from the U.S. National Heart, Lung, and Blood Institute (NHLBI) confirms.

The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.

All three trials have paused enrollment of critically ill COVID-19 patients requiring intensive care unit support for whom therapeutic doses of anticoagulation drugs did not reduce the need for organ support, the NHLBI statement notes.

The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.   

The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs. lower prophylactic doses in COVID-19 patients.

Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. 

Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes.  

“Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question,” the NHLBI statement says.

Patients who require full dose anticoagulants for another medical indication are not included in these trials.

The statement explains that COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, myocardial infarction, and stroke. 

The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC).

The trials, which span four continents, have the common goal of assessing the benefit of full doses of anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.

In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.  

The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).

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

Parts of three linked studies investigating increased levels of anticoagulation in hospitalized COVID-19 patients have been “paused” because of futility and safety concerns, a statement from the U.S. National Heart, Lung, and Blood Institute (NHLBI) confirms.

The trials involved are the REMAP-CAP, ACTIV-4, and ATTACC studies.

All three trials have paused enrollment of critically ill COVID-19 patients requiring intensive care unit support for whom therapeutic doses of anticoagulation drugs did not reduce the need for organ support, the NHLBI statement notes.

The statement also says that a potential for harm in this subgroup could not be excluded, noting that increased bleeding is a known complication of full-dose anticoagulation. The trials are working urgently to undertake additional analyses, which will be made available as soon as possible.   

The three clinical trial platforms are working together to test the effects of full therapeutic doses of anticoagulants vs. lower prophylactic doses in COVID-19 patients.

Informed by the deliberations of the data safety monitoring boards of these trials, all of the trial sites have paused enrollment of the most critically ill hospitalized patients with COVID-19. 

Enrollment continues in the trials for moderately ill hospitalized COVID-19 patients, the statement notes.  

“Whether the use of full-dose compared to low-dose anticoagulants leads to better outcomes in hospitalized patients with less COVID-19 severe disease remains a very important question,” the NHLBI statement says.

Patients who require full dose anticoagulants for another medical indication are not included in these trials.

The statement explains that COVID-19 is associated with significant inflammation and clinical and pathologic evidence of widespread blood clots. These trials were launched because clinicians have observed that many patients ill with COVID-19, including those who have died from the disease, formed blood clots throughout their bodies, even in their smallest blood vessels. This unusual clotting can cause multiple health complications, including lung failure, myocardial infarction, and stroke. 

The three trials are the result of a collaboration between major international partners. The trials include: the Randomized, Embedded, Multi-factorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) Therapeutic Anticoagulation; Accelerating COVID-19 Therapeutic Interventions and Vaccines-4 (ACTIV-4) Antithrombotics Inpatient; and Antithrombotic Therapy to Ameliorate Complications of COVID-19 (ATTACC).

The trials, which span four continents, have the common goal of assessing the benefit of full doses of anticoagulants to treat moderately ill or critically ill adults hospitalized for COVID-19, compared with a lower dose often used to prevent blood clots in hospitalized patients.

In the United States, the ACTIV-4 trial is being led by a collaborative effort involving a number of universities, including the University of Pittsburgh and New York University.  

The trials are supported by multiple international funding organizations including the National Institutes of Health, Canadian Institutes of Health Research, the National Institute for Health Research (UK), the National Health and Medical Research Council (Australia), and the PREPARE and RECOVER consortia (European Union).

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

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

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

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

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

Physicians who developed a protocol for treating hospitalized patients with COVID-19 they call MATH+ have now published a literature review with observational mortality rates in the Journal of Intensive Care Medicine (JICM) that they say supports the protocol’s use.

The physicians have been promoting their MATH+ protocol as a way to improve survival from severe COVID-19 since the spring, and this is the first time their protocol and any results have been published in a peer-reviewed journal. But because the paper contains only hospital-level mortality rates compared with previously published observational data and clinical trials (not data from a randomized controlled trial testing the protocol), experts remain unconvinced the protocol benefits patients.

“This is not a study by any stretch of the imagination,” Hugh Cassiere, MD, director of critical care medicine at North Shore University Hospital in Manhasset, New York, told Medscape Medical News via email. “It is comparative data which should never be used to make conclusions of one therapy over another.”

“It’s food for thought for those clinicians [treating COVID-19] and it gives them some options,” said Pierre Kory, MD, MPA, a pulmonary critical care specialist in Wisconsin and one of the protocol developers. “What we really emphasize for this disease is it has to be a combination therapy protocol.”

As Medscape previously reported, MATH+ stands for methylprednisolone, ascorbic acid, thiamine, and heparin. The “+” includes additional therapies like vitamin D, zinc, melatonin, statins, and famotidine. The protocol originated as a variation of the “HAT therapy,” a combination of hydrocortisone, ascorbic acid, and thiamine, which critical care specialist Paul Marik, MD, created for treating critically ill patients with sepsis.

The protocol evolved over a few weeks this spring as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action. In March, when Marik and his colleagues formalized the MATH+ protocol, healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients.

Determined to spread a different message, the MATH+ physicians began publicizing the protocol with a website and a small communications team. They tried to get their protocol in front of leading healthcare organizations, like the WHO, and Kory testified remotely in front of the Senate Homeland Security Committee in early May. (Kory testified in front of the committee again earlier this month about the use of ivermectin as a COVID-19 treatment. He told Medscape the MATH+ protocol has been updated to include ivermectin since the submission to JICM.)

The physicians have continued promoting the protocol in the summer and fall, even after the RECOVERY trial showed dexamethasone treatment decreased mortality in hospitalized patients with severe COVID-19 and the WHO and other organizations started recommending the drug.

In the newly published JICM article, the researchers describe a mix of randomized controlled trials, observational studies, and basic science research that inform each of the individual pieces of the MATH+ protocol. Some of the cited research pertains specifically to the treatment of COVID-19.

Other studies the authors use to support the protocol are based on data from other viral outbreaks, like H1N1 and SARS-CoV, as well as other medical conditions, like nonviral acute respiratory distress syndrome and sepsis. The researchers did not conduct a randomized controlled trial of MATH+ for patients with COVID-19 because, as they write in the article, they did not believe they had the clinical equipoise required for such a study.

“With respect to each of the individual ‘core’ therapies of MATH+, all authors felt the therapies either superior to any placebo or possessed evidence of minimal risk and cost compared to potential benefit,” they wrote in the paper.

“With a new disease, it is totally reasonable to take your best guess at a therapy,” wrote F. Perry Wilson, MD, MSCE, director of the Clinical and Translational Research Accelerator at Yale University School of Medicine, in an email to Medscape. “When there is limited information, you go with what you have. What I take issue with here is the authors’ implication that that’s where the scientific process stops. In my mind, it’s actually just the beginning.” Every investigator believes his or her intervention is beneficial but is not sure — that’s why they conduct a randomized controlled trial, Wilson said.

“Without robust trials, we are left with too many options on the table and no way to know what helps — leading to this ‘throw the book at them’ approach, where you just pick your favorite molecule and give it,” said Wilson. 

Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, echoed this sentiment: “Many of the individual components could be expected to provide benefit and combining therapies is something physicians often do,” Parnia said in an email to Medscape. “I think this is a promising approach; however, this ultimately needs to be studied.”

The article includes previously unpublished observational mortality rates from two hospitals where the physicians have used the protocol: United Memorial Hospital in Houston, Texas and Norfolk General Hospital in Norfolk, Virginia. At United Memorial, MATH+ was “systematically” followed for patients admitted to the hospital, and at Norfolk General it was followed for patients admitted to the ICU. The two hospitals treated 140 and 191 COVID-19 patients with MATH+, respectively, as of July 20.

The average observed hospital or 28-day mortality rate at United Memorial was 4.4% and at Norfolk General was 6.1%, for a combined mortality rate of 5.1%. The researchers compared this rate with reported outcomes from 10 studies of more than 400 hospitals in the United States (72 hospitals), the United Kingdom (386), and China (3). The mortality rate for COVID-19 patients at these hospitals ranged from 15.6% to 32%, for an average mortality rate of 22.9%.

The difference in average mortality rates represents a “more than 75% absolute risk reduction in mortality” with MATH+, according to the authors. The data from other hospitals were reported from January to early June, representative of death rates early in the pandemic and before the announcement of the RECOVERY trial results spurred increased use of dexamethasone. 

The new numbers may not be convincing to other physicians.

“The comparison of the outcomes in the two hospitals where this protocol is implemented vs mortality rates in other published studies is quite a stretch,” Wilson told Medscape. “Hospitals with robust research programs that publish large cohorts tend to be tertiary care centers where sick patients get referred. Without data on the baseline characteristics of the patients in these studies, it’s really not appropriate to draw apples-to-apples comparisons.”

“There are many factors that lead to different mortality rates [between hospitals] and it often reflects the quality of general ICU care,” said Parnia. For example, many ICUs were overwhelmed and stretched during the pandemic, while others were not.

“This protocol remains a hypothesis in need of a prospective clinical trial,” said Daniel Kaul, MD, professor of infectious diseases at the University of Michigan, Ann Arbor. “Comparing gross mortality rates from different centers at different times with different case mixes is at most hypothesis generating.”

“The use of comparative data is useless information…not based on true comparison of groups,” said Cassiere of the average mortality rates. Only a randomized, placebo-controlled trial can prove if a treatment is effective. “This protocol should be abandoned.”

“The MATH+ is based on negative evidence,” Cassiere told Medscape, pointing to trials that showed no effect for vitamin C (ascorbic acid) and thiamine in critical illnesses. And, given the “overwhelming positive data’’ for dexamethasone to treat patients with severe COVID-19, its exclusion from MATH+ in favor of a steroid that has not been extensively studied for COVID-19 is “reckless and irresponsible,” he said. 

Kory pushed back strongly against this assertion, pointing to the decades of research on methylprednisolone as a treatment for lung disease and ARDS outlined in the article. “It has far more evidence than dexamethasone,” he told Medscape over the phone.

“Our recommendation is based on a clear understanding of the pharmacological principle to guide prolonged glucocorticoid administration in ARDS and COVID-19,” wrote G. Umberto Meduri, MD, a MATH+ coauthor and professor in the Division of Pulmonary, Critical Care, and Sleep Medicine at the University of Tennessee Health Science Center in Memphis.

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

A recent analysis of the incidence of gout in men, published in JAMA Network Open, offers new insights on the role of lifestyle changes in preventing gout, particularly the importance of obesity and its modification.

Prior gout research, although it addressed lifestyle issues, had not quantified the impact of obesity on incident gout cases, noted first author Natalie McCormick, PhD, and colleagues at Harvard Medical School and Massachusetts General Hospital in Boston. “To date the proportion of actual gout itself that could potentially be prevented by modifying such risk factors remains unknown.” To address that lack of data, they set out to estimate the proportion of avoidable incident gout in a large database in the Health Professionals Follow-up Study, initially of some 51,529 male health professionals who have completed a biannual personal health questionnaire since 1986. The follow-up rate for completing these questionnaires exceeds 90%.

For their analysis, the researchers tracked 44,654 of these men, with an average age of 54 at the 1986 baseline and no history of gout, through the year 2012. They looked at four lifestyle risk factors attributed to gout: body mass index; alcohol intake; adherence to a Dietary Approach to Stop Hypertension (DASH)-style diet, which recommends less red meat and sweetened beverages and more fruits, vegetables, and low-fat dairy products; and the absence of diuretic drugs, which are used to treat blood pressure or heart failure, in order to observe and compare their effects on new reports of gout. Over the subsequent 26 years, nearly 4% of the men developed gout, the most common inflammatory arthritis. Obese men had 2.65 times greater risk for developing gout than did those with a normal body mass index.

If one addressed all four risk factors – modifying obesity, having no alcohol intake, not taking diuretic drugs, and following a DASH-style, lower-fat diet – 77% of new gout cases would disappear, the study’s corresponding author, Hyon K. Choi, MD, DrPH, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, said in an interview. “But we learned that if you don’t include modifying obesity as a targetable risk factor, none of the other factors alone reaches significance. We can’t make firm conclusions about cause and effect, but modifying obesity seems to be a prerequisite to preventing gout through lifestyle. It’s a very interesting finding that needs to be confirmed in further research,” he said.

A worldwide gout epidemic

Currently, there is a kind of worldwide gout epidemic linked to obesity, Dr. Choi said. The disease burden of gout is increasing worldwide. “This may be more of an issue for family practice or primary care physicians, who see 80%-90% of gout cases, rather than for rheumatologists, who are more likely to see advanced cases in need of drug therapy. But we would say: Don’t lose sight of the lifestyle risk factors, which are interrelated. This is not only the responsibility of one doctor or the other.”

The new findings should give practicing rheumatologists more confidence in addressing lifestyle issues, particularly weight loss, with their patients, said Angelo Gaffo, MD, section chief of rheumatology at the Birmingham VA Medical Center and associate professor of medicine in the division of rheumatology at the University of Alabama at Birmingham.

Other studies have also looked at how weight loss led to serum urate reduction. This study adds to a growing body of literature emphasizing that the most important lifestyle factor relative to gout risk is weight gain, and the simplest, most effective intervention is counseling patients about weight loss, he said.

This research was supported by grants from the National Institutes of Health. Dr. Choi reported receiving research support from Ironwood and Horizon and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. No other relevant financial disclosures were reported.

SOURCE: McCormick N et al. JAMA Netw Open. 2020;3(11):e2027421. doi: 10.1001/jamanetworkopen.2020.27421.

A recent analysis of the incidence of gout in men, published in JAMA Network Open, offers new insights on the role of lifestyle changes in preventing gout, particularly the importance of obesity and its modification.

Prior gout research, although it addressed lifestyle issues, had not quantified the impact of obesity on incident gout cases, noted first author Natalie McCormick, PhD, and colleagues at Harvard Medical School and Massachusetts General Hospital in Boston. “To date the proportion of actual gout itself that could potentially be prevented by modifying such risk factors remains unknown.” To address that lack of data, they set out to estimate the proportion of avoidable incident gout in a large database in the Health Professionals Follow-up Study, initially of some 51,529 male health professionals who have completed a biannual personal health questionnaire since 1986. The follow-up rate for completing these questionnaires exceeds 90%.

For their analysis, the researchers tracked 44,654 of these men, with an average age of 54 at the 1986 baseline and no history of gout, through the year 2012. They looked at four lifestyle risk factors attributed to gout: body mass index; alcohol intake; adherence to a Dietary Approach to Stop Hypertension (DASH)-style diet, which recommends less red meat and sweetened beverages and more fruits, vegetables, and low-fat dairy products; and the absence of diuretic drugs, which are used to treat blood pressure or heart failure, in order to observe and compare their effects on new reports of gout. Over the subsequent 26 years, nearly 4% of the men developed gout, the most common inflammatory arthritis. Obese men had 2.65 times greater risk for developing gout than did those with a normal body mass index.

If one addressed all four risk factors – modifying obesity, having no alcohol intake, not taking diuretic drugs, and following a DASH-style, lower-fat diet – 77% of new gout cases would disappear, the study’s corresponding author, Hyon K. Choi, MD, DrPH, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, said in an interview. “But we learned that if you don’t include modifying obesity as a targetable risk factor, none of the other factors alone reaches significance. We can’t make firm conclusions about cause and effect, but modifying obesity seems to be a prerequisite to preventing gout through lifestyle. It’s a very interesting finding that needs to be confirmed in further research,” he said.

A worldwide gout epidemic

Currently, there is a kind of worldwide gout epidemic linked to obesity, Dr. Choi said. The disease burden of gout is increasing worldwide. “This may be more of an issue for family practice or primary care physicians, who see 80%-90% of gout cases, rather than for rheumatologists, who are more likely to see advanced cases in need of drug therapy. But we would say: Don’t lose sight of the lifestyle risk factors, which are interrelated. This is not only the responsibility of one doctor or the other.”

The new findings should give practicing rheumatologists more confidence in addressing lifestyle issues, particularly weight loss, with their patients, said Angelo Gaffo, MD, section chief of rheumatology at the Birmingham VA Medical Center and associate professor of medicine in the division of rheumatology at the University of Alabama at Birmingham.

Other studies have also looked at how weight loss led to serum urate reduction. This study adds to a growing body of literature emphasizing that the most important lifestyle factor relative to gout risk is weight gain, and the simplest, most effective intervention is counseling patients about weight loss, he said.

This research was supported by grants from the National Institutes of Health. Dr. Choi reported receiving research support from Ironwood and Horizon and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. No other relevant financial disclosures were reported.

SOURCE: McCormick N et al. JAMA Netw Open. 2020;3(11):e2027421. doi: 10.1001/jamanetworkopen.2020.27421.

A recent analysis of the incidence of gout in men, published in JAMA Network Open, offers new insights on the role of lifestyle changes in preventing gout, particularly the importance of obesity and its modification.

Prior gout research, although it addressed lifestyle issues, had not quantified the impact of obesity on incident gout cases, noted first author Natalie McCormick, PhD, and colleagues at Harvard Medical School and Massachusetts General Hospital in Boston. “To date the proportion of actual gout itself that could potentially be prevented by modifying such risk factors remains unknown.” To address that lack of data, they set out to estimate the proportion of avoidable incident gout in a large database in the Health Professionals Follow-up Study, initially of some 51,529 male health professionals who have completed a biannual personal health questionnaire since 1986. The follow-up rate for completing these questionnaires exceeds 90%.

For their analysis, the researchers tracked 44,654 of these men, with an average age of 54 at the 1986 baseline and no history of gout, through the year 2012. They looked at four lifestyle risk factors attributed to gout: body mass index; alcohol intake; adherence to a Dietary Approach to Stop Hypertension (DASH)-style diet, which recommends less red meat and sweetened beverages and more fruits, vegetables, and low-fat dairy products; and the absence of diuretic drugs, which are used to treat blood pressure or heart failure, in order to observe and compare their effects on new reports of gout. Over the subsequent 26 years, nearly 4% of the men developed gout, the most common inflammatory arthritis. Obese men had 2.65 times greater risk for developing gout than did those with a normal body mass index.

If one addressed all four risk factors – modifying obesity, having no alcohol intake, not taking diuretic drugs, and following a DASH-style, lower-fat diet – 77% of new gout cases would disappear, the study’s corresponding author, Hyon K. Choi, MD, DrPH, of the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, said in an interview. “But we learned that if you don’t include modifying obesity as a targetable risk factor, none of the other factors alone reaches significance. We can’t make firm conclusions about cause and effect, but modifying obesity seems to be a prerequisite to preventing gout through lifestyle. It’s a very interesting finding that needs to be confirmed in further research,” he said.

A worldwide gout epidemic

Currently, there is a kind of worldwide gout epidemic linked to obesity, Dr. Choi said. The disease burden of gout is increasing worldwide. “This may be more of an issue for family practice or primary care physicians, who see 80%-90% of gout cases, rather than for rheumatologists, who are more likely to see advanced cases in need of drug therapy. But we would say: Don’t lose sight of the lifestyle risk factors, which are interrelated. This is not only the responsibility of one doctor or the other.”

The new findings should give practicing rheumatologists more confidence in addressing lifestyle issues, particularly weight loss, with their patients, said Angelo Gaffo, MD, section chief of rheumatology at the Birmingham VA Medical Center and associate professor of medicine in the division of rheumatology at the University of Alabama at Birmingham.

Other studies have also looked at how weight loss led to serum urate reduction. This study adds to a growing body of literature emphasizing that the most important lifestyle factor relative to gout risk is weight gain, and the simplest, most effective intervention is counseling patients about weight loss, he said.

This research was supported by grants from the National Institutes of Health. Dr. Choi reported receiving research support from Ironwood and Horizon and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. No other relevant financial disclosures were reported.

SOURCE: McCormick N et al. JAMA Netw Open. 2020;3(11):e2027421. doi: 10.1001/jamanetworkopen.2020.27421.

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

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

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

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

Researchers have detected a highly contagious coronavirus variant in the United Kingdom, leading Prime Minister Boris Johnson to shut down parts of the country and triggering other nations to impose travel and shipping restrictions on England.

Mr. Johnson held a crisis meeting with ministers Monday after Saturday’s shutdown announcement. The prime minister said in a nationally televised address that this coronavirus variant may be “up to 70% more transmissible than the old variant” and was probably responsible for an increase in cases in southeastern England.

“There is still much we don’t know. While we are fairly certain the variant is transmitted more quickly, there is no evidence to suggest that it is more lethal or causes more severe illness. Equally there is no evidence to suggest the vaccine will be any less effective against the new variant,” he said.

Public Health England says it is working to learn as much about the variant as possible. “We know that mortality is a lagging indicator, and we will need to continually monitor this over the coming weeks,” the agency says.

That scientific uncertainty about the variant’s threat shook European nations that were rushing to ship goods to England in advance of a Dec. 31 Brexit deadline. Under Brexit, which is short for “British exit,” the United Kingdom will leave the European Union on Jan. 31, 2020. Until then, the two sides will come up with new trade and security relationships.

European Union members Austria, Belgium, Bulgaria, France, Germany, Ireland, Italy, and the Netherlands announced travel restrictions hours after Johnson’s speech.

Those restrictions created food uncertainty across the U.K., which imports about a quarter of its food from the EU, according to The New York Times. Long lines of trucks heading to ports in the U.K. came to a standstill on major roads such as the M20 near Kent and the Port of Dover.

Outside Europe, Canada, India, Iran, Israel, Hong Kong, Saudi Arabia, and Turkey banned all incoming flights from the U.K. And more bans could come.
 

The U.S. reaction

The United States has not imposed any new limits on travel with the United Kingdom, although New York Gov. Andrew Cuomo (D) has requested all passengers bound for John F. Kennedy International Airport from the U.K. be tested before boarding and a new travel ban be placed for Europe. He says the federal government must take action now to avoid a crisis situation like the one New York experienced in March and April.

“The United States has a number of flights coming in from the U.K. each day, and we have done absolutely nothing,” Mr. Cuomo said in a statement on the governor’s webpage. “To me, this is reprehensible because this is what happened in the spring. How many times in life do you have to make the same mistake before you learn?”

Leading U.S. health officials have downplayed the dangers of the virus.

“We don’t know that it’s more dangerous, and very importantly, we have not seen a single mutation yet that would make it evade the vaccine,” U.S. Assistant Secretary of Health and Human Services Adm. Brett Giroir, MD, said Sunday on ABC’s This Week with George Stephanopoulos. “I can’t say that won’t happen in the future, but right now it looks like the vaccine will cover everything that we see.”

Dr. Giroir said the HHS and other U.S. government agencies will monitor the variant.

“Viruses mutate,” he said. “We’ve seen almost 4,000 different mutations among this virus. There is no indication that the mutation right now that they’re talking about is overcoming England.”
 

Where did the variant come from?

Public Health England says the coronavirus variant had existed in the U.K. since September and circulated at very low levels until mid-November.

“The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex,” the agency said.

Public Health England says there’s no evidence the new variant is resistant to the Pfizer-BioNTech vaccine, which is now being given across the country to high-priority groups such as health care workers.

An article in The BMJ, a British medical journal, says the variant was first detected by Covid-19 Genomics UK, a consortium that tests the random genetic sequencing of positive COVID-19 samples around the U.K. The variant cases were mostly in the southeast of England.

A University of Birmingham professor said in a Dec. 15 briefing that the variant accounts for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk. “There are no data to suggest it had been imported from abroad, so it is likely to have evolved in the U.K.,” he said.

The variant is named VUI-202012/01, for the first “variant under investigation” in December 2020, BMJ says. It’s defined by a set of 17 mutations, with the most significant mutation in the spike protein the virus uses to bind to the human ACE2 receptor.

“Changes in this part of spike protein may, in theory, result in the virus becoming more infectious and spreading more easily between people,” the article says.

The European Centre for Disease Prevention and Control says the variant emerged during the time of year when people usually socialize more.

“There is no indication at this point of increased infection severity associated with the new variant,” the agency said. “A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.”

Mr. Johnson announced tighter restrictions on England’s hardest-hit areas, such as the southeast and east of England, where new coronavirus cases have continued to rise. And he said people must cut back on their Christmas socializing.

“In England, those living in tier 4 areas should not mix with anyone outside their own household at Christmas, though support bubbles will remain in place for those at particular risk of loneliness or isolation,” he said.

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

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

The pretreatment gut microbiome can determine response to methotrexate therapy in patients with newly diagnosed rheumatoid arthritis, according to recent research published in Arthritis & Rheumatology.

About half of patients do not respond to methotrexate (MTX), despite it being a first-line therapy for RA, according to Alejandro Artacho of the Centro Superior de Investigación en Salud Pública in Valencia, Spain, and colleagues. In addition, there is currently no way to predict which patients will respond to MTX.

Dr. Veena Taneja, a researcher and associate professor in the Department of Immunology and Division of Rheumatology at the Mayo Clinic in Rochester, Minn.

The role of the microbiome in drug response for patients with RA “has been known since it was discovered in 1972 that sulfasalazine requires gut bacteria for its activity,” Veena Taneja, PhD, a researcher and associate professor of immunology at the Mayo Clinic in Rochester, Minn., said in an interview. The microbiome and how it functions “needs to be explored as biomarkers as well as for treatment options for RA and other diseases,” added Dr. Taneja, who was not involved with the study.

Using 16S rRNA gene and shotgun metagenomic sequencing, the researchers evaluated whether the gut microbiome of a patient newly diagnosed with RA (NORA) influenced their response to MTX. The researchers extracted DNA from fecal samples in 26 patients from New York University Langone Medical Center, Lutheran Hospital, Staten Island, and Mount Sinai School of Medicine rheumatology clinics 48 hours prior to treatment with MTX and determined the bacterial taxa, operational taxonomic units (OTUs), and ribosomal sequence variants in each sample. These patients then received oral MTX with an average dose of 20 mg per week (range, 15-25 mg). The patients were grouped based on whether they responded (39%) or did not respond (61%) to MTX based on improvement of at least 1.8 in their Disease Activity Score in 28 joints (DAS28) after 4 months and no need to add a biologic.

Patients with a statistically significantly lower level of microbial diversity (P < .05) as measured by OTU level tended to respond better to MTX therapy. In patients who did not respond to MTX, there was a significantly higher abundance of Firmicutes, a significantly lower abundance of Bacteroidetes (P < .05), and a higher ratio of Firmicutes to Bacteroidetes.

There was also a consistent difference between abundance of gut microbial genes in patients who did not respond to MTX. “Taken together, these results indicate that the gut microbiome of NORA patients that respond favorably to MTX is distinct from that of MTX-NR, prompting us to hypothesize that the pretreatment microbiome could be used to predict clinical nonresponse,” the researchers said.

Using machine learning, Mr. Artacho and colleagues developed a predictive model based on the initial training cohort of 26 patients to assess MTX response. When the researchers tested the model in a validation cohort of 21 patients, they found it correctly predicted 78% of MTX responders and 83.3% of patients who did not respond to MTX, with the percentage of correct predictions increasing “when considering only those patients with the highest probability score of belonging to either group.”

In a separate set of 20 patients with RA who were prescribed either different conventional synthetic disease-modifying antirheumatic drugs or biologics or had not started any medications, the researchers’ model could not predict clinical response, “suggesting that the potential clinical utility of the model is restricted to RA patients that are both drug naive and exposed directly to MTX, but not to other drugs.”

“Our results open the possibility to rationally design microbiome-modulating strategies to improve oral absorption of MTX and its downstream immune effects, inform clinical decision-making or both,” they said.

Clinical application

Dr. Taneja said the findings of the study are novel and intriguing. “The observations suggest a strong influence of [the] host’s microbiome in response to MTX and in future may inform best treatment options for patients. The study speculates that certain microbial clades or microbes can be used to derive a favorable response in patients. This could explain why “one drug fits all” does not apply in treatment for RA,” she said.

The study is also a “step forward” in using the microbiome in regular clinical practice, she noted. “Since MTX is used as a first line of treatment and is one of the most affordable treatments for RA, the observations are definitely exciting.”

In an interview, Martin Kriegel, MD, PhD, of the department of immunobiology at Yale University, New Haven, Conn., and chair of rheumatology and clinical immunology at the University of Münster (Germany), explained that the prediction model has the potential to one day be a tool for clinicians to predict MTX response in patients with RA. However, he noted the researchers did not test a functional link between MTX and gut microbes in vivo.

“It would be useful to test mechanistic effects of MTX on gut microbial communities in vitro and in vivo,” he said. “In addition, it would be informative to apply the prediction model in other cohorts of RA with a different geographic background, possibly also a different duration of disease. If confirmed in a more heterogeneous group of patients, the tool could potentially be used in the clinic to tell some patients that they might not respond to MTX and therefore start therapy with another agent.”

This study was funded by the National Institutes of Health, the Rheumatology Research Foundation, the Searle Scholars Program, various funds from the Spanish government, the UCSF Breakthrough Program for Rheumatoid Arthritis-related Research, and the Arthritis Foundation Center for Excellence. Four authors report consultancies and memberships on scientific advisory boards with pharmaceutical and biotechnology companies that do not overlap with the current study.

Dr. Taneja reported that her institution holds a patent for developing Prevotella histicola as an anti-inflammatory treatment, of which she is a coinventor. Evelo Biosciences is a licensee for the patent, and Dr. Taneja reported receiving research support from the company. Dr. Kriegel reported receiving salary, consulting fees, honoraria, or research funds from AbbVie, Bristol-Myers Squibb, Cell Applications, Eligo Bioscience, and Roche. He also holds a patent on the use of antibiotics and commensal vaccination to treat autoimmunity.

SOURCE: Artacho A et al. Arthritis Rheumatol. 2020 Dec 13. doi: 10.1002/art.41622.

About twice as many patients were admitted to hospitals in France for COVID-19 during a 2-month period than were admitted for seasonal influenza during a 3-month period the previous year, according to a study published online in The Lancet Respiratory Medicine.

In-hospital mortality was nearly three times higher for COVID-19 than for seasonal influenza, researchers found. In addition, patients with COVID-19 were more likely to require invasive mechanical ventilation (9.7% vs. 4%) and had longer average ICU stays (15 days vs. 8 days).

“SARS-CoV-2 appears to have a higher potential for respiratory pathogenicity, leading to more respiratory complications in patients with fewer comorbidities, and it is associated with a higher risk of mortality, particularly in adolescents, although any conclusions for this age group must be treated with caution considering the small number of deaths,” wrote Lionel Piroth, MD, PhD, of the infectious diseases department, Dijon (France) University Hospital, and colleagues.

The study “is the largest to date to compare the two diseases and confirms that COVID-19 is far more serious than the flu,” study author Catherine Quantin, MD, PhD, said in a news release. “The finding that the COVID-19 death rate was three times higher than for seasonal influenza is particularly striking when reminded that the 2018/2019 flu season had been the worst in the past five years in France in terms of number of deaths,” continued Dr. Quantin, who jointly led the research. She is affiliated with the University Hospital of Dijon and Inserm.

The investigators analyzed data from a national database and compared 89,530 COVID-19 hospital admissions between March 1 and April 30, 2020, with 45,819 seasonal flu hospital admissions between Dec. 1, 2018, and Feb. 28, 2019.

The death rate was 16.9% among patients hospitalized with COVID-19, compared with 5.8% among patients hospitalized with influenza.

Fewer patients younger 18 years were hospitalized with COVID-19 than with seasonal influenza (1.4% vs. 19.5%; 1,227 vs. 8,942), but a larger proportion of those younger than 5 years required intensive care for COVID-19 (2.9% vs. 0.9%). The fatality rates in children younger than 5 years were similar for both groups (0.5% vs. 0.2%).

Among patients aged 11-17 years, 5 of 548 (1.1%) patients with COVID-19 died, compared with 1 of 804 (0.1%) patients with flu.

Testing practices for influenza likely varied across hospitals, whereas testing for COVID-19 may have been more standardized. This could be a limitation of the study, the researchers noted. In addition, flu seasons vary year to year, and influenza cases may depend on vaccination coverage and residual population immunity.

“The large sample size is an important strength of the study and it is assumed that the indication for hospital admission in the two periods was the same and thus does not bias the results,” Eskild Petersen, MD, DMsc, wrote in a comment accompanying the study. “The results ... clearly show that COVID-19 is more serious than seasonal influenza.”

Furthermore, this study and prior research show that “COVID-19 is not an innocent infection in children and adolescents,” said Dr. Petersen, who is affiliated with the University of Aarhus in Denmark and the European Society for Clinical Microbiology and Infectious Diseases Emerging Infections Task Force.

The study was funded by the French National Research Agency. Two authors have various financial ties to several pharmaceutical companies, details of which are available in the journal article. Dr. Petersen has disclosed no relevant financial relationships.

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

About twice as many patients were admitted to hospitals in France for COVID-19 during a 2-month period than were admitted for seasonal influenza during a 3-month period the previous year, according to a study published online in The Lancet Respiratory Medicine.

In-hospital mortality was nearly three times higher for COVID-19 than for seasonal influenza, researchers found. In addition, patients with COVID-19 were more likely to require invasive mechanical ventilation (9.7% vs. 4%) and had longer average ICU stays (15 days vs. 8 days).

“SARS-CoV-2 appears to have a higher potential for respiratory pathogenicity, leading to more respiratory complications in patients with fewer comorbidities, and it is associated with a higher risk of mortality, particularly in adolescents, although any conclusions for this age group must be treated with caution considering the small number of deaths,” wrote Lionel Piroth, MD, PhD, of the infectious diseases department, Dijon (France) University Hospital, and colleagues.

The study “is the largest to date to compare the two diseases and confirms that COVID-19 is far more serious than the flu,” study author Catherine Quantin, MD, PhD, said in a news release. “The finding that the COVID-19 death rate was three times higher than for seasonal influenza is particularly striking when reminded that the 2018/2019 flu season had been the worst in the past five years in France in terms of number of deaths,” continued Dr. Quantin, who jointly led the research. She is affiliated with the University Hospital of Dijon and Inserm.

The investigators analyzed data from a national database and compared 89,530 COVID-19 hospital admissions between March 1 and April 30, 2020, with 45,819 seasonal flu hospital admissions between Dec. 1, 2018, and Feb. 28, 2019.

The death rate was 16.9% among patients hospitalized with COVID-19, compared with 5.8% among patients hospitalized with influenza.

Fewer patients younger 18 years were hospitalized with COVID-19 than with seasonal influenza (1.4% vs. 19.5%; 1,227 vs. 8,942), but a larger proportion of those younger than 5 years required intensive care for COVID-19 (2.9% vs. 0.9%). The fatality rates in children younger than 5 years were similar for both groups (0.5% vs. 0.2%).

Among patients aged 11-17 years, 5 of 548 (1.1%) patients with COVID-19 died, compared with 1 of 804 (0.1%) patients with flu.

Testing practices for influenza likely varied across hospitals, whereas testing for COVID-19 may have been more standardized. This could be a limitation of the study, the researchers noted. In addition, flu seasons vary year to year, and influenza cases may depend on vaccination coverage and residual population immunity.

“The large sample size is an important strength of the study and it is assumed that the indication for hospital admission in the two periods was the same and thus does not bias the results,” Eskild Petersen, MD, DMsc, wrote in a comment accompanying the study. “The results ... clearly show that COVID-19 is more serious than seasonal influenza.”

Furthermore, this study and prior research show that “COVID-19 is not an innocent infection in children and adolescents,” said Dr. Petersen, who is affiliated with the University of Aarhus in Denmark and the European Society for Clinical Microbiology and Infectious Diseases Emerging Infections Task Force.

The study was funded by the French National Research Agency. Two authors have various financial ties to several pharmaceutical companies, details of which are available in the journal article. Dr. Petersen has disclosed no relevant financial relationships.

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

About twice as many patients were admitted to hospitals in France for COVID-19 during a 2-month period than were admitted for seasonal influenza during a 3-month period the previous year, according to a study published online in The Lancet Respiratory Medicine.

In-hospital mortality was nearly three times higher for COVID-19 than for seasonal influenza, researchers found. In addition, patients with COVID-19 were more likely to require invasive mechanical ventilation (9.7% vs. 4%) and had longer average ICU stays (15 days vs. 8 days).

“SARS-CoV-2 appears to have a higher potential for respiratory pathogenicity, leading to more respiratory complications in patients with fewer comorbidities, and it is associated with a higher risk of mortality, particularly in adolescents, although any conclusions for this age group must be treated with caution considering the small number of deaths,” wrote Lionel Piroth, MD, PhD, of the infectious diseases department, Dijon (France) University Hospital, and colleagues.

The study “is the largest to date to compare the two diseases and confirms that COVID-19 is far more serious than the flu,” study author Catherine Quantin, MD, PhD, said in a news release. “The finding that the COVID-19 death rate was three times higher than for seasonal influenza is particularly striking when reminded that the 2018/2019 flu season had been the worst in the past five years in France in terms of number of deaths,” continued Dr. Quantin, who jointly led the research. She is affiliated with the University Hospital of Dijon and Inserm.

The investigators analyzed data from a national database and compared 89,530 COVID-19 hospital admissions between March 1 and April 30, 2020, with 45,819 seasonal flu hospital admissions between Dec. 1, 2018, and Feb. 28, 2019.

The death rate was 16.9% among patients hospitalized with COVID-19, compared with 5.8% among patients hospitalized with influenza.

Fewer patients younger 18 years were hospitalized with COVID-19 than with seasonal influenza (1.4% vs. 19.5%; 1,227 vs. 8,942), but a larger proportion of those younger than 5 years required intensive care for COVID-19 (2.9% vs. 0.9%). The fatality rates in children younger than 5 years were similar for both groups (0.5% vs. 0.2%).

Among patients aged 11-17 years, 5 of 548 (1.1%) patients with COVID-19 died, compared with 1 of 804 (0.1%) patients with flu.

Testing practices for influenza likely varied across hospitals, whereas testing for COVID-19 may have been more standardized. This could be a limitation of the study, the researchers noted. In addition, flu seasons vary year to year, and influenza cases may depend on vaccination coverage and residual population immunity.

“The large sample size is an important strength of the study and it is assumed that the indication for hospital admission in the two periods was the same and thus does not bias the results,” Eskild Petersen, MD, DMsc, wrote in a comment accompanying the study. “The results ... clearly show that COVID-19 is more serious than seasonal influenza.”

Furthermore, this study and prior research show that “COVID-19 is not an innocent infection in children and adolescents,” said Dr. Petersen, who is affiliated with the University of Aarhus in Denmark and the European Society for Clinical Microbiology and Infectious Diseases Emerging Infections Task Force.

The study was funded by the French National Research Agency. Two authors have various financial ties to several pharmaceutical companies, details of which are available in the journal article. Dr. Petersen has disclosed no relevant financial relationships.

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

Moderna’s COVID-19 vaccine — the second now cleared for emergency use in the United States — was endorsed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) on December 19.

The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.

On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.

Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.

“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.

“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA  “represents progress towards ending this horrific pandemic,” she said.

In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.

ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”

Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.

ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.

Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.

There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.

“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”

Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.

V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.

“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.

Anaphylaxis concerns

The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.

Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.

People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.

Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.

“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.

Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.

Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.

“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.

The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.

The other panel members have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Moderna’s COVID-19 vaccine — the second now cleared for emergency use in the United States — was endorsed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) on December 19.

The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.

On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.

Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.

“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.

“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA  “represents progress towards ending this horrific pandemic,” she said.

In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.

ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”

Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.

ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.

Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.

There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.

“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”

Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.

V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.

“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.

Anaphylaxis concerns

The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.

Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.

People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.

Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.

“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.

Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.

Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.

“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.

The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.

The other panel members have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Moderna’s COVID-19 vaccine — the second now cleared for emergency use in the United States — was endorsed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) on December 19.

The panel voted 11-0, with three recusals, to recommend use of Moderna’s vaccine for people aged 18 years and older, while seeking more information on risk for anaphylaxis. This vote followed the December 18th decision by the US Food and Drug Administration (FDA) to grant emergency use authorization (EUA) for the vaccine, known as mRNA-1273.

On December 11, the FDA granted the first US emergency clearance for a COVID-19 vaccine to the Pfizer-BioNTech product. ACIP met the following day and voted to endorse the use of that vaccine, with a vote of 11-0 and three recusals. The Pfizer-BioNTech COVID-19 vaccine is recommended for use in people aged 16 years and older.

Moderna’s vaccine is expected to help curb the pandemic, with clinical trial data showing a 94.1% efficacy rate. But there’s also concerns about side effects noted in testing of both vaccines and in the early rollout of the Pfizer vaccine, particularly anaphylaxis.

“There are likely going to be lots of bumps in the road” with the introduction of the COVID-19 vaccines, but these are being disclosed to the public in a way that is “fair and transparent,” said ACIP member Beth P. Bell, MD, MPH.

“Our systems so far appear to be doing what they are supposed to do” in terms of determining risks from the COVID-19 vaccine, added Bell, who is a clinical professor in the department of global health at the University of Washington’s School of Public Health in Seattle. The Moderna EUA  “represents progress towards ending this horrific pandemic,” she said.

In a new forecast released this week, the CDC projects that the number of newly reported COVID-19 deaths will likely increase over the next 4 weeks, with 15,800 to 27,700 new deaths likely to be reported in the week ending January 9, 2021. That could bring the total number of COVID-19 deaths in the United States to between 357,000 and 391,000 by this date, according to the agency.

ACIP panelist Lynn Bahta, RN, MPH, CPH, said she had been “eager” to have the panel proceed with its endorsement of the Moderna vaccine, “especially in light of the fact that we are seeing an average 2600 deaths a day.”

Having two COVID-19 vaccines available might help slow down the pandemic, “despite the fact that we still have a lot to learn both about the disease and the vaccine,” said Bahta, who is an immunization consultant with the Minnesota Department of Health in Saint Paul.

ACIP members encouraged Moderna officials who presented at the meeting to continue studies for potential complications associated with the vaccine when given to women who are pregnant or breastfeeding.

Panelists also pressed for more data on the risk for Bell’s palsy, which the FDA staff also had noted in the agency’s review of Moderna’s vaccine. Moderna has reported four cases from a pivotal study, one in the placebo group and three among study participants who received the company’s vaccine. These cases occurred between 15 and 33 days after vaccination, and are all resolved or resolving, according to Moderna.

There was also a question raised about how many doses of vaccine might be squeezed out of a vial. CDC will explore this topic further at its meeting on COVID-19 vaccines December 20, said Nancy Messonnier, MD, director of the agency’s National Center for Immunization and Respiratory Diseases, at the Saturday meeting.

“In this time of public health crisis, none of us would want to squander a single dose of a vaccine that’s potentially lifesaving,” CDC’s Messonnier said. “We’re going to plan to have a short discussion of that issue tomorrow.”

Messonnier also responded to a comment made during the meeting about cases where people who received COVID-19 vaccine were unaware of the CDC’s V-safe tool.

V-safe is a smartphone-based tool that uses text messaging and web surveys to help people keep in touch with the medical community after getting the COVID-19 vaccine and is seen as a way to help spot side effects. Messonnier asked that people listening to the webcast of the ACIP meeting help spread the word about the CDC’s V-safe tool.

“Our perception, based on the number of people who have enrolled in V-safe, is that the message is getting out to many places, but even one site that doesn’t have this information is something that we want to try to correct,” she said.

Anaphylaxis concerns

The chief concern for ACIP members and CDC staff about COVID-19 vaccines appeared to be reports of allergic reactions. Thomas Clark, MD, MPH, a CDC staff member, told the ACIP panel that, as of December 18, the agency had identified six cases of anaphylaxis following administration of the Pfizer-BioNTech vaccine that met a certain standard, known as the Brighton Collaboration criteria.

Additional case reports have been reviewed and determined not to be anaphylaxis, Clark said. All suspect cases were identified through processes such as the federal Vaccine Adverse Event Reporting System (VAERS), he said.

People who experience anaphylaxis following COVID-19 vaccination should not receive additional doses of the shot, Clark said in his presentation to ACIP. Members of the panel asked Clark whether there have been any discernible patterns to these cases, such as geographic clusters.

Clark replied that it was “early” in the process to make reports, with investigations still ongoing. He did note that the people who had anaphylaxis following vaccination had received their doses from more than one production lot, with multiple lots having been distributed.

“You folks may have seen in the news a couple of cases from Alaska, but we’ve had reports from other jurisdictions so there’s no obvious clustering geographically,” Clark said.

Another CDC staff member, Sarah Mbaeyi, MD, MPH, noted in her presentation that there should be an observation period of 30 minutes following COVID-19 vaccination for anyone with a history of anaphylaxis for any reason, and of at least 15 minutes for other recipients.

Disclosure of ingredients used in the COVID-19 vaccines might help people with an allergy assess these products, the representative for the American Medical Association, Sandra Fryhofer, MD, told ACIP. As such, she thanked CDC’s Mbaeyi for including a breakout of ingredients in her presentation to the panel. Fryhofer encouraged Moderna officials to be as transparent as possible in disclosing the ingredients of the company’s COVID-19 vaccine.

“That might be important because I think it’s very essential that we figure out what might be triggering these anaphylactic reactions, because that is definitely going to affect the vaccine implementation,” Fryhofer said.

The three ACIP members who had conflicts that prevented their voting were Robert L. Atmar, MD, who said at the Saturday meeting he had participated in COVID-19 trials, including research on the Moderna vaccine; Sharon E. Frey, MD, who said at the Saturday meeting that she had been involved with research on COVID-19 vaccines, including Moderna’s; and Paul Hunter, MD, who said he has received a grant from Pfizer for pneumococcal vaccines.

The other panel members have reported no relevant financial relationships.

This article first appeared on Medscape.com.

As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18. The vaccine becomes the second authorized for emergency use in the United States, and will likely increase the number of vaccine doses available in the coming days.

There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.

The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.

Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).

The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.


Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.

“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”

“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.

Ramping up healthcare provider immunizations

“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.

“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.

The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.

Unanswered questions remain

Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”

Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”

“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.

Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.

Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.  

“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”

“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.

During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.

“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.

Advantages beyond the numbers?

“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”

“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”

Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.

In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.

As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.

“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.

She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”

Future outlook

Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”

“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”

“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”

“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”

Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.

“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”

El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.

This article first appeared on Medscape.com.

As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18. The vaccine becomes the second authorized for emergency use in the United States, and will likely increase the number of vaccine doses available in the coming days.

There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.

The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.

Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).

The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.


Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.

“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”

“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.

Ramping up healthcare provider immunizations

“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.

“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.

The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.

Unanswered questions remain

Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”

Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”

“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.

Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.

Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.  

“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”

“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.

During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.

“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.

Advantages beyond the numbers?

“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”

“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”

Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.

In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.

As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.

“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.

She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”

Future outlook

Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”

“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”

“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”

“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”

Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.

“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”

El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.

This article first appeared on Medscape.com.

As expected, the US Food and Drug Administration granted Moderna an emergency use authorization (EUA) for its messenger RNA COVID-19 vaccine December 18. The vaccine becomes the second authorized for emergency use in the United States, and will likely increase the number of vaccine doses available in the coming days.

There is one final step — the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices will need to recommend its use, as it did 2 days after the Pfizer/BioNTech mRNA vaccine received its EUA on December 10.

The EUA for the Moderna vaccine is “a major milestone in trying to contain this pandemic,” Hana Mohammed El Sahly, MD, told Medscape Medical News.

Scaling up distribution of the two vaccine products will come next. She notes that even under less emergent conditions, making sure people who need a vaccine receive it can be hard. “I hope the media attention around this will make more people aware that there are vaccines that might help them,” said El Sahly, chair of the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC).

The EUA for the Moderna vaccine follows a review by the independent VRBPAC members on December 17, which voted 20-0 with one abstention to recommend the EUA. The vaccine is authorized for use in people 18 and older.


Emergency approval of a second COVID-19 vaccine “is great — we need all the tools we can to fight this pandemic,” Stephen Schrantz, MD, infectious disease specialist and assistant professor of medicine at the University of Chicago, told Medscape Medical News. “The early data coming from Moderna looks good, and I agree with the FDA that an EUA is indicated.

“It’s incumbent upon all us healthcare professionals to put ourselves out there as supporting this vaccine and supporting people getting it,” Schrantz continued. “We want to make sure people who are on the fence understand this is a safe vaccine that has been vetted appropriately through the FDA and through phase 3 clinical trials.”

“I know the critical role physicians play as vaccine influencers,” AMA President Susan Bailey, MD, said during a December 14 webinar for journalists reporting on COVID-19 vaccines. “We have to continue to do what physicians have always done: review the evidence and trust the science. Lives are at stake.” The webinar was cosponsored by the AMA and the Poynter Institute.

Ramping up healthcare provider immunizations

“I am very excited to see the FDA’s positive review of the Moderna vaccine. We have been waiting to have another vaccine we can use for healthcare workers and staff, and now we have it,” Aneesh Mehta, MD, of Emory University School of Medicine in Atlanta, Georgia, told Medscape Medical News.

“We had been hoping for a vaccine with a 70% or 80% efficacy, and to see two vaccines now with greater than 90% efficacy is remarkable,” he added.

The efficacy levels associated with both mRNA vaccines “did exceed expectations for sure — this is not what we built the studies around. It was surprising in the good sense of the word,” said El Sahly, who is also associate professor of molecular virology and microbiology at Baylor College of Medicine in Houston, Texas.

Unanswered questions remain

Schrantz likewise said the high efficacy rate was important but not all that is needed. “[W]hat we know about this vaccine is it is very effective at preventing disease. We don’t have any understanding at this time whether or not these vaccines prevent infection and transmissibility.”

Bailey said, “The jury is still out on whether or not you can still transmit the virus after you’ve had the vaccine. Hopefully not, but we don’t really know that for sure.”

“It’s risky to think that once you get the shot in your arm everything goes back to normal. It doesn’t,” Bailey added.

Another unknown is the duration of protection following immunization. The Pfizer and Moderna products “have similar constructs, seem to have a reasonable safety profile, and excellent short-term efficacy,” El Sahly said. She cautioned, however, that long-term efficacy still needs to be determined.

Whether any rare adverse events will emerge in the long run is another question. Answers could come over time from the ongoing phase 3 trials, as well as from post-EUA surveillance among vaccine recipients.  

“Our work is not done after issuing an EUA,” FDA Commissioner Stephen Hahn, MD, said in a JAMA webinar on December 14. The FDA is closely monitoring for any adverse event rates above the normal background incidence. “We are going to be transparent about it if we are seeing anything that is not at base level.”

“The key is to be humble, keep your eyes open and know that once the vaccine is out there, there may be things we learn that we don’t know now. That is true for virtually any medical innovation,” Paul Offit, MD, director of The Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA VRBPAC, said during the AMA/Poynter Institute webinar.

During the same webinar, an attendee asked about prioritizing immunization for spouses and family members of healthcare workers. “My husband wants to know that too,” replied Patricia A. Stinchfield, APRN, CNP, pediatric nurse practitioner in infectious diseases at Children’s Minnesota, St. Paul.

“It is true we should be thinking about our healthcare workers’ family members. But at this point in time we just don’t have the supplies to address it that way,” said Stinchfield, who is also the president-elect of the National Foundation for Infectious Diseases.

Advantages beyond the numbers?

“The major advantage of having two vaccines is sheer volume,” Mehta said. An additional advantage of more than one product is the potential to offer an option when a specific vaccine is contraindicated. “We could offer someone a different vaccine…similar to what we do with the influenza vaccine.”

“The more the merrier in terms of having more vaccine products,” Schrantz said. Despite differences in shipping, storage, minimum age requirements, and dosing intervals, the Pfizer and Moderna vaccines are very similar, he said. “Really the only difference between these two vaccines is the proprietary lipid nanoparticle — the delivery vehicle if you will.”

Both vaccines “appear very similar in their capacity to protect against disease, to protect [people in] various racial and ethnic backgrounds, and in their capacity to protect against severe disease,” Offit said.

In terms of vaccines in the development pipeline, “We don’t know but we might start to see a difference with the Johnson & Johnson vaccine or the Janssen vaccine, which are single dose. They might confer some advantages, but we are waiting on the safety and efficacy data,” Schrantz said.

As a two-dose vaccine, the AstraZeneca product does not offer an advantage on the dosing strategy, “but it is easier to transport than the mRNA vaccines,” he said. Some concerns with the initial data on the AstraZeneca vaccine will likely need to be addressed before the company applies for an EUA, Schrantz added.

“That is an important question,” El Sahly said. The ongoing studies should provide more data from participants of all ages and ethnic backgrounds that “will allow us to make a determination as to whether there is any difference between these two vaccines.

She added that the Pfizer and Moderna vaccines seem comparable from the early data. “We’ll see if this stands in the long run.”

Future outlook

Now that the FDA approved emergency use of two COVID-19 vaccines, “we need each state to quickly implement their plans to get the vaccines into the hands of providers who need to give the vaccines,” Mehta said. “We are seeing very effective rollout in multiple regions of the country. And we hope to see that continue as we get more vaccines from manufacturers over the coming months.”

“Within a year of identifying the sequence of this virus we have two large clinical vaccine trials that show efficacy,” Offit said. “That was an amazing technologic accomplishment, but now comes the hard part. Mass producing this vaccine, getting it out there, making sure everybody who most benefits gets it, is going to be really, really hard.”

“But I’m optimistic,” Offit said. “If we can do this by next Thanksgiving, we’re going to see a dramatic drop in the number of cases, hospitalizations and deaths, and we can get our lives back together again.”

“My greatest hope is that a year from now we look back and realize we did something really amazing together,” Bailey said, “and we have a feeling of accomplishment and appreciation for all the hard work that has been done.”

Mehta shared the important message he shares when walking around the hospital: “While these vaccines are coming and they are very promising, we need to continue to remember the 3 Ws: wearing a mask, washing your hands, and watching your distance,” he said.

“With the combination of those 3Ws and those vaccines, we will hopefully come through this COVID pandemic.”

El Sahly receives funding through the NIH for her research, including her role as co-chair of the Moderna vaccine phase 3 clinical trial. Schrantz is a site investigator for the Moderna and Janssen vaccine trials. Mehta also receives funding through the NIH. None of these experts had any relevant financial disclosures.

This article first appeared on Medscape.com.

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577