The Hospitalist

Serious neurologic complications in patients with COVID-19 are not limited to the severely ill, new research confirms.

“We found a range of neurologic diagnoses, including stroke and seizures, among hospitalized patients with COVID-19 and the majority were not critically ill, suggesting that these complications are not limited just to those patients who require ICU care or a ventilator,” study investigator Pria Anand, MD, division of neuro-infectious diseases, Boston University, said in an interview.

The study was published online Dec. 9 in Neurology Clinical Practice.
 

‘Moderately severe’ disability

For the study, the investigators reviewed the medical records of 74 adults (mean age, 64 years) who were hospitalized with COVID-19 and evaluated for neurologic conditions at Boston Medical Center, a safety-net hospital caring primarily for underserved, low-income, racial and ethnic minority populations.

The most common COVID-19 symptoms on arrival to the hospital were cough (39%), dyspnea (36%), and fever (34%). Eleven patients required intubation (15%) and 28 required some form of supplemental oxygen (38%). Thirty-four patients required intensive care (46%).

The most common neurologic COVID-19 symptoms at presentation were altered mental status (53%), myalgia (24%), fatigue (24%), and headache (18%). 

After neurologic assessment, the most common final neurologic diagnosis was multifactorial or toxic-metabolic encephalopathy (35%), followed by seizure (20%), ischemic stroke (20%), primary movement disorder (9%), peripheral neuropathy (8%), and hemorrhagic stroke (4%).

Three patients (4%) suffered traumatic brain injuries after falling in their homes after developing COVID-19.

Ten (14%) patients died in the hospital. Survivors had “moderately severe” disability at discharge (median modified Rankin Scale score of 4 from a preadmission mRS score of 2) and many were discharged to nursing facilities or rehabilitation hospitals.

“Although we do not have data on their posthospital course, this suggests that patients with neurologic complications of COVID-19 are likely to require ongoing rehabilitation, even after they leave the hospital,” Dr. Anand, a member of the American Academy of Neurology, said in an interview.

“There are a diverse range of mechanisms by which COVID-19 can cause neurologic complications,” Dr. Anand said.

“These complications can result from the body’s immunological response to the virus (e.g., Guillain-Barré syndrome, an autoimmune disorder affecting the nerves), from having a systemic severe illness (e.g., brain injury as a result of insufficient oxygenation), from the increased tendency to form blood clots (e.g., stroke), from worsening of preexisting neurologic disorders, and possibly from involvement of the nervous system by the virus itself,” she explained.

The researchers said more study is needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.
 

Lingering issues

In an interview, Kenneth L. Tyler, MD, chair of neurology, University of Colorado, Denver, noted that this is one of the larger series published to date of the neurologic complications associated with COVID-19, and the first to come from a U.S. safety-net hospital in a large metropolitan area.

“Overall, the types and categories of neurological complications reported including encephalopathy (35%) and acute cerebrovascular events (~20%) are similar to those reported elsewhere,” said Dr. Tyler.

However, the frequency of stroke (~20%) is higher than in some other reports, “likely reflecting the comorbidities such as diabetes, hypertension, limited access to care [that are] present in this population,” he said.

Dr. Tyler also noted that the “relatively high frequency” of primary movement disorders, notably myoclonus, “hasn’t been particularly well recognized or described, although one of the authors has written on this in COVID-19, so perhaps there is a bit of an ‘ascertainment bias’ – as they were looking harder for it?”

Finally, he noted, it’s important to understand that all the published studies “vary tremendously in the populations they examine, so direct comparisons can be difficult.”

Also weighing in on the report in an interview, Richard Temes, MD, director, Northwell Health’s Center for Neurocritical Care in Manhasset, N.Y., said neurologic problems have been noted since the start of COVID-19 and have been well described.

“It’s common for patients to present with very nonspecific neurological complaints like confusion, disorientation, altered mental status, lethargy, but also neurological disease such as strokes, brain hemorrhages, and seizures are quite common as well,” said Dr. Temes. 

He also noted that a number of patients with COVID-19 will have “lingering effects, especially patients who are hospitalized, that can range from memory deficit, cognitive slowing, and trouble with activities of daily living and depression.

“These effects can occur with any patient who is hospitalized for a [significant] period of time, especially in the intensive care unit, so it’s hard to tease out whether or not this is truly from COVID itself or if it’s just being a survivor from a very severe, critical illness. We don’t know yet. We need more data on that,” he cautioned.
 

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

Serious neurologic complications in patients with COVID-19 are not limited to the severely ill, new research confirms.

“We found a range of neurologic diagnoses, including stroke and seizures, among hospitalized patients with COVID-19 and the majority were not critically ill, suggesting that these complications are not limited just to those patients who require ICU care or a ventilator,” study investigator Pria Anand, MD, division of neuro-infectious diseases, Boston University, said in an interview.

The study was published online Dec. 9 in Neurology Clinical Practice.
 

‘Moderately severe’ disability

For the study, the investigators reviewed the medical records of 74 adults (mean age, 64 years) who were hospitalized with COVID-19 and evaluated for neurologic conditions at Boston Medical Center, a safety-net hospital caring primarily for underserved, low-income, racial and ethnic minority populations.

The most common COVID-19 symptoms on arrival to the hospital were cough (39%), dyspnea (36%), and fever (34%). Eleven patients required intubation (15%) and 28 required some form of supplemental oxygen (38%). Thirty-four patients required intensive care (46%).

The most common neurologic COVID-19 symptoms at presentation were altered mental status (53%), myalgia (24%), fatigue (24%), and headache (18%). 

After neurologic assessment, the most common final neurologic diagnosis was multifactorial or toxic-metabolic encephalopathy (35%), followed by seizure (20%), ischemic stroke (20%), primary movement disorder (9%), peripheral neuropathy (8%), and hemorrhagic stroke (4%).

Three patients (4%) suffered traumatic brain injuries after falling in their homes after developing COVID-19.

Ten (14%) patients died in the hospital. Survivors had “moderately severe” disability at discharge (median modified Rankin Scale score of 4 from a preadmission mRS score of 2) and many were discharged to nursing facilities or rehabilitation hospitals.

“Although we do not have data on their posthospital course, this suggests that patients with neurologic complications of COVID-19 are likely to require ongoing rehabilitation, even after they leave the hospital,” Dr. Anand, a member of the American Academy of Neurology, said in an interview.

“There are a diverse range of mechanisms by which COVID-19 can cause neurologic complications,” Dr. Anand said.

“These complications can result from the body’s immunological response to the virus (e.g., Guillain-Barré syndrome, an autoimmune disorder affecting the nerves), from having a systemic severe illness (e.g., brain injury as a result of insufficient oxygenation), from the increased tendency to form blood clots (e.g., stroke), from worsening of preexisting neurologic disorders, and possibly from involvement of the nervous system by the virus itself,” she explained.

The researchers said more study is needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.
 

Lingering issues

In an interview, Kenneth L. Tyler, MD, chair of neurology, University of Colorado, Denver, noted that this is one of the larger series published to date of the neurologic complications associated with COVID-19, and the first to come from a U.S. safety-net hospital in a large metropolitan area.

“Overall, the types and categories of neurological complications reported including encephalopathy (35%) and acute cerebrovascular events (~20%) are similar to those reported elsewhere,” said Dr. Tyler.

However, the frequency of stroke (~20%) is higher than in some other reports, “likely reflecting the comorbidities such as diabetes, hypertension, limited access to care [that are] present in this population,” he said.

Dr. Tyler also noted that the “relatively high frequency” of primary movement disorders, notably myoclonus, “hasn’t been particularly well recognized or described, although one of the authors has written on this in COVID-19, so perhaps there is a bit of an ‘ascertainment bias’ – as they were looking harder for it?”

Finally, he noted, it’s important to understand that all the published studies “vary tremendously in the populations they examine, so direct comparisons can be difficult.”

Also weighing in on the report in an interview, Richard Temes, MD, director, Northwell Health’s Center for Neurocritical Care in Manhasset, N.Y., said neurologic problems have been noted since the start of COVID-19 and have been well described.

“It’s common for patients to present with very nonspecific neurological complaints like confusion, disorientation, altered mental status, lethargy, but also neurological disease such as strokes, brain hemorrhages, and seizures are quite common as well,” said Dr. Temes. 

He also noted that a number of patients with COVID-19 will have “lingering effects, especially patients who are hospitalized, that can range from memory deficit, cognitive slowing, and trouble with activities of daily living and depression.

“These effects can occur with any patient who is hospitalized for a [significant] period of time, especially in the intensive care unit, so it’s hard to tease out whether or not this is truly from COVID itself or if it’s just being a survivor from a very severe, critical illness. We don’t know yet. We need more data on that,” he cautioned.
 

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

Serious neurologic complications in patients with COVID-19 are not limited to the severely ill, new research confirms.

“We found a range of neurologic diagnoses, including stroke and seizures, among hospitalized patients with COVID-19 and the majority were not critically ill, suggesting that these complications are not limited just to those patients who require ICU care or a ventilator,” study investigator Pria Anand, MD, division of neuro-infectious diseases, Boston University, said in an interview.

The study was published online Dec. 9 in Neurology Clinical Practice.
 

‘Moderately severe’ disability

For the study, the investigators reviewed the medical records of 74 adults (mean age, 64 years) who were hospitalized with COVID-19 and evaluated for neurologic conditions at Boston Medical Center, a safety-net hospital caring primarily for underserved, low-income, racial and ethnic minority populations.

The most common COVID-19 symptoms on arrival to the hospital were cough (39%), dyspnea (36%), and fever (34%). Eleven patients required intubation (15%) and 28 required some form of supplemental oxygen (38%). Thirty-four patients required intensive care (46%).

The most common neurologic COVID-19 symptoms at presentation were altered mental status (53%), myalgia (24%), fatigue (24%), and headache (18%). 

After neurologic assessment, the most common final neurologic diagnosis was multifactorial or toxic-metabolic encephalopathy (35%), followed by seizure (20%), ischemic stroke (20%), primary movement disorder (9%), peripheral neuropathy (8%), and hemorrhagic stroke (4%).

Three patients (4%) suffered traumatic brain injuries after falling in their homes after developing COVID-19.

Ten (14%) patients died in the hospital. Survivors had “moderately severe” disability at discharge (median modified Rankin Scale score of 4 from a preadmission mRS score of 2) and many were discharged to nursing facilities or rehabilitation hospitals.

“Although we do not have data on their posthospital course, this suggests that patients with neurologic complications of COVID-19 are likely to require ongoing rehabilitation, even after they leave the hospital,” Dr. Anand, a member of the American Academy of Neurology, said in an interview.

“There are a diverse range of mechanisms by which COVID-19 can cause neurologic complications,” Dr. Anand said.

“These complications can result from the body’s immunological response to the virus (e.g., Guillain-Barré syndrome, an autoimmune disorder affecting the nerves), from having a systemic severe illness (e.g., brain injury as a result of insufficient oxygenation), from the increased tendency to form blood clots (e.g., stroke), from worsening of preexisting neurologic disorders, and possibly from involvement of the nervous system by the virus itself,” she explained.

The researchers said more study is needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.
 

Lingering issues

In an interview, Kenneth L. Tyler, MD, chair of neurology, University of Colorado, Denver, noted that this is one of the larger series published to date of the neurologic complications associated with COVID-19, and the first to come from a U.S. safety-net hospital in a large metropolitan area.

“Overall, the types and categories of neurological complications reported including encephalopathy (35%) and acute cerebrovascular events (~20%) are similar to those reported elsewhere,” said Dr. Tyler.

However, the frequency of stroke (~20%) is higher than in some other reports, “likely reflecting the comorbidities such as diabetes, hypertension, limited access to care [that are] present in this population,” he said.

Dr. Tyler also noted that the “relatively high frequency” of primary movement disorders, notably myoclonus, “hasn’t been particularly well recognized or described, although one of the authors has written on this in COVID-19, so perhaps there is a bit of an ‘ascertainment bias’ – as they were looking harder for it?”

Finally, he noted, it’s important to understand that all the published studies “vary tremendously in the populations they examine, so direct comparisons can be difficult.”

Also weighing in on the report in an interview, Richard Temes, MD, director, Northwell Health’s Center for Neurocritical Care in Manhasset, N.Y., said neurologic problems have been noted since the start of COVID-19 and have been well described.

“It’s common for patients to present with very nonspecific neurological complaints like confusion, disorientation, altered mental status, lethargy, but also neurological disease such as strokes, brain hemorrhages, and seizures are quite common as well,” said Dr. Temes. 

He also noted that a number of patients with COVID-19 will have “lingering effects, especially patients who are hospitalized, that can range from memory deficit, cognitive slowing, and trouble with activities of daily living and depression.

“These effects can occur with any patient who is hospitalized for a [significant] period of time, especially in the intensive care unit, so it’s hard to tease out whether or not this is truly from COVID itself or if it’s just being a survivor from a very severe, critical illness. We don’t know yet. We need more data on that,” he cautioned.
 

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

Among people hospitalized with COVID-19, a combination of baricitinib and remdesivir reduces the median time to recovery, compared with remdesivir plus placebo, according to trial results published Dec. 11 in the New England Journal of Medicine.

Median time to recovery was 7 days for patients who received baricitinib versus 8 days for patients who received placebo.

The difference was greater in patients who required high-flow oxygen or noninvasive ventilation during their hospitalization. In this group, baricitinib shortened median time to recovery from 18 days to 10 days.

“Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status, notably among patients receiving high-flow oxygen or noninvasive mechanical ventilation,” reported Andre C. Kalil, MD, MPH, from the University of Nebraska Medical Center, Omaha, and colleagues. In addition, the combination was associated with fewer adverse events.

The study details data from the ACTT-2 trial that the Food and Drug Administration used to issue an emergency-use authorization for baricitinib in combination with remdesivir on Nov. 19.

Under the emergency-use authorization, baricitinib (Olumiant, Eli Lilly), a Janus kinase inhibitor approved for the treatment of rheumatoid arthritis, may be used in combination with remdesivir (Veklury, Gilead), an antiviral, for treating hospitalized adults and children aged at least 2 years with suspected or confirmed COVID-19.

The combination is intended for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation.
 

Combo treatment favored

It is unclear how baricitinib compares with dexamethasone, which improved survival and led to a 1-day shorter hospital stay in another trial. There are differences between the drugs and trial designs, and only a “head-to-head comparison ... will allow the efficacy and safety differences between these two approaches to be fully understood,” Dr. Kalil and coauthors wrote.

“Dexamethasone has a long half-life, acts on glucocorticoid receptors, and reduces inflammation through a broad-pathway approach that has been associated with immunosuppression, hospital-acquired infections, gastrointestinal bleeding, hyperglycemia, and neuromuscular weakness, even with short courses,” they wrote. “Baricitinib has a short half-life, acts on targeted critical pathways to reduce inflammation while minimizing biologic redundancy with less immunosuppression, and may have antiviral activity.”

The ACTT-2 trial started in May and enrolled 1,033 patients in eight countries. Participants were randomly assigned to receive oral baricitinib tablets plus intravenous remdesivir or oral placebo tablets plus remdesivir. 

Participants who received both drugs had significantly improved clinical status at day 15. Patients who received both treatments also had fewer serious adverse events.

“Although ACTT-2 was not powered to detect a difference in mortality between the two groups, both the survival rate and the time-to-death analyses favored combination treatment,” the researchers wrote.

The trial was sponsored by the National Institute of Allergy and Infectious Diseases. Some of the authors disclosed funding from government grants and financial ties to Eli Lilly, Gilead, and other companies.

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

Among people hospitalized with COVID-19, a combination of baricitinib and remdesivir reduces the median time to recovery, compared with remdesivir plus placebo, according to trial results published Dec. 11 in the New England Journal of Medicine.

Median time to recovery was 7 days for patients who received baricitinib versus 8 days for patients who received placebo.

The difference was greater in patients who required high-flow oxygen or noninvasive ventilation during their hospitalization. In this group, baricitinib shortened median time to recovery from 18 days to 10 days.

“Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status, notably among patients receiving high-flow oxygen or noninvasive mechanical ventilation,” reported Andre C. Kalil, MD, MPH, from the University of Nebraska Medical Center, Omaha, and colleagues. In addition, the combination was associated with fewer adverse events.

The study details data from the ACTT-2 trial that the Food and Drug Administration used to issue an emergency-use authorization for baricitinib in combination with remdesivir on Nov. 19.

Under the emergency-use authorization, baricitinib (Olumiant, Eli Lilly), a Janus kinase inhibitor approved for the treatment of rheumatoid arthritis, may be used in combination with remdesivir (Veklury, Gilead), an antiviral, for treating hospitalized adults and children aged at least 2 years with suspected or confirmed COVID-19.

The combination is intended for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation.
 

Combo treatment favored

It is unclear how baricitinib compares with dexamethasone, which improved survival and led to a 1-day shorter hospital stay in another trial. There are differences between the drugs and trial designs, and only a “head-to-head comparison ... will allow the efficacy and safety differences between these two approaches to be fully understood,” Dr. Kalil and coauthors wrote.

“Dexamethasone has a long half-life, acts on glucocorticoid receptors, and reduces inflammation through a broad-pathway approach that has been associated with immunosuppression, hospital-acquired infections, gastrointestinal bleeding, hyperglycemia, and neuromuscular weakness, even with short courses,” they wrote. “Baricitinib has a short half-life, acts on targeted critical pathways to reduce inflammation while minimizing biologic redundancy with less immunosuppression, and may have antiviral activity.”

The ACTT-2 trial started in May and enrolled 1,033 patients in eight countries. Participants were randomly assigned to receive oral baricitinib tablets plus intravenous remdesivir or oral placebo tablets plus remdesivir. 

Participants who received both drugs had significantly improved clinical status at day 15. Patients who received both treatments also had fewer serious adverse events.

“Although ACTT-2 was not powered to detect a difference in mortality between the two groups, both the survival rate and the time-to-death analyses favored combination treatment,” the researchers wrote.

The trial was sponsored by the National Institute of Allergy and Infectious Diseases. Some of the authors disclosed funding from government grants and financial ties to Eli Lilly, Gilead, and other companies.

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

Among people hospitalized with COVID-19, a combination of baricitinib and remdesivir reduces the median time to recovery, compared with remdesivir plus placebo, according to trial results published Dec. 11 in the New England Journal of Medicine.

Median time to recovery was 7 days for patients who received baricitinib versus 8 days for patients who received placebo.

The difference was greater in patients who required high-flow oxygen or noninvasive ventilation during their hospitalization. In this group, baricitinib shortened median time to recovery from 18 days to 10 days.

“Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status, notably among patients receiving high-flow oxygen or noninvasive mechanical ventilation,” reported Andre C. Kalil, MD, MPH, from the University of Nebraska Medical Center, Omaha, and colleagues. In addition, the combination was associated with fewer adverse events.

The study details data from the ACTT-2 trial that the Food and Drug Administration used to issue an emergency-use authorization for baricitinib in combination with remdesivir on Nov. 19.

Under the emergency-use authorization, baricitinib (Olumiant, Eli Lilly), a Janus kinase inhibitor approved for the treatment of rheumatoid arthritis, may be used in combination with remdesivir (Veklury, Gilead), an antiviral, for treating hospitalized adults and children aged at least 2 years with suspected or confirmed COVID-19.

The combination is intended for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation.
 

Combo treatment favored

It is unclear how baricitinib compares with dexamethasone, which improved survival and led to a 1-day shorter hospital stay in another trial. There are differences between the drugs and trial designs, and only a “head-to-head comparison ... will allow the efficacy and safety differences between these two approaches to be fully understood,” Dr. Kalil and coauthors wrote.

“Dexamethasone has a long half-life, acts on glucocorticoid receptors, and reduces inflammation through a broad-pathway approach that has been associated with immunosuppression, hospital-acquired infections, gastrointestinal bleeding, hyperglycemia, and neuromuscular weakness, even with short courses,” they wrote. “Baricitinib has a short half-life, acts on targeted critical pathways to reduce inflammation while minimizing biologic redundancy with less immunosuppression, and may have antiviral activity.”

The ACTT-2 trial started in May and enrolled 1,033 patients in eight countries. Participants were randomly assigned to receive oral baricitinib tablets plus intravenous remdesivir or oral placebo tablets plus remdesivir. 

Participants who received both drugs had significantly improved clinical status at day 15. Patients who received both treatments also had fewer serious adverse events.

“Although ACTT-2 was not powered to detect a difference in mortality between the two groups, both the survival rate and the time-to-death analyses favored combination treatment,” the researchers wrote.

The trial was sponsored by the National Institute of Allergy and Infectious Diseases. Some of the authors disclosed funding from government grants and financial ties to Eli Lilly, Gilead, and other companies.

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

How quickly things change. On September 23, 2019 – months before the COVID-19 pandemic struck – at a UN High-Level Meeting on Universal Health Coverage, heads of state from around the world pledged to achieve universal health coverage by 2030.

“This will be an unprecedented moment in public health: according to the declaration being negotiated by member states, this commitment is being made globally ‘for the first time.’ Whether or not the new commitment succeeds will depend on a large degree of advocacy at the national level.”
 

Reference

1. Carter M, Emmel A. The Global Community Has Pledged To Achieve Universal Health Coverage: What’s It Going To Take? Health Affairs Blog, 2019 Sept 23. doi: 10.1377/hblog20190920.827005.

How quickly things change. On September 23, 2019 – months before the COVID-19 pandemic struck – at a UN High-Level Meeting on Universal Health Coverage, heads of state from around the world pledged to achieve universal health coverage by 2030.

“This will be an unprecedented moment in public health: according to the declaration being negotiated by member states, this commitment is being made globally ‘for the first time.’ Whether or not the new commitment succeeds will depend on a large degree of advocacy at the national level.”
 

Reference

1. Carter M, Emmel A. The Global Community Has Pledged To Achieve Universal Health Coverage: What’s It Going To Take? Health Affairs Blog, 2019 Sept 23. doi: 10.1377/hblog20190920.827005.

How quickly things change. On September 23, 2019 – months before the COVID-19 pandemic struck – at a UN High-Level Meeting on Universal Health Coverage, heads of state from around the world pledged to achieve universal health coverage by 2030.

“This will be an unprecedented moment in public health: according to the declaration being negotiated by member states, this commitment is being made globally ‘for the first time.’ Whether or not the new commitment succeeds will depend on a large degree of advocacy at the national level.”
 

Reference

1. Carter M, Emmel A. The Global Community Has Pledged To Achieve Universal Health Coverage: What’s It Going To Take? Health Affairs Blog, 2019 Sept 23. doi: 10.1377/hblog20190920.827005.

The American College of Cardiology and American Heart Association Task Force on Performance Measures have made two changes to performance measures for adults with atrial fibrillation or atrial flutter.

The 2020 Update to the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults With Atrial Fibrillation or Atrial Flutter was published online Dec. 7 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes. It was developed in collaboration with the Heart Rhythm Society.

Both performance measure changes were prompted by, and are in accordance with, the 2019 ACC/AHA/Heart Rhythm Society atrial fibrillation guideline focused update issued in January 2019, and reported by this news organization at that time.

The first change is the clarification that valvular atrial fibrillation is atrial fibrillation with either moderate or severe mitral stenosis or a mechanical heart valve. This change is incorporated into all the performance measures.

The second change, which only applies to the performance measure of anticoagulation prescribed, is the separation of a male and female threshold for the CHA₂DS₂-VASc score.

This threshold is now a score higher than 1 for men and higher than 2 for women, further demonstrating that the risk for stroke differs for men and women with atrial fibrillation or atrial flutter, the ACC/AHA noted in a press release.

“Successful implementation of these updated performance measures by clinicians and healthcare organizations will lead to quality improvement for adult patients with atrial fibrillation or atrial flutter,” they said.

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

The American College of Cardiology and American Heart Association Task Force on Performance Measures have made two changes to performance measures for adults with atrial fibrillation or atrial flutter.

The 2020 Update to the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults With Atrial Fibrillation or Atrial Flutter was published online Dec. 7 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes. It was developed in collaboration with the Heart Rhythm Society.

Both performance measure changes were prompted by, and are in accordance with, the 2019 ACC/AHA/Heart Rhythm Society atrial fibrillation guideline focused update issued in January 2019, and reported by this news organization at that time.

The first change is the clarification that valvular atrial fibrillation is atrial fibrillation with either moderate or severe mitral stenosis or a mechanical heart valve. This change is incorporated into all the performance measures.

The second change, which only applies to the performance measure of anticoagulation prescribed, is the separation of a male and female threshold for the CHA₂DS₂-VASc score.

This threshold is now a score higher than 1 for men and higher than 2 for women, further demonstrating that the risk for stroke differs for men and women with atrial fibrillation or atrial flutter, the ACC/AHA noted in a press release.

“Successful implementation of these updated performance measures by clinicians and healthcare organizations will lead to quality improvement for adult patients with atrial fibrillation or atrial flutter,” they said.

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

The American College of Cardiology and American Heart Association Task Force on Performance Measures have made two changes to performance measures for adults with atrial fibrillation or atrial flutter.

The 2020 Update to the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults With Atrial Fibrillation or Atrial Flutter was published online Dec. 7 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes. It was developed in collaboration with the Heart Rhythm Society.

Both performance measure changes were prompted by, and are in accordance with, the 2019 ACC/AHA/Heart Rhythm Society atrial fibrillation guideline focused update issued in January 2019, and reported by this news organization at that time.

The first change is the clarification that valvular atrial fibrillation is atrial fibrillation with either moderate or severe mitral stenosis or a mechanical heart valve. This change is incorporated into all the performance measures.

The second change, which only applies to the performance measure of anticoagulation prescribed, is the separation of a male and female threshold for the CHA₂DS₂-VASc score.

This threshold is now a score higher than 1 for men and higher than 2 for women, further demonstrating that the risk for stroke differs for men and women with atrial fibrillation or atrial flutter, the ACC/AHA noted in a press release.

“Successful implementation of these updated performance measures by clinicians and healthcare organizations will lead to quality improvement for adult patients with atrial fibrillation or atrial flutter,” they said.

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

The Centers for Disease Control and Prevention (CDC) advisory committee recommended on December 12 the recently authorized Pfizer-BioNTech COVID-19 vaccine for people age 16 and over in the United States, stating they found it was safe and effective.

The agency said it will quickly issue guidance to clinicians so they can determine when and when not to give the vaccine, and to help them communicate the risks and benefits to patients.

CDC staff gave a preview of those clinical considerations at the agency’s Advisory Committee on Immunization Practices (ACIP) meeting on December 12 and said it would be holding calls with clinicians on December 13 and 14.

The CDC will also issue guidance December 13 on how organizations can handle the workforce problems that might arise as health care workers experience side effects from vaccination.

ACIP voted 11-0, with three recusals, to recommend use of the Pfizer-BioNTech mRNA vaccine in individuals 16 years or older according to the guidelines of the Food and Drug Administration’s (FDA’s) emergency use authorization issued December 11.

The panel also voted unanimously to include the vaccine in 2021 immunization schedules. All panel members said the recommendation should go hand-in-hand with ACIP’s previous recommendation on December 1 that allocation of the vaccine be phased-in, with health care workers and residents and staff of long-term care facilities in phase 1a.

Allergies, pregnant women?

ACIP panelists said clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies.

The FDA health care provider information sheet said there is not enough data to recommend vaccinating those women or the immunocompromised, and also advises against giving the vaccine to individuals who have a history of serious allergic reaction to any component of the vaccine.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologic Evaluation and Research (CBER) clarified this in a briefing on December 12, noting that women who are pregnant or lactating can make the decision in consultation with their physician. And, he said, patients with any other history of allergy should be able to safely get the vaccine.

The CDC — in its soon-to-be-released guidance — will make the same recommendations. For any woman considering vaccination, she should consider the level of COVID-19 in the community, her personal risk of contracting the virus, the risks to her or her fetus of developing the disease, and the vaccine’s known side effects, Sarah Mbaeyi, MD, MPH, a medical officer at the agency, said during the panel meeting December 12.

She added that the CDC will also urge physicians to advise women to take acetaminophen if they develop a fever after vaccination — to protect the developing fetus from fever.

Sandra Fryhofer, MD, representing the American Medical Association, commended the CDC for these recommendations. But she also called on Pfizer, the FDA, and the CDC to make data from the developmental and reproductive toxicity (DART) studies public as soon as possible.

“We really need to put those results on warp speed and get them out there to give our physicians and pregnant women more information,” said Fryhofer, an adjunct associate professor of medicine at Emory University School of Medicine in Atlanta, Georgia.

The American College of Obstetricians and Gynecologists (ACOG) will also soon release guidance for vaccinating pregnant and breastfeeding women, said Linda Eckert, MD, FACOG, an ACOG representative on the panel.

ACOG and the CDC met the morning of December 12 to discuss risks and benefits with experts in immunology, placental pathology, and vaccine kinetics, she said.

“The overall complete consensus was that we don’t see biological plausibility at this time for placental transfer of the mRNA and that we see that direct fetal exposure or the possibility of fetal inflammatory response is extremely unlikely,” said Eckert, professor of obstetrics and gynecology at the University of Washington, Seattle. “Clearly we are waiting on the data.”

A Pfizer official told the ACIP panel that preliminary data “show no indication of either developmental or reproductive toxicity,” and that the company plans to send the final DART data to the FDA at the end of December.

On the potential for allergic reactions, the CDC concurred with the FDA that the vaccine should not be given to people with a history of serious reactions. The agency added that the category should include anyone who has had a reaction to any vaccine or injectable drug product because injectables may contain the same ingredients as the Pfizer vaccine, said Mbaeyi.

The CDC will also urge clinicians to observe patients with a history of anaphylaxis for 30 minutes after vaccination and all patients for at least 15 minutes afterward.

Should teens be a special population?

At least one ACIP panel member — Henry Bernstein, DO, MHCM, FAAP — said he was concerned that backing use of the vaccine in 16- and 17-year-olds was a leap of faith, given that Pfizer had extremely limited data on this cohort.

Bernstein, professor of pediatrics at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, also said that systemic reactions were more common in that age group.

He argued for making the 16- and 17-year-olds a “special population” that would get specific attention and guidance for vaccination from the federal agencies and professional societies.

Bernstein said he did not want to sow any more doubts in parents’ minds about vaccination, noting that hesitancy was a growing concern. “A successful pediatric vaccination program depends on creating and sustaining parental confidence in both the safety and effectiveness of this vaccine,” he said.

Many panelists, however, noted that there has been no evidence to suggest that the vaccine is not safe or less effective in that younger age group.

Yvonne Maldonado, MD, the American Academy of Pediatrics representative on the panel, said that this age group should not be denied the vaccine as they often have essential or front-line jobs that put them at higher risk for infection.

“I am very concerned about this message being sent out that this vaccine will not be safe in children,” said Maldonado, professor of pediatrics and health research and policy at Stanford University School of Medicine in California.

“We currently have no evidence that that is the case,” she said, adding there is also no indication younger children are biologically or physiologically different in their response or safety risk than 18-year-olds.

Vaccine = hope

Committee members breathed a sigh of relief at the end of the 2-day meeting, saying that although the Pfizer vaccine is not perfect, it represents a scientific milestone and a significant advance against the continuing march of the SARS-CoV-2 pandemic.

“This vaccine and future vaccines do provide a promise for a lot of progress in the future,” said panelist Beth P. Bell, MD, MPH, clinical professor of global health at the University of Washington School of Public Health in Seattle.

Peter Szilagyi, MD, MPH, executive vice-chair and vice-chair for research at the University of California, Los Angeles pediatrics department, said, “I’m really hopeful that this is the beginning of the end of the coronavirus pandemic.”

“The need for this vaccine is profound,” said Veronica McNally, president and CEO of the Franny Strong Foundation in West Bloomfield, Michigan.

The ACIP panel also made the argument that while the at least $10 billion spent on vaccine development by the federal government’s Operation Warp Speed alone has been a good investment, more spending is needed to actually get Americans vaccinated.

The imbalance between the two is “shocking and needs to be corrected,” said Bell. “We are not going to be able to protect the American public if we don’t have a way to deliver the vaccine to them.”

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention (CDC) advisory committee recommended on December 12 the recently authorized Pfizer-BioNTech COVID-19 vaccine for people age 16 and over in the United States, stating they found it was safe and effective.

The agency said it will quickly issue guidance to clinicians so they can determine when and when not to give the vaccine, and to help them communicate the risks and benefits to patients.

CDC staff gave a preview of those clinical considerations at the agency’s Advisory Committee on Immunization Practices (ACIP) meeting on December 12 and said it would be holding calls with clinicians on December 13 and 14.

The CDC will also issue guidance December 13 on how organizations can handle the workforce problems that might arise as health care workers experience side effects from vaccination.

ACIP voted 11-0, with three recusals, to recommend use of the Pfizer-BioNTech mRNA vaccine in individuals 16 years or older according to the guidelines of the Food and Drug Administration’s (FDA’s) emergency use authorization issued December 11.

The panel also voted unanimously to include the vaccine in 2021 immunization schedules. All panel members said the recommendation should go hand-in-hand with ACIP’s previous recommendation on December 1 that allocation of the vaccine be phased-in, with health care workers and residents and staff of long-term care facilities in phase 1a.

Allergies, pregnant women?

ACIP panelists said clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies.

The FDA health care provider information sheet said there is not enough data to recommend vaccinating those women or the immunocompromised, and also advises against giving the vaccine to individuals who have a history of serious allergic reaction to any component of the vaccine.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologic Evaluation and Research (CBER) clarified this in a briefing on December 12, noting that women who are pregnant or lactating can make the decision in consultation with their physician. And, he said, patients with any other history of allergy should be able to safely get the vaccine.

The CDC — in its soon-to-be-released guidance — will make the same recommendations. For any woman considering vaccination, she should consider the level of COVID-19 in the community, her personal risk of contracting the virus, the risks to her or her fetus of developing the disease, and the vaccine’s known side effects, Sarah Mbaeyi, MD, MPH, a medical officer at the agency, said during the panel meeting December 12.

She added that the CDC will also urge physicians to advise women to take acetaminophen if they develop a fever after vaccination — to protect the developing fetus from fever.

Sandra Fryhofer, MD, representing the American Medical Association, commended the CDC for these recommendations. But she also called on Pfizer, the FDA, and the CDC to make data from the developmental and reproductive toxicity (DART) studies public as soon as possible.

“We really need to put those results on warp speed and get them out there to give our physicians and pregnant women more information,” said Fryhofer, an adjunct associate professor of medicine at Emory University School of Medicine in Atlanta, Georgia.

The American College of Obstetricians and Gynecologists (ACOG) will also soon release guidance for vaccinating pregnant and breastfeeding women, said Linda Eckert, MD, FACOG, an ACOG representative on the panel.

ACOG and the CDC met the morning of December 12 to discuss risks and benefits with experts in immunology, placental pathology, and vaccine kinetics, she said.

“The overall complete consensus was that we don’t see biological plausibility at this time for placental transfer of the mRNA and that we see that direct fetal exposure or the possibility of fetal inflammatory response is extremely unlikely,” said Eckert, professor of obstetrics and gynecology at the University of Washington, Seattle. “Clearly we are waiting on the data.”

A Pfizer official told the ACIP panel that preliminary data “show no indication of either developmental or reproductive toxicity,” and that the company plans to send the final DART data to the FDA at the end of December.

On the potential for allergic reactions, the CDC concurred with the FDA that the vaccine should not be given to people with a history of serious reactions. The agency added that the category should include anyone who has had a reaction to any vaccine or injectable drug product because injectables may contain the same ingredients as the Pfizer vaccine, said Mbaeyi.

The CDC will also urge clinicians to observe patients with a history of anaphylaxis for 30 minutes after vaccination and all patients for at least 15 minutes afterward.

Should teens be a special population?

At least one ACIP panel member — Henry Bernstein, DO, MHCM, FAAP — said he was concerned that backing use of the vaccine in 16- and 17-year-olds was a leap of faith, given that Pfizer had extremely limited data on this cohort.

Bernstein, professor of pediatrics at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, also said that systemic reactions were more common in that age group.

He argued for making the 16- and 17-year-olds a “special population” that would get specific attention and guidance for vaccination from the federal agencies and professional societies.

Bernstein said he did not want to sow any more doubts in parents’ minds about vaccination, noting that hesitancy was a growing concern. “A successful pediatric vaccination program depends on creating and sustaining parental confidence in both the safety and effectiveness of this vaccine,” he said.

Many panelists, however, noted that there has been no evidence to suggest that the vaccine is not safe or less effective in that younger age group.

Yvonne Maldonado, MD, the American Academy of Pediatrics representative on the panel, said that this age group should not be denied the vaccine as they often have essential or front-line jobs that put them at higher risk for infection.

“I am very concerned about this message being sent out that this vaccine will not be safe in children,” said Maldonado, professor of pediatrics and health research and policy at Stanford University School of Medicine in California.

“We currently have no evidence that that is the case,” she said, adding there is also no indication younger children are biologically or physiologically different in their response or safety risk than 18-year-olds.

Vaccine = hope

Committee members breathed a sigh of relief at the end of the 2-day meeting, saying that although the Pfizer vaccine is not perfect, it represents a scientific milestone and a significant advance against the continuing march of the SARS-CoV-2 pandemic.

“This vaccine and future vaccines do provide a promise for a lot of progress in the future,” said panelist Beth P. Bell, MD, MPH, clinical professor of global health at the University of Washington School of Public Health in Seattle.

Peter Szilagyi, MD, MPH, executive vice-chair and vice-chair for research at the University of California, Los Angeles pediatrics department, said, “I’m really hopeful that this is the beginning of the end of the coronavirus pandemic.”

“The need for this vaccine is profound,” said Veronica McNally, president and CEO of the Franny Strong Foundation in West Bloomfield, Michigan.

The ACIP panel also made the argument that while the at least $10 billion spent on vaccine development by the federal government’s Operation Warp Speed alone has been a good investment, more spending is needed to actually get Americans vaccinated.

The imbalance between the two is “shocking and needs to be corrected,” said Bell. “We are not going to be able to protect the American public if we don’t have a way to deliver the vaccine to them.”

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention (CDC) advisory committee recommended on December 12 the recently authorized Pfizer-BioNTech COVID-19 vaccine for people age 16 and over in the United States, stating they found it was safe and effective.

The agency said it will quickly issue guidance to clinicians so they can determine when and when not to give the vaccine, and to help them communicate the risks and benefits to patients.

CDC staff gave a preview of those clinical considerations at the agency’s Advisory Committee on Immunization Practices (ACIP) meeting on December 12 and said it would be holding calls with clinicians on December 13 and 14.

The CDC will also issue guidance December 13 on how organizations can handle the workforce problems that might arise as health care workers experience side effects from vaccination.

ACIP voted 11-0, with three recusals, to recommend use of the Pfizer-BioNTech mRNA vaccine in individuals 16 years or older according to the guidelines of the Food and Drug Administration’s (FDA’s) emergency use authorization issued December 11.

The panel also voted unanimously to include the vaccine in 2021 immunization schedules. All panel members said the recommendation should go hand-in-hand with ACIP’s previous recommendation on December 1 that allocation of the vaccine be phased-in, with health care workers and residents and staff of long-term care facilities in phase 1a.

Allergies, pregnant women?

ACIP panelists said clinicians need more guidance on whether to use the vaccine in pregnant or breastfeeding women, the immunocompromised, or those who have a history of allergies.

The FDA health care provider information sheet said there is not enough data to recommend vaccinating those women or the immunocompromised, and also advises against giving the vaccine to individuals who have a history of serious allergic reaction to any component of the vaccine.

Peter Marks, MD, PhD, director of the FDA’s Center for Biologic Evaluation and Research (CBER) clarified this in a briefing on December 12, noting that women who are pregnant or lactating can make the decision in consultation with their physician. And, he said, patients with any other history of allergy should be able to safely get the vaccine.

The CDC — in its soon-to-be-released guidance — will make the same recommendations. For any woman considering vaccination, she should consider the level of COVID-19 in the community, her personal risk of contracting the virus, the risks to her or her fetus of developing the disease, and the vaccine’s known side effects, Sarah Mbaeyi, MD, MPH, a medical officer at the agency, said during the panel meeting December 12.

She added that the CDC will also urge physicians to advise women to take acetaminophen if they develop a fever after vaccination — to protect the developing fetus from fever.

Sandra Fryhofer, MD, representing the American Medical Association, commended the CDC for these recommendations. But she also called on Pfizer, the FDA, and the CDC to make data from the developmental and reproductive toxicity (DART) studies public as soon as possible.

“We really need to put those results on warp speed and get them out there to give our physicians and pregnant women more information,” said Fryhofer, an adjunct associate professor of medicine at Emory University School of Medicine in Atlanta, Georgia.

The American College of Obstetricians and Gynecologists (ACOG) will also soon release guidance for vaccinating pregnant and breastfeeding women, said Linda Eckert, MD, FACOG, an ACOG representative on the panel.

ACOG and the CDC met the morning of December 12 to discuss risks and benefits with experts in immunology, placental pathology, and vaccine kinetics, she said.

“The overall complete consensus was that we don’t see biological plausibility at this time for placental transfer of the mRNA and that we see that direct fetal exposure or the possibility of fetal inflammatory response is extremely unlikely,” said Eckert, professor of obstetrics and gynecology at the University of Washington, Seattle. “Clearly we are waiting on the data.”

A Pfizer official told the ACIP panel that preliminary data “show no indication of either developmental or reproductive toxicity,” and that the company plans to send the final DART data to the FDA at the end of December.

On the potential for allergic reactions, the CDC concurred with the FDA that the vaccine should not be given to people with a history of serious reactions. The agency added that the category should include anyone who has had a reaction to any vaccine or injectable drug product because injectables may contain the same ingredients as the Pfizer vaccine, said Mbaeyi.

The CDC will also urge clinicians to observe patients with a history of anaphylaxis for 30 minutes after vaccination and all patients for at least 15 minutes afterward.

Should teens be a special population?

At least one ACIP panel member — Henry Bernstein, DO, MHCM, FAAP — said he was concerned that backing use of the vaccine in 16- and 17-year-olds was a leap of faith, given that Pfizer had extremely limited data on this cohort.

Bernstein, professor of pediatrics at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, also said that systemic reactions were more common in that age group.

He argued for making the 16- and 17-year-olds a “special population” that would get specific attention and guidance for vaccination from the federal agencies and professional societies.

Bernstein said he did not want to sow any more doubts in parents’ minds about vaccination, noting that hesitancy was a growing concern. “A successful pediatric vaccination program depends on creating and sustaining parental confidence in both the safety and effectiveness of this vaccine,” he said.

Many panelists, however, noted that there has been no evidence to suggest that the vaccine is not safe or less effective in that younger age group.

Yvonne Maldonado, MD, the American Academy of Pediatrics representative on the panel, said that this age group should not be denied the vaccine as they often have essential or front-line jobs that put them at higher risk for infection.

“I am very concerned about this message being sent out that this vaccine will not be safe in children,” said Maldonado, professor of pediatrics and health research and policy at Stanford University School of Medicine in California.

“We currently have no evidence that that is the case,” she said, adding there is also no indication younger children are biologically or physiologically different in their response or safety risk than 18-year-olds.

Vaccine = hope

Committee members breathed a sigh of relief at the end of the 2-day meeting, saying that although the Pfizer vaccine is not perfect, it represents a scientific milestone and a significant advance against the continuing march of the SARS-CoV-2 pandemic.

“This vaccine and future vaccines do provide a promise for a lot of progress in the future,” said panelist Beth P. Bell, MD, MPH, clinical professor of global health at the University of Washington School of Public Health in Seattle.

Peter Szilagyi, MD, MPH, executive vice-chair and vice-chair for research at the University of California, Los Angeles pediatrics department, said, “I’m really hopeful that this is the beginning of the end of the coronavirus pandemic.”

“The need for this vaccine is profound,” said Veronica McNally, president and CEO of the Franny Strong Foundation in West Bloomfield, Michigan.

The ACIP panel also made the argument that while the at least $10 billion spent on vaccine development by the federal government’s Operation Warp Speed alone has been a good investment, more spending is needed to actually get Americans vaccinated.

The imbalance between the two is “shocking and needs to be corrected,” said Bell. “We are not going to be able to protect the American public if we don’t have a way to deliver the vaccine to them.”

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has authorized Pfizer/BioNTech’s COVID-19 vaccine for emergency use in people 16 years of age and older. 

The much-anticipated emergency use authorization (EUA) of this vaccine — the first such approval in the United States — was greeted with optimism by infectious disease and pulmonary experts, although unanswered questions remain regarding use in people with allergic hypersensitivity, safety in pregnant women, and how smooth distribution will be.

“I am delighted. This is a first, firm step on a long path to getting this COVID pandemic under control,” William Schaffner, MD, professor of infectious diseases at the Vanderbilt University School of Medicine in Nashville, Tennessee, said in an interview.

The FDA gave the green light after the December 10 recommendation from the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting. The committee voted 17-4 in favor of the emergency authorization.

Allergic reactions reported in the UK

After vaccinations with the Pfizer vaccine began in the UK on December 8, reports surfaced of two healthcare workers who experienced allergic reactions. They have since recovered, but officials warned that people with a history of severe allergic reactions should not receive the Pfizer vaccine at this time.

“For the moment, they are asking people who have had notable allergic reactions to step aside while this is investigated. It shows you that the system is working,” Schaffner said.

Both vaccine recipients who experienced anaphylaxis carried EpiPens, as they were at high risk for allergic reactions, Hewlett said. Also, if other COVID-19 vaccines are approved for use in the future, people allergic to the Pfizer vaccine might have another option, he added.

Reassuring role models

Schaffner supports the CDC Advisory Committee on Immunization Practices (ACIP) decision to start vaccinations with healthcare workers and residents of long-term care facilities.

“Vaccinating healthcare workers, in particular, will be a model for the general public,” said Schaffner, who is also a former member of the IDSA board of directors. “If they see those of us in white coats and blue scrubs lining up for the vaccine, that will provide confidence.”

To further increase acceptance of the COVID-19 vaccine, public health officials need to provide information and reassure the general public, Schaffner said.

Hewlett agreed. “I know there are a lot of people in the population who are very hesitant about vaccines. As infection disease specialists and people in public health, we are trying to allay a lot of concerns people have.”

Reassurance will be especially important in minority communities. “They have been disproportionately affected by the virus, and they have a traditional history of not being optimally vaccinated,” Schaffner said. “We need to reach them in particular with good information and reassurance…so they can make good decisions for themselves and their families.”

No vaccine is 100% effective or completely free of side effects. “There is always a chance there can be adverse reactions, but we think for the most part this is going to be a safe and effective vaccine,” said Hewlett, medical director at the Division of Disease Control and deputy to commissioner of health at the Westchester County Department of Health in White Plains, New York.

Distribution: Smooth or full of strife?

In addition to the concern that some people will not take advantage of vaccination against COVID-19, there could be vaccine supply issues down the road, Schaffner said.

Culver agreed. “In the early phases, I expect that there will be some kinks to work out, but because the numbers are relatively small, this should be okay,” he said.

“I think when we start to get into larger-scale vaccination programs — the supply chain, transport, and storage will be a Herculean undertaking,” Culver added. “It will take careful coordination between healthcare providers, distributors, suppliers, and public health officials to pull this off.”

Planning and distribution also should focus beyond US borders. Any issues in vaccine distribution or administration in the United States “will only be multiplied in several other parts of the world,” Culver said. Because COVID-19 is a pandemic, “we need to think about vaccinating globally.”

Investigating adverse events

Adverse events common to vaccinations in general — injection site pain, headaches, and fever — would not be unexpected with the COVID-19 vaccines. However, experts remain concerned that other, unrelated adverse events might be erroneously attributed to vaccination. For example, if a fall, heart attack, or death occurs within days of immunization, some might immediately blame the vaccine product.

“It’s important to remember that any new, highly touted medical therapy like this will receive a lot of scrutiny, so it would be unusual not to hear about something happening to somebody,” Culver said. Vaccine companies and health agencies will be carefully evaluating any reported adverse events to ensure no safety signal was missed in the trials.

“Fortunately, there are systems in place to investigate these events immediately,” Schaffner said.

Pregnancy recommendations pending

One question still looms: Is the COVID-19 vaccination safe for pregnant women? This isn’t just a question for the general public, either, Schaffner said. He estimated that about 70 percent of healthcare workers are women, and data suggests about 300,000 of these healthcare workers are pregnant.

“The CDC’s Advisory Committee on Immunization Practices will speak to that just as soon as the EUA is issued,” he added.

Patients are asking Culver about the priority order for vaccination. He said it’s difficult to provide firm guidance at this point.

People also have “lingering skepticism” about whether vaccine development was done in a prudent way, Culver said. Some people question whether the Pfizer vaccine and others were rushed to market. “So we try to spend time with the patients, reassuring them that all the usual safety evaluations were carefully done,” he said.

Another concern is whether mRNA vaccines can interact with human DNA. “The quick, short, and definitive answer is no,” Schaffner said. The m stands for messenger — the vaccines transmit information. "Once it gets into a cell, the mRNA does not go anywhere near the DNA, and once it transmits its information to the cell appropriately, it gets metabolized, and we excrete all the remnants."

Hewlett pointed out that investigations and surveillance will continue. Because this is an EUA and not full approval, “that essentially means they will still be obligated to collect a lot more data than they would ordinarily,” he said.

How long immunoprotection will last also remains an unknown. “The big question left on the table now is the durability,” Culver said. “Of course, we won’t know the answer to that for quite some time.”

Schaffner and Culver have disclosed no relevant financial relationships. Hewlett was an employee of Pfizer until mid-2019. His previous work as Pfizer’s senior medical director of global medical product evaluation was not associated with development of the COVID-19 vaccine.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has authorized Pfizer/BioNTech’s COVID-19 vaccine for emergency use in people 16 years of age and older. 

The much-anticipated emergency use authorization (EUA) of this vaccine — the first such approval in the United States — was greeted with optimism by infectious disease and pulmonary experts, although unanswered questions remain regarding use in people with allergic hypersensitivity, safety in pregnant women, and how smooth distribution will be.

“I am delighted. This is a first, firm step on a long path to getting this COVID pandemic under control,” William Schaffner, MD, professor of infectious diseases at the Vanderbilt University School of Medicine in Nashville, Tennessee, said in an interview.

The FDA gave the green light after the December 10 recommendation from the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting. The committee voted 17-4 in favor of the emergency authorization.

Allergic reactions reported in the UK

After vaccinations with the Pfizer vaccine began in the UK on December 8, reports surfaced of two healthcare workers who experienced allergic reactions. They have since recovered, but officials warned that people with a history of severe allergic reactions should not receive the Pfizer vaccine at this time.

“For the moment, they are asking people who have had notable allergic reactions to step aside while this is investigated. It shows you that the system is working,” Schaffner said.

Both vaccine recipients who experienced anaphylaxis carried EpiPens, as they were at high risk for allergic reactions, Hewlett said. Also, if other COVID-19 vaccines are approved for use in the future, people allergic to the Pfizer vaccine might have another option, he added.

Reassuring role models

Schaffner supports the CDC Advisory Committee on Immunization Practices (ACIP) decision to start vaccinations with healthcare workers and residents of long-term care facilities.

“Vaccinating healthcare workers, in particular, will be a model for the general public,” said Schaffner, who is also a former member of the IDSA board of directors. “If they see those of us in white coats and blue scrubs lining up for the vaccine, that will provide confidence.”

To further increase acceptance of the COVID-19 vaccine, public health officials need to provide information and reassure the general public, Schaffner said.

Hewlett agreed. “I know there are a lot of people in the population who are very hesitant about vaccines. As infection disease specialists and people in public health, we are trying to allay a lot of concerns people have.”

Reassurance will be especially important in minority communities. “They have been disproportionately affected by the virus, and they have a traditional history of not being optimally vaccinated,” Schaffner said. “We need to reach them in particular with good information and reassurance…so they can make good decisions for themselves and their families.”

No vaccine is 100% effective or completely free of side effects. “There is always a chance there can be adverse reactions, but we think for the most part this is going to be a safe and effective vaccine,” said Hewlett, medical director at the Division of Disease Control and deputy to commissioner of health at the Westchester County Department of Health in White Plains, New York.

Distribution: Smooth or full of strife?

In addition to the concern that some people will not take advantage of vaccination against COVID-19, there could be vaccine supply issues down the road, Schaffner said.

Culver agreed. “In the early phases, I expect that there will be some kinks to work out, but because the numbers are relatively small, this should be okay,” he said.

“I think when we start to get into larger-scale vaccination programs — the supply chain, transport, and storage will be a Herculean undertaking,” Culver added. “It will take careful coordination between healthcare providers, distributors, suppliers, and public health officials to pull this off.”

Planning and distribution also should focus beyond US borders. Any issues in vaccine distribution or administration in the United States “will only be multiplied in several other parts of the world,” Culver said. Because COVID-19 is a pandemic, “we need to think about vaccinating globally.”

Investigating adverse events

Adverse events common to vaccinations in general — injection site pain, headaches, and fever — would not be unexpected with the COVID-19 vaccines. However, experts remain concerned that other, unrelated adverse events might be erroneously attributed to vaccination. For example, if a fall, heart attack, or death occurs within days of immunization, some might immediately blame the vaccine product.

“It’s important to remember that any new, highly touted medical therapy like this will receive a lot of scrutiny, so it would be unusual not to hear about something happening to somebody,” Culver said. Vaccine companies and health agencies will be carefully evaluating any reported adverse events to ensure no safety signal was missed in the trials.

“Fortunately, there are systems in place to investigate these events immediately,” Schaffner said.

Pregnancy recommendations pending

One question still looms: Is the COVID-19 vaccination safe for pregnant women? This isn’t just a question for the general public, either, Schaffner said. He estimated that about 70 percent of healthcare workers are women, and data suggests about 300,000 of these healthcare workers are pregnant.

“The CDC’s Advisory Committee on Immunization Practices will speak to that just as soon as the EUA is issued,” he added.

Patients are asking Culver about the priority order for vaccination. He said it’s difficult to provide firm guidance at this point.

People also have “lingering skepticism” about whether vaccine development was done in a prudent way, Culver said. Some people question whether the Pfizer vaccine and others were rushed to market. “So we try to spend time with the patients, reassuring them that all the usual safety evaluations were carefully done,” he said.

Another concern is whether mRNA vaccines can interact with human DNA. “The quick, short, and definitive answer is no,” Schaffner said. The m stands for messenger — the vaccines transmit information. "Once it gets into a cell, the mRNA does not go anywhere near the DNA, and once it transmits its information to the cell appropriately, it gets metabolized, and we excrete all the remnants."

Hewlett pointed out that investigations and surveillance will continue. Because this is an EUA and not full approval, “that essentially means they will still be obligated to collect a lot more data than they would ordinarily,” he said.

How long immunoprotection will last also remains an unknown. “The big question left on the table now is the durability,” Culver said. “Of course, we won’t know the answer to that for quite some time.”

Schaffner and Culver have disclosed no relevant financial relationships. Hewlett was an employee of Pfizer until mid-2019. His previous work as Pfizer’s senior medical director of global medical product evaluation was not associated with development of the COVID-19 vaccine.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has authorized Pfizer/BioNTech’s COVID-19 vaccine for emergency use in people 16 years of age and older. 

The much-anticipated emergency use authorization (EUA) of this vaccine — the first such approval in the United States — was greeted with optimism by infectious disease and pulmonary experts, although unanswered questions remain regarding use in people with allergic hypersensitivity, safety in pregnant women, and how smooth distribution will be.

“I am delighted. This is a first, firm step on a long path to getting this COVID pandemic under control,” William Schaffner, MD, professor of infectious diseases at the Vanderbilt University School of Medicine in Nashville, Tennessee, said in an interview.

The FDA gave the green light after the December 10 recommendation from the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting. The committee voted 17-4 in favor of the emergency authorization.

Allergic reactions reported in the UK

After vaccinations with the Pfizer vaccine began in the UK on December 8, reports surfaced of two healthcare workers who experienced allergic reactions. They have since recovered, but officials warned that people with a history of severe allergic reactions should not receive the Pfizer vaccine at this time.

“For the moment, they are asking people who have had notable allergic reactions to step aside while this is investigated. It shows you that the system is working,” Schaffner said.

Both vaccine recipients who experienced anaphylaxis carried EpiPens, as they were at high risk for allergic reactions, Hewlett said. Also, if other COVID-19 vaccines are approved for use in the future, people allergic to the Pfizer vaccine might have another option, he added.

Reassuring role models

Schaffner supports the CDC Advisory Committee on Immunization Practices (ACIP) decision to start vaccinations with healthcare workers and residents of long-term care facilities.

“Vaccinating healthcare workers, in particular, will be a model for the general public,” said Schaffner, who is also a former member of the IDSA board of directors. “If they see those of us in white coats and blue scrubs lining up for the vaccine, that will provide confidence.”

To further increase acceptance of the COVID-19 vaccine, public health officials need to provide information and reassure the general public, Schaffner said.

Hewlett agreed. “I know there are a lot of people in the population who are very hesitant about vaccines. As infection disease specialists and people in public health, we are trying to allay a lot of concerns people have.”

Reassurance will be especially important in minority communities. “They have been disproportionately affected by the virus, and they have a traditional history of not being optimally vaccinated,” Schaffner said. “We need to reach them in particular with good information and reassurance…so they can make good decisions for themselves and their families.”

No vaccine is 100% effective or completely free of side effects. “There is always a chance there can be adverse reactions, but we think for the most part this is going to be a safe and effective vaccine,” said Hewlett, medical director at the Division of Disease Control and deputy to commissioner of health at the Westchester County Department of Health in White Plains, New York.

Distribution: Smooth or full of strife?

In addition to the concern that some people will not take advantage of vaccination against COVID-19, there could be vaccine supply issues down the road, Schaffner said.

Culver agreed. “In the early phases, I expect that there will be some kinks to work out, but because the numbers are relatively small, this should be okay,” he said.

“I think when we start to get into larger-scale vaccination programs — the supply chain, transport, and storage will be a Herculean undertaking,” Culver added. “It will take careful coordination between healthcare providers, distributors, suppliers, and public health officials to pull this off.”

Planning and distribution also should focus beyond US borders. Any issues in vaccine distribution or administration in the United States “will only be multiplied in several other parts of the world,” Culver said. Because COVID-19 is a pandemic, “we need to think about vaccinating globally.”

Investigating adverse events

Adverse events common to vaccinations in general — injection site pain, headaches, and fever — would not be unexpected with the COVID-19 vaccines. However, experts remain concerned that other, unrelated adverse events might be erroneously attributed to vaccination. For example, if a fall, heart attack, or death occurs within days of immunization, some might immediately blame the vaccine product.

“It’s important to remember that any new, highly touted medical therapy like this will receive a lot of scrutiny, so it would be unusual not to hear about something happening to somebody,” Culver said. Vaccine companies and health agencies will be carefully evaluating any reported adverse events to ensure no safety signal was missed in the trials.

“Fortunately, there are systems in place to investigate these events immediately,” Schaffner said.

Pregnancy recommendations pending

One question still looms: Is the COVID-19 vaccination safe for pregnant women? This isn’t just a question for the general public, either, Schaffner said. He estimated that about 70 percent of healthcare workers are women, and data suggests about 300,000 of these healthcare workers are pregnant.

“The CDC’s Advisory Committee on Immunization Practices will speak to that just as soon as the EUA is issued,” he added.

Patients are asking Culver about the priority order for vaccination. He said it’s difficult to provide firm guidance at this point.

People also have “lingering skepticism” about whether vaccine development was done in a prudent way, Culver said. Some people question whether the Pfizer vaccine and others were rushed to market. “So we try to spend time with the patients, reassuring them that all the usual safety evaluations were carefully done,” he said.

Another concern is whether mRNA vaccines can interact with human DNA. “The quick, short, and definitive answer is no,” Schaffner said. The m stands for messenger — the vaccines transmit information. "Once it gets into a cell, the mRNA does not go anywhere near the DNA, and once it transmits its information to the cell appropriately, it gets metabolized, and we excrete all the remnants."

Hewlett pointed out that investigations and surveillance will continue. Because this is an EUA and not full approval, “that essentially means they will still be obligated to collect a lot more data than they would ordinarily,” he said.

How long immunoprotection will last also remains an unknown. “The big question left on the table now is the durability,” Culver said. “Of course, we won’t know the answer to that for quite some time.”

Schaffner and Culver have disclosed no relevant financial relationships. Hewlett was an employee of Pfizer until mid-2019. His previous work as Pfizer’s senior medical director of global medical product evaluation was not associated with development of the COVID-19 vaccine.

This article first appeared on Medscape.com.

With U.S. approval of one coronavirus vaccine likely imminent and approval of a second one expected soon after, physicians will likely be deluged with questions. Public attitudes about the vaccines vary by demographics, with a recent poll showing that men and older adults are more likely to choose vaccination, and women and people of color evincing more wariness.

Although the reasons for reluctance may vary, questions from patient will likely be similar. Some are related to the “warp speed” language about the vaccines. Other concerns arise from the fact that the platform – mRNA – has not been used in human vaccines before. And as with any vaccine, there are rumors and false claims making the rounds on social media.

In anticipation of the most common questions physicians may encounter, two experts, Krutika Kuppalli, MD, assistant professor of medicine in the division of infectious diseases at the Medical University of South Carolina, Charleston, and Angela Rasmussen, PhD, virologist and nonresident affiliate at Georgetown University’s Center for Global Health Science and Security, Washington, talked in an interview about what clinicians can expect and what evidence-based – as well as compassionate – answers might look like.
 

Q: Will this vaccine give me COVID-19?

“There is not an intact virus in there,” Dr. Rasmussen said. The mRNA-based vaccines cannot cause COVID-19 because they don’t use any part of the coronavirus itself. Instead, the Moderna and Pfizer vaccines contain manufactured mRNA molecules that carry the instructions for building the virus’ spike protein. After vaccine administration, the recipient’s own cells take up this mRNA, use it to build this bit of protein, and display it on their surfaces. The foreign protein flag triggers the immune system response.

The mRNA does not enter the cell nucleus or interact with the recipient’s DNA. And because it’s so fragile, it degrades quite quickly. To keep that from happening before cell entry, the mRNAs are cushioned in protective fats.

Q: Was this vaccine made too quickly?

“People have been working on this platform for 30 years, so it’s not that this is brand new,” Dr. Kuppalli said.

Researchers began working on mRNA vaccines in the 1990s. Technological developments in the last decade have meant that their use has become feasible, and they have been tested in animals against many viral diseases. The mRNA vaccines are attractive because they’re expected to be safe and easily manufactured from common materials. That’s what we’ve seen in the COVID-19 pandemic, the  Centers for Disease Control and Prevention says on its website. Design of the spike protein mRNA component began as soon as the viral genome became available in January.

Usually, rolling out a vaccine takes years, so less than a year under a program called Operation Warp Speed can seem like moving too fast, Dr. Rasmussen acknowledged. “The name has given people the impression that by going at warp speed, we’re cutting all the corners. [But] the reality is that Operation Warp Speed is mostly for manufacturing and distribution.”

What underlies the speed is a restructuring of the normal vaccine development process, Dr. Kuppalli said. The same phases of development – animal testing, a small initial human phase, a second for safety testing, a third large phase for efficacy – were all conducted as for any vaccine. But in this case, some phases were completed in parallel, rather than sequentially. This approach has proved so successful that there is already talk about making it the model for developing future vaccines.

Two other factors contributed to the speed, said Dr. Kuppalli and Dr. Rasmussen. First, gearing up production can slow a rollout, but with these vaccines, companies ramped up production even before anyone knew if the vaccines would work – the “warp speed” part. The second factor has been the large number of cases, making exposures more likely and thus accelerating the results of the efficacy trials. “There is so much COVID being transmitted everywhere in the United States that it did not take long to hit the threshold of events to read out phase 3,” Dr. Rasmussen said.

Q: This vaccine has never been used in humans. How do we know it’s safe?

The Pfizer phase 3 trial included more than 43,000 people, and Moderna’s had more than 30,000. The first humans received mRNA-based COVID-19 vaccines in March. The most common adverse events emerge right after a vaccination, Dr. Kuppalli said.

As with any vaccine that gains approval, monitoring will continue.

UK health officials have reported that two health care workers vaccinated in the initial rollout of the Pfizer vaccine had what seems to have been a severe allergic response. Both recipients had a history of anaphylactic allergic responses and carried EpiPens, and both recovered. During the trial, allergic reaction rates were 0.63% in the vaccine group and 0.51% in the placebo group.

As a result of the two reactions, UK regulators are now recommending that patients with a history of severe allergies not receive the vaccine at the current time.

Q: What are the likely side effects?

So far, the most common side effects are pain at the injection site and an achy, flu-like feeling, Dr. Kuppalli said. More severe reactions have been reported, but were not common in the trials.

Dr. Rasmussen noted that the common side effects are a good sign, and signal that the recipient is generating “a robust immune response.”

“Everybody I’ve talked to who’s had the response has said they would go through it again,” Dr. Kruppalli said. “I definitely plan on lining up and being one of the first people to get the vaccine.”

Q: I already had COVID-19 or had a positive antibody test. Do I still need to get the vaccine?

Dr. Rasmussen said that there are “too many unknowns” to say if a history of COVID-19 would make a difference. “We don’t know how long neutralizing antibodies last” after infection, she said. “What we know is that the vaccine tends to produce antibody titers towards the higher end of the spectrum,” suggesting better immunity with vaccination than after natural infection.

Q: Can patients of color feel safe getting the vaccine?

“People of color might be understandably reluctant to take a vaccine that was developed in a way that appears to be faster [than past development],” said Dr. Rasmussen. She said physicians should acknowledge and understand the history that has led them to feel that way, “everything from Tuskegee to Henrietta Lacks to today.”

Empathy is key, and “providers should meet patients where they are and not condescend to them.”

Dr. Kuppalli agreed. “Clinicians really need to work on trying to strip away their biases.”

Thus far there are no safety signals that differ by race or ethnicity, according to the companies. The Pfizer phase 3 trial enrolled just over 9% Black participants, 0.5% Native American/Alaska Native, 0.2% Native Hawaiian/Pacific Islander, 2.3% multiracial participants, and 28% Hispanic/Latinx. For its part, Moderna says that approximately 37% of participants in its phase 3 trial come from communities of color.

Q: What about children and pregnant women?

Although the trials included participants from many different age groups and backgrounds, children and pregnant or lactating women were not among them. Pfizer gained approval in October to include participants as young as age 12 years, and a Moderna spokesperson said in an interview that the company planned pediatric inclusion at the end of 2020, pending approval.

“Unfortunately, we don’t have data on pregnant and lactating women,” Dr. Kuppalli said. She said she hopes that public health organizations such as the CDC will address that in the coming weeks. Dr. Rasmussen called the lack of data in pregnant women and children “a big oversight.”

Dr. Rasmussen has disclosed no relevant financial relationships. Dr. Kuppalli is a consultant with GlaxoSmithKline.

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

With U.S. approval of one coronavirus vaccine likely imminent and approval of a second one expected soon after, physicians will likely be deluged with questions. Public attitudes about the vaccines vary by demographics, with a recent poll showing that men and older adults are more likely to choose vaccination, and women and people of color evincing more wariness.

Although the reasons for reluctance may vary, questions from patient will likely be similar. Some are related to the “warp speed” language about the vaccines. Other concerns arise from the fact that the platform – mRNA – has not been used in human vaccines before. And as with any vaccine, there are rumors and false claims making the rounds on social media.

In anticipation of the most common questions physicians may encounter, two experts, Krutika Kuppalli, MD, assistant professor of medicine in the division of infectious diseases at the Medical University of South Carolina, Charleston, and Angela Rasmussen, PhD, virologist and nonresident affiliate at Georgetown University’s Center for Global Health Science and Security, Washington, talked in an interview about what clinicians can expect and what evidence-based – as well as compassionate – answers might look like.
 

Q: Will this vaccine give me COVID-19?

“There is not an intact virus in there,” Dr. Rasmussen said. The mRNA-based vaccines cannot cause COVID-19 because they don’t use any part of the coronavirus itself. Instead, the Moderna and Pfizer vaccines contain manufactured mRNA molecules that carry the instructions for building the virus’ spike protein. After vaccine administration, the recipient’s own cells take up this mRNA, use it to build this bit of protein, and display it on their surfaces. The foreign protein flag triggers the immune system response.

The mRNA does not enter the cell nucleus or interact with the recipient’s DNA. And because it’s so fragile, it degrades quite quickly. To keep that from happening before cell entry, the mRNAs are cushioned in protective fats.

Q: Was this vaccine made too quickly?

“People have been working on this platform for 30 years, so it’s not that this is brand new,” Dr. Kuppalli said.

Researchers began working on mRNA vaccines in the 1990s. Technological developments in the last decade have meant that their use has become feasible, and they have been tested in animals against many viral diseases. The mRNA vaccines are attractive because they’re expected to be safe and easily manufactured from common materials. That’s what we’ve seen in the COVID-19 pandemic, the  Centers for Disease Control and Prevention says on its website. Design of the spike protein mRNA component began as soon as the viral genome became available in January.

Usually, rolling out a vaccine takes years, so less than a year under a program called Operation Warp Speed can seem like moving too fast, Dr. Rasmussen acknowledged. “The name has given people the impression that by going at warp speed, we’re cutting all the corners. [But] the reality is that Operation Warp Speed is mostly for manufacturing and distribution.”

What underlies the speed is a restructuring of the normal vaccine development process, Dr. Kuppalli said. The same phases of development – animal testing, a small initial human phase, a second for safety testing, a third large phase for efficacy – were all conducted as for any vaccine. But in this case, some phases were completed in parallel, rather than sequentially. This approach has proved so successful that there is already talk about making it the model for developing future vaccines.

Two other factors contributed to the speed, said Dr. Kuppalli and Dr. Rasmussen. First, gearing up production can slow a rollout, but with these vaccines, companies ramped up production even before anyone knew if the vaccines would work – the “warp speed” part. The second factor has been the large number of cases, making exposures more likely and thus accelerating the results of the efficacy trials. “There is so much COVID being transmitted everywhere in the United States that it did not take long to hit the threshold of events to read out phase 3,” Dr. Rasmussen said.

Q: This vaccine has never been used in humans. How do we know it’s safe?

The Pfizer phase 3 trial included more than 43,000 people, and Moderna’s had more than 30,000. The first humans received mRNA-based COVID-19 vaccines in March. The most common adverse events emerge right after a vaccination, Dr. Kuppalli said.

As with any vaccine that gains approval, monitoring will continue.

UK health officials have reported that two health care workers vaccinated in the initial rollout of the Pfizer vaccine had what seems to have been a severe allergic response. Both recipients had a history of anaphylactic allergic responses and carried EpiPens, and both recovered. During the trial, allergic reaction rates were 0.63% in the vaccine group and 0.51% in the placebo group.

As a result of the two reactions, UK regulators are now recommending that patients with a history of severe allergies not receive the vaccine at the current time.

Q: What are the likely side effects?

So far, the most common side effects are pain at the injection site and an achy, flu-like feeling, Dr. Kuppalli said. More severe reactions have been reported, but were not common in the trials.

Dr. Rasmussen noted that the common side effects are a good sign, and signal that the recipient is generating “a robust immune response.”

“Everybody I’ve talked to who’s had the response has said they would go through it again,” Dr. Kruppalli said. “I definitely plan on lining up and being one of the first people to get the vaccine.”

Q: I already had COVID-19 or had a positive antibody test. Do I still need to get the vaccine?

Dr. Rasmussen said that there are “too many unknowns” to say if a history of COVID-19 would make a difference. “We don’t know how long neutralizing antibodies last” after infection, she said. “What we know is that the vaccine tends to produce antibody titers towards the higher end of the spectrum,” suggesting better immunity with vaccination than after natural infection.

Q: Can patients of color feel safe getting the vaccine?

“People of color might be understandably reluctant to take a vaccine that was developed in a way that appears to be faster [than past development],” said Dr. Rasmussen. She said physicians should acknowledge and understand the history that has led them to feel that way, “everything from Tuskegee to Henrietta Lacks to today.”

Empathy is key, and “providers should meet patients where they are and not condescend to them.”

Dr. Kuppalli agreed. “Clinicians really need to work on trying to strip away their biases.”

Thus far there are no safety signals that differ by race or ethnicity, according to the companies. The Pfizer phase 3 trial enrolled just over 9% Black participants, 0.5% Native American/Alaska Native, 0.2% Native Hawaiian/Pacific Islander, 2.3% multiracial participants, and 28% Hispanic/Latinx. For its part, Moderna says that approximately 37% of participants in its phase 3 trial come from communities of color.

Q: What about children and pregnant women?

Although the trials included participants from many different age groups and backgrounds, children and pregnant or lactating women were not among them. Pfizer gained approval in October to include participants as young as age 12 years, and a Moderna spokesperson said in an interview that the company planned pediatric inclusion at the end of 2020, pending approval.

“Unfortunately, we don’t have data on pregnant and lactating women,” Dr. Kuppalli said. She said she hopes that public health organizations such as the CDC will address that in the coming weeks. Dr. Rasmussen called the lack of data in pregnant women and children “a big oversight.”

Dr. Rasmussen has disclosed no relevant financial relationships. Dr. Kuppalli is a consultant with GlaxoSmithKline.

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

With U.S. approval of one coronavirus vaccine likely imminent and approval of a second one expected soon after, physicians will likely be deluged with questions. Public attitudes about the vaccines vary by demographics, with a recent poll showing that men and older adults are more likely to choose vaccination, and women and people of color evincing more wariness.

Although the reasons for reluctance may vary, questions from patient will likely be similar. Some are related to the “warp speed” language about the vaccines. Other concerns arise from the fact that the platform – mRNA – has not been used in human vaccines before. And as with any vaccine, there are rumors and false claims making the rounds on social media.

In anticipation of the most common questions physicians may encounter, two experts, Krutika Kuppalli, MD, assistant professor of medicine in the division of infectious diseases at the Medical University of South Carolina, Charleston, and Angela Rasmussen, PhD, virologist and nonresident affiliate at Georgetown University’s Center for Global Health Science and Security, Washington, talked in an interview about what clinicians can expect and what evidence-based – as well as compassionate – answers might look like.
 

Q: Will this vaccine give me COVID-19?

“There is not an intact virus in there,” Dr. Rasmussen said. The mRNA-based vaccines cannot cause COVID-19 because they don’t use any part of the coronavirus itself. Instead, the Moderna and Pfizer vaccines contain manufactured mRNA molecules that carry the instructions for building the virus’ spike protein. After vaccine administration, the recipient’s own cells take up this mRNA, use it to build this bit of protein, and display it on their surfaces. The foreign protein flag triggers the immune system response.

The mRNA does not enter the cell nucleus or interact with the recipient’s DNA. And because it’s so fragile, it degrades quite quickly. To keep that from happening before cell entry, the mRNAs are cushioned in protective fats.

Q: Was this vaccine made too quickly?

“People have been working on this platform for 30 years, so it’s not that this is brand new,” Dr. Kuppalli said.

Researchers began working on mRNA vaccines in the 1990s. Technological developments in the last decade have meant that their use has become feasible, and they have been tested in animals against many viral diseases. The mRNA vaccines are attractive because they’re expected to be safe and easily manufactured from common materials. That’s what we’ve seen in the COVID-19 pandemic, the  Centers for Disease Control and Prevention says on its website. Design of the spike protein mRNA component began as soon as the viral genome became available in January.

Usually, rolling out a vaccine takes years, so less than a year under a program called Operation Warp Speed can seem like moving too fast, Dr. Rasmussen acknowledged. “The name has given people the impression that by going at warp speed, we’re cutting all the corners. [But] the reality is that Operation Warp Speed is mostly for manufacturing and distribution.”

What underlies the speed is a restructuring of the normal vaccine development process, Dr. Kuppalli said. The same phases of development – animal testing, a small initial human phase, a second for safety testing, a third large phase for efficacy – were all conducted as for any vaccine. But in this case, some phases were completed in parallel, rather than sequentially. This approach has proved so successful that there is already talk about making it the model for developing future vaccines.

Two other factors contributed to the speed, said Dr. Kuppalli and Dr. Rasmussen. First, gearing up production can slow a rollout, but with these vaccines, companies ramped up production even before anyone knew if the vaccines would work – the “warp speed” part. The second factor has been the large number of cases, making exposures more likely and thus accelerating the results of the efficacy trials. “There is so much COVID being transmitted everywhere in the United States that it did not take long to hit the threshold of events to read out phase 3,” Dr. Rasmussen said.

Q: This vaccine has never been used in humans. How do we know it’s safe?

The Pfizer phase 3 trial included more than 43,000 people, and Moderna’s had more than 30,000. The first humans received mRNA-based COVID-19 vaccines in March. The most common adverse events emerge right after a vaccination, Dr. Kuppalli said.

As with any vaccine that gains approval, monitoring will continue.

UK health officials have reported that two health care workers vaccinated in the initial rollout of the Pfizer vaccine had what seems to have been a severe allergic response. Both recipients had a history of anaphylactic allergic responses and carried EpiPens, and both recovered. During the trial, allergic reaction rates were 0.63% in the vaccine group and 0.51% in the placebo group.

As a result of the two reactions, UK regulators are now recommending that patients with a history of severe allergies not receive the vaccine at the current time.

Q: What are the likely side effects?

So far, the most common side effects are pain at the injection site and an achy, flu-like feeling, Dr. Kuppalli said. More severe reactions have been reported, but were not common in the trials.

Dr. Rasmussen noted that the common side effects are a good sign, and signal that the recipient is generating “a robust immune response.”

“Everybody I’ve talked to who’s had the response has said they would go through it again,” Dr. Kruppalli said. “I definitely plan on lining up and being one of the first people to get the vaccine.”

Q: I already had COVID-19 or had a positive antibody test. Do I still need to get the vaccine?

Dr. Rasmussen said that there are “too many unknowns” to say if a history of COVID-19 would make a difference. “We don’t know how long neutralizing antibodies last” after infection, she said. “What we know is that the vaccine tends to produce antibody titers towards the higher end of the spectrum,” suggesting better immunity with vaccination than after natural infection.

Q: Can patients of color feel safe getting the vaccine?

“People of color might be understandably reluctant to take a vaccine that was developed in a way that appears to be faster [than past development],” said Dr. Rasmussen. She said physicians should acknowledge and understand the history that has led them to feel that way, “everything from Tuskegee to Henrietta Lacks to today.”

Empathy is key, and “providers should meet patients where they are and not condescend to them.”

Dr. Kuppalli agreed. “Clinicians really need to work on trying to strip away their biases.”

Thus far there are no safety signals that differ by race or ethnicity, according to the companies. The Pfizer phase 3 trial enrolled just over 9% Black participants, 0.5% Native American/Alaska Native, 0.2% Native Hawaiian/Pacific Islander, 2.3% multiracial participants, and 28% Hispanic/Latinx. For its part, Moderna says that approximately 37% of participants in its phase 3 trial come from communities of color.

Q: What about children and pregnant women?

Although the trials included participants from many different age groups and backgrounds, children and pregnant or lactating women were not among them. Pfizer gained approval in October to include participants as young as age 12 years, and a Moderna spokesperson said in an interview that the company planned pediatric inclusion at the end of 2020, pending approval.

“Unfortunately, we don’t have data on pregnant and lactating women,” Dr. Kuppalli said. She said she hopes that public health organizations such as the CDC will address that in the coming weeks. Dr. Rasmussen called the lack of data in pregnant women and children “a big oversight.”

Dr. Rasmussen has disclosed no relevant financial relationships. Dr. Kuppalli is a consultant with GlaxoSmithKline.

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

Vitamin D deficiency on admission to hospital was associated with a 3.7-fold increase in the odds of dying from COVID-19, according to an observational study looking back at data from the first wave of the pandemic.

Nearly 60% of patients with COVID-19 were vitamin D deficient upon hospitalization, with men in the advanced stages of COVID-19 pneumonia showing the greatest deficit.

Importantly, the results were independent of comorbidities known to be affected by vitamin D deficiency, wrote the authors, led by Dieter De Smet, MD, from AZ Delta General Hospital, Roeselare, Belgium.

“[The findings] highlight the need for randomized, controlled trials specifically targeting vitamin D–deficient patients at intake, and make a call for general avoidance of vitamin D deficiency as a safe and inexpensive possible mitigation of the SARS-CoV-2 pandemic,” Dr. De Smet and colleagues wrote in their article, published online Nov. 25 in the American Journal of Clinical Pathology.

A search of ClinicalTrials.gov reveals there are currently close to 40 ongoing intervention trials with vitamin D in COVID-19 around the world for varying purposes, including prevention, and varying forms of treatment.
 

Consider vitamin D to prevent COVID-19 infection

With regard to the potential role in prevention, “Numerous observational studies have shown that low vitamin D levels are a major predictor for poor COVID outcomes,” noted Jacob Teitelbaum, MD, an internist who specializes in treating chronic fatigue syndrome and fibromyalgia who also has an interest in COVID-19.

“This study shows how severe a problem this is,” Dr. Teitelbaum said in an interview. “A 3.7-fold increase in death rate if someone’s vitamin D level was below 20 [ng/mL] is staggering. It is arguably one of the most important risk factors to consider.”

“What is not clear is whether vitamin D levels are acting as an acute-phase reactant, dropping because of the infection, with larger drops indicating more severe disease, or whether vitamin D deficiency is causing worse outcomes,” added Dr. Teitelbaum, who is director of the Center for Effective CFIDS/Fibromyalgia Therapies, Kailua-Kona, Hawaii.

Also asked to comment, Andrea Giustina, MD, president of the European Society of Endocrinology, said: “The paper by De Smet et al confirms what we already hypothesized in BMJ last March: that patients with low vitamin D levels are at high risk of hospitalization for COVID-19 and developing severe and lethal disease. This is likely due to the loss in the protective action of vitamin D on the immune system and against the SARS-CoV-2–induced cytokine storm.”

He said it is particularly interesting that the authors of the new study had reported more prevalent vitamin D deficiency among men than women, most likely because women are more often treated with vitamin D for osteoporosis.

The new study should prompt all clinicians and health authorities to seriously consider vitamin D supplementation as an additional tool in the fight against COVID-19, particularly for the prevention of infection in those at high risk of both COVID-19 and hypovitaminosis D, such the elderly, urged Dr. Giustina, of San Raffaele Vita-Salute University, Milan.
 

Results adjusted for multiple confounders

Dr. De Smet and colleagues looked at serum 25-hydroxyvitamin D (25[OH]D) levels in 186 patients hospitalized for severe COVID-19 infection as a function of radiologic stage of COVID-19 pneumonia as well as the association between vitamin D status on admission and COVID-19 mortality.

Cognizant of the potential for confounding by multiple factors, they adjusted for age, sex, and known vitamin D–affected comorbidities such as diabetes, chronic lung disease, and coronary artery disease.

Patients were hospitalized from March 1 to April 7, 2020 (the peak of the first wave of the pandemic) at their institution, AZ Delta General Hospital, a tertiary network hospital.

The mean age of patients was 69 years, 41% were women, and 59% had coronary artery disease. Upon admission to hospital, median vitamin D level was 18 ng/mL (women, 20.7 ng/mL; men, 17.6 ng/mL).

A remarkably high percentage (59%, 109/186) of patients with COVID-19 were vitamin D deficient (25[OH]D <20 ng/mL) when admitted (47% of women and 67% of men), wrote the authors.

“What surprises me,” said Dr. Teitelbaum, is that almost 60% “of these patients had 25(OH)D under 20 ng/mL but most clinicians consider under 50 to be low.”

All patients had a chest CT scan to determine the radiologic stage of COVID-19 pneumonia and serum vitamin D measurement on admission. Radiologic stage of pneumonia was used as a proxy for immunologic phase of COVID-19.
 

Vitamin D deficiency correlated with worsening pneumonia

Among men, rates of vitamin D deficiency increased with advancing disease, with rates of 55% in stage 1, 67% in stage 2, and up to 74% in stage 3 pneumonia.

There is therefore “a clear correlation between 25(OH)D level and temporal stages of viral pneumonia, particularly in male patients,” the authors wrote.

“Vitamin D dampens excessive inflammation,” said Dr. Teitelbaum. “In these patients with acute respiratory distress syndrome, the immune system has gone wild.”

“The study was carried out in Belgium, so there’s less sunlight there than some other places, but even here in Hawaii, with plenty of sunshine, we have vitamin D deficiency,” he added.

“More studies are needed, but I think there are enough data to suggest a multivitamin should be used to aid prophylaxis, and this is reflected in [some] infectious disease recommendations,” he noted.

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

Vitamin D deficiency on admission to hospital was associated with a 3.7-fold increase in the odds of dying from COVID-19, according to an observational study looking back at data from the first wave of the pandemic.

Nearly 60% of patients with COVID-19 were vitamin D deficient upon hospitalization, with men in the advanced stages of COVID-19 pneumonia showing the greatest deficit.

Importantly, the results were independent of comorbidities known to be affected by vitamin D deficiency, wrote the authors, led by Dieter De Smet, MD, from AZ Delta General Hospital, Roeselare, Belgium.

“[The findings] highlight the need for randomized, controlled trials specifically targeting vitamin D–deficient patients at intake, and make a call for general avoidance of vitamin D deficiency as a safe and inexpensive possible mitigation of the SARS-CoV-2 pandemic,” Dr. De Smet and colleagues wrote in their article, published online Nov. 25 in the American Journal of Clinical Pathology.

A search of ClinicalTrials.gov reveals there are currently close to 40 ongoing intervention trials with vitamin D in COVID-19 around the world for varying purposes, including prevention, and varying forms of treatment.
 

Consider vitamin D to prevent COVID-19 infection

With regard to the potential role in prevention, “Numerous observational studies have shown that low vitamin D levels are a major predictor for poor COVID outcomes,” noted Jacob Teitelbaum, MD, an internist who specializes in treating chronic fatigue syndrome and fibromyalgia who also has an interest in COVID-19.

“This study shows how severe a problem this is,” Dr. Teitelbaum said in an interview. “A 3.7-fold increase in death rate if someone’s vitamin D level was below 20 [ng/mL] is staggering. It is arguably one of the most important risk factors to consider.”

“What is not clear is whether vitamin D levels are acting as an acute-phase reactant, dropping because of the infection, with larger drops indicating more severe disease, or whether vitamin D deficiency is causing worse outcomes,” added Dr. Teitelbaum, who is director of the Center for Effective CFIDS/Fibromyalgia Therapies, Kailua-Kona, Hawaii.

Also asked to comment, Andrea Giustina, MD, president of the European Society of Endocrinology, said: “The paper by De Smet et al confirms what we already hypothesized in BMJ last March: that patients with low vitamin D levels are at high risk of hospitalization for COVID-19 and developing severe and lethal disease. This is likely due to the loss in the protective action of vitamin D on the immune system and against the SARS-CoV-2–induced cytokine storm.”

He said it is particularly interesting that the authors of the new study had reported more prevalent vitamin D deficiency among men than women, most likely because women are more often treated with vitamin D for osteoporosis.

The new study should prompt all clinicians and health authorities to seriously consider vitamin D supplementation as an additional tool in the fight against COVID-19, particularly for the prevention of infection in those at high risk of both COVID-19 and hypovitaminosis D, such the elderly, urged Dr. Giustina, of San Raffaele Vita-Salute University, Milan.
 

Results adjusted for multiple confounders

Dr. De Smet and colleagues looked at serum 25-hydroxyvitamin D (25[OH]D) levels in 186 patients hospitalized for severe COVID-19 infection as a function of radiologic stage of COVID-19 pneumonia as well as the association between vitamin D status on admission and COVID-19 mortality.

Cognizant of the potential for confounding by multiple factors, they adjusted for age, sex, and known vitamin D–affected comorbidities such as diabetes, chronic lung disease, and coronary artery disease.

Patients were hospitalized from March 1 to April 7, 2020 (the peak of the first wave of the pandemic) at their institution, AZ Delta General Hospital, a tertiary network hospital.

The mean age of patients was 69 years, 41% were women, and 59% had coronary artery disease. Upon admission to hospital, median vitamin D level was 18 ng/mL (women, 20.7 ng/mL; men, 17.6 ng/mL).

A remarkably high percentage (59%, 109/186) of patients with COVID-19 were vitamin D deficient (25[OH]D <20 ng/mL) when admitted (47% of women and 67% of men), wrote the authors.

“What surprises me,” said Dr. Teitelbaum, is that almost 60% “of these patients had 25(OH)D under 20 ng/mL but most clinicians consider under 50 to be low.”

All patients had a chest CT scan to determine the radiologic stage of COVID-19 pneumonia and serum vitamin D measurement on admission. Radiologic stage of pneumonia was used as a proxy for immunologic phase of COVID-19.
 

Vitamin D deficiency correlated with worsening pneumonia

Among men, rates of vitamin D deficiency increased with advancing disease, with rates of 55% in stage 1, 67% in stage 2, and up to 74% in stage 3 pneumonia.

There is therefore “a clear correlation between 25(OH)D level and temporal stages of viral pneumonia, particularly in male patients,” the authors wrote.

“Vitamin D dampens excessive inflammation,” said Dr. Teitelbaum. “In these patients with acute respiratory distress syndrome, the immune system has gone wild.”

“The study was carried out in Belgium, so there’s less sunlight there than some other places, but even here in Hawaii, with plenty of sunshine, we have vitamin D deficiency,” he added.

“More studies are needed, but I think there are enough data to suggest a multivitamin should be used to aid prophylaxis, and this is reflected in [some] infectious disease recommendations,” he noted.

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

Vitamin D deficiency on admission to hospital was associated with a 3.7-fold increase in the odds of dying from COVID-19, according to an observational study looking back at data from the first wave of the pandemic.

Nearly 60% of patients with COVID-19 were vitamin D deficient upon hospitalization, with men in the advanced stages of COVID-19 pneumonia showing the greatest deficit.

Importantly, the results were independent of comorbidities known to be affected by vitamin D deficiency, wrote the authors, led by Dieter De Smet, MD, from AZ Delta General Hospital, Roeselare, Belgium.

“[The findings] highlight the need for randomized, controlled trials specifically targeting vitamin D–deficient patients at intake, and make a call for general avoidance of vitamin D deficiency as a safe and inexpensive possible mitigation of the SARS-CoV-2 pandemic,” Dr. De Smet and colleagues wrote in their article, published online Nov. 25 in the American Journal of Clinical Pathology.

A search of ClinicalTrials.gov reveals there are currently close to 40 ongoing intervention trials with vitamin D in COVID-19 around the world for varying purposes, including prevention, and varying forms of treatment.
 

Consider vitamin D to prevent COVID-19 infection

With regard to the potential role in prevention, “Numerous observational studies have shown that low vitamin D levels are a major predictor for poor COVID outcomes,” noted Jacob Teitelbaum, MD, an internist who specializes in treating chronic fatigue syndrome and fibromyalgia who also has an interest in COVID-19.

“This study shows how severe a problem this is,” Dr. Teitelbaum said in an interview. “A 3.7-fold increase in death rate if someone’s vitamin D level was below 20 [ng/mL] is staggering. It is arguably one of the most important risk factors to consider.”

“What is not clear is whether vitamin D levels are acting as an acute-phase reactant, dropping because of the infection, with larger drops indicating more severe disease, or whether vitamin D deficiency is causing worse outcomes,” added Dr. Teitelbaum, who is director of the Center for Effective CFIDS/Fibromyalgia Therapies, Kailua-Kona, Hawaii.

Also asked to comment, Andrea Giustina, MD, president of the European Society of Endocrinology, said: “The paper by De Smet et al confirms what we already hypothesized in BMJ last March: that patients with low vitamin D levels are at high risk of hospitalization for COVID-19 and developing severe and lethal disease. This is likely due to the loss in the protective action of vitamin D on the immune system and against the SARS-CoV-2–induced cytokine storm.”

He said it is particularly interesting that the authors of the new study had reported more prevalent vitamin D deficiency among men than women, most likely because women are more often treated with vitamin D for osteoporosis.

The new study should prompt all clinicians and health authorities to seriously consider vitamin D supplementation as an additional tool in the fight against COVID-19, particularly for the prevention of infection in those at high risk of both COVID-19 and hypovitaminosis D, such the elderly, urged Dr. Giustina, of San Raffaele Vita-Salute University, Milan.
 

Results adjusted for multiple confounders

Dr. De Smet and colleagues looked at serum 25-hydroxyvitamin D (25[OH]D) levels in 186 patients hospitalized for severe COVID-19 infection as a function of radiologic stage of COVID-19 pneumonia as well as the association between vitamin D status on admission and COVID-19 mortality.

Cognizant of the potential for confounding by multiple factors, they adjusted for age, sex, and known vitamin D–affected comorbidities such as diabetes, chronic lung disease, and coronary artery disease.

Patients were hospitalized from March 1 to April 7, 2020 (the peak of the first wave of the pandemic) at their institution, AZ Delta General Hospital, a tertiary network hospital.

The mean age of patients was 69 years, 41% were women, and 59% had coronary artery disease. Upon admission to hospital, median vitamin D level was 18 ng/mL (women, 20.7 ng/mL; men, 17.6 ng/mL).

A remarkably high percentage (59%, 109/186) of patients with COVID-19 were vitamin D deficient (25[OH]D <20 ng/mL) when admitted (47% of women and 67% of men), wrote the authors.

“What surprises me,” said Dr. Teitelbaum, is that almost 60% “of these patients had 25(OH)D under 20 ng/mL but most clinicians consider under 50 to be low.”

All patients had a chest CT scan to determine the radiologic stage of COVID-19 pneumonia and serum vitamin D measurement on admission. Radiologic stage of pneumonia was used as a proxy for immunologic phase of COVID-19.
 

Vitamin D deficiency correlated with worsening pneumonia

Among men, rates of vitamin D deficiency increased with advancing disease, with rates of 55% in stage 1, 67% in stage 2, and up to 74% in stage 3 pneumonia.

There is therefore “a clear correlation between 25(OH)D level and temporal stages of viral pneumonia, particularly in male patients,” the authors wrote.

“Vitamin D dampens excessive inflammation,” said Dr. Teitelbaum. “In these patients with acute respiratory distress syndrome, the immune system has gone wild.”

“The study was carried out in Belgium, so there’s less sunlight there than some other places, but even here in Hawaii, with plenty of sunshine, we have vitamin D deficiency,” he added.

“More studies are needed, but I think there are enough data to suggest a multivitamin should be used to aid prophylaxis, and this is reflected in [some] infectious disease recommendations,” he noted.

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

Hospitalists and health care teams struggle with issues related to text messaging in the workplace. “It’s happening whether an institution has a secure text messaging platform or not,” said Philip Hagedorn, MD, MBI, associate chief medical information officer at Cincinnati Children’s Hospital Medical Center.

“Many places reacted to this reality by procuring a solution – take your pick of secure text messaging platforms – and implementing it, but bypassed an opportunity to think about how we tailor the use of this culturally ubiquitous medium to the health care setting,” he said.It doesn’t work to just drop a secure text messaging platform into clinical systems and expect that health care practitioners will know how to use them appropriately, Dr. Hagedorn says. “The way we use text messaging in our lives outside health care inevitably bleeds into how we use the medium at work, but it shouldn’t. The needs are different and the stakes are higher for communication in the health care setting.”

In a paper looking at the issue, Dr. Hagedorn and co-authors laid out critical areas of concern, such as text messaging becoming a form of alarm fatigue and also increasing the likelihood of communication error.

“It’s my hope that fellow hospitalists can use this as an opportunity to think deeply about how we communicate in health care,” he said. “If we don’t think critically about how and where something like text messaging should be used in medicine, we risk facing unintended consequences for our patients.”The article discusses several steps for mitigating the risks laid out, including proactive surveillance and targeted training. “These are starting points, and I’m sure there are plenty of other creative solutions out there. We wanted to get the conversation going. We’d love to hear from others who face similar issues or have come up with interesting solutions.”
 

Reference

1. Hagedorn PA, et al. Secure Text Messaging in Healthcare: Latent Threats and Opportunities to Improve Patient Safety. J Hosp Med. 2020 June;15(6):378-380. Published Online First 2019 Sept 18. doi: 10.12788/jhm.3305

Hospitalists and health care teams struggle with issues related to text messaging in the workplace. “It’s happening whether an institution has a secure text messaging platform or not,” said Philip Hagedorn, MD, MBI, associate chief medical information officer at Cincinnati Children’s Hospital Medical Center.

“Many places reacted to this reality by procuring a solution – take your pick of secure text messaging platforms – and implementing it, but bypassed an opportunity to think about how we tailor the use of this culturally ubiquitous medium to the health care setting,” he said.It doesn’t work to just drop a secure text messaging platform into clinical systems and expect that health care practitioners will know how to use them appropriately, Dr. Hagedorn says. “The way we use text messaging in our lives outside health care inevitably bleeds into how we use the medium at work, but it shouldn’t. The needs are different and the stakes are higher for communication in the health care setting.”

In a paper looking at the issue, Dr. Hagedorn and co-authors laid out critical areas of concern, such as text messaging becoming a form of alarm fatigue and also increasing the likelihood of communication error.

“It’s my hope that fellow hospitalists can use this as an opportunity to think deeply about how we communicate in health care,” he said. “If we don’t think critically about how and where something like text messaging should be used in medicine, we risk facing unintended consequences for our patients.”The article discusses several steps for mitigating the risks laid out, including proactive surveillance and targeted training. “These are starting points, and I’m sure there are plenty of other creative solutions out there. We wanted to get the conversation going. We’d love to hear from others who face similar issues or have come up with interesting solutions.”
 

Reference

1. Hagedorn PA, et al. Secure Text Messaging in Healthcare: Latent Threats and Opportunities to Improve Patient Safety. J Hosp Med. 2020 June;15(6):378-380. Published Online First 2019 Sept 18. doi: 10.12788/jhm.3305

Hospitalists and health care teams struggle with issues related to text messaging in the workplace. “It’s happening whether an institution has a secure text messaging platform or not,” said Philip Hagedorn, MD, MBI, associate chief medical information officer at Cincinnati Children’s Hospital Medical Center.

“Many places reacted to this reality by procuring a solution – take your pick of secure text messaging platforms – and implementing it, but bypassed an opportunity to think about how we tailor the use of this culturally ubiquitous medium to the health care setting,” he said.It doesn’t work to just drop a secure text messaging platform into clinical systems and expect that health care practitioners will know how to use them appropriately, Dr. Hagedorn says. “The way we use text messaging in our lives outside health care inevitably bleeds into how we use the medium at work, but it shouldn’t. The needs are different and the stakes are higher for communication in the health care setting.”

In a paper looking at the issue, Dr. Hagedorn and co-authors laid out critical areas of concern, such as text messaging becoming a form of alarm fatigue and also increasing the likelihood of communication error.

“It’s my hope that fellow hospitalists can use this as an opportunity to think deeply about how we communicate in health care,” he said. “If we don’t think critically about how and where something like text messaging should be used in medicine, we risk facing unintended consequences for our patients.”The article discusses several steps for mitigating the risks laid out, including proactive surveillance and targeted training. “These are starting points, and I’m sure there are plenty of other creative solutions out there. We wanted to get the conversation going. We’d love to hear from others who face similar issues or have come up with interesting solutions.”
 

Reference

1. Hagedorn PA, et al. Secure Text Messaging in Healthcare: Latent Threats and Opportunities to Improve Patient Safety. J Hosp Med. 2020 June;15(6):378-380. Published Online First 2019 Sept 18. doi: 10.12788/jhm.3305

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.