COVID-19 Updates

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

A year into the COVID-19 pandemic, the share of the U.S. adult population reporting symptoms of elevated depression had more than tripled from prepandemic levels and worsened significantly since restrictions went into effect, a study of more than 1,000 adults surveyed at the start of the pandemic and 1 year into it has reported.

The study also found that younger adults, people with lower incomes and savings, unmarried people, and those exposed to multiple stress factors were most vulnerable to elevated levels of depression through the first year of the pandemic.

“The pandemic has been an ongoing exposure,” lead author Catherine K. Ettman, a PhD candidate at Brown University, Providence, R.I., said in an interview. “Mental health is sensitive to economic and social conditions. While living conditions have improved for some people over the last 12 months, the pandemic has been disruptive to life and economic well-being for many,” said Ms. Ettman, who is also chief of staff and director of strategic initiatives in the office of the dean at Boston University. Her study was published in Lancet Regional Health – Americas.

Ms. Ettman and coauthors reported that 32.8% (95% confidence interval, 29.1%-36.8%) of surveyed adults had elevated depressive symptoms in 2021, compared with 27.8% (95% CI, 24.9%-30.9%) in the early months of the pandemic in 2020 (P = .0016). That compares with a rate of 8.5% before the pandemic, a figure based on a prepandemic sample of 5,065 patients from the National Health and Nutrition Examination Survey reported previously by Ms. Ettman and associates.

“The COVID-19 pandemic and its economic consequences have displaced social networks, created ongoing stressors, and reduced access to the resources that protect mental health,” Ms. Ettman said.
 

Four groups most affected

In this latest research, a longitudinal panel study of a nationally representative group of U.S. adults, the researchers surveyed participants in March and April 2020 (n = 1,414) and the same group again in March and April 2021 (n = 1,161). The participants completed the Patient Health Questionnaire–9 (PHQ-9) and were enrolled in the COVID-19 and Life Stressors Impact on Mental Health and Well-Being study.

The study found that elevated depressive symptoms were most prevalent in four groups:

• Younger patients, with 43.9% of patients aged 18-39 years self-reporting elevated depressive symptoms, compared with 32.4% of those aged 40-59, and 19.1% of patients aged 60 and older.
• People with lower incomes, with 58.1% of people making $19,999 or less reporting elevated symptoms, compared with 41.3% of those making $20,000-$44,999, 31.4% of people making $45,000-$74,999, and 14.1% of those making $75,000 or more.
• People with less than $5,000 in family savings, with a rate of 51.1%, compared with 24.2% of those with more than that.
• People never married, with a rate of 39.8% versus 37.7% of those living with a partner; 31.5% widowed, divorced, or separated; and 18.3% married.

The study also found correlations between the number of self-reported stressors and elevated depression symptoms: a rate of 51.1% in people with four or more stressors; 25.8% in those with two or three stressors; and 17% in people with one or no stressors.

Among the groups reporting the lowest rates of depressive symptoms in 2021 were people making more than $75,000 a year; those with one or no COVID-19 stressors; and non-Hispanic Asian persons.

“Stressors such as difficulties finding childcare, difficulties paying for housing, and job loss were associated with greater depression 12 months into the COVID-19 pandemic,” Ms. Ettman said. “Efforts to address stressors and improve access to childcare, housing, employment, and fair wages can improve mental health.”

The duration of the pandemic is another explanation for the significant rise in depressive symptoms, senior author Sandro Galea, MD, MPH, DrPH, said in an interview. “The COVID-19 pandemic is different from other traumatic events in its ongoing length, in its widespread reach, and in its inequities,” Dr. Galea added. “Unlike acute traumatic events, the COVID-19 pandemic has been ongoing.”

He said clinicians, public health officials, and policy makers need to be aware of the impact COVID-19 has had on mental health. “We can take steps as a society to treat and prevent depression and create conditions that allow all populations to be healthy,” said Dr. Galea, who is dean and a professor of family medicine at Boston University.
 

Age of sample cited as limitation

The study builds on existing evidence linking depression trends and the COVID-19 pandemic, David Puder, MD, a medical director at Loma Linda (Calif.) University, said in an interview. However, he noted it had some limitations. “The age range is only 18 and older, so we don’t get to see what is happening with a highly impacted group of students who have not been able to go to school and be with their friends during COVID,” said Dr. Puder, who also hosts the podcast “Psychiatry & Psychotherapy.” “Further, the PHQ-9 is often a screening tool for depression and is not best used for changes in mental health over time.”

At the same time, Dr. Puder said, one of the study’s strengths was that it showed how depressive symptoms increased during the COVID lockdown. “It shows certain groups are at higher risk, including those with less financial resources and those with higher amounts of stress,” Dr. Puder said.

Ms. Ettman, Dr. Galea, and Dr. Puder reported no relevant disclosures.

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

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

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

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

Pfizer asked the FDA on Thursday to expand emergency use authorization of its COVID-19 vaccine to children ages 5 to 11.

The request comes after the drugmaker submitted clinical trial data to the FDA on Sept. 28. Pfizer said the study of 2,268 children showed the vaccine was safe and produced a robust immune response.

Participants in the studies received a lower dose of the vaccine, 10 micrograms. Their response 2 weeks after a second dose was reportedly equal to the immune protection in a control group of 16- to 25-year-olds who received the fully approved 30-microgram doses.

Currently, the Pfizer EUA applies to 12- to 15-year-olds and people eligible for a Pfizer booster shot. The drugmaker received full FDA approval for the vaccine for Americans 16 years and older in August.

The filing for authorization in 5- to 11-year-olds comes as overall cases of COVID-19 in the United States continue to decline. The decrease includes a drop in new cases in children for the fourth consecutive week, according to analysis of data from the American Academy of Pediatrics and the Children’s Hospital Association.

The next step is an FDA decision on whether to expand the current emergency use authorization (EUA) for teenagers to the younger age group.

Timing of any official word from the agency is unknown. But possibly in anticipation of today’s filing, the FDA already scheduled a meeting of its Vaccines and Related Biological Products Advisory Committee for Oct. 25.

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

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

An 8-year-old girl who was infected with SARS-CoV-2 died after developing an extremely rare condition known as acute fulminant cerebral edema (AFCE), according to pediatric neurologists who are urging colleagues to watch out for similar cases.

At least one other child in the United States has died after becoming infected with the virus and developing cerebral edema. “The rapid and devastating clinical course in both of these cases highlights the need for early recognition of a cerebral edema and AFCE as potential complications of COVID-19 in pediatric patients,” the neurologists wrote.

The case was highlighted in a poster presented at the annual meeting of the Child Neurology Society and in a report published earlier this year in Child Neurology Open.

According to pediatric neurologist Timothy Gershon, MD, PhD , of the University of North Carolina at Chapel Hill, the child appeared in clinic in July 2020. She had been healthy but was suffering from 1 day of fever, seizure-like activity (generalized convulsions and drooling), anorexia, and lethargy.

The girl, who was subsequently diagnosed with COVID-19, deteriorated in the hospital. “She received IV dexamethasone in attempts to reduce cerebral edema,” the neurologists wrote. “Regarding immunomodulatory therapy, she received intravenous immunoglobulin (2 g/kg), anakinra, and hydrocortisone; despite approval for remdesivir and COVID-19 convalescent plasma, these were ultimately withheld due to poor prognosis.”

Brain death examinations at 24 and 48 hours after cardiac arrest were consistent with brain death, they reported.

Neurologists believe the patient suffered from AFCE, “an often fatal pediatric clinical entity consisting of fever, encephalopathy, and new-onset seizures followed by rapid, diffuse, and medically-refractory cerebral edema.” They add that “AFCE occurs as a rare complication of a variety of common pediatric infections, and a CNS [central nervous system] pathogen is identified in only a minority of cases, suggesting a para-infectious mechanism of edema.”

Neurologists offered a case definition of the “recently recognized” AFCE earlier this year.

“This was an extremely rare rapid progression to cerebral edema. I think it was related to the patient’s COVID infection, but why this patient got it and others don’t is unknown,” Dr. Gershon said in an interview. “The full spectrum of neurological complications of COVID were not yet known [at the time]. We didn’t know, and still don’t know, what the causative links are between COVID and suddenly having seizures and brain swelling.”

He said he’d treat a similar patient differently now and give dexamethasone earlier in the clinical course, although “there is no data to tell us if any therapy could have reversed it.” Specifically, he said, “I’d give dexamethasone at the first sign of brain involvement, using the dosing recommended for cerebral edema, and try to get the MRI earlier in the course.”

Dr. Gershon and colleagues noted another case of fatal cerebral edema in a child, a 7-year-old boy who was treated in New York state. That case “shows that fatal cerebral edema may complicate pediatric multisystem inflammatory syndrome,” they wrote.

Pediatric critical care specialist Preetha Krishnan, MD, of Randall Children’s Hospital at Legacy Emanuel in Portland, Ore., helped develop the new definition of AFCE. In an interview, she said AFCE is difficult to diagnose because the signs/symptoms – such as fever, altered sensorium, and seizures – are found in other conditions such as febrile status epilepticus with a viral illness. 
“The key to recognition of AFCE is that unlike other disease processes, these children have rapid neurologic progression,” she said. “In addition, many of our AFCE patients also had vomiting and/or headache, which in retrospect was likely an indication of elevated ICP [intracranial pressure] rather than viral infection.”
She added that “if a child with fever, seizures, and encephalopathy has cerebral edema on imaging and/or has neurologic progression, AFCE should be considered. Most of our cases of AFCE had fulminant progression within the first 3 days of their head imaging noting cerebral edema. There are other neurologic diseases, such as acute necrotizing encephalopathy of childhood, that also have progressive signs/symptoms, but head imaging and lab work should help differentiate many of these etiologies.”
In regard to treatment, she said, “our unit would likely err on the side of providing as much neuroprotective measures as is reasonable, such as maintaining normothermia, consideration of hyperosmolar therapy, maintaining normocarbia and normoxemia, managing seizures, etc. I would recommend getting the entire neurocritical care team involved in the management discussion. This varies by center, but will likely include neurology, ID [infectious disease], possibly neurosurgery, and PICU.”
As for the new case report, Krishnan said COVID-19 has been linked to neurologic complications, “so it does not surprise me that AFCE is part of the neurologic spectrum of disease.”
No funding was reported, and the authors report no relevant disclosures. Dr. Krishnan has no disclosures.

Exhaustion. Defeat. Hopelessness. Physicians, nurses, physician assistants, and nurse practitioners are overwhelmed with burnout.

The recent round of COVID-19 is more frustrating than the first, with scientific evidence supporting ways we can prevent disease and disease progression. The health care team is no longer viewed as heroes but as the enemy, fraudulently proposing a vaccine and painting a fictional story of death, though it’s all true. The daily educational battle with patients and family members creates a challenging environment that cultivates hopelessness.

Clinicians are physically exhausted from the numerous COVID cases. Gone are the medical patients we trained for, who either remain home and risk their health or lack access to medical providers because of excessive wait times. Empathy for COVID patients is being tested even more with this new surge, and without the two-way bond of trust, clinicians are running out of fuel. Anger and distrust regarding vaccination guidance dominate the interaction when patients present demanding urgent intervention, while clinicians know that more than 95% of hospitalized patients are unvaccinated.

The struggle to find the commitment to medicine and serving patients is made worse by the pandemic fog and loss of trust from patients. Every day, health care teams risk their personal well-being to provide medical care and intervention. Not by choice do we gown up, mask up, and glove up. Each time we enter a COVID patient’s room, we expose ourselves and risk our own lives and the lives of our families for the patients who have elected to ignore medical guidance.

This national wave of resistance to vaccination is spurring an exodus from health care. Physicians are retiring early and physician assistants and nurse practitioners are seeking non–patient-facing positions to improve their own wellness and balance. A national nursing shortage is impacting patients seeking care in every medical discipline. The underlying wave of exhaustion and frustration has not completely destroyed their empathy but has depleted their drive.

How can we regain this drive amid exhausting work hours and angry patients?

As much as we have heard it, we need to protect our time to recharge. The demand to pick up extra shifts and support our colleagues has affected our personal health. Setting boundaries and building time for exercise, meditation, and connecting with family is essential for survival. Mental health is key to retaining empathy and finding hope. Education is one path to reigniting the fires of critical thinking and commitment to patient care – consider precepting students to support the growth of health care teams. Memories of patient care before this pandemic give us the hope that there is light at the end of this tunnel.

Dr. Gadalla is a hospitalist at Treasure Coast Hospitalists in Port St. Lucie, Fla. She is a member of the Hospitalist’s editorial advisory board and also serves as a physician assistant program director at South University in West Palm Beach, Fla. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Exhaustion. Defeat. Hopelessness. Physicians, nurses, physician assistants, and nurse practitioners are overwhelmed with burnout.

The recent round of COVID-19 is more frustrating than the first, with scientific evidence supporting ways we can prevent disease and disease progression. The health care team is no longer viewed as heroes but as the enemy, fraudulently proposing a vaccine and painting a fictional story of death, though it’s all true. The daily educational battle with patients and family members creates a challenging environment that cultivates hopelessness.

Clinicians are physically exhausted from the numerous COVID cases. Gone are the medical patients we trained for, who either remain home and risk their health or lack access to medical providers because of excessive wait times. Empathy for COVID patients is being tested even more with this new surge, and without the two-way bond of trust, clinicians are running out of fuel. Anger and distrust regarding vaccination guidance dominate the interaction when patients present demanding urgent intervention, while clinicians know that more than 95% of hospitalized patients are unvaccinated.

The struggle to find the commitment to medicine and serving patients is made worse by the pandemic fog and loss of trust from patients. Every day, health care teams risk their personal well-being to provide medical care and intervention. Not by choice do we gown up, mask up, and glove up. Each time we enter a COVID patient’s room, we expose ourselves and risk our own lives and the lives of our families for the patients who have elected to ignore medical guidance.

This national wave of resistance to vaccination is spurring an exodus from health care. Physicians are retiring early and physician assistants and nurse practitioners are seeking non–patient-facing positions to improve their own wellness and balance. A national nursing shortage is impacting patients seeking care in every medical discipline. The underlying wave of exhaustion and frustration has not completely destroyed their empathy but has depleted their drive.

How can we regain this drive amid exhausting work hours and angry patients?

As much as we have heard it, we need to protect our time to recharge. The demand to pick up extra shifts and support our colleagues has affected our personal health. Setting boundaries and building time for exercise, meditation, and connecting with family is essential for survival. Mental health is key to retaining empathy and finding hope. Education is one path to reigniting the fires of critical thinking and commitment to patient care – consider precepting students to support the growth of health care teams. Memories of patient care before this pandemic give us the hope that there is light at the end of this tunnel.

Dr. Gadalla is a hospitalist at Treasure Coast Hospitalists in Port St. Lucie, Fla. She is a member of the Hospitalist’s editorial advisory board and also serves as a physician assistant program director at South University in West Palm Beach, Fla. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Exhaustion. Defeat. Hopelessness. Physicians, nurses, physician assistants, and nurse practitioners are overwhelmed with burnout.

The recent round of COVID-19 is more frustrating than the first, with scientific evidence supporting ways we can prevent disease and disease progression. The health care team is no longer viewed as heroes but as the enemy, fraudulently proposing a vaccine and painting a fictional story of death, though it’s all true. The daily educational battle with patients and family members creates a challenging environment that cultivates hopelessness.

Clinicians are physically exhausted from the numerous COVID cases. Gone are the medical patients we trained for, who either remain home and risk their health or lack access to medical providers because of excessive wait times. Empathy for COVID patients is being tested even more with this new surge, and without the two-way bond of trust, clinicians are running out of fuel. Anger and distrust regarding vaccination guidance dominate the interaction when patients present demanding urgent intervention, while clinicians know that more than 95% of hospitalized patients are unvaccinated.

The struggle to find the commitment to medicine and serving patients is made worse by the pandemic fog and loss of trust from patients. Every day, health care teams risk their personal well-being to provide medical care and intervention. Not by choice do we gown up, mask up, and glove up. Each time we enter a COVID patient’s room, we expose ourselves and risk our own lives and the lives of our families for the patients who have elected to ignore medical guidance.

This national wave of resistance to vaccination is spurring an exodus from health care. Physicians are retiring early and physician assistants and nurse practitioners are seeking non–patient-facing positions to improve their own wellness and balance. A national nursing shortage is impacting patients seeking care in every medical discipline. The underlying wave of exhaustion and frustration has not completely destroyed their empathy but has depleted their drive.

How can we regain this drive amid exhausting work hours and angry patients?

As much as we have heard it, we need to protect our time to recharge. The demand to pick up extra shifts and support our colleagues has affected our personal health. Setting boundaries and building time for exercise, meditation, and connecting with family is essential for survival. Mental health is key to retaining empathy and finding hope. Education is one path to reigniting the fires of critical thinking and commitment to patient care – consider precepting students to support the growth of health care teams. Memories of patient care before this pandemic give us the hope that there is light at the end of this tunnel.

Dr. Gadalla is a hospitalist at Treasure Coast Hospitalists in Port St. Lucie, Fla. She is a member of the Hospitalist’s editorial advisory board and also serves as a physician assistant program director at South University in West Palm Beach, Fla. She disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Soon after Merck announced on Oct. 1 that it would ask federal regulators for emergency use authorization (EUA) for its auspicious new COVID-19 pill, the accolades began.

Former Food and Drug Administration chief Scott Gottlieb, MD, told CNBC the drug was “a profound game changer.” Top infectious disease expert Anthony S. Fauci, MD, called the early data “impressive.” The World Health Organization termed it “certainly good news,” while saying it awaits more data.

Merck, partnering with Ridgeback Biotherapeutics on the investigational oral antiviral medicine molnupiravir, plans to submit applications to regulatory agencies worldwide, hoping to deliver the first oral antiviral medication for COVID-19. 

Interim clinical trial results show that the drug may slash the risk for hospitalization or death by 50% in those with mild to moderate COVID-19.

When the results were found to be so favorable, the study was halted at the recommendation of an independent data-monitoring committee and in consultation with the FDA.

That initial enthusiasm is now tempered with some perspective on the pros and cons. “This anticipated drug has gotten a little more hype than it deserves,” said William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center in Nashville, Tenn. He and others suggest a reality check.

“It’s not exactly a home run, like penicillin for strep throat,” agreed Carl Fichtenbaum, MD, professor of infectious diseases at the University of Cincinnati, who is investigating a similar pill for a rival company, Atea, partnering with Roche. 

“But it is encouraging,” he said. “It will probably be an incremental improvement on what we have.” The fact that it can be taken at home is a plus: “Anything we can do to keep people from getting sicker is a good thing.”

“The data show in this higher risk group [those who were studied had at least one risk factor for severe COVID-19, such as age or a medical condition], it reduces the risk of advancing to severe disease by 50%,” Dr. Schaffner said. While that’s a clear benefit for half, it of course leaves the other half without benefit, he said.

Others critiqued the predicted cost of the drug. The U.S. government has already agreed to pay about $700 per patient, according to a new report from Harvard T. H. Chan School of Public Health, Boston, and King’s College Hospital, London. That analysis concluded that the actual cost of production for the 5-day course is $17.74.

“We fully expect that having an oral treatment that reduces the risk of hospitalizations will be significantly cost effective for society,” Melissa Moody, a Merck spokesperson, told this news organization. “We are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic.”

Merck expects to produce 10 million courses of treatment by the end of the year, with additional doses expected to be produced in 2022, according to a company press release. Earlier in 2021, Merck finalized its agreement with the U.S. government to supply about 1.7 million courses of the drug at the $700 price, once an EUA or FDA approval is given.

Merck also has supply and purchase agreements with other governments worldwide, pending regulatory approval.
 

Study details

Details about the study findings came from a Merck press release. In the planned interim analysis, Merck and Ridgeback evaluated data from 775 patients initially enrolled in the phase 3 MOVe-OUT trial.

All adults had lab-confirmed mild to moderate COVID-19, and reported onset of symptoms within 5 days of being randomly assigned to the drug or placebo. All had at least one risk factor linked with poor disease outcome (such as older age or obesity).

The drug is a ribonucleoside and works by creating mutations in the virus’s genome, halting the ability of the virus to replicate.

Through day 29 of the study, the drug reduced the risk or hospitalization or death by about 50%. While 7.3% of those who received the drug either died or were hospitalized by day 29, 14.1% of those on placebo did, a statistically significant difference (P = .0012).

Side effects were similar in both groups, with 35% of the drug-treated and 40% of the placebo group reporting some side effect, Merck reported. Adverse drug-related events were 12% in the drug group and 11% in the placebo group. While 1.3% of the drug-treated group quit the study because of an adverse event, 3.4% of the placebo group quit.
 

Pros, cons, and unknowns

The ability to take the drug orally, and at home, is a definite plus, Dr. Schaffner said,  compared with the monoclonal antibody treatment currently approved that must be given intravenously or subcutaneously and in certain locations.

More people could be reached and helped with the option of an at-home, oral medicine, he and others agreed.

The regimen for molnupiravir is four pills, two times daily, for 5 days, even if symptoms are mild. As with other prescription drugs, “there will always be folks who don’t comply completely” with the prescribed regimen, Dr. Schaffner said. With this pill, that might be especially true if the symptoms are very mild.

The 50% reduction is not as effective as the benefit often quoted for monoclonal antibody treatment. In clinical trials of Regeneron’s monoclonal antibody treatment, the regimen reduced COVID-19–related hospitalization or death in high-risk patients by 70%.

Even so, the new pill could change the pandemic’s course, others say. “I think molnupiravir has the potential to change how we take care of people who have COVID and risk factors for developing severe disease,” Rajesh Tim Gandhi, MD, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization. 

“What we’ll need to do, however, is make sure that people get tested quickly after they develop symptoms and, if they’re confirmed to have COVID, start on the pills within 5 days of developing symptoms,” he said, while warning that more data are needed about the drug and the trial results.

Another concern is that the promise of a pill will stall vaccination rates, with some people figuring why get vaccinated when they can obtain the pill if they do get sick.

Relying on treatment alone won’t work, Dr. Schaffner said. “Let’s [also] focus on prevention, which is the vaccine. We have to keep working both sides of the street.”

Dr. Gandhi added: “It’s important to remember that even though molnupiravir reduced the likelihood of hospitalization and death, a number of people who received the drug still got sick enough to end up in the hospital.”

Also unknown, he said, is how severe their disease was and whether they will develop long COVID.

The Merck study included only unvaccinated people. Might it work for those vaccinated people who get a breakthrough infection? “From a purely scientific perspective, there is no reason to believe molnupiravir would not work in people who are vaccinated, but the overall efficacy on top of the vaccine is likely dependent on how well they were able to mount a protective immune response to the vaccine,” Ms. Moody said. Still, Merck believes the pill could be of benefit for these infections too, she added.

As for the expected cost, Ms. Moody said that the company takes into account a number of factors in setting pricing, “but fundamentally we look at the impact of the disease, the benefits that the drug delivers to patients and to society, and at supporting ongoing drug development.”
 

On Merck’s heels: Pfizer, Roche, Atea

Pfizer is studying an antiviral pill, PF-07321332, a protease inhibitor that blocks the protease enzymes and halts replication of the virus.

In addition to studying the drug in infected patients at high risk of severe illness and in those at typical risk, Pfizer launched a phase 2-3 study in late September that will enroll people who live in the same household as a person with a confirmed, symptomatic COVID-19 infection to see if the drug can prevent disease in those who have been exposed.

Atea and Roche’s COVID pill, AT527, is in phase 3 trials as well. AT527 is an inhibitor of polymerase, an enzyme many viruses have, to stop replications. Atea is evaluating the drug to reduce disease “burden” and for both pre- and postexposure prevention.
 

Big picture: Role of COVID-19 pills

It may be necessary to target the coronavirus with more than one antiviral agent, said Dr. Fichtenbaum, a principal investigator for the AT527 trials. 

“Sometimes viruses require two or three active agents to control their replication,” he said, citing information gleaned from other viral research, such as HIV. For control of HIV infection, a cocktail or combination of antivirals is often recommended.

That may well be the case for COVID-19, Dr. Fichtenbaum said. The goal would be to attack the virus at more than one pathway.

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

Soon after Merck announced on Oct. 1 that it would ask federal regulators for emergency use authorization (EUA) for its auspicious new COVID-19 pill, the accolades began.

Former Food and Drug Administration chief Scott Gottlieb, MD, told CNBC the drug was “a profound game changer.” Top infectious disease expert Anthony S. Fauci, MD, called the early data “impressive.” The World Health Organization termed it “certainly good news,” while saying it awaits more data.

Merck, partnering with Ridgeback Biotherapeutics on the investigational oral antiviral medicine molnupiravir, plans to submit applications to regulatory agencies worldwide, hoping to deliver the first oral antiviral medication for COVID-19. 

Interim clinical trial results show that the drug may slash the risk for hospitalization or death by 50% in those with mild to moderate COVID-19.

When the results were found to be so favorable, the study was halted at the recommendation of an independent data-monitoring committee and in consultation with the FDA.

That initial enthusiasm is now tempered with some perspective on the pros and cons. “This anticipated drug has gotten a little more hype than it deserves,” said William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center in Nashville, Tenn. He and others suggest a reality check.

“It’s not exactly a home run, like penicillin for strep throat,” agreed Carl Fichtenbaum, MD, professor of infectious diseases at the University of Cincinnati, who is investigating a similar pill for a rival company, Atea, partnering with Roche. 

“But it is encouraging,” he said. “It will probably be an incremental improvement on what we have.” The fact that it can be taken at home is a plus: “Anything we can do to keep people from getting sicker is a good thing.”

“The data show in this higher risk group [those who were studied had at least one risk factor for severe COVID-19, such as age or a medical condition], it reduces the risk of advancing to severe disease by 50%,” Dr. Schaffner said. While that’s a clear benefit for half, it of course leaves the other half without benefit, he said.

Others critiqued the predicted cost of the drug. The U.S. government has already agreed to pay about $700 per patient, according to a new report from Harvard T. H. Chan School of Public Health, Boston, and King’s College Hospital, London. That analysis concluded that the actual cost of production for the 5-day course is $17.74.

“We fully expect that having an oral treatment that reduces the risk of hospitalizations will be significantly cost effective for society,” Melissa Moody, a Merck spokesperson, told this news organization. “We are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic.”

Merck expects to produce 10 million courses of treatment by the end of the year, with additional doses expected to be produced in 2022, according to a company press release. Earlier in 2021, Merck finalized its agreement with the U.S. government to supply about 1.7 million courses of the drug at the $700 price, once an EUA or FDA approval is given.

Merck also has supply and purchase agreements with other governments worldwide, pending regulatory approval.
 

Study details

Details about the study findings came from a Merck press release. In the planned interim analysis, Merck and Ridgeback evaluated data from 775 patients initially enrolled in the phase 3 MOVe-OUT trial.

All adults had lab-confirmed mild to moderate COVID-19, and reported onset of symptoms within 5 days of being randomly assigned to the drug or placebo. All had at least one risk factor linked with poor disease outcome (such as older age or obesity).

The drug is a ribonucleoside and works by creating mutations in the virus’s genome, halting the ability of the virus to replicate.

Through day 29 of the study, the drug reduced the risk or hospitalization or death by about 50%. While 7.3% of those who received the drug either died or were hospitalized by day 29, 14.1% of those on placebo did, a statistically significant difference (P = .0012).

Side effects were similar in both groups, with 35% of the drug-treated and 40% of the placebo group reporting some side effect, Merck reported. Adverse drug-related events were 12% in the drug group and 11% in the placebo group. While 1.3% of the drug-treated group quit the study because of an adverse event, 3.4% of the placebo group quit.
 

Pros, cons, and unknowns

The ability to take the drug orally, and at home, is a definite plus, Dr. Schaffner said,  compared with the monoclonal antibody treatment currently approved that must be given intravenously or subcutaneously and in certain locations.

More people could be reached and helped with the option of an at-home, oral medicine, he and others agreed.

The regimen for molnupiravir is four pills, two times daily, for 5 days, even if symptoms are mild. As with other prescription drugs, “there will always be folks who don’t comply completely” with the prescribed regimen, Dr. Schaffner said. With this pill, that might be especially true if the symptoms are very mild.

The 50% reduction is not as effective as the benefit often quoted for monoclonal antibody treatment. In clinical trials of Regeneron’s monoclonal antibody treatment, the regimen reduced COVID-19–related hospitalization or death in high-risk patients by 70%.

Even so, the new pill could change the pandemic’s course, others say. “I think molnupiravir has the potential to change how we take care of people who have COVID and risk factors for developing severe disease,” Rajesh Tim Gandhi, MD, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization. 

“What we’ll need to do, however, is make sure that people get tested quickly after they develop symptoms and, if they’re confirmed to have COVID, start on the pills within 5 days of developing symptoms,” he said, while warning that more data are needed about the drug and the trial results.

Another concern is that the promise of a pill will stall vaccination rates, with some people figuring why get vaccinated when they can obtain the pill if they do get sick.

Relying on treatment alone won’t work, Dr. Schaffner said. “Let’s [also] focus on prevention, which is the vaccine. We have to keep working both sides of the street.”

Dr. Gandhi added: “It’s important to remember that even though molnupiravir reduced the likelihood of hospitalization and death, a number of people who received the drug still got sick enough to end up in the hospital.”

Also unknown, he said, is how severe their disease was and whether they will develop long COVID.

The Merck study included only unvaccinated people. Might it work for those vaccinated people who get a breakthrough infection? “From a purely scientific perspective, there is no reason to believe molnupiravir would not work in people who are vaccinated, but the overall efficacy on top of the vaccine is likely dependent on how well they were able to mount a protective immune response to the vaccine,” Ms. Moody said. Still, Merck believes the pill could be of benefit for these infections too, she added.

As for the expected cost, Ms. Moody said that the company takes into account a number of factors in setting pricing, “but fundamentally we look at the impact of the disease, the benefits that the drug delivers to patients and to society, and at supporting ongoing drug development.”
 

On Merck’s heels: Pfizer, Roche, Atea

Pfizer is studying an antiviral pill, PF-07321332, a protease inhibitor that blocks the protease enzymes and halts replication of the virus.

In addition to studying the drug in infected patients at high risk of severe illness and in those at typical risk, Pfizer launched a phase 2-3 study in late September that will enroll people who live in the same household as a person with a confirmed, symptomatic COVID-19 infection to see if the drug can prevent disease in those who have been exposed.

Atea and Roche’s COVID pill, AT527, is in phase 3 trials as well. AT527 is an inhibitor of polymerase, an enzyme many viruses have, to stop replications. Atea is evaluating the drug to reduce disease “burden” and for both pre- and postexposure prevention.
 

Big picture: Role of COVID-19 pills

It may be necessary to target the coronavirus with more than one antiviral agent, said Dr. Fichtenbaum, a principal investigator for the AT527 trials. 

“Sometimes viruses require two or three active agents to control their replication,” he said, citing information gleaned from other viral research, such as HIV. For control of HIV infection, a cocktail or combination of antivirals is often recommended.

That may well be the case for COVID-19, Dr. Fichtenbaum said. The goal would be to attack the virus at more than one pathway.

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

Soon after Merck announced on Oct. 1 that it would ask federal regulators for emergency use authorization (EUA) for its auspicious new COVID-19 pill, the accolades began.

Former Food and Drug Administration chief Scott Gottlieb, MD, told CNBC the drug was “a profound game changer.” Top infectious disease expert Anthony S. Fauci, MD, called the early data “impressive.” The World Health Organization termed it “certainly good news,” while saying it awaits more data.

Merck, partnering with Ridgeback Biotherapeutics on the investigational oral antiviral medicine molnupiravir, plans to submit applications to regulatory agencies worldwide, hoping to deliver the first oral antiviral medication for COVID-19. 

Interim clinical trial results show that the drug may slash the risk for hospitalization or death by 50% in those with mild to moderate COVID-19.

When the results were found to be so favorable, the study was halted at the recommendation of an independent data-monitoring committee and in consultation with the FDA.

That initial enthusiasm is now tempered with some perspective on the pros and cons. “This anticipated drug has gotten a little more hype than it deserves,” said William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center in Nashville, Tenn. He and others suggest a reality check.

“It’s not exactly a home run, like penicillin for strep throat,” agreed Carl Fichtenbaum, MD, professor of infectious diseases at the University of Cincinnati, who is investigating a similar pill for a rival company, Atea, partnering with Roche. 

“But it is encouraging,” he said. “It will probably be an incremental improvement on what we have.” The fact that it can be taken at home is a plus: “Anything we can do to keep people from getting sicker is a good thing.”

“The data show in this higher risk group [those who were studied had at least one risk factor for severe COVID-19, such as age or a medical condition], it reduces the risk of advancing to severe disease by 50%,” Dr. Schaffner said. While that’s a clear benefit for half, it of course leaves the other half without benefit, he said.

Others critiqued the predicted cost of the drug. The U.S. government has already agreed to pay about $700 per patient, according to a new report from Harvard T. H. Chan School of Public Health, Boston, and King’s College Hospital, London. That analysis concluded that the actual cost of production for the 5-day course is $17.74.

“We fully expect that having an oral treatment that reduces the risk of hospitalizations will be significantly cost effective for society,” Melissa Moody, a Merck spokesperson, told this news organization. “We are optimistic that molnupiravir can become an important medicine as part of the global effort to fight the pandemic.”

Merck expects to produce 10 million courses of treatment by the end of the year, with additional doses expected to be produced in 2022, according to a company press release. Earlier in 2021, Merck finalized its agreement with the U.S. government to supply about 1.7 million courses of the drug at the $700 price, once an EUA or FDA approval is given.

Merck also has supply and purchase agreements with other governments worldwide, pending regulatory approval.
 

Study details

Details about the study findings came from a Merck press release. In the planned interim analysis, Merck and Ridgeback evaluated data from 775 patients initially enrolled in the phase 3 MOVe-OUT trial.

All adults had lab-confirmed mild to moderate COVID-19, and reported onset of symptoms within 5 days of being randomly assigned to the drug or placebo. All had at least one risk factor linked with poor disease outcome (such as older age or obesity).

The drug is a ribonucleoside and works by creating mutations in the virus’s genome, halting the ability of the virus to replicate.

Through day 29 of the study, the drug reduced the risk or hospitalization or death by about 50%. While 7.3% of those who received the drug either died or were hospitalized by day 29, 14.1% of those on placebo did, a statistically significant difference (P = .0012).

Side effects were similar in both groups, with 35% of the drug-treated and 40% of the placebo group reporting some side effect, Merck reported. Adverse drug-related events were 12% in the drug group and 11% in the placebo group. While 1.3% of the drug-treated group quit the study because of an adverse event, 3.4% of the placebo group quit.
 

Pros, cons, and unknowns

The ability to take the drug orally, and at home, is a definite plus, Dr. Schaffner said,  compared with the monoclonal antibody treatment currently approved that must be given intravenously or subcutaneously and in certain locations.

More people could be reached and helped with the option of an at-home, oral medicine, he and others agreed.

The regimen for molnupiravir is four pills, two times daily, for 5 days, even if symptoms are mild. As with other prescription drugs, “there will always be folks who don’t comply completely” with the prescribed regimen, Dr. Schaffner said. With this pill, that might be especially true if the symptoms are very mild.

The 50% reduction is not as effective as the benefit often quoted for monoclonal antibody treatment. In clinical trials of Regeneron’s monoclonal antibody treatment, the regimen reduced COVID-19–related hospitalization or death in high-risk patients by 70%.

Even so, the new pill could change the pandemic’s course, others say. “I think molnupiravir has the potential to change how we take care of people who have COVID and risk factors for developing severe disease,” Rajesh Tim Gandhi, MD, an infectious disease physician at Massachusetts General Hospital and Harvard Medical School in Boston, told this news organization. 

“What we’ll need to do, however, is make sure that people get tested quickly after they develop symptoms and, if they’re confirmed to have COVID, start on the pills within 5 days of developing symptoms,” he said, while warning that more data are needed about the drug and the trial results.

Another concern is that the promise of a pill will stall vaccination rates, with some people figuring why get vaccinated when they can obtain the pill if they do get sick.

Relying on treatment alone won’t work, Dr. Schaffner said. “Let’s [also] focus on prevention, which is the vaccine. We have to keep working both sides of the street.”

Dr. Gandhi added: “It’s important to remember that even though molnupiravir reduced the likelihood of hospitalization and death, a number of people who received the drug still got sick enough to end up in the hospital.”

Also unknown, he said, is how severe their disease was and whether they will develop long COVID.

The Merck study included only unvaccinated people. Might it work for those vaccinated people who get a breakthrough infection? “From a purely scientific perspective, there is no reason to believe molnupiravir would not work in people who are vaccinated, but the overall efficacy on top of the vaccine is likely dependent on how well they were able to mount a protective immune response to the vaccine,” Ms. Moody said. Still, Merck believes the pill could be of benefit for these infections too, she added.

As for the expected cost, Ms. Moody said that the company takes into account a number of factors in setting pricing, “but fundamentally we look at the impact of the disease, the benefits that the drug delivers to patients and to society, and at supporting ongoing drug development.”
 

On Merck’s heels: Pfizer, Roche, Atea

Pfizer is studying an antiviral pill, PF-07321332, a protease inhibitor that blocks the protease enzymes and halts replication of the virus.

In addition to studying the drug in infected patients at high risk of severe illness and in those at typical risk, Pfizer launched a phase 2-3 study in late September that will enroll people who live in the same household as a person with a confirmed, symptomatic COVID-19 infection to see if the drug can prevent disease in those who have been exposed.

Atea and Roche’s COVID pill, AT527, is in phase 3 trials as well. AT527 is an inhibitor of polymerase, an enzyme many viruses have, to stop replications. Atea is evaluating the drug to reduce disease “burden” and for both pre- and postexposure prevention.
 

Big picture: Role of COVID-19 pills

It may be necessary to target the coronavirus with more than one antiviral agent, said Dr. Fichtenbaum, a principal investigator for the AT527 trials. 

“Sometimes viruses require two or three active agents to control their replication,” he said, citing information gleaned from other viral research, such as HIV. For control of HIV infection, a cocktail or combination of antivirals is often recommended.

That may well be the case for COVID-19, Dr. Fichtenbaum said. The goal would be to attack the virus at more than one pathway.

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

CASE 1st prenatal appointment for young, pregnant migrant

A 21-year-old primigravid woman at 12 weeks’ gestation recently immigrated to the United States from an impoverished rural area of Southeast Asia. On the first prenatal appointment, she is noted to have no evidence of immunity to rubella, measles, or varicella. Her hepatitis B surface antigen and hepatitis C antibody tests are negative. She also has negative test results for gonorrhea, chlamydia, syphilis, and HIV infection. Her pap test is negative.

• What vaccinations should this patient receive during her pregnancy?
• What additional vaccinations are indicated postpartum?

Preventive vaccinations: What to know

As ObGyns, we serve as the primary care physician for many women throughout their early and middle decades of life. Accordingly, we have an obligation to be well informed about preventive health services such as vaccinations. The purpose of this article is to review the principal vaccines with which ObGyns should be familiar. I will discuss the vaccines in alphabetical order and then focus on the indications and timing for each vaccine and the relative cost of each immunization. Key points are summarized in the TABLE.

COVID-19 vaccine

In the latter part of 2020 and early part of 2021, three COVID-19 vaccines received emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for individuals 16 years of age and older (Pfizer-BioNTech) and 18 years of age and older (Moderna and Johnson & Johnson).¹ The cost of their administration is borne by the federal government. Two of the vaccines are mRNA agents—Moderna and Pfizer-BioNTech. Both are administered in a 2-dose series, separated by 4 and 3 weeks, respectively. The efficacy of these vaccines in preventing serious or critical illness approaches 95%. The Pfizer-BioNTech vaccine has now been fully FDA approved for administration to individuals older than age 16, with EUA for those down to age 12. Full approval of the Moderna vaccine will not be far behind. Because of some evidence suggesting waning immunity over time and because of growing concerns about the increased transmissibility of the delta variant of the virus, the FDA has been strongly considering a recommendation for a third (booster) dose of each of these vaccines, administered 8 months after the second dose for all eligible Americans. On September 17, 2021, the FDA advisory committee recommended a booster for the Pfizer-BioNTech vaccine for people older than age 65 and for those over the age of 16 at high risk for severe COVID-19. Several days later, full FDA approval was granted for this recommendation. Subsequently, the Director of the Centers for Disease Control and Prevention (CDC) included health care workers and pregnant women in the group for whom the booster is recommended.

The third vaccine formulation is the Johnson & Johnson DNA vaccine, which is prepared with a human adenovirus vector. This vaccine is administered in a single intramuscular dose and has a reported efficacy of 66% to 85%, though it may approach 95% in preventing critical illness. The FDA is expected to announce decisions about booster doses for the Johnson & Johnson and Moderna vaccines in the coming weeks.

Although initial trials of the COVID-19vaccines excluded pregnant and lactating women, the vaccines are safe in pregnancy or postpartum. In fact the vaccines do not contain either a killed or attenuated viral particle that is capable of transmitting infection. Therefore, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine now support routine immunization during pregnancy.

A recent report by Shimabukuro and colleagues² demonstrated that the risk of vaccine-related complications in pregnant women receiving the Pfizer-BioNTech or Moderna vaccines was no different than in nonpregnant patients and that there was no evidence of teratogenic effects. The trial included more than 35,000 pregnant women; 2.3% were vaccinated in the periconception period, 28.6% in the first trimester, 43.3% in the second trimester, and 25.7% in the third trimester. Given this, and in light of isolated reports of unusual thromboembolic complications associated with the Johnson & Johnson vaccine, I strongly recommend use of either the Moderna or Pfizer-BioNTech vaccine in our prenatal and postpartum patients.

Continue to: Hepatitis A vaccine...

The hepatitis A vaccine is an inactivated vaccine and is safe for use in pregnancy. It is available in two monovalent preparations—Havrix (GlaxoSmithKline) and Vaqta (Merck & Co.) and is administered in a 2-dose intramuscular injection at time zero and 6 to 12 months later.³ The vaccine is also available in a bivalent form with recombinant hepatitis B vaccine—Twinrix (GlaxoSmithKline). When administered in this form, the vaccine should be given at time zero, 1 month, and 6 months. The wholesale cost of the monovalent vaccine is $66 to $119, depending upon whether the provider uses a multi-dose or a single-dose vial. The cost of Twinrix is $149.

The hepatitis A vaccine is indicated for select pregnant and nonpregnant patients:

• international travelers
• intravenous drug users
• those with occupational exposure (eg, individuals who work in a primate laboratory)
• residents and staff in chronic care facilities
• individuals with chronic liver disease
• individuals with clotting factor disorders
• residents in endemic areas.

Hepatitis B vaccine

The hepatitis B vaccine is a recombinant vaccine that contains an inactivated portion of the hepatitis B surface antigen. It was originally produced in two monovalent formulations: Engerix B (GlaxoSmithKline) and Recombivax-HB (Merck & Co.). These original formulations are given in a 3-dose series at time zero, 1 month, and 6 months. Recently, a new and more potent formulation was introduced into clinical practice. Heplisav-B (Dynavax Technologies Co.) is also a recombinant vaccine that contains a boosting adjuvant. It is programed to be administered in a 2-dose series at time zero and 1 month.^4-6

The wholesale cost of the monovalent vaccines varies from $60 to $173, depending upon use of a multi-dose vial versus a single-use vial. The cost of Heplisav-B varies from $146 to $173, depending upon use of a prefilled syringe versus a single-dose vial.

Although the hepatitis B vaccine should be part of the childhood immunization series, it also should be administered to any pregnant woman who has not been vaccinated previously or who does not already have evidence of immunity as a result of natural infection.

Continue to: Herpes zoster vaccine...

Herpes zoster infection (shingles) can be a particularly disabling condition in older patients and results from reactivation of a latent varicella-zoster infection. Shingles can cause extremely painful skin lesions, threaten the patient’s vision, and result in long-lasting postherpetic neuralgia. Both cellular and hormonal immunity are essential to protect against recurrent infection.

The original herpes zoster vaccine (Zoster Vaccine Live; ZVL, Zostavax) is no longer produced in the United States because it is not as effective as the newer vaccine—Recombinant Zoster Vaccine (Shingrix, GlaxoSmithKline).^7,8 The antigen in the new vaccine is a component of the surface glycoprotein E, and it is combined with an adjuvant to enhance immunoreactivity. The vaccine is given intramuscularly in two doses at time zero and again at 2 to 6 months and is indicated for all individuals >50 years, including those who may have had an episode of shingles. This newer vaccine is 97% effective in patients >50 years and 90% effective in patients >70. The wholesale cost of each injection is about $160.

Human papillomavirus vaccine

The HPV vaccine (Gardasil-9, Merck & Co.) is a recombinant 9-valent vaccine directed against the human papillomavirus. It induces immunity to serotypes 6 and 11 (which cause 90% of genital warts), 16 and 18 (which cause 80% of genital cancers), and 31, 33, 45, 52, and 58 (viral strains that are responsible for both genital and oropharyngeal cancers). The vaccine is administered intramuscularly in a 3-dose series at time zero, 1-2 months, and 6 months. The principal target groups for the vaccine are males and females, ages 9 to 45 years. Ideally, children of both sexes should receive this vaccine prior to the onset of sexual activity. The wholesale cost of each vaccine injection is approximately $222.⁹

Influenza vaccine

The inactivated, intramuscular flu vaccine is recommended for anyone over age 2, including pregnant women. Although pregnant women are not more likely to acquire flu compared with those who are not pregnant, if they do become infected, they are likely to become more seriously ill, with higher mortality. Accordingly, all pregnant women should receive, in any trimester, the inactivated flu vaccine beginning in the late summer and early fall of each year and extending through March of the next year.^10,11

Multiple formulations of the inactivated vaccine are marketed, all targeting two strains of influenza A and two strains of influenza B. The components of the vaccine vary each year as scientists try to match the new vaccine with the most highly prevalent strains in the previous flu season. The vaccine should be administered in a single intramuscular dose. The cost varies from approximately $20 to $70.

The intranasal influenza vaccine is a live virus vaccine that is intended primarily for children and should not be administered in pregnancy. In addition, there is a higher dose of the inactivated quadrivalent vaccine that is available for administration to patients over age 65. This higher dose is more likely to cause adverse effects and is not indicated in pregnancy.

Continue to: Measles, mumps, rubella vaccine (MMR)...

Measles, mumps, rubella vaccine (MMR)

The MMR is a standard component of the childhood vaccination series. The trivalent preparation is a live, attenuated vaccine that is typically given subcutaneously in a 2-dose series. The first dose is administered at age 12-15 months, and the second dose at age 4-6 years. The vaccine is highly immunogenic, with vaccine-induced immunity usually life-long. In some patients, however, immunity wanes over time. Accordingly, all pregnant women should be screened for immunity to rubella since, of the 3, this infection poses the greatest risk to the fetus. Women who do not have evidence of immunity should be advised to avoid contact with children who may have a viral exanthem. They should then receive a booster dose of the vaccine immediately postpartum and should practice secure contraception for 1 month. The vaccine cost is approximately $60.

Pneumococcal vaccine

The inactivated pneumococcal vaccine is produced in two forms, both of which are safe for administration in pregnancy.¹² The original vaccine, introduced in 1983, was PPSV23 (Pneumovax 23, Merck & Co), a 23-serovalent vaccine that was intended primarily for adults. This vaccine is administered in a single subcutaneous or intramuscular dose. The newest vaccine, introduced in 2010, is PCV13 (Prevnar 13, Pfizer Inc), a 13-serovalent vaccine. It was intended primarily for children, in whom it is administered in a 4-dose series beginning at 6 to 8 weeks of age. The cost of the former is approximately $98 to $120; the cost of the latter is $228.

Vaccination against pneumococcal infection is routinely indicated for those older than the age of 65 and for the following at-risk patients, including those who are pregnant¹¹:

• individuals who have had a splenectomy or who have a medical illness that produces functional asplenia (eg, sickle cell anemia)
• individuals with chronic cardiac, pulmonic, hepatic, or renal disease
• individuals with immunosuppressive conditions such as HIV infection or a disseminated malignancy
• individuals who have a cochlear implant
• individuals who have a chronic leak of cerebrospinal fluid.

The recommendations for timing of these 2 vaccines in adults can initially appear confusing. Put most simply, if a high-risk patient first receives the PCV13 vaccine, she should receive the PPSV23 vaccine in about 8 weeks. The PPSV23 vaccine should be repeated in 5 years. If an at-risk patient initially receives the PPSV23 vaccine, the PCV13 vaccine should be given 1 year later.¹²

Tdap vaccine

The Tdap vaccine contains tetanus toxoid, reduced diptheria toxoid, and an acellular component of the pertussis bacterium. Although it has long been part of the childhood vaccinations series, immunity to each component, particularly pertussis, tends to wane over time.

Pertussis poses a serious risk to the health of the pregnant woman and the newborn infant. Accordingly, the Advisory Committee on Immunization Practices (ACIP), CDC, and the ACOG now advise administration of a booster dose of this vaccine in the early third trimester of each pregnancy.^13-15 The vaccine should be administered as a single intramuscular injection. The approximate cost of the vaccine is $64 to $71, depending upon whether the provider uses a single-dose vial or a single-dose prefilled syringe. In nonpregnant patients, the ACIP currently recommends administration of a booster dose of the vaccine every 10 years, primarily to provide durable protection against tetanus.

Continue to: Varicella vaccine...

Varicella vaccine

The varicella vaccine is also one of the main components of the childhood immunization series. This live virus vaccine can be administered subcutaneously as a monovalent agent or as a quadrivalent agent in association with the MMR vaccine.

Pregnant women who do not have a well-documented history of natural infection should be tested for IgG antibody to the varicella-zoster virus at the time of their first prenatal appointment. Interestingly, approximately 70% of patients with an uncertain history actually have immunity when tested. If the patient lacks immunity, she should be vaccinated immediately postpartum.^16,17 The vaccine should be administered in a 2-dose series at time zero and then 4 to 8 weeks later. Patients should adhere to secure contraception from the time of the first dose until 1 month after the second dose. The cost of each dose of the vaccine is approximately $145.

Adverse effects of vaccination

All vaccines have many of the same side effects. The most common is simply a reaction at the site of injection, characterized by pain, increased warmth, erythema, swelling, and tenderness. Other common side effects include systemic manifestations, such as low-grade fever, nausea and vomiting, malaise, fatigue, headache, lymphadenopathy, myalgias, and arthralgias. Some vaccines, notably varicella, herpes zoster, measles, and rubella may cause a disseminated rash. Most of these minor side effects are easily managed by rest, hydration, and administration of an analgesic such as acetaminophen or ibuprofen. More serious side effects include rare complications such as anaphylaxis, Bell palsy, Guillain-Barre syndrome, and venous thromboembolism (Johnson & Johnson COVID-19 vaccine). Any of the vaccines discussed above should not be given, or given only with extreme caution, to an individual who has experienced any of these reactions with a previous vaccine.

Barriers to vaccination

Although the vaccines reviewed above are highly effective in preventing serious illness in recipients, the medical profession’s “report card” in ensuring adherence with vaccine protocols is not optimal. In fact, it probably merits a grade no higher than C+, with vaccination rates in the range of 50% to 70%.

One of the major barriers to vaccination is lack of detailed information about vaccine efficacy and safety on the part of both provider and patient. Another is the problem of misinformation (eg, the persistent belief on the part of some individuals that vaccines may cause a serious problem, such as autism).^18,19 Another important barrier to widespread vaccination is the logistical problem associated with proper scheduling of multidose regimens (such as those for hepatitis A and B, varicella, and COVID-19). A final barrier, and in my own university-based practice, the most important obstacle is the expense of vaccination. Most, but not all, private insurance companies provide coverage for vaccines approved by the Centers for Disease Control and Prevention and the US Preventive Services Task Force. However, public insurance agencies often provide disappointingly inconsistent coverage for essential vaccines.

By keeping well informed about the most recent public health recommendations for vaccinations for adults and by leading important initiatives within our own practices, we should be able to overcome the first 3 barriers listed above. For example, Morgan and colleagues²⁰ recently achieved a 97% success rate with Tdap administration in pregnancy by placing a best-practice alert in the patients’ electronic medical records. Surmounting the final barrier will require intense effort on the part of individual practitioners and professional organizations to advocate for coverage for essential vaccinations for our patients.

CASE Resolved

This patient was raised in an area of the world where her family did not have easy access to medical care. Accordingly, she did not receive the usual childhood vaccines, such as measles, mumps, rubella, varicella, hepatitis B, and almost certainly, tetanus, diphtheria, and pertussis (Tdap), and the HPV vaccine. The MMR vaccine and the varicella vaccine are live virus vaccines and should not be given during pregnancy. However, these vaccines should be administered postpartum, and the patient should be instructed to practice secure contraception for a minimum of 1 month following vaccination. She also should be offered the HPV vaccine postpartum. During pregnancy, she definitely should receive the COVID-19 vaccine, the 3-dose hepatitis B vaccine series, the influenza vaccine, and Tdap. If her present living conditions place her at risk for hepatitis A, she also should be vaccinated against this illness. ●

CASE 1st prenatal appointment for young, pregnant migrant

A 21-year-old primigravid woman at 12 weeks’ gestation recently immigrated to the United States from an impoverished rural area of Southeast Asia. On the first prenatal appointment, she is noted to have no evidence of immunity to rubella, measles, or varicella. Her hepatitis B surface antigen and hepatitis C antibody tests are negative. She also has negative test results for gonorrhea, chlamydia, syphilis, and HIV infection. Her pap test is negative.

• What vaccinations should this patient receive during her pregnancy?
• What additional vaccinations are indicated postpartum?

Preventive vaccinations: What to know

As ObGyns, we serve as the primary care physician for many women throughout their early and middle decades of life. Accordingly, we have an obligation to be well informed about preventive health services such as vaccinations. The purpose of this article is to review the principal vaccines with which ObGyns should be familiar. I will discuss the vaccines in alphabetical order and then focus on the indications and timing for each vaccine and the relative cost of each immunization. Key points are summarized in the TABLE.

COVID-19 vaccine

In the latter part of 2020 and early part of 2021, three COVID-19 vaccines received emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for individuals 16 years of age and older (Pfizer-BioNTech) and 18 years of age and older (Moderna and Johnson & Johnson).¹ The cost of their administration is borne by the federal government. Two of the vaccines are mRNA agents—Moderna and Pfizer-BioNTech. Both are administered in a 2-dose series, separated by 4 and 3 weeks, respectively. The efficacy of these vaccines in preventing serious or critical illness approaches 95%. The Pfizer-BioNTech vaccine has now been fully FDA approved for administration to individuals older than age 16, with EUA for those down to age 12. Full approval of the Moderna vaccine will not be far behind. Because of some evidence suggesting waning immunity over time and because of growing concerns about the increased transmissibility of the delta variant of the virus, the FDA has been strongly considering a recommendation for a third (booster) dose of each of these vaccines, administered 8 months after the second dose for all eligible Americans. On September 17, 2021, the FDA advisory committee recommended a booster for the Pfizer-BioNTech vaccine for people older than age 65 and for those over the age of 16 at high risk for severe COVID-19. Several days later, full FDA approval was granted for this recommendation. Subsequently, the Director of the Centers for Disease Control and Prevention (CDC) included health care workers and pregnant women in the group for whom the booster is recommended.

The third vaccine formulation is the Johnson & Johnson DNA vaccine, which is prepared with a human adenovirus vector. This vaccine is administered in a single intramuscular dose and has a reported efficacy of 66% to 85%, though it may approach 95% in preventing critical illness. The FDA is expected to announce decisions about booster doses for the Johnson & Johnson and Moderna vaccines in the coming weeks.

Although initial trials of the COVID-19vaccines excluded pregnant and lactating women, the vaccines are safe in pregnancy or postpartum. In fact the vaccines do not contain either a killed or attenuated viral particle that is capable of transmitting infection. Therefore, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine now support routine immunization during pregnancy.

A recent report by Shimabukuro and colleagues² demonstrated that the risk of vaccine-related complications in pregnant women receiving the Pfizer-BioNTech or Moderna vaccines was no different than in nonpregnant patients and that there was no evidence of teratogenic effects. The trial included more than 35,000 pregnant women; 2.3% were vaccinated in the periconception period, 28.6% in the first trimester, 43.3% in the second trimester, and 25.7% in the third trimester. Given this, and in light of isolated reports of unusual thromboembolic complications associated with the Johnson & Johnson vaccine, I strongly recommend use of either the Moderna or Pfizer-BioNTech vaccine in our prenatal and postpartum patients.

Continue to: Hepatitis A vaccine...

The hepatitis A vaccine is an inactivated vaccine and is safe for use in pregnancy. It is available in two monovalent preparations—Havrix (GlaxoSmithKline) and Vaqta (Merck & Co.) and is administered in a 2-dose intramuscular injection at time zero and 6 to 12 months later.³ The vaccine is also available in a bivalent form with recombinant hepatitis B vaccine—Twinrix (GlaxoSmithKline). When administered in this form, the vaccine should be given at time zero, 1 month, and 6 months. The wholesale cost of the monovalent vaccine is $66 to $119, depending upon whether the provider uses a multi-dose or a single-dose vial. The cost of Twinrix is $149.

The hepatitis A vaccine is indicated for select pregnant and nonpregnant patients:

• international travelers
• intravenous drug users
• those with occupational exposure (eg, individuals who work in a primate laboratory)
• residents and staff in chronic care facilities
• individuals with chronic liver disease
• individuals with clotting factor disorders
• residents in endemic areas.

Hepatitis B vaccine

The hepatitis B vaccine is a recombinant vaccine that contains an inactivated portion of the hepatitis B surface antigen. It was originally produced in two monovalent formulations: Engerix B (GlaxoSmithKline) and Recombivax-HB (Merck & Co.). These original formulations are given in a 3-dose series at time zero, 1 month, and 6 months. Recently, a new and more potent formulation was introduced into clinical practice. Heplisav-B (Dynavax Technologies Co.) is also a recombinant vaccine that contains a boosting adjuvant. It is programed to be administered in a 2-dose series at time zero and 1 month.^4-6

The wholesale cost of the monovalent vaccines varies from $60 to $173, depending upon use of a multi-dose vial versus a single-use vial. The cost of Heplisav-B varies from $146 to $173, depending upon use of a prefilled syringe versus a single-dose vial.

Although the hepatitis B vaccine should be part of the childhood immunization series, it also should be administered to any pregnant woman who has not been vaccinated previously or who does not already have evidence of immunity as a result of natural infection.

Continue to: Herpes zoster vaccine...

Herpes zoster infection (shingles) can be a particularly disabling condition in older patients and results from reactivation of a latent varicella-zoster infection. Shingles can cause extremely painful skin lesions, threaten the patient’s vision, and result in long-lasting postherpetic neuralgia. Both cellular and hormonal immunity are essential to protect against recurrent infection.

The original herpes zoster vaccine (Zoster Vaccine Live; ZVL, Zostavax) is no longer produced in the United States because it is not as effective as the newer vaccine—Recombinant Zoster Vaccine (Shingrix, GlaxoSmithKline).^7,8 The antigen in the new vaccine is a component of the surface glycoprotein E, and it is combined with an adjuvant to enhance immunoreactivity. The vaccine is given intramuscularly in two doses at time zero and again at 2 to 6 months and is indicated for all individuals >50 years, including those who may have had an episode of shingles. This newer vaccine is 97% effective in patients >50 years and 90% effective in patients >70. The wholesale cost of each injection is about $160.

Human papillomavirus vaccine

The HPV vaccine (Gardasil-9, Merck & Co.) is a recombinant 9-valent vaccine directed against the human papillomavirus. It induces immunity to serotypes 6 and 11 (which cause 90% of genital warts), 16 and 18 (which cause 80% of genital cancers), and 31, 33, 45, 52, and 58 (viral strains that are responsible for both genital and oropharyngeal cancers). The vaccine is administered intramuscularly in a 3-dose series at time zero, 1-2 months, and 6 months. The principal target groups for the vaccine are males and females, ages 9 to 45 years. Ideally, children of both sexes should receive this vaccine prior to the onset of sexual activity. The wholesale cost of each vaccine injection is approximately $222.⁹

Influenza vaccine

The inactivated, intramuscular flu vaccine is recommended for anyone over age 2, including pregnant women. Although pregnant women are not more likely to acquire flu compared with those who are not pregnant, if they do become infected, they are likely to become more seriously ill, with higher mortality. Accordingly, all pregnant women should receive, in any trimester, the inactivated flu vaccine beginning in the late summer and early fall of each year and extending through March of the next year.^10,11

Multiple formulations of the inactivated vaccine are marketed, all targeting two strains of influenza A and two strains of influenza B. The components of the vaccine vary each year as scientists try to match the new vaccine with the most highly prevalent strains in the previous flu season. The vaccine should be administered in a single intramuscular dose. The cost varies from approximately $20 to $70.

The intranasal influenza vaccine is a live virus vaccine that is intended primarily for children and should not be administered in pregnancy. In addition, there is a higher dose of the inactivated quadrivalent vaccine that is available for administration to patients over age 65. This higher dose is more likely to cause adverse effects and is not indicated in pregnancy.

Continue to: Measles, mumps, rubella vaccine (MMR)...

Measles, mumps, rubella vaccine (MMR)

The MMR is a standard component of the childhood vaccination series. The trivalent preparation is a live, attenuated vaccine that is typically given subcutaneously in a 2-dose series. The first dose is administered at age 12-15 months, and the second dose at age 4-6 years. The vaccine is highly immunogenic, with vaccine-induced immunity usually life-long. In some patients, however, immunity wanes over time. Accordingly, all pregnant women should be screened for immunity to rubella since, of the 3, this infection poses the greatest risk to the fetus. Women who do not have evidence of immunity should be advised to avoid contact with children who may have a viral exanthem. They should then receive a booster dose of the vaccine immediately postpartum and should practice secure contraception for 1 month. The vaccine cost is approximately $60.

Pneumococcal vaccine

The inactivated pneumococcal vaccine is produced in two forms, both of which are safe for administration in pregnancy.¹² The original vaccine, introduced in 1983, was PPSV23 (Pneumovax 23, Merck & Co), a 23-serovalent vaccine that was intended primarily for adults. This vaccine is administered in a single subcutaneous or intramuscular dose. The newest vaccine, introduced in 2010, is PCV13 (Prevnar 13, Pfizer Inc), a 13-serovalent vaccine. It was intended primarily for children, in whom it is administered in a 4-dose series beginning at 6 to 8 weeks of age. The cost of the former is approximately $98 to $120; the cost of the latter is $228.

Vaccination against pneumococcal infection is routinely indicated for those older than the age of 65 and for the following at-risk patients, including those who are pregnant¹¹:

• individuals who have had a splenectomy or who have a medical illness that produces functional asplenia (eg, sickle cell anemia)
• individuals with chronic cardiac, pulmonic, hepatic, or renal disease
• individuals with immunosuppressive conditions such as HIV infection or a disseminated malignancy
• individuals who have a cochlear implant
• individuals who have a chronic leak of cerebrospinal fluid.

The recommendations for timing of these 2 vaccines in adults can initially appear confusing. Put most simply, if a high-risk patient first receives the PCV13 vaccine, she should receive the PPSV23 vaccine in about 8 weeks. The PPSV23 vaccine should be repeated in 5 years. If an at-risk patient initially receives the PPSV23 vaccine, the PCV13 vaccine should be given 1 year later.¹²

Tdap vaccine

The Tdap vaccine contains tetanus toxoid, reduced diptheria toxoid, and an acellular component of the pertussis bacterium. Although it has long been part of the childhood vaccinations series, immunity to each component, particularly pertussis, tends to wane over time.

Pertussis poses a serious risk to the health of the pregnant woman and the newborn infant. Accordingly, the Advisory Committee on Immunization Practices (ACIP), CDC, and the ACOG now advise administration of a booster dose of this vaccine in the early third trimester of each pregnancy.^13-15 The vaccine should be administered as a single intramuscular injection. The approximate cost of the vaccine is $64 to $71, depending upon whether the provider uses a single-dose vial or a single-dose prefilled syringe. In nonpregnant patients, the ACIP currently recommends administration of a booster dose of the vaccine every 10 years, primarily to provide durable protection against tetanus.

Continue to: Varicella vaccine...

Varicella vaccine

The varicella vaccine is also one of the main components of the childhood immunization series. This live virus vaccine can be administered subcutaneously as a monovalent agent or as a quadrivalent agent in association with the MMR vaccine.

Pregnant women who do not have a well-documented history of natural infection should be tested for IgG antibody to the varicella-zoster virus at the time of their first prenatal appointment. Interestingly, approximately 70% of patients with an uncertain history actually have immunity when tested. If the patient lacks immunity, she should be vaccinated immediately postpartum.^16,17 The vaccine should be administered in a 2-dose series at time zero and then 4 to 8 weeks later. Patients should adhere to secure contraception from the time of the first dose until 1 month after the second dose. The cost of each dose of the vaccine is approximately $145.

Adverse effects of vaccination

All vaccines have many of the same side effects. The most common is simply a reaction at the site of injection, characterized by pain, increased warmth, erythema, swelling, and tenderness. Other common side effects include systemic manifestations, such as low-grade fever, nausea and vomiting, malaise, fatigue, headache, lymphadenopathy, myalgias, and arthralgias. Some vaccines, notably varicella, herpes zoster, measles, and rubella may cause a disseminated rash. Most of these minor side effects are easily managed by rest, hydration, and administration of an analgesic such as acetaminophen or ibuprofen. More serious side effects include rare complications such as anaphylaxis, Bell palsy, Guillain-Barre syndrome, and venous thromboembolism (Johnson & Johnson COVID-19 vaccine). Any of the vaccines discussed above should not be given, or given only with extreme caution, to an individual who has experienced any of these reactions with a previous vaccine.

Barriers to vaccination

Although the vaccines reviewed above are highly effective in preventing serious illness in recipients, the medical profession’s “report card” in ensuring adherence with vaccine protocols is not optimal. In fact, it probably merits a grade no higher than C+, with vaccination rates in the range of 50% to 70%.

One of the major barriers to vaccination is lack of detailed information about vaccine efficacy and safety on the part of both provider and patient. Another is the problem of misinformation (eg, the persistent belief on the part of some individuals that vaccines may cause a serious problem, such as autism).^18,19 Another important barrier to widespread vaccination is the logistical problem associated with proper scheduling of multidose regimens (such as those for hepatitis A and B, varicella, and COVID-19). A final barrier, and in my own university-based practice, the most important obstacle is the expense of vaccination. Most, but not all, private insurance companies provide coverage for vaccines approved by the Centers for Disease Control and Prevention and the US Preventive Services Task Force. However, public insurance agencies often provide disappointingly inconsistent coverage for essential vaccines.

By keeping well informed about the most recent public health recommendations for vaccinations for adults and by leading important initiatives within our own practices, we should be able to overcome the first 3 barriers listed above. For example, Morgan and colleagues²⁰ recently achieved a 97% success rate with Tdap administration in pregnancy by placing a best-practice alert in the patients’ electronic medical records. Surmounting the final barrier will require intense effort on the part of individual practitioners and professional organizations to advocate for coverage for essential vaccinations for our patients.

CASE Resolved

This patient was raised in an area of the world where her family did not have easy access to medical care. Accordingly, she did not receive the usual childhood vaccines, such as measles, mumps, rubella, varicella, hepatitis B, and almost certainly, tetanus, diphtheria, and pertussis (Tdap), and the HPV vaccine. The MMR vaccine and the varicella vaccine are live virus vaccines and should not be given during pregnancy. However, these vaccines should be administered postpartum, and the patient should be instructed to practice secure contraception for a minimum of 1 month following vaccination. She also should be offered the HPV vaccine postpartum. During pregnancy, she definitely should receive the COVID-19 vaccine, the 3-dose hepatitis B vaccine series, the influenza vaccine, and Tdap. If her present living conditions place her at risk for hepatitis A, she also should be vaccinated against this illness. ●

CASE 1st prenatal appointment for young, pregnant migrant

A 21-year-old primigravid woman at 12 weeks’ gestation recently immigrated to the United States from an impoverished rural area of Southeast Asia. On the first prenatal appointment, she is noted to have no evidence of immunity to rubella, measles, or varicella. Her hepatitis B surface antigen and hepatitis C antibody tests are negative. She also has negative test results for gonorrhea, chlamydia, syphilis, and HIV infection. Her pap test is negative.

• What vaccinations should this patient receive during her pregnancy?
• What additional vaccinations are indicated postpartum?

Preventive vaccinations: What to know

As ObGyns, we serve as the primary care physician for many women throughout their early and middle decades of life. Accordingly, we have an obligation to be well informed about preventive health services such as vaccinations. The purpose of this article is to review the principal vaccines with which ObGyns should be familiar. I will discuss the vaccines in alphabetical order and then focus on the indications and timing for each vaccine and the relative cost of each immunization. Key points are summarized in the TABLE.

COVID-19 vaccine

In the latter part of 2020 and early part of 2021, three COVID-19 vaccines received emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for individuals 16 years of age and older (Pfizer-BioNTech) and 18 years of age and older (Moderna and Johnson & Johnson).¹ The cost of their administration is borne by the federal government. Two of the vaccines are mRNA agents—Moderna and Pfizer-BioNTech. Both are administered in a 2-dose series, separated by 4 and 3 weeks, respectively. The efficacy of these vaccines in preventing serious or critical illness approaches 95%. The Pfizer-BioNTech vaccine has now been fully FDA approved for administration to individuals older than age 16, with EUA for those down to age 12. Full approval of the Moderna vaccine will not be far behind. Because of some evidence suggesting waning immunity over time and because of growing concerns about the increased transmissibility of the delta variant of the virus, the FDA has been strongly considering a recommendation for a third (booster) dose of each of these vaccines, administered 8 months after the second dose for all eligible Americans. On September 17, 2021, the FDA advisory committee recommended a booster for the Pfizer-BioNTech vaccine for people older than age 65 and for those over the age of 16 at high risk for severe COVID-19. Several days later, full FDA approval was granted for this recommendation. Subsequently, the Director of the Centers for Disease Control and Prevention (CDC) included health care workers and pregnant women in the group for whom the booster is recommended.

The third vaccine formulation is the Johnson & Johnson DNA vaccine, which is prepared with a human adenovirus vector. This vaccine is administered in a single intramuscular dose and has a reported efficacy of 66% to 85%, though it may approach 95% in preventing critical illness. The FDA is expected to announce decisions about booster doses for the Johnson & Johnson and Moderna vaccines in the coming weeks.

Although initial trials of the COVID-19vaccines excluded pregnant and lactating women, the vaccines are safe in pregnancy or postpartum. In fact the vaccines do not contain either a killed or attenuated viral particle that is capable of transmitting infection. Therefore, both the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine now support routine immunization during pregnancy.

A recent report by Shimabukuro and colleagues² demonstrated that the risk of vaccine-related complications in pregnant women receiving the Pfizer-BioNTech or Moderna vaccines was no different than in nonpregnant patients and that there was no evidence of teratogenic effects. The trial included more than 35,000 pregnant women; 2.3% were vaccinated in the periconception period, 28.6% in the first trimester, 43.3% in the second trimester, and 25.7% in the third trimester. Given this, and in light of isolated reports of unusual thromboembolic complications associated with the Johnson & Johnson vaccine, I strongly recommend use of either the Moderna or Pfizer-BioNTech vaccine in our prenatal and postpartum patients.

Continue to: Hepatitis A vaccine...

The hepatitis A vaccine is an inactivated vaccine and is safe for use in pregnancy. It is available in two monovalent preparations—Havrix (GlaxoSmithKline) and Vaqta (Merck & Co.) and is administered in a 2-dose intramuscular injection at time zero and 6 to 12 months later.³ The vaccine is also available in a bivalent form with recombinant hepatitis B vaccine—Twinrix (GlaxoSmithKline). When administered in this form, the vaccine should be given at time zero, 1 month, and 6 months. The wholesale cost of the monovalent vaccine is $66 to $119, depending upon whether the provider uses a multi-dose or a single-dose vial. The cost of Twinrix is $149.

The hepatitis A vaccine is indicated for select pregnant and nonpregnant patients:

• international travelers
• intravenous drug users
• those with occupational exposure (eg, individuals who work in a primate laboratory)
• residents and staff in chronic care facilities
• individuals with chronic liver disease
• individuals with clotting factor disorders
• residents in endemic areas.

Hepatitis B vaccine

The hepatitis B vaccine is a recombinant vaccine that contains an inactivated portion of the hepatitis B surface antigen. It was originally produced in two monovalent formulations: Engerix B (GlaxoSmithKline) and Recombivax-HB (Merck & Co.). These original formulations are given in a 3-dose series at time zero, 1 month, and 6 months. Recently, a new and more potent formulation was introduced into clinical practice. Heplisav-B (Dynavax Technologies Co.) is also a recombinant vaccine that contains a boosting adjuvant. It is programed to be administered in a 2-dose series at time zero and 1 month.^4-6

The wholesale cost of the monovalent vaccines varies from $60 to $173, depending upon use of a multi-dose vial versus a single-use vial. The cost of Heplisav-B varies from $146 to $173, depending upon use of a prefilled syringe versus a single-dose vial.

Although the hepatitis B vaccine should be part of the childhood immunization series, it also should be administered to any pregnant woman who has not been vaccinated previously or who does not already have evidence of immunity as a result of natural infection.

Continue to: Herpes zoster vaccine...

Herpes zoster infection (shingles) can be a particularly disabling condition in older patients and results from reactivation of a latent varicella-zoster infection. Shingles can cause extremely painful skin lesions, threaten the patient’s vision, and result in long-lasting postherpetic neuralgia. Both cellular and hormonal immunity are essential to protect against recurrent infection.

The original herpes zoster vaccine (Zoster Vaccine Live; ZVL, Zostavax) is no longer produced in the United States because it is not as effective as the newer vaccine—Recombinant Zoster Vaccine (Shingrix, GlaxoSmithKline).^7,8 The antigen in the new vaccine is a component of the surface glycoprotein E, and it is combined with an adjuvant to enhance immunoreactivity. The vaccine is given intramuscularly in two doses at time zero and again at 2 to 6 months and is indicated for all individuals >50 years, including those who may have had an episode of shingles. This newer vaccine is 97% effective in patients >50 years and 90% effective in patients >70. The wholesale cost of each injection is about $160.

Human papillomavirus vaccine

The HPV vaccine (Gardasil-9, Merck & Co.) is a recombinant 9-valent vaccine directed against the human papillomavirus. It induces immunity to serotypes 6 and 11 (which cause 90% of genital warts), 16 and 18 (which cause 80% of genital cancers), and 31, 33, 45, 52, and 58 (viral strains that are responsible for both genital and oropharyngeal cancers). The vaccine is administered intramuscularly in a 3-dose series at time zero, 1-2 months, and 6 months. The principal target groups for the vaccine are males and females, ages 9 to 45 years. Ideally, children of both sexes should receive this vaccine prior to the onset of sexual activity. The wholesale cost of each vaccine injection is approximately $222.⁹

Influenza vaccine

The inactivated, intramuscular flu vaccine is recommended for anyone over age 2, including pregnant women. Although pregnant women are not more likely to acquire flu compared with those who are not pregnant, if they do become infected, they are likely to become more seriously ill, with higher mortality. Accordingly, all pregnant women should receive, in any trimester, the inactivated flu vaccine beginning in the late summer and early fall of each year and extending through March of the next year.^10,11

Multiple formulations of the inactivated vaccine are marketed, all targeting two strains of influenza A and two strains of influenza B. The components of the vaccine vary each year as scientists try to match the new vaccine with the most highly prevalent strains in the previous flu season. The vaccine should be administered in a single intramuscular dose. The cost varies from approximately $20 to $70.

The intranasal influenza vaccine is a live virus vaccine that is intended primarily for children and should not be administered in pregnancy. In addition, there is a higher dose of the inactivated quadrivalent vaccine that is available for administration to patients over age 65. This higher dose is more likely to cause adverse effects and is not indicated in pregnancy.

Continue to: Measles, mumps, rubella vaccine (MMR)...

Measles, mumps, rubella vaccine (MMR)

The MMR is a standard component of the childhood vaccination series. The trivalent preparation is a live, attenuated vaccine that is typically given subcutaneously in a 2-dose series. The first dose is administered at age 12-15 months, and the second dose at age 4-6 years. The vaccine is highly immunogenic, with vaccine-induced immunity usually life-long. In some patients, however, immunity wanes over time. Accordingly, all pregnant women should be screened for immunity to rubella since, of the 3, this infection poses the greatest risk to the fetus. Women who do not have evidence of immunity should be advised to avoid contact with children who may have a viral exanthem. They should then receive a booster dose of the vaccine immediately postpartum and should practice secure contraception for 1 month. The vaccine cost is approximately $60.

Pneumococcal vaccine

The inactivated pneumococcal vaccine is produced in two forms, both of which are safe for administration in pregnancy.¹² The original vaccine, introduced in 1983, was PPSV23 (Pneumovax 23, Merck & Co), a 23-serovalent vaccine that was intended primarily for adults. This vaccine is administered in a single subcutaneous or intramuscular dose. The newest vaccine, introduced in 2010, is PCV13 (Prevnar 13, Pfizer Inc), a 13-serovalent vaccine. It was intended primarily for children, in whom it is administered in a 4-dose series beginning at 6 to 8 weeks of age. The cost of the former is approximately $98 to $120; the cost of the latter is $228.

Vaccination against pneumococcal infection is routinely indicated for those older than the age of 65 and for the following at-risk patients, including those who are pregnant¹¹:

• individuals who have had a splenectomy or who have a medical illness that produces functional asplenia (eg, sickle cell anemia)
• individuals with chronic cardiac, pulmonic, hepatic, or renal disease
• individuals with immunosuppressive conditions such as HIV infection or a disseminated malignancy
• individuals who have a cochlear implant
• individuals who have a chronic leak of cerebrospinal fluid.

The recommendations for timing of these 2 vaccines in adults can initially appear confusing. Put most simply, if a high-risk patient first receives the PCV13 vaccine, she should receive the PPSV23 vaccine in about 8 weeks. The PPSV23 vaccine should be repeated in 5 years. If an at-risk patient initially receives the PPSV23 vaccine, the PCV13 vaccine should be given 1 year later.¹²

Tdap vaccine

The Tdap vaccine contains tetanus toxoid, reduced diptheria toxoid, and an acellular component of the pertussis bacterium. Although it has long been part of the childhood vaccinations series, immunity to each component, particularly pertussis, tends to wane over time.

Pertussis poses a serious risk to the health of the pregnant woman and the newborn infant. Accordingly, the Advisory Committee on Immunization Practices (ACIP), CDC, and the ACOG now advise administration of a booster dose of this vaccine in the early third trimester of each pregnancy.^13-15 The vaccine should be administered as a single intramuscular injection. The approximate cost of the vaccine is $64 to $71, depending upon whether the provider uses a single-dose vial or a single-dose prefilled syringe. In nonpregnant patients, the ACIP currently recommends administration of a booster dose of the vaccine every 10 years, primarily to provide durable protection against tetanus.

Continue to: Varicella vaccine...

Varicella vaccine

The varicella vaccine is also one of the main components of the childhood immunization series. This live virus vaccine can be administered subcutaneously as a monovalent agent or as a quadrivalent agent in association with the MMR vaccine.

Pregnant women who do not have a well-documented history of natural infection should be tested for IgG antibody to the varicella-zoster virus at the time of their first prenatal appointment. Interestingly, approximately 70% of patients with an uncertain history actually have immunity when tested. If the patient lacks immunity, she should be vaccinated immediately postpartum.^16,17 The vaccine should be administered in a 2-dose series at time zero and then 4 to 8 weeks later. Patients should adhere to secure contraception from the time of the first dose until 1 month after the second dose. The cost of each dose of the vaccine is approximately $145.

Adverse effects of vaccination

All vaccines have many of the same side effects. The most common is simply a reaction at the site of injection, characterized by pain, increased warmth, erythema, swelling, and tenderness. Other common side effects include systemic manifestations, such as low-grade fever, nausea and vomiting, malaise, fatigue, headache, lymphadenopathy, myalgias, and arthralgias. Some vaccines, notably varicella, herpes zoster, measles, and rubella may cause a disseminated rash. Most of these minor side effects are easily managed by rest, hydration, and administration of an analgesic such as acetaminophen or ibuprofen. More serious side effects include rare complications such as anaphylaxis, Bell palsy, Guillain-Barre syndrome, and venous thromboembolism (Johnson & Johnson COVID-19 vaccine). Any of the vaccines discussed above should not be given, or given only with extreme caution, to an individual who has experienced any of these reactions with a previous vaccine.

Barriers to vaccination

Although the vaccines reviewed above are highly effective in preventing serious illness in recipients, the medical profession’s “report card” in ensuring adherence with vaccine protocols is not optimal. In fact, it probably merits a grade no higher than C+, with vaccination rates in the range of 50% to 70%.

One of the major barriers to vaccination is lack of detailed information about vaccine efficacy and safety on the part of both provider and patient. Another is the problem of misinformation (eg, the persistent belief on the part of some individuals that vaccines may cause a serious problem, such as autism).^18,19 Another important barrier to widespread vaccination is the logistical problem associated with proper scheduling of multidose regimens (such as those for hepatitis A and B, varicella, and COVID-19). A final barrier, and in my own university-based practice, the most important obstacle is the expense of vaccination. Most, but not all, private insurance companies provide coverage for vaccines approved by the Centers for Disease Control and Prevention and the US Preventive Services Task Force. However, public insurance agencies often provide disappointingly inconsistent coverage for essential vaccines.

By keeping well informed about the most recent public health recommendations for vaccinations for adults and by leading important initiatives within our own practices, we should be able to overcome the first 3 barriers listed above. For example, Morgan and colleagues²⁰ recently achieved a 97% success rate with Tdap administration in pregnancy by placing a best-practice alert in the patients’ electronic medical records. Surmounting the final barrier will require intense effort on the part of individual practitioners and professional organizations to advocate for coverage for essential vaccinations for our patients.

CASE Resolved

This patient was raised in an area of the world where her family did not have easy access to medical care. Accordingly, she did not receive the usual childhood vaccines, such as measles, mumps, rubella, varicella, hepatitis B, and almost certainly, tetanus, diphtheria, and pertussis (Tdap), and the HPV vaccine. The MMR vaccine and the varicella vaccine are live virus vaccines and should not be given during pregnancy. However, these vaccines should be administered postpartum, and the patient should be instructed to practice secure contraception for a minimum of 1 month following vaccination. She also should be offered the HPV vaccine postpartum. During pregnancy, she definitely should receive the COVID-19 vaccine, the 3-dose hepatitis B vaccine series, the influenza vaccine, and Tdap. If her present living conditions place her at risk for hepatitis A, she also should be vaccinated against this illness. ●

Northwell Health, the largest hospital system in New York state, fired 1,400 employees Oct. 3 for not complying with the state’s COVID-19 vaccine mandate.

The employees represented less than 2% of Northwell’s 76,000 employees, who are now all fully vaccinated against COVID-19, Joe Kemp, the assistant vice president of public relations for the company, told The Hill.

“Northwell Health is proud to announce that our workforce -- the largest in New York State -- is 100% vaccinated,” the company said in a statement to several news outlets.

“This allows us to continue to provide exceptional care at all of our facilities, without interruption and remain open and fully operational,” Northwell Health said.

Having a fully vaccinated workforce is part of the health system’s duty to protect others, the company said. Northwell Health includes 23 hospitals and more than 830 outpatient facilities, according to ABC News.

“Northwell regrets losing any employee under such circumstances,” the company said. “We owe it to our staff, our patients, and the communities we serve to be 100% vaccinated against COVID-19.”

Former New York Gov. Andrew Cuomo announced in August that the state would require health care workers to receive at least one COVID-19 vaccine shot by Sept. 27. Employees didn’t have the option for weekly testing or religious exemptions, which is being challenged in several lawsuits, according to The New York Times.

The order went into effect last week, prompting tens of thousands of employees to get vaccinated. As of last week, 87% of hospital staff were fully vaccinated, and 92% of hospital and retirement home workers had received at least one dose, according to state health data.

Northwell announced its own vaccine mandate in August as well, which sparked protests among some workers. The order applied to both clinical and non-clinical staff.

A few thousand Northwell employees got vaccinated as the deadline approached, Mr. Kemp told The New York Times. Some who lost their jobs at first were able to return to work, and those who have been terminated can interview for reinstatement for 30 days. The hospital system is also “openly recruiting” for the vacant positions.

“The goal was to get people vaccinated, not to get people terminated,” Mr. Kemp said.

Hospitalized COVID-19 patients in New York hit a low of 350 in mid-July, according to state hospitalization data. Now, about 2,200 people are hospitalized throughout the state, most of whom are unvaccinated.

As of Oct. 3, nearly 72% of New York residents had received at least one vaccine dose, according to the latest state data. About 64% are fully vaccinated.

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

Northwell Health, the largest hospital system in New York state, fired 1,400 employees Oct. 3 for not complying with the state’s COVID-19 vaccine mandate.

The employees represented less than 2% of Northwell’s 76,000 employees, who are now all fully vaccinated against COVID-19, Joe Kemp, the assistant vice president of public relations for the company, told The Hill.

“Northwell Health is proud to announce that our workforce -- the largest in New York State -- is 100% vaccinated,” the company said in a statement to several news outlets.

“This allows us to continue to provide exceptional care at all of our facilities, without interruption and remain open and fully operational,” Northwell Health said.

Having a fully vaccinated workforce is part of the health system’s duty to protect others, the company said. Northwell Health includes 23 hospitals and more than 830 outpatient facilities, according to ABC News.

“Northwell regrets losing any employee under such circumstances,” the company said. “We owe it to our staff, our patients, and the communities we serve to be 100% vaccinated against COVID-19.”

Former New York Gov. Andrew Cuomo announced in August that the state would require health care workers to receive at least one COVID-19 vaccine shot by Sept. 27. Employees didn’t have the option for weekly testing or religious exemptions, which is being challenged in several lawsuits, according to The New York Times.

The order went into effect last week, prompting tens of thousands of employees to get vaccinated. As of last week, 87% of hospital staff were fully vaccinated, and 92% of hospital and retirement home workers had received at least one dose, according to state health data.

Northwell announced its own vaccine mandate in August as well, which sparked protests among some workers. The order applied to both clinical and non-clinical staff.

A few thousand Northwell employees got vaccinated as the deadline approached, Mr. Kemp told The New York Times. Some who lost their jobs at first were able to return to work, and those who have been terminated can interview for reinstatement for 30 days. The hospital system is also “openly recruiting” for the vacant positions.

“The goal was to get people vaccinated, not to get people terminated,” Mr. Kemp said.

Hospitalized COVID-19 patients in New York hit a low of 350 in mid-July, according to state hospitalization data. Now, about 2,200 people are hospitalized throughout the state, most of whom are unvaccinated.

As of Oct. 3, nearly 72% of New York residents had received at least one vaccine dose, according to the latest state data. About 64% are fully vaccinated.

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

Northwell Health, the largest hospital system in New York state, fired 1,400 employees Oct. 3 for not complying with the state’s COVID-19 vaccine mandate.

The employees represented less than 2% of Northwell’s 76,000 employees, who are now all fully vaccinated against COVID-19, Joe Kemp, the assistant vice president of public relations for the company, told The Hill.

“Northwell Health is proud to announce that our workforce -- the largest in New York State -- is 100% vaccinated,” the company said in a statement to several news outlets.

“This allows us to continue to provide exceptional care at all of our facilities, without interruption and remain open and fully operational,” Northwell Health said.

Having a fully vaccinated workforce is part of the health system’s duty to protect others, the company said. Northwell Health includes 23 hospitals and more than 830 outpatient facilities, according to ABC News.

“Northwell regrets losing any employee under such circumstances,” the company said. “We owe it to our staff, our patients, and the communities we serve to be 100% vaccinated against COVID-19.”

Former New York Gov. Andrew Cuomo announced in August that the state would require health care workers to receive at least one COVID-19 vaccine shot by Sept. 27. Employees didn’t have the option for weekly testing or religious exemptions, which is being challenged in several lawsuits, according to The New York Times.

The order went into effect last week, prompting tens of thousands of employees to get vaccinated. As of last week, 87% of hospital staff were fully vaccinated, and 92% of hospital and retirement home workers had received at least one dose, according to state health data.

Northwell announced its own vaccine mandate in August as well, which sparked protests among some workers. The order applied to both clinical and non-clinical staff.

A few thousand Northwell employees got vaccinated as the deadline approached, Mr. Kemp told The New York Times. Some who lost their jobs at first were able to return to work, and those who have been terminated can interview for reinstatement for 30 days. The hospital system is also “openly recruiting” for the vacant positions.

“The goal was to get people vaccinated, not to get people terminated,” Mr. Kemp said.

Hospitalized COVID-19 patients in New York hit a low of 350 in mid-July, according to state hospitalization data. Now, about 2,200 people are hospitalized throughout the state, most of whom are unvaccinated.

As of Oct. 3, nearly 72% of New York residents had received at least one vaccine dose, according to the latest state data. About 64% are fully vaccinated.

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

The continuing decline in COVID-19 incidence suggests the latest surge has peaked as new cases in children dropped for the 4th consecutive week, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Preliminary data from the Centers for Disease Control and Prevention, however, show an uptick in new cases in late September, largely among younger children, that may indicate otherwise. Those data have a potential 2-week reporting delay, the CDC said on its COVID Data Tracker, so the most recent points on the graph (see above) could still go up.

The AAP and the CHA said that 173,000 new cases were reported for the week of Sept. 24-30, down 16% from the week before and 31% from the peak in early September. Those new cases made up almost 27% of all cases for the week, and the nearly 5.9 million child cases that have been reported since the start of the pandemic represent 16.2% of cases among Americans of all ages, the two groups said in their weekly COVID-19 report.

The CDC data on new cases by age group suggest that younger children have borne a heavier burden in the summer surge of COVID than they did last winter. The rate of new cases was not as high for 16- and 17-year-olds in the summer, but the other age groups all reached higher peaks than in the winter, including the 12- to 15-year-olds, who have been getting vaccinated since May, according to the COVID Data Tracker.

With vaccination approval getting closer for children under age 12 years, initiation in those already eligible continues to slide. Those aged 12-15 made up just 6.9% of new vaccinations during the 2 weeks from Sept. 21 to Oct. 4, and that figure has been dropping since July 13-26, when it was 14.1%. Vaccine initiation among 16- and 17-year-olds over that time has dropped by almost half, from 5.4% to 2.9%, the CDC data show.

All the vaccinations so far add up to this: Almost 55% of those aged 12-15 have gotten at least one dose of COVID vaccine, as have over 62% of those aged 16-17, and 52% of the older group is fully vaccinated, as is 44% of the younger group. Altogether, 10.8 million children were fully vaccinated as of Oct. 4, including those under 12 who may be participating in clinical trials or had a birth date entered incorrectly, the CDC said.

[email protected]

The continuing decline in COVID-19 incidence suggests the latest surge has peaked as new cases in children dropped for the 4th consecutive week, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Preliminary data from the Centers for Disease Control and Prevention, however, show an uptick in new cases in late September, largely among younger children, that may indicate otherwise. Those data have a potential 2-week reporting delay, the CDC said on its COVID Data Tracker, so the most recent points on the graph (see above) could still go up.

The AAP and the CHA said that 173,000 new cases were reported for the week of Sept. 24-30, down 16% from the week before and 31% from the peak in early September. Those new cases made up almost 27% of all cases for the week, and the nearly 5.9 million child cases that have been reported since the start of the pandemic represent 16.2% of cases among Americans of all ages, the two groups said in their weekly COVID-19 report.

The CDC data on new cases by age group suggest that younger children have borne a heavier burden in the summer surge of COVID than they did last winter. The rate of new cases was not as high for 16- and 17-year-olds in the summer, but the other age groups all reached higher peaks than in the winter, including the 12- to 15-year-olds, who have been getting vaccinated since May, according to the COVID Data Tracker.

With vaccination approval getting closer for children under age 12 years, initiation in those already eligible continues to slide. Those aged 12-15 made up just 6.9% of new vaccinations during the 2 weeks from Sept. 21 to Oct. 4, and that figure has been dropping since July 13-26, when it was 14.1%. Vaccine initiation among 16- and 17-year-olds over that time has dropped by almost half, from 5.4% to 2.9%, the CDC data show.

All the vaccinations so far add up to this: Almost 55% of those aged 12-15 have gotten at least one dose of COVID vaccine, as have over 62% of those aged 16-17, and 52% of the older group is fully vaccinated, as is 44% of the younger group. Altogether, 10.8 million children were fully vaccinated as of Oct. 4, including those under 12 who may be participating in clinical trials or had a birth date entered incorrectly, the CDC said.

[email protected]

The continuing decline in COVID-19 incidence suggests the latest surge has peaked as new cases in children dropped for the 4th consecutive week, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Preliminary data from the Centers for Disease Control and Prevention, however, show an uptick in new cases in late September, largely among younger children, that may indicate otherwise. Those data have a potential 2-week reporting delay, the CDC said on its COVID Data Tracker, so the most recent points on the graph (see above) could still go up.

The AAP and the CHA said that 173,000 new cases were reported for the week of Sept. 24-30, down 16% from the week before and 31% from the peak in early September. Those new cases made up almost 27% of all cases for the week, and the nearly 5.9 million child cases that have been reported since the start of the pandemic represent 16.2% of cases among Americans of all ages, the two groups said in their weekly COVID-19 report.

The CDC data on new cases by age group suggest that younger children have borne a heavier burden in the summer surge of COVID than they did last winter. The rate of new cases was not as high for 16- and 17-year-olds in the summer, but the other age groups all reached higher peaks than in the winter, including the 12- to 15-year-olds, who have been getting vaccinated since May, according to the COVID Data Tracker.

With vaccination approval getting closer for children under age 12 years, initiation in those already eligible continues to slide. Those aged 12-15 made up just 6.9% of new vaccinations during the 2 weeks from Sept. 21 to Oct. 4, and that figure has been dropping since July 13-26, when it was 14.1%. Vaccine initiation among 16- and 17-year-olds over that time has dropped by almost half, from 5.4% to 2.9%, the CDC data show.

All the vaccinations so far add up to this: Almost 55% of those aged 12-15 have gotten at least one dose of COVID vaccine, as have over 62% of those aged 16-17, and 52% of the older group is fully vaccinated, as is 44% of the younger group. Altogether, 10.8 million children were fully vaccinated as of Oct. 4, including those under 12 who may be participating in clinical trials or had a birth date entered incorrectly, the CDC said.

[email protected]

Johnson & Johnson asked the Food and Drug Administration (FDA) on Tuesday to authorize an extra dose of its COVID-19 vaccine as a booster shot.

The company said it filed a request for people ages 18 and older who have received the one-shot vaccine. Johnson & Johnson submitted data for several different booster intervals -- ranging from 2 months to 6 months -- but didn’t formally recommend one to the FDA, The Associated Press reported.

“We’re describing the data to them,” Mathai Mammen, MD, head of global research and development for Janssen, the company’s vaccine division, told CNN.

“The process is not that we asked for a very specific interval -- we’re providing them data and we’re going to be presenting to the committee,” he said. “They’ll take all that into consideration when they ultimately decide on an appropriate interval.”

The FDA’s independent vaccine advisory committee meets next week to review data on booster shots from both Johnson & Johnson and Moderna. It’s the first step in the review process, which then requires approval from leaders at the FDA and Centers for Disease Control and Prevention. If both agencies authorize the extra shots, Americans could receive boosters from Johnson & Johnson and Moderna later this month, the AP reported.

Johnson & Johnson previously released data that showed the vaccine remains highly effective against COVID-19 at least 5 months after vaccination, with 81% efficacy against hospitalizations in the United States.

Two weeks ago, the company reported that a booster dose at 2 months or 6 months further lifted immunity, with a booster at 2 months providing 94% protection against moderate and severe COVID-19. The company said the 6-month booster raised antibodies by 12 times but didn’t release additional data at that time.

In September, the FDA authorized booster shots of the Pfizer vaccine for ages 65 and older, those who live in long-term care facilities, and those with higher risks for contracting COVID-19. The Biden administration is supporting a booster campaign to address potential waning vaccine immunity and remaining surges of the more contagious Delta variant, the AP reported.

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

Johnson & Johnson asked the Food and Drug Administration (FDA) on Tuesday to authorize an extra dose of its COVID-19 vaccine as a booster shot.

The company said it filed a request for people ages 18 and older who have received the one-shot vaccine. Johnson & Johnson submitted data for several different booster intervals -- ranging from 2 months to 6 months -- but didn’t formally recommend one to the FDA, The Associated Press reported.

“We’re describing the data to them,” Mathai Mammen, MD, head of global research and development for Janssen, the company’s vaccine division, told CNN.

“The process is not that we asked for a very specific interval -- we’re providing them data and we’re going to be presenting to the committee,” he said. “They’ll take all that into consideration when they ultimately decide on an appropriate interval.”

The FDA’s independent vaccine advisory committee meets next week to review data on booster shots from both Johnson & Johnson and Moderna. It’s the first step in the review process, which then requires approval from leaders at the FDA and Centers for Disease Control and Prevention. If both agencies authorize the extra shots, Americans could receive boosters from Johnson & Johnson and Moderna later this month, the AP reported.

Johnson & Johnson previously released data that showed the vaccine remains highly effective against COVID-19 at least 5 months after vaccination, with 81% efficacy against hospitalizations in the United States.

Two weeks ago, the company reported that a booster dose at 2 months or 6 months further lifted immunity, with a booster at 2 months providing 94% protection against moderate and severe COVID-19. The company said the 6-month booster raised antibodies by 12 times but didn’t release additional data at that time.

In September, the FDA authorized booster shots of the Pfizer vaccine for ages 65 and older, those who live in long-term care facilities, and those with higher risks for contracting COVID-19. The Biden administration is supporting a booster campaign to address potential waning vaccine immunity and remaining surges of the more contagious Delta variant, the AP reported.

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

Johnson & Johnson asked the Food and Drug Administration (FDA) on Tuesday to authorize an extra dose of its COVID-19 vaccine as a booster shot.

The company said it filed a request for people ages 18 and older who have received the one-shot vaccine. Johnson & Johnson submitted data for several different booster intervals -- ranging from 2 months to 6 months -- but didn’t formally recommend one to the FDA, The Associated Press reported.

“We’re describing the data to them,” Mathai Mammen, MD, head of global research and development for Janssen, the company’s vaccine division, told CNN.

“The process is not that we asked for a very specific interval -- we’re providing them data and we’re going to be presenting to the committee,” he said. “They’ll take all that into consideration when they ultimately decide on an appropriate interval.”

The FDA’s independent vaccine advisory committee meets next week to review data on booster shots from both Johnson & Johnson and Moderna. It’s the first step in the review process, which then requires approval from leaders at the FDA and Centers for Disease Control and Prevention. If both agencies authorize the extra shots, Americans could receive boosters from Johnson & Johnson and Moderna later this month, the AP reported.

Johnson & Johnson previously released data that showed the vaccine remains highly effective against COVID-19 at least 5 months after vaccination, with 81% efficacy against hospitalizations in the United States.

Two weeks ago, the company reported that a booster dose at 2 months or 6 months further lifted immunity, with a booster at 2 months providing 94% protection against moderate and severe COVID-19. The company said the 6-month booster raised antibodies by 12 times but didn’t release additional data at that time.

In September, the FDA authorized booster shots of the Pfizer vaccine for ages 65 and older, those who live in long-term care facilities, and those with higher risks for contracting COVID-19. The Biden administration is supporting a booster campaign to address potential waning vaccine immunity and remaining surges of the more contagious Delta variant, the AP reported.

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

Houston architect Lanson Jones is one of the nearly 80 million Americans who refuse to get a COVID-19 vaccine, arguing the shots are experimental, were rushed to market, may cause side effects, and aren’t all fully approved by federal officials.

But when he contracted COVID in September, he didn’t hesitate to seek treatment with monoclonal antibodies -- a year-old, laboratory-created therapy no less experimental than the vaccines that is not fully approved by the FDA and can also cause rare side effects.

“I haven’t done the shot because I hear a lot -- a lot -- of information about what are some of the effects of these vaccines and how it’s really not being reported, and I just felt I didn’t want to put something in me that has some question,” says Mr. Jones, 65.

“But with this monoclonal antibody treatment, I didn’t hesitate. I had no doubt in my mind -- not even one ounce of doubt about it. Not one person said, ‘Oh, well some people have had a reaction to it.’”

Mr. Jones, who was treated at Houston Methodist Hospital, is one of more than a million Americans who have received antibody IVs after getting the virus.

Those numbers are growing, with the federal government recently taking over distribution of the supplies of the drugs, which are limited in many states.

The treatment has been effective against COVID, in helping patients recover, stay out of the hospital, or die from the illness.

But what doctors and public health experts say is most surprising is that so many of those embracing it are unvaccinated Americans who have refused the shot for reasons that could very well apply to the newly developed and experimental monoclonal antibody therapy, as well.

“I think it’s irrational, quite frankly, if you have to boil it down to one word,” says Howard Huang, MD, who heads up Houston Methodist’s infusion program, which is providing up to 900 doses a week. “It really doesn’t make any sense on multiple levels.”

For one thing, he says, the FDA has just granted full approval for the COVID vaccine produced by Pfizer and BioNTech, upgrading its status from its emergency use authorization (EUA). Many experts expect the FDA to grant similar full approvals to the Moderna vaccine and possibly the Johnson and Johnson shot, which currently have EUA designations.

Many vaccine holdouts have cited the EUA status of the COVID vaccines -- one step shy of full approval -- as a reason they don’t trust the shot. But the antibody treatments have also been granted only EUA approval, which hasn’t stopped vaccine-resistant Americans from seeking them.

“So, they’re refusing an FDA-approved and tested [vaccine], and then they’re seeking something that’s still under an FDA EUA,” says Dr. Huang. “I just don’t get it. I really don’t.”

Amesh Adalja, MD, an emerging infectious diseases specialist with the Johns Hopkins University Center for Health Security, calls it “paradoxical” thinking for vaccine holdouts to refuse a shot that boosts your natural antibodies to prevent COVID, but take an antibody drug to treat it after infection.

“I don’t understand it, I can’t,” he says. “But the pandemic has been politicized and … I think consistency is not something to expect from people who are thinking about this irrationally [and] for people engaging in these conspiracies about the vaccine.

“I do think the fact that people like Joe Rogan and Gov. Abbot and Donald Trump received the monoclonal antibodies does probably play a role in some of the thinking in some of these individuals.”

Terry Scoggin, CEO of Titus Regional Medical Center in Mount Pleasant, Tex., says even the hospital’s doctors have been shocked by the demand for the new therapy among unvaccinated Texans.

“It’s mind-blowing that there’s been such resistance to the vaccine, but that demand for the monoclonal antibodies is so high,” he says, noting only 47% of adults in the region have received at least one dose of the shot. That’s far below CDC estimates that say 75.2% of American adults have received one shot, while 64.7% are fully vaccinated.

“But our doctors believe in the monoclonal antibodies, so it’s a trust factor -- they trust our community physicians,” Mr. Scoggin says. “I’ve never put the two and two together about the fear of the vaccine vs. [lack of fear] of the treatment. But it’s really interesting.”
 

Treatments effective, costly

Like the COVID vaccines given to nearly 214 million Americans, the antibody treatments taken by more than 1 million in the United States are highly effective and cause only rare (and usually minor) side effects.

Federal health officials say the infusions have helped keep the U.S. death toll -- now about 2,000 per day-- from soaring even higher, even as vaccine hesitancy persists, particularly in Southern states.

The FDA first authorized monoclonal antibody drugs in November 2020 -- just weeks before the vaccines were approved. But their popularity has soared as the Delta variant of the virus that causes COVID-19 has surged in recent months.

Clinical trials show that the drugs can cut COVID-related hospitalization or death in high-risk patients by as much as 70%-80%. They also can prevent infection in healthy people who have been exposed to an infected person, according to research published this month in The New England Journal of Medicine.

Monoclonal antibodies have been used for decades to treat cancer, autoimmune disorders, and other diseases, with the FDA approving nearly 100 such treatments since 1994.

The FDA has granted EUA approvals to four antibody treatments for COVID-19.

A two-antibody drug combination from Regeneron -- containing casirivimab and imdevimab -- has been shown to reduce the risk of hospitalization and death by 70% in people infected with COVID. Sotrovimab, made by GlaxoSmithKline and Vir, has had similar results.

The FDA approved a third treatment -- Eli Lilly’s combination of bamlanivimab and etesevimab -- in 2020, but the agency recommended against its use earlier this year after it proved ineffective against the Delta variant. The combination came back on the market in late August, but only in states where fewer than 5% of COVID infections are from strains, such as Delta, that are resistant to the treatment.

In June, the FDA authorized a fourth drug combination, Genentech’s tocilizumab, for people already hospitalized with COVID. But it is only moderately effective against the disease.

Lab-made monoclonal antibodies mimic the antibodies the body makes to fight viruses and illnesses. They work by targeting the spike protein on the surface of the virus. COVID vaccines work by priming the body’s immune system to recognize this very same spike protein and block it from entering your body’s cells, preventing infection.

Antibody treatments are given as an IV to treat an infection but can also be given as shots into the belly for people who have been exposed to the virus but have not yet been sickened by it, Dr. Huang says.

Timing is critical, he says, noting antibodies are most effective when given in the first few days after symptoms emerge.
 

Demands, concerns on the rise

Orders for monoclonal antibodies have skyrocketed in recent weeks -- to 168,000 doses per week in late August, up from 27,000 in July. The Biden administration, which has been covering the cost of the treatment for most patients, took over its distribution as well this week.

But experts foresee potential problems as patient demand increases.

Federal officials have already warned states of potential shortages ahead. Only about 2.4 million monoclonal antibody doses have been shipped nationally so far, less than half of which have been administered.

More supplies are on the way, with the federal government recently buying another 1.8 million doses for delivery in the months ahead. But for now, some hospitals are uncertain of supplies and are already struggling to meet the demand for the treatments.

Seven Southern states account for 70% of orders: Texas, Alabama, Florida, Mississippi, Tennessee, Georgia, and Louisiana. Those states have among the nation’s lowest vaccine rates and highest infection numbers.

Florida officials said the state’s latest weekly allotment left clinics 41,000 doses short of what they need. Tennessee has begun limiting treatments for unvaccinated patients to give priority to those most at risk of dying from COVID. And in Texas, elective surgeries have been postponed to make room for COVID-19 patients at some hospitals, as operating room nurses have been enlisted to give IVs.

Some strong proponents of monoclonal antibody treatments have been frustrated by Republican governors who are scrambling to push and deliver them, while opposing vaccine and mask mandates.

Raising vaccination rates, scientists say, would make the antibody treatments unnecessary in many cases.

Experts also note the drugs are far more costly than the vaccines -- with a price tag of about $2,100 for each IV, compared to $20-$40 for the shot.

“When you’re talking about just the cost to society as a whole -- turning down a [vaccine] that costs a couple dozen dollars for therapies that cost thousands of dollars -- it just doesn’t make any sense,” says Dr. Huang.

“And the tragedy is that a lot of these infections right now are preventable. It’s not like the pre-vaccine days, when we didn’t have anything better. And for these people, it’s just hard to justify that line of thinking. And so, the challenge is changing people’s minds. And that’s really been the difficult thing.”

In addition, the treatments take 90 minutes to administer, taxing health care workers in hard-hit states that have been slammed by the influx of patients.

Beyond these issues, Dr. Huang cites other public health costs of people choosing treatment over vaccination. The vaccine protects others because it limits transmission of the virus. By contrast, a single antibody IV helps only that patient and does not keep people from infecting others or becoming reinfected, requiring another IV.

“Getting the vaccine helps people beyond yourself; it helps the community, too,” he notes. “There’s just a strong argument for getting the vaccine. I obviously have a very biased opinion, but I would hope I have more of a scientific or expert opinion, but that doesn’t seem to matter these days.”
 

Vaccine resistance still remains for some

Seth Thurman, an IT technician from Mount Pleasant, Tex., acknowledges he was hesitant to get the vaccine at first because he felt it was fast-tracked, “experimental,” might cause unknown side effects, was developed quickly, and was being pushed by government officials.

“I shared the same sentiments as a lot of other people [as] some of the reasons why I might have been hesitant in the beginning to get the vaccine, says Mr. Thurman, 47. “A lot of people don’t trust what’s out there, maybe what the government is pushing, so I was taking a wait-and-see approach.”

In August, he relented and received the first of the two-shot Moderna vaccine. But several weeks later, he developed COVID and took his doctor’s advice to receive antibody therapy at Titus Regional Medical Center.

The results were almost immediate.

“I noticed within just a few hours of getting that infusion I was feeling better,” he says. “And by the next day, I was feeling great. No more temperature and no cough and no loss of taste and smell. And today, I’m 100%.”

Having had COVID convinced him of the importance of getting the vaccine, and he plans to get the second dose of the shot after the prescribed 90-day waiting period.

But Mr. Jones, the Houston architect, remains unconvinced, even after suffering what he describes as a “horrible” experience with COVID.

“It’s something I’m still thinking about,” he says of the vaccine. “But I can’t imagine that there wouldn’t be some sort of side effects from something that was developed so fast and had not gone through 4 or 5 years of vetting or trials. So that kind of just leaves doubt in my mind.

“And it’s just so weird that something so personal has become so public -- like people’s medical decisions now are on the front page of The New York Times. When did we think something like that would ever happen?”

The quick results of his treatment were so “remarkable” that he’d recommend it to anyone without hesitation, he says.

“If my story can help people be willing to seek out this infusion and take it early on in their COVID experience, I think it would not only save lives and keep people out of our hospitals and not overwhelm our hospital systems,” he says.

Dr. Huang agrees that the IV therapy is a great “fallback option” for people who’ve been infected, who have weakened immune systems, or can’t receive the vaccine for other health reasons. But for most people, he argues, the vaccine is the best way to go. That’s why Houston Methodist advises the shot for every patient like Mr. Jones, who’s been treated for COVID.

“Getting the vaccine is the way to go for the vast number of people,” he says.

Frederick Thurmond, MD, who oversees COVID-related care at Titus Regional Medical Center, believes it will take more than just doctors’ recommendations to move some patients to get the vaccine. The only thing that will motivate some will be contracting COVID, or knowing someone who does, he says.

“It’s clear that at least here in Texas, I swear man, you tell people they need to do something, and they just say, ‘Well, then I’m NOT going to do it,’” he says. “But once you’ve got COVID, the game becomes a whole lot more serious. And I think most people in the U.S. know someone who’s died from COVID at this point.”

Dr. Thurmond says that for some patients, stubborn resistance to legitimate medical advice persists -- on the vaccine and even treatment -- even after infection.

“We have seen more than one person avoid any medical care whatsoever after they knew they had COVID,” he says. “They languish in private and eventually come to the emergency room extremely sick and doing things with little to no medical value -- such as taking a friend’s hydroxychloroquine, random antibiotics, a horse de-worming dose of ivermectin, and gargling with Betadine and even bleach.”

But most of his patients who have the IV therapy take his advice to get the vaccine afterward.

“The only way to end the pandemic is to vaccinate everybody,” he says.

Dr. Adalja agrees.

“The monoclonal antibodies work, they are great drugs, so I think it is appropriate to praise them,” says Dr. Adalja, who’s given them to his own patients. “But it’s not appropriate to use them as an alternative to vaccination or to think, you know, don’t worry about the getting the vaccine because if you get infected and get the monoclonal antibodies to get through this -- that’s not the way to approach it.

He also worries about what he calls “dark-age mentalities” that have fueled the anti-vaccine movement, which has sought to heighten fears of modern medicine and doctors.

“The anti-vaccine movement has really capitalized on COVID-19, and it’s really a much more virulent form of the anti-vaccine movement than what we’ve seen with measles and other diseases in the past,” he notes. “And I think it’s going to be very difficult to contend with in the future, because no one thought we’d be battling the anti-vaccine movement this late in the pandemic.”

The biggest takeaway?

“When it comes to an infectious disease, prevention is always much better than treatment,” Dr. Adalja says. “If you don’t even need to get to the treatment stage because you prevent people from getting infected, that’s the goal.”

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

Houston architect Lanson Jones is one of the nearly 80 million Americans who refuse to get a COVID-19 vaccine, arguing the shots are experimental, were rushed to market, may cause side effects, and aren’t all fully approved by federal officials.

But when he contracted COVID in September, he didn’t hesitate to seek treatment with monoclonal antibodies -- a year-old, laboratory-created therapy no less experimental than the vaccines that is not fully approved by the FDA and can also cause rare side effects.

“I haven’t done the shot because I hear a lot -- a lot -- of information about what are some of the effects of these vaccines and how it’s really not being reported, and I just felt I didn’t want to put something in me that has some question,” says Mr. Jones, 65.

“But with this monoclonal antibody treatment, I didn’t hesitate. I had no doubt in my mind -- not even one ounce of doubt about it. Not one person said, ‘Oh, well some people have had a reaction to it.’”

Mr. Jones, who was treated at Houston Methodist Hospital, is one of more than a million Americans who have received antibody IVs after getting the virus.

Those numbers are growing, with the federal government recently taking over distribution of the supplies of the drugs, which are limited in many states.

The treatment has been effective against COVID, in helping patients recover, stay out of the hospital, or die from the illness.

But what doctors and public health experts say is most surprising is that so many of those embracing it are unvaccinated Americans who have refused the shot for reasons that could very well apply to the newly developed and experimental monoclonal antibody therapy, as well.

“I think it’s irrational, quite frankly, if you have to boil it down to one word,” says Howard Huang, MD, who heads up Houston Methodist’s infusion program, which is providing up to 900 doses a week. “It really doesn’t make any sense on multiple levels.”

For one thing, he says, the FDA has just granted full approval for the COVID vaccine produced by Pfizer and BioNTech, upgrading its status from its emergency use authorization (EUA). Many experts expect the FDA to grant similar full approvals to the Moderna vaccine and possibly the Johnson and Johnson shot, which currently have EUA designations.

Many vaccine holdouts have cited the EUA status of the COVID vaccines -- one step shy of full approval -- as a reason they don’t trust the shot. But the antibody treatments have also been granted only EUA approval, which hasn’t stopped vaccine-resistant Americans from seeking them.

“So, they’re refusing an FDA-approved and tested [vaccine], and then they’re seeking something that’s still under an FDA EUA,” says Dr. Huang. “I just don’t get it. I really don’t.”

Amesh Adalja, MD, an emerging infectious diseases specialist with the Johns Hopkins University Center for Health Security, calls it “paradoxical” thinking for vaccine holdouts to refuse a shot that boosts your natural antibodies to prevent COVID, but take an antibody drug to treat it after infection.

“I don’t understand it, I can’t,” he says. “But the pandemic has been politicized and … I think consistency is not something to expect from people who are thinking about this irrationally [and] for people engaging in these conspiracies about the vaccine.

“I do think the fact that people like Joe Rogan and Gov. Abbot and Donald Trump received the monoclonal antibodies does probably play a role in some of the thinking in some of these individuals.”

Terry Scoggin, CEO of Titus Regional Medical Center in Mount Pleasant, Tex., says even the hospital’s doctors have been shocked by the demand for the new therapy among unvaccinated Texans.

“It’s mind-blowing that there’s been such resistance to the vaccine, but that demand for the monoclonal antibodies is so high,” he says, noting only 47% of adults in the region have received at least one dose of the shot. That’s far below CDC estimates that say 75.2% of American adults have received one shot, while 64.7% are fully vaccinated.

“But our doctors believe in the monoclonal antibodies, so it’s a trust factor -- they trust our community physicians,” Mr. Scoggin says. “I’ve never put the two and two together about the fear of the vaccine vs. [lack of fear] of the treatment. But it’s really interesting.”
 

Treatments effective, costly

Like the COVID vaccines given to nearly 214 million Americans, the antibody treatments taken by more than 1 million in the United States are highly effective and cause only rare (and usually minor) side effects.

Federal health officials say the infusions have helped keep the U.S. death toll -- now about 2,000 per day-- from soaring even higher, even as vaccine hesitancy persists, particularly in Southern states.

The FDA first authorized monoclonal antibody drugs in November 2020 -- just weeks before the vaccines were approved. But their popularity has soared as the Delta variant of the virus that causes COVID-19 has surged in recent months.

Clinical trials show that the drugs can cut COVID-related hospitalization or death in high-risk patients by as much as 70%-80%. They also can prevent infection in healthy people who have been exposed to an infected person, according to research published this month in The New England Journal of Medicine.

Monoclonal antibodies have been used for decades to treat cancer, autoimmune disorders, and other diseases, with the FDA approving nearly 100 such treatments since 1994.

The FDA has granted EUA approvals to four antibody treatments for COVID-19.

A two-antibody drug combination from Regeneron -- containing casirivimab and imdevimab -- has been shown to reduce the risk of hospitalization and death by 70% in people infected with COVID. Sotrovimab, made by GlaxoSmithKline and Vir, has had similar results.

The FDA approved a third treatment -- Eli Lilly’s combination of bamlanivimab and etesevimab -- in 2020, but the agency recommended against its use earlier this year after it proved ineffective against the Delta variant. The combination came back on the market in late August, but only in states where fewer than 5% of COVID infections are from strains, such as Delta, that are resistant to the treatment.

In June, the FDA authorized a fourth drug combination, Genentech’s tocilizumab, for people already hospitalized with COVID. But it is only moderately effective against the disease.

Lab-made monoclonal antibodies mimic the antibodies the body makes to fight viruses and illnesses. They work by targeting the spike protein on the surface of the virus. COVID vaccines work by priming the body’s immune system to recognize this very same spike protein and block it from entering your body’s cells, preventing infection.

Antibody treatments are given as an IV to treat an infection but can also be given as shots into the belly for people who have been exposed to the virus but have not yet been sickened by it, Dr. Huang says.

Timing is critical, he says, noting antibodies are most effective when given in the first few days after symptoms emerge.
 

Demands, concerns on the rise

Orders for monoclonal antibodies have skyrocketed in recent weeks -- to 168,000 doses per week in late August, up from 27,000 in July. The Biden administration, which has been covering the cost of the treatment for most patients, took over its distribution as well this week.

But experts foresee potential problems as patient demand increases.

Federal officials have already warned states of potential shortages ahead. Only about 2.4 million monoclonal antibody doses have been shipped nationally so far, less than half of which have been administered.

More supplies are on the way, with the federal government recently buying another 1.8 million doses for delivery in the months ahead. But for now, some hospitals are uncertain of supplies and are already struggling to meet the demand for the treatments.

Seven Southern states account for 70% of orders: Texas, Alabama, Florida, Mississippi, Tennessee, Georgia, and Louisiana. Those states have among the nation’s lowest vaccine rates and highest infection numbers.

Florida officials said the state’s latest weekly allotment left clinics 41,000 doses short of what they need. Tennessee has begun limiting treatments for unvaccinated patients to give priority to those most at risk of dying from COVID. And in Texas, elective surgeries have been postponed to make room for COVID-19 patients at some hospitals, as operating room nurses have been enlisted to give IVs.

Some strong proponents of monoclonal antibody treatments have been frustrated by Republican governors who are scrambling to push and deliver them, while opposing vaccine and mask mandates.

Raising vaccination rates, scientists say, would make the antibody treatments unnecessary in many cases.

Experts also note the drugs are far more costly than the vaccines -- with a price tag of about $2,100 for each IV, compared to $20-$40 for the shot.

“When you’re talking about just the cost to society as a whole -- turning down a [vaccine] that costs a couple dozen dollars for therapies that cost thousands of dollars -- it just doesn’t make any sense,” says Dr. Huang.

“And the tragedy is that a lot of these infections right now are preventable. It’s not like the pre-vaccine days, when we didn’t have anything better. And for these people, it’s just hard to justify that line of thinking. And so, the challenge is changing people’s minds. And that’s really been the difficult thing.”

In addition, the treatments take 90 minutes to administer, taxing health care workers in hard-hit states that have been slammed by the influx of patients.

Beyond these issues, Dr. Huang cites other public health costs of people choosing treatment over vaccination. The vaccine protects others because it limits transmission of the virus. By contrast, a single antibody IV helps only that patient and does not keep people from infecting others or becoming reinfected, requiring another IV.

“Getting the vaccine helps people beyond yourself; it helps the community, too,” he notes. “There’s just a strong argument for getting the vaccine. I obviously have a very biased opinion, but I would hope I have more of a scientific or expert opinion, but that doesn’t seem to matter these days.”
 

Vaccine resistance still remains for some

Seth Thurman, an IT technician from Mount Pleasant, Tex., acknowledges he was hesitant to get the vaccine at first because he felt it was fast-tracked, “experimental,” might cause unknown side effects, was developed quickly, and was being pushed by government officials.

“I shared the same sentiments as a lot of other people [as] some of the reasons why I might have been hesitant in the beginning to get the vaccine, says Mr. Thurman, 47. “A lot of people don’t trust what’s out there, maybe what the government is pushing, so I was taking a wait-and-see approach.”

In August, he relented and received the first of the two-shot Moderna vaccine. But several weeks later, he developed COVID and took his doctor’s advice to receive antibody therapy at Titus Regional Medical Center.

The results were almost immediate.

“I noticed within just a few hours of getting that infusion I was feeling better,” he says. “And by the next day, I was feeling great. No more temperature and no cough and no loss of taste and smell. And today, I’m 100%.”

Having had COVID convinced him of the importance of getting the vaccine, and he plans to get the second dose of the shot after the prescribed 90-day waiting period.

But Mr. Jones, the Houston architect, remains unconvinced, even after suffering what he describes as a “horrible” experience with COVID.

“It’s something I’m still thinking about,” he says of the vaccine. “But I can’t imagine that there wouldn’t be some sort of side effects from something that was developed so fast and had not gone through 4 or 5 years of vetting or trials. So that kind of just leaves doubt in my mind.

“And it’s just so weird that something so personal has become so public -- like people’s medical decisions now are on the front page of The New York Times. When did we think something like that would ever happen?”

The quick results of his treatment were so “remarkable” that he’d recommend it to anyone without hesitation, he says.

“If my story can help people be willing to seek out this infusion and take it early on in their COVID experience, I think it would not only save lives and keep people out of our hospitals and not overwhelm our hospital systems,” he says.

Dr. Huang agrees that the IV therapy is a great “fallback option” for people who’ve been infected, who have weakened immune systems, or can’t receive the vaccine for other health reasons. But for most people, he argues, the vaccine is the best way to go. That’s why Houston Methodist advises the shot for every patient like Mr. Jones, who’s been treated for COVID.

“Getting the vaccine is the way to go for the vast number of people,” he says.

Frederick Thurmond, MD, who oversees COVID-related care at Titus Regional Medical Center, believes it will take more than just doctors’ recommendations to move some patients to get the vaccine. The only thing that will motivate some will be contracting COVID, or knowing someone who does, he says.

“It’s clear that at least here in Texas, I swear man, you tell people they need to do something, and they just say, ‘Well, then I’m NOT going to do it,’” he says. “But once you’ve got COVID, the game becomes a whole lot more serious. And I think most people in the U.S. know someone who’s died from COVID at this point.”

Dr. Thurmond says that for some patients, stubborn resistance to legitimate medical advice persists -- on the vaccine and even treatment -- even after infection.

“We have seen more than one person avoid any medical care whatsoever after they knew they had COVID,” he says. “They languish in private and eventually come to the emergency room extremely sick and doing things with little to no medical value -- such as taking a friend’s hydroxychloroquine, random antibiotics, a horse de-worming dose of ivermectin, and gargling with Betadine and even bleach.”

But most of his patients who have the IV therapy take his advice to get the vaccine afterward.

“The only way to end the pandemic is to vaccinate everybody,” he says.

Dr. Adalja agrees.

“The monoclonal antibodies work, they are great drugs, so I think it is appropriate to praise them,” says Dr. Adalja, who’s given them to his own patients. “But it’s not appropriate to use them as an alternative to vaccination or to think, you know, don’t worry about the getting the vaccine because if you get infected and get the monoclonal antibodies to get through this -- that’s not the way to approach it.

He also worries about what he calls “dark-age mentalities” that have fueled the anti-vaccine movement, which has sought to heighten fears of modern medicine and doctors.

“The anti-vaccine movement has really capitalized on COVID-19, and it’s really a much more virulent form of the anti-vaccine movement than what we’ve seen with measles and other diseases in the past,” he notes. “And I think it’s going to be very difficult to contend with in the future, because no one thought we’d be battling the anti-vaccine movement this late in the pandemic.”

The biggest takeaway?

“When it comes to an infectious disease, prevention is always much better than treatment,” Dr. Adalja says. “If you don’t even need to get to the treatment stage because you prevent people from getting infected, that’s the goal.”

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

Houston architect Lanson Jones is one of the nearly 80 million Americans who refuse to get a COVID-19 vaccine, arguing the shots are experimental, were rushed to market, may cause side effects, and aren’t all fully approved by federal officials.

But when he contracted COVID in September, he didn’t hesitate to seek treatment with monoclonal antibodies -- a year-old, laboratory-created therapy no less experimental than the vaccines that is not fully approved by the FDA and can also cause rare side effects.

“I haven’t done the shot because I hear a lot -- a lot -- of information about what are some of the effects of these vaccines and how it’s really not being reported, and I just felt I didn’t want to put something in me that has some question,” says Mr. Jones, 65.

“But with this monoclonal antibody treatment, I didn’t hesitate. I had no doubt in my mind -- not even one ounce of doubt about it. Not one person said, ‘Oh, well some people have had a reaction to it.’”

Mr. Jones, who was treated at Houston Methodist Hospital, is one of more than a million Americans who have received antibody IVs after getting the virus.

Those numbers are growing, with the federal government recently taking over distribution of the supplies of the drugs, which are limited in many states.

The treatment has been effective against COVID, in helping patients recover, stay out of the hospital, or die from the illness.

But what doctors and public health experts say is most surprising is that so many of those embracing it are unvaccinated Americans who have refused the shot for reasons that could very well apply to the newly developed and experimental monoclonal antibody therapy, as well.

“I think it’s irrational, quite frankly, if you have to boil it down to one word,” says Howard Huang, MD, who heads up Houston Methodist’s infusion program, which is providing up to 900 doses a week. “It really doesn’t make any sense on multiple levels.”

For one thing, he says, the FDA has just granted full approval for the COVID vaccine produced by Pfizer and BioNTech, upgrading its status from its emergency use authorization (EUA). Many experts expect the FDA to grant similar full approvals to the Moderna vaccine and possibly the Johnson and Johnson shot, which currently have EUA designations.

Many vaccine holdouts have cited the EUA status of the COVID vaccines -- one step shy of full approval -- as a reason they don’t trust the shot. But the antibody treatments have also been granted only EUA approval, which hasn’t stopped vaccine-resistant Americans from seeking them.

“So, they’re refusing an FDA-approved and tested [vaccine], and then they’re seeking something that’s still under an FDA EUA,” says Dr. Huang. “I just don’t get it. I really don’t.”

Amesh Adalja, MD, an emerging infectious diseases specialist with the Johns Hopkins University Center for Health Security, calls it “paradoxical” thinking for vaccine holdouts to refuse a shot that boosts your natural antibodies to prevent COVID, but take an antibody drug to treat it after infection.

“I don’t understand it, I can’t,” he says. “But the pandemic has been politicized and … I think consistency is not something to expect from people who are thinking about this irrationally [and] for people engaging in these conspiracies about the vaccine.

“I do think the fact that people like Joe Rogan and Gov. Abbot and Donald Trump received the monoclonal antibodies does probably play a role in some of the thinking in some of these individuals.”

Terry Scoggin, CEO of Titus Regional Medical Center in Mount Pleasant, Tex., says even the hospital’s doctors have been shocked by the demand for the new therapy among unvaccinated Texans.

“It’s mind-blowing that there’s been such resistance to the vaccine, but that demand for the monoclonal antibodies is so high,” he says, noting only 47% of adults in the region have received at least one dose of the shot. That’s far below CDC estimates that say 75.2% of American adults have received one shot, while 64.7% are fully vaccinated.

“But our doctors believe in the monoclonal antibodies, so it’s a trust factor -- they trust our community physicians,” Mr. Scoggin says. “I’ve never put the two and two together about the fear of the vaccine vs. [lack of fear] of the treatment. But it’s really interesting.”
 

Treatments effective, costly

Like the COVID vaccines given to nearly 214 million Americans, the antibody treatments taken by more than 1 million in the United States are highly effective and cause only rare (and usually minor) side effects.

Federal health officials say the infusions have helped keep the U.S. death toll -- now about 2,000 per day-- from soaring even higher, even as vaccine hesitancy persists, particularly in Southern states.

The FDA first authorized monoclonal antibody drugs in November 2020 -- just weeks before the vaccines were approved. But their popularity has soared as the Delta variant of the virus that causes COVID-19 has surged in recent months.

Clinical trials show that the drugs can cut COVID-related hospitalization or death in high-risk patients by as much as 70%-80%. They also can prevent infection in healthy people who have been exposed to an infected person, according to research published this month in The New England Journal of Medicine.

Monoclonal antibodies have been used for decades to treat cancer, autoimmune disorders, and other diseases, with the FDA approving nearly 100 such treatments since 1994.

The FDA has granted EUA approvals to four antibody treatments for COVID-19.

A two-antibody drug combination from Regeneron -- containing casirivimab and imdevimab -- has been shown to reduce the risk of hospitalization and death by 70% in people infected with COVID. Sotrovimab, made by GlaxoSmithKline and Vir, has had similar results.

The FDA approved a third treatment -- Eli Lilly’s combination of bamlanivimab and etesevimab -- in 2020, but the agency recommended against its use earlier this year after it proved ineffective against the Delta variant. The combination came back on the market in late August, but only in states where fewer than 5% of COVID infections are from strains, such as Delta, that are resistant to the treatment.

In June, the FDA authorized a fourth drug combination, Genentech’s tocilizumab, for people already hospitalized with COVID. But it is only moderately effective against the disease.

Lab-made monoclonal antibodies mimic the antibodies the body makes to fight viruses and illnesses. They work by targeting the spike protein on the surface of the virus. COVID vaccines work by priming the body’s immune system to recognize this very same spike protein and block it from entering your body’s cells, preventing infection.

Antibody treatments are given as an IV to treat an infection but can also be given as shots into the belly for people who have been exposed to the virus but have not yet been sickened by it, Dr. Huang says.

Timing is critical, he says, noting antibodies are most effective when given in the first few days after symptoms emerge.
 

Demands, concerns on the rise

Orders for monoclonal antibodies have skyrocketed in recent weeks -- to 168,000 doses per week in late August, up from 27,000 in July. The Biden administration, which has been covering the cost of the treatment for most patients, took over its distribution as well this week.

But experts foresee potential problems as patient demand increases.

Federal officials have already warned states of potential shortages ahead. Only about 2.4 million monoclonal antibody doses have been shipped nationally so far, less than half of which have been administered.

More supplies are on the way, with the federal government recently buying another 1.8 million doses for delivery in the months ahead. But for now, some hospitals are uncertain of supplies and are already struggling to meet the demand for the treatments.

Seven Southern states account for 70% of orders: Texas, Alabama, Florida, Mississippi, Tennessee, Georgia, and Louisiana. Those states have among the nation’s lowest vaccine rates and highest infection numbers.

Florida officials said the state’s latest weekly allotment left clinics 41,000 doses short of what they need. Tennessee has begun limiting treatments for unvaccinated patients to give priority to those most at risk of dying from COVID. And in Texas, elective surgeries have been postponed to make room for COVID-19 patients at some hospitals, as operating room nurses have been enlisted to give IVs.

Some strong proponents of monoclonal antibody treatments have been frustrated by Republican governors who are scrambling to push and deliver them, while opposing vaccine and mask mandates.

Raising vaccination rates, scientists say, would make the antibody treatments unnecessary in many cases.

Experts also note the drugs are far more costly than the vaccines -- with a price tag of about $2,100 for each IV, compared to $20-$40 for the shot.

“When you’re talking about just the cost to society as a whole -- turning down a [vaccine] that costs a couple dozen dollars for therapies that cost thousands of dollars -- it just doesn’t make any sense,” says Dr. Huang.

“And the tragedy is that a lot of these infections right now are preventable. It’s not like the pre-vaccine days, when we didn’t have anything better. And for these people, it’s just hard to justify that line of thinking. And so, the challenge is changing people’s minds. And that’s really been the difficult thing.”

In addition, the treatments take 90 minutes to administer, taxing health care workers in hard-hit states that have been slammed by the influx of patients.

Beyond these issues, Dr. Huang cites other public health costs of people choosing treatment over vaccination. The vaccine protects others because it limits transmission of the virus. By contrast, a single antibody IV helps only that patient and does not keep people from infecting others or becoming reinfected, requiring another IV.

“Getting the vaccine helps people beyond yourself; it helps the community, too,” he notes. “There’s just a strong argument for getting the vaccine. I obviously have a very biased opinion, but I would hope I have more of a scientific or expert opinion, but that doesn’t seem to matter these days.”
 

Vaccine resistance still remains for some

Seth Thurman, an IT technician from Mount Pleasant, Tex., acknowledges he was hesitant to get the vaccine at first because he felt it was fast-tracked, “experimental,” might cause unknown side effects, was developed quickly, and was being pushed by government officials.

“I shared the same sentiments as a lot of other people [as] some of the reasons why I might have been hesitant in the beginning to get the vaccine, says Mr. Thurman, 47. “A lot of people don’t trust what’s out there, maybe what the government is pushing, so I was taking a wait-and-see approach.”

In August, he relented and received the first of the two-shot Moderna vaccine. But several weeks later, he developed COVID and took his doctor’s advice to receive antibody therapy at Titus Regional Medical Center.

The results were almost immediate.

“I noticed within just a few hours of getting that infusion I was feeling better,” he says. “And by the next day, I was feeling great. No more temperature and no cough and no loss of taste and smell. And today, I’m 100%.”

Having had COVID convinced him of the importance of getting the vaccine, and he plans to get the second dose of the shot after the prescribed 90-day waiting period.

But Mr. Jones, the Houston architect, remains unconvinced, even after suffering what he describes as a “horrible” experience with COVID.

“It’s something I’m still thinking about,” he says of the vaccine. “But I can’t imagine that there wouldn’t be some sort of side effects from something that was developed so fast and had not gone through 4 or 5 years of vetting or trials. So that kind of just leaves doubt in my mind.

“And it’s just so weird that something so personal has become so public -- like people’s medical decisions now are on the front page of The New York Times. When did we think something like that would ever happen?”

The quick results of his treatment were so “remarkable” that he’d recommend it to anyone without hesitation, he says.

“If my story can help people be willing to seek out this infusion and take it early on in their COVID experience, I think it would not only save lives and keep people out of our hospitals and not overwhelm our hospital systems,” he says.

Dr. Huang agrees that the IV therapy is a great “fallback option” for people who’ve been infected, who have weakened immune systems, or can’t receive the vaccine for other health reasons. But for most people, he argues, the vaccine is the best way to go. That’s why Houston Methodist advises the shot for every patient like Mr. Jones, who’s been treated for COVID.

“Getting the vaccine is the way to go for the vast number of people,” he says.

Frederick Thurmond, MD, who oversees COVID-related care at Titus Regional Medical Center, believes it will take more than just doctors’ recommendations to move some patients to get the vaccine. The only thing that will motivate some will be contracting COVID, or knowing someone who does, he says.

“It’s clear that at least here in Texas, I swear man, you tell people they need to do something, and they just say, ‘Well, then I’m NOT going to do it,’” he says. “But once you’ve got COVID, the game becomes a whole lot more serious. And I think most people in the U.S. know someone who’s died from COVID at this point.”

Dr. Thurmond says that for some patients, stubborn resistance to legitimate medical advice persists -- on the vaccine and even treatment -- even after infection.

“We have seen more than one person avoid any medical care whatsoever after they knew they had COVID,” he says. “They languish in private and eventually come to the emergency room extremely sick and doing things with little to no medical value -- such as taking a friend’s hydroxychloroquine, random antibiotics, a horse de-worming dose of ivermectin, and gargling with Betadine and even bleach.”

But most of his patients who have the IV therapy take his advice to get the vaccine afterward.

“The only way to end the pandemic is to vaccinate everybody,” he says.

Dr. Adalja agrees.

“The monoclonal antibodies work, they are great drugs, so I think it is appropriate to praise them,” says Dr. Adalja, who’s given them to his own patients. “But it’s not appropriate to use them as an alternative to vaccination or to think, you know, don’t worry about the getting the vaccine because if you get infected and get the monoclonal antibodies to get through this -- that’s not the way to approach it.

He also worries about what he calls “dark-age mentalities” that have fueled the anti-vaccine movement, which has sought to heighten fears of modern medicine and doctors.

“The anti-vaccine movement has really capitalized on COVID-19, and it’s really a much more virulent form of the anti-vaccine movement than what we’ve seen with measles and other diseases in the past,” he notes. “And I think it’s going to be very difficult to contend with in the future, because no one thought we’d be battling the anti-vaccine movement this late in the pandemic.”

The biggest takeaway?

“When it comes to an infectious disease, prevention is always much better than treatment,” Dr. Adalja says. “If you don’t even need to get to the treatment stage because you prevent people from getting infected, that’s the goal.”

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