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COVID-19 effect: Prescription fills mostly down for leading drugs
Prescription fills for hydroxychloroquine/chloroquine spiked right after COVID-19 was declared a national emergency in March, but use of the drugs still remains well above 2019 levels, based on data from more than 58,000 U.S. pharmacies.
Hydroxychloroquine/chloroquine are also doing better than any of the prescription drugs in the top 10 based on total claims in 2019, Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital, Boston, and associates reported May 28 in a research letter in JAMA.
Prescription fills for hydroxychloroquine/chloroquine have been above 2019 levels every week since the national emergency was declared on March 13, with the high occurring during the week of March 15-21, when fills were 214% higher than the corresponding week in 2019. The lowest level in that time came during the week of April 12-18, with growth of 14.6% over 2019, the investigators said.
The drugs occupying the top 10 – amlodipine, amoxicillin, atorvastatin, gabapentin, hydrocodone-acetaminophen, levothyroxine, lisinopril, losartan, omeprazole, and sertraline – have not done as well. Losartan, the only one that hasn’t lost ground in any week since March 13, rose by almost 49% during March 15-21, but was down to a 1.7% rise by the end of the study period, they reported.
Meanwhile, the other drug touted as a treatment for COVID-19, azithromycin, has fallen farther than most of the top 10. By April 19-25, the last week of the study period, fills for the antibiotic were down 62.7%, compared with last year, the analysis showed. Only amoxicillin had dropped more (64.4%).
“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” Dr. Vaduganathan and associates wrote.
The investigators “used all-payer U.S. pharmacy data from 58,332 chain, independent, and mail-order pharmacies across 14,421 zip codes in 50 states, reflecting approximately 17 million deidentified claims,” to estimate national prescription fills, they explained.
SOURCE: Vaduganathan M et al. JAMA 2020 May 28. doi: 10.1001/jama.2020.9184.
Prescription fills for hydroxychloroquine/chloroquine spiked right after COVID-19 was declared a national emergency in March, but use of the drugs still remains well above 2019 levels, based on data from more than 58,000 U.S. pharmacies.
Hydroxychloroquine/chloroquine are also doing better than any of the prescription drugs in the top 10 based on total claims in 2019, Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital, Boston, and associates reported May 28 in a research letter in JAMA.
Prescription fills for hydroxychloroquine/chloroquine have been above 2019 levels every week since the national emergency was declared on March 13, with the high occurring during the week of March 15-21, when fills were 214% higher than the corresponding week in 2019. The lowest level in that time came during the week of April 12-18, with growth of 14.6% over 2019, the investigators said.
The drugs occupying the top 10 – amlodipine, amoxicillin, atorvastatin, gabapentin, hydrocodone-acetaminophen, levothyroxine, lisinopril, losartan, omeprazole, and sertraline – have not done as well. Losartan, the only one that hasn’t lost ground in any week since March 13, rose by almost 49% during March 15-21, but was down to a 1.7% rise by the end of the study period, they reported.
Meanwhile, the other drug touted as a treatment for COVID-19, azithromycin, has fallen farther than most of the top 10. By April 19-25, the last week of the study period, fills for the antibiotic were down 62.7%, compared with last year, the analysis showed. Only amoxicillin had dropped more (64.4%).
“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” Dr. Vaduganathan and associates wrote.
The investigators “used all-payer U.S. pharmacy data from 58,332 chain, independent, and mail-order pharmacies across 14,421 zip codes in 50 states, reflecting approximately 17 million deidentified claims,” to estimate national prescription fills, they explained.
SOURCE: Vaduganathan M et al. JAMA 2020 May 28. doi: 10.1001/jama.2020.9184.
Prescription fills for hydroxychloroquine/chloroquine spiked right after COVID-19 was declared a national emergency in March, but use of the drugs still remains well above 2019 levels, based on data from more than 58,000 U.S. pharmacies.
Hydroxychloroquine/chloroquine are also doing better than any of the prescription drugs in the top 10 based on total claims in 2019, Muthiah Vaduganathan, MD, MPH, of Brigham and Women’s Hospital, Boston, and associates reported May 28 in a research letter in JAMA.
Prescription fills for hydroxychloroquine/chloroquine have been above 2019 levels every week since the national emergency was declared on March 13, with the high occurring during the week of March 15-21, when fills were 214% higher than the corresponding week in 2019. The lowest level in that time came during the week of April 12-18, with growth of 14.6% over 2019, the investigators said.
The drugs occupying the top 10 – amlodipine, amoxicillin, atorvastatin, gabapentin, hydrocodone-acetaminophen, levothyroxine, lisinopril, losartan, omeprazole, and sertraline – have not done as well. Losartan, the only one that hasn’t lost ground in any week since March 13, rose by almost 49% during March 15-21, but was down to a 1.7% rise by the end of the study period, they reported.
Meanwhile, the other drug touted as a treatment for COVID-19, azithromycin, has fallen farther than most of the top 10. By April 19-25, the last week of the study period, fills for the antibiotic were down 62.7%, compared with last year, the analysis showed. Only amoxicillin had dropped more (64.4%).
“The modest decline for most common long-term therapies after peak could represent reduced contact with prescribing clinicians, restricted access to pharmacies, pharmacist rationing, loss of insurance from unemployment, or replete supplies from early stockpiling,” Dr. Vaduganathan and associates wrote.
The investigators “used all-payer U.S. pharmacy data from 58,332 chain, independent, and mail-order pharmacies across 14,421 zip codes in 50 states, reflecting approximately 17 million deidentified claims,” to estimate national prescription fills, they explained.
SOURCE: Vaduganathan M et al. JAMA 2020 May 28. doi: 10.1001/jama.2020.9184.
FROM JAMA
FDA okays first tau radiotracer to aid Alzheimer’s disease diagnosis
to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adults with cognitive impairment who are being evaluated for Alzheimer disease.
“While there are FDA-approved imaging drugs for amyloid pathology, this is the first drug approved for imaging tau pathology, one of the two neuropathological hallmarks of Alzheimer’s disease, and represents a major advance for patients with cognitive impairment being evaluated for the condition,” Charles Ganley, MD, director of the Office of Specialty Medicine at the Center for Drug Evaluation and Research, said in an FDA news release.
“The use of diagnostic imaging can help patients and their families plan for the future and make informed choices about their health and well-being, in addition to facilitating appropriate patient management for physicians,” Reisa Sperling, MD, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, said in a company news release.
“Determining the anatomic distribution and density of tau NFTs in the brain was previously possible only at autopsy. Now we have a way to obtain this important information in patients,” said Dr. Sperling.
Clinical trial results
Following intravenous administration, flortaucipir F18 binds to tau pathology in the brain and can be seen on a PET scan.
The safety and effectiveness of the tau tracer were demonstrated in two clinical studies. In each study, five evaluators, blinded to clinical information, interpreted the flortaucipir F18 PET scan results as positive or negative.
The first study included 156 terminally ill patients who agreed to undergo flortaucipir F18 PET imaging and to donate their brains after death. Of these patients, 64 died within 9 months of undergoing brain scanning. The evaluators’ readings of these scans were compared with postmortem readings from independent pathologists blinded to scan results.
Evaluators reading the flortaucipir F18 PET scans had a “high probability” of correctly evaluating patients with tau pathology and had an “average to high probability” of correctly evaluating patients without tau pathology, the FDA said in the release.
According to the company, reader sensitivity ranged from 92% (95% confidence interval, 80%-97%) to 100% (95% CI, 91%-100%). Specificity ranged from 52% (95% CI, 34%-70%) to 92% (95% CI, 75%-98%).
Initial limited availability
The second study included the same patients with terminal illness as the first study, plus 18 additional patients who had terminal illness and 159 patients who had cognitive impairment and were being evaluated for Alzheimer’s disease (the indicated population).
The study gauged how well evaluators’ readings of flortaucipir F18 PET scans agreed with each other’s assessments of the readings. In this study, reader agreement was 0.87 (perfect agreement was indicated as 1) across all 241 patients.
In a separate subgroup analysis that included the 82 terminally ill patients who were diagnosed after death and the 159 patients with cognitive impairment, reader agreement was 0.90 for the patients in the indicated population and 0.82 in the terminally ill patients.
The FDA noted that the ability of flortaucipir F18 PET scans to detect tau pathology was assessed in patients with generally severe stages of dementia and may be lower in patients with cognitive decline of earlier stages.
The most common adverse reactions among patients who received flortaucipir F18 injection were headache, injection site pain, and an increase in blood pressure. The tau radiotracer is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy.
The FDA granted flortaucipir F18 priority review, in which the FDA aims to take action on an application within 6 months of the time the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition.
The company said that the availability of flortaucipir F18 will initially be “limited and will expand in response to commercial demand and payor reimbursement.”
Alzheimer’s disease is among the top 10 leading causes of death in the United States. In 2014, 5 million Americans were living with the disease, according to federal health officials. That number is projected to nearly triple to 14 million by 2060.
A version of this article originally appeared on Medscape.com.
to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adults with cognitive impairment who are being evaluated for Alzheimer disease.
“While there are FDA-approved imaging drugs for amyloid pathology, this is the first drug approved for imaging tau pathology, one of the two neuropathological hallmarks of Alzheimer’s disease, and represents a major advance for patients with cognitive impairment being evaluated for the condition,” Charles Ganley, MD, director of the Office of Specialty Medicine at the Center for Drug Evaluation and Research, said in an FDA news release.
“The use of diagnostic imaging can help patients and their families plan for the future and make informed choices about their health and well-being, in addition to facilitating appropriate patient management for physicians,” Reisa Sperling, MD, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, said in a company news release.
“Determining the anatomic distribution and density of tau NFTs in the brain was previously possible only at autopsy. Now we have a way to obtain this important information in patients,” said Dr. Sperling.
Clinical trial results
Following intravenous administration, flortaucipir F18 binds to tau pathology in the brain and can be seen on a PET scan.
The safety and effectiveness of the tau tracer were demonstrated in two clinical studies. In each study, five evaluators, blinded to clinical information, interpreted the flortaucipir F18 PET scan results as positive or negative.
The first study included 156 terminally ill patients who agreed to undergo flortaucipir F18 PET imaging and to donate their brains after death. Of these patients, 64 died within 9 months of undergoing brain scanning. The evaluators’ readings of these scans were compared with postmortem readings from independent pathologists blinded to scan results.
Evaluators reading the flortaucipir F18 PET scans had a “high probability” of correctly evaluating patients with tau pathology and had an “average to high probability” of correctly evaluating patients without tau pathology, the FDA said in the release.
According to the company, reader sensitivity ranged from 92% (95% confidence interval, 80%-97%) to 100% (95% CI, 91%-100%). Specificity ranged from 52% (95% CI, 34%-70%) to 92% (95% CI, 75%-98%).
Initial limited availability
The second study included the same patients with terminal illness as the first study, plus 18 additional patients who had terminal illness and 159 patients who had cognitive impairment and were being evaluated for Alzheimer’s disease (the indicated population).
The study gauged how well evaluators’ readings of flortaucipir F18 PET scans agreed with each other’s assessments of the readings. In this study, reader agreement was 0.87 (perfect agreement was indicated as 1) across all 241 patients.
In a separate subgroup analysis that included the 82 terminally ill patients who were diagnosed after death and the 159 patients with cognitive impairment, reader agreement was 0.90 for the patients in the indicated population and 0.82 in the terminally ill patients.
The FDA noted that the ability of flortaucipir F18 PET scans to detect tau pathology was assessed in patients with generally severe stages of dementia and may be lower in patients with cognitive decline of earlier stages.
The most common adverse reactions among patients who received flortaucipir F18 injection were headache, injection site pain, and an increase in blood pressure. The tau radiotracer is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy.
The FDA granted flortaucipir F18 priority review, in which the FDA aims to take action on an application within 6 months of the time the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition.
The company said that the availability of flortaucipir F18 will initially be “limited and will expand in response to commercial demand and payor reimbursement.”
Alzheimer’s disease is among the top 10 leading causes of death in the United States. In 2014, 5 million Americans were living with the disease, according to federal health officials. That number is projected to nearly triple to 14 million by 2060.
A version of this article originally appeared on Medscape.com.
to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adults with cognitive impairment who are being evaluated for Alzheimer disease.
“While there are FDA-approved imaging drugs for amyloid pathology, this is the first drug approved for imaging tau pathology, one of the two neuropathological hallmarks of Alzheimer’s disease, and represents a major advance for patients with cognitive impairment being evaluated for the condition,” Charles Ganley, MD, director of the Office of Specialty Medicine at the Center for Drug Evaluation and Research, said in an FDA news release.
“The use of diagnostic imaging can help patients and their families plan for the future and make informed choices about their health and well-being, in addition to facilitating appropriate patient management for physicians,” Reisa Sperling, MD, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, said in a company news release.
“Determining the anatomic distribution and density of tau NFTs in the brain was previously possible only at autopsy. Now we have a way to obtain this important information in patients,” said Dr. Sperling.
Clinical trial results
Following intravenous administration, flortaucipir F18 binds to tau pathology in the brain and can be seen on a PET scan.
The safety and effectiveness of the tau tracer were demonstrated in two clinical studies. In each study, five evaluators, blinded to clinical information, interpreted the flortaucipir F18 PET scan results as positive or negative.
The first study included 156 terminally ill patients who agreed to undergo flortaucipir F18 PET imaging and to donate their brains after death. Of these patients, 64 died within 9 months of undergoing brain scanning. The evaluators’ readings of these scans were compared with postmortem readings from independent pathologists blinded to scan results.
Evaluators reading the flortaucipir F18 PET scans had a “high probability” of correctly evaluating patients with tau pathology and had an “average to high probability” of correctly evaluating patients without tau pathology, the FDA said in the release.
According to the company, reader sensitivity ranged from 92% (95% confidence interval, 80%-97%) to 100% (95% CI, 91%-100%). Specificity ranged from 52% (95% CI, 34%-70%) to 92% (95% CI, 75%-98%).
Initial limited availability
The second study included the same patients with terminal illness as the first study, plus 18 additional patients who had terminal illness and 159 patients who had cognitive impairment and were being evaluated for Alzheimer’s disease (the indicated population).
The study gauged how well evaluators’ readings of flortaucipir F18 PET scans agreed with each other’s assessments of the readings. In this study, reader agreement was 0.87 (perfect agreement was indicated as 1) across all 241 patients.
In a separate subgroup analysis that included the 82 terminally ill patients who were diagnosed after death and the 159 patients with cognitive impairment, reader agreement was 0.90 for the patients in the indicated population and 0.82 in the terminally ill patients.
The FDA noted that the ability of flortaucipir F18 PET scans to detect tau pathology was assessed in patients with generally severe stages of dementia and may be lower in patients with cognitive decline of earlier stages.
The most common adverse reactions among patients who received flortaucipir F18 injection were headache, injection site pain, and an increase in blood pressure. The tau radiotracer is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy.
The FDA granted flortaucipir F18 priority review, in which the FDA aims to take action on an application within 6 months of the time the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition.
The company said that the availability of flortaucipir F18 will initially be “limited and will expand in response to commercial demand and payor reimbursement.”
Alzheimer’s disease is among the top 10 leading causes of death in the United States. In 2014, 5 million Americans were living with the disease, according to federal health officials. That number is projected to nearly triple to 14 million by 2060.
A version of this article originally appeared on Medscape.com.
APA, others lobby to make COVID-19 telehealth waivers permanent
The American Psychiatric Association (APA) is calling on Congress to permanently lift restrictions that have allowed unfettered delivery of telehealth services during the COVID-19 pandemic, which experts say has been a boon to patients and physicians alike.
“We ask Congress to extend the telehealth waiver authority under COVID-19 beyond the emergency and to study its impact while doing so,” said APA President Jeffrey Geller, MD, in a May 27 video briefing with congressional staff and reporters.
The APA is also seeking to make permanent certain waivers granted by the Centers for Medicare & Medicaid Services on April 30, including elimination of geographic restrictions on behavioral health and allowing patients be seen at home, said Dr. Geller.
The APA also is asking for the elimination of the rule that requires clinicians to have an initial face-to-face meeting with patients before they can prescribe controlled substances, Dr. Geller said. The Drug Enforcement Administration waived that requirement, known as the Ryan Haight Act, on March 17 for the duration of the national emergency.
Telemedicine has supporters on both sides of the aisle in Congress, including Rep. Paul Tonko (D-N.Y.) who said at the APA briefing he would fight to make the waivers permanent.
“The expanded use of telehealth has enormous potential during normal times as well, especially in behavioral health,” said Mr. Tonko. “I am pushing fiercely for these current flexibilities to be extended for a reasonable time after the public health emergency so that we can have time to evaluate which should be made permanent,” he said.
Dr. Geller, other clinicians, and advocates in the briefing praised CMS for facilitating telepsychiatry for Medicare. That follows in the footsteps of most private insurers, who have also relaxed requirements into the summer, according to the Medical Group Management Association.
Game changer
The Medicare waivers “have dramatically changed the entire scene for someone like myself as a clinician to allow me to see my patients in a much easier way,” said Peter Yellowlees, MBBS, MD, chief wellness officer, University of California Davis Health. Within 2 weeks in March, the health system converted almost all of its regular outpatient visits to telemedicine, he said.
Dr. Yellowlees added government still needs to address, what he called, outdated HIPAA regulations that ban certain technologies.
“It makes no sense that I can talk to someone on an iPhone, but the moment I talk to them on FaceTime, it’s illegal,” said Dr. Yellowlees, a former president of the American Telemedicine Association.
Dr. Geller said that “psychiatric care provided by telehealth is as effective as in-person psychiatric services,” adding that “some patients prefer telepsychiatry because of its convenience and as a means of reducing stigma associated with seeking help for mental health.”
Shabana Khan, MD, a child psychiatrist and director of telepsychiatry at New York University Langone Health, said audio and video conferencing are helping address a shortage and maldistribution of child and adolescent psychiatrists.
Americans’ mental health is suffering during the pandemic. The U.S. Census Bureau recently released data showing that half of those surveyed reported depressed mood and that one-third are reporting anxiety, depression, or both, as reported by the Washington Post.
“At this very time that anxiety, depression, substance use, and other mental health problems are rising, our nation’s already strained mental health system is really being pushed to the brink,” said Jodi Kwarciany, manager for mental health policy for the National Alliance on Mental Illness, during the briefing.
Telemedicine can help “by connecting people to providers at the time and the place and using the technology that works best for them,” she said, adding that NAMI would press policymakers to address barriers to access.
The clinicians on the briefing said they’ve observed that some patients are more comfortable with video or audio interactions than with in-person visits.
Increased access to care
Telepsychiatry seems to be convincing some to reconsider therapy, since they can do it at home, said Dr. Yellowlees. he said.
For instance, he said, he has been able to consult by phone and video with several patients who receive care through the Indian Health Service who had not be able to get into the physical clinic.
Dr. Yellowlees said video sessions also may encourage patients to be more, not less, talkative. “Video is actually counterintuitively a very intimate experience,” he said, in part because of the perceived distance and people’s tendency to be less inhibited on technology platforms.“It’s less embarrassing,” he said. “If you’ve got really dramatic, difficult, traumatic things to talk about, it’s slightly easier to talk to someone who’s slightly further apart from you on video,” said Dr. Yellowlees.
“Individuals who have a significant amount of anxiety may actually feel more comfortable with the distance that this technology affords,” agreed Dr. Khan. She said telemedicine had made sessions more comfortable for some of her patients with autism spectrum disorder.
Dr. Geller said audio and video have been important to his practice during the pandemic. One of his patients never leaves the house and does not use computers. “He spends his time sequestered at home listening to records on his record player,” said Dr. Geller. But he’s been amenable to phone sessions. “What I’ve found with him, and I’ve found with several other patients, is that they actually talk more easily when they’re not face to face,” he said.
Far fewer no-shows
Another plus for his New England–based practice during the last few months: patients have not been anxious about missing sessions because of the weather. The clinicians all noted that telepsychiatry seemed to reduce missed visits.
Dr. Yellowlees said that no-show rates had decreased by half at UC Davis. “That means no significant loss of income,” during the pandemic, he said.
“The no-show rate is incredibly low, particularly because when you call the patients and they don’t remember they had an appointment, you have the appointment anyway, most of the time,” said Dr. Geller.
For Dr. Khan, being able to conduct audio and video sessions during the pandemic has meant keeping up continuity of care.
As a result of the pandemic, many college students in New York City had to go home – often to another state. The waivers granted by New York’s Medicaid program and other insurers have allowed Dr. Khan to continue care for these patients.
The NYU clinic also operates day programs in rural areas 5 hours from the city. Dr. Khan recently evaluated a 12-year-old girl with significant anxiety and low mood, both of which had worsened.
“She would not have been able to access care otherwise,” said Dr. Khan. And for rural patients who do not have access to broadband or smartphones, audio visits “have been immensely helpful,” she said.
Dr. Khan, Dr. Geller, and Dr. Yellowlees have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The American Psychiatric Association (APA) is calling on Congress to permanently lift restrictions that have allowed unfettered delivery of telehealth services during the COVID-19 pandemic, which experts say has been a boon to patients and physicians alike.
“We ask Congress to extend the telehealth waiver authority under COVID-19 beyond the emergency and to study its impact while doing so,” said APA President Jeffrey Geller, MD, in a May 27 video briefing with congressional staff and reporters.
The APA is also seeking to make permanent certain waivers granted by the Centers for Medicare & Medicaid Services on April 30, including elimination of geographic restrictions on behavioral health and allowing patients be seen at home, said Dr. Geller.
The APA also is asking for the elimination of the rule that requires clinicians to have an initial face-to-face meeting with patients before they can prescribe controlled substances, Dr. Geller said. The Drug Enforcement Administration waived that requirement, known as the Ryan Haight Act, on March 17 for the duration of the national emergency.
Telemedicine has supporters on both sides of the aisle in Congress, including Rep. Paul Tonko (D-N.Y.) who said at the APA briefing he would fight to make the waivers permanent.
“The expanded use of telehealth has enormous potential during normal times as well, especially in behavioral health,” said Mr. Tonko. “I am pushing fiercely for these current flexibilities to be extended for a reasonable time after the public health emergency so that we can have time to evaluate which should be made permanent,” he said.
Dr. Geller, other clinicians, and advocates in the briefing praised CMS for facilitating telepsychiatry for Medicare. That follows in the footsteps of most private insurers, who have also relaxed requirements into the summer, according to the Medical Group Management Association.
Game changer
The Medicare waivers “have dramatically changed the entire scene for someone like myself as a clinician to allow me to see my patients in a much easier way,” said Peter Yellowlees, MBBS, MD, chief wellness officer, University of California Davis Health. Within 2 weeks in March, the health system converted almost all of its regular outpatient visits to telemedicine, he said.
Dr. Yellowlees added government still needs to address, what he called, outdated HIPAA regulations that ban certain technologies.
“It makes no sense that I can talk to someone on an iPhone, but the moment I talk to them on FaceTime, it’s illegal,” said Dr. Yellowlees, a former president of the American Telemedicine Association.
Dr. Geller said that “psychiatric care provided by telehealth is as effective as in-person psychiatric services,” adding that “some patients prefer telepsychiatry because of its convenience and as a means of reducing stigma associated with seeking help for mental health.”
Shabana Khan, MD, a child psychiatrist and director of telepsychiatry at New York University Langone Health, said audio and video conferencing are helping address a shortage and maldistribution of child and adolescent psychiatrists.
Americans’ mental health is suffering during the pandemic. The U.S. Census Bureau recently released data showing that half of those surveyed reported depressed mood and that one-third are reporting anxiety, depression, or both, as reported by the Washington Post.
“At this very time that anxiety, depression, substance use, and other mental health problems are rising, our nation’s already strained mental health system is really being pushed to the brink,” said Jodi Kwarciany, manager for mental health policy for the National Alliance on Mental Illness, during the briefing.
Telemedicine can help “by connecting people to providers at the time and the place and using the technology that works best for them,” she said, adding that NAMI would press policymakers to address barriers to access.
The clinicians on the briefing said they’ve observed that some patients are more comfortable with video or audio interactions than with in-person visits.
Increased access to care
Telepsychiatry seems to be convincing some to reconsider therapy, since they can do it at home, said Dr. Yellowlees. he said.
For instance, he said, he has been able to consult by phone and video with several patients who receive care through the Indian Health Service who had not be able to get into the physical clinic.
Dr. Yellowlees said video sessions also may encourage patients to be more, not less, talkative. “Video is actually counterintuitively a very intimate experience,” he said, in part because of the perceived distance and people’s tendency to be less inhibited on technology platforms.“It’s less embarrassing,” he said. “If you’ve got really dramatic, difficult, traumatic things to talk about, it’s slightly easier to talk to someone who’s slightly further apart from you on video,” said Dr. Yellowlees.
“Individuals who have a significant amount of anxiety may actually feel more comfortable with the distance that this technology affords,” agreed Dr. Khan. She said telemedicine had made sessions more comfortable for some of her patients with autism spectrum disorder.
Dr. Geller said audio and video have been important to his practice during the pandemic. One of his patients never leaves the house and does not use computers. “He spends his time sequestered at home listening to records on his record player,” said Dr. Geller. But he’s been amenable to phone sessions. “What I’ve found with him, and I’ve found with several other patients, is that they actually talk more easily when they’re not face to face,” he said.
Far fewer no-shows
Another plus for his New England–based practice during the last few months: patients have not been anxious about missing sessions because of the weather. The clinicians all noted that telepsychiatry seemed to reduce missed visits.
Dr. Yellowlees said that no-show rates had decreased by half at UC Davis. “That means no significant loss of income,” during the pandemic, he said.
“The no-show rate is incredibly low, particularly because when you call the patients and they don’t remember they had an appointment, you have the appointment anyway, most of the time,” said Dr. Geller.
For Dr. Khan, being able to conduct audio and video sessions during the pandemic has meant keeping up continuity of care.
As a result of the pandemic, many college students in New York City had to go home – often to another state. The waivers granted by New York’s Medicaid program and other insurers have allowed Dr. Khan to continue care for these patients.
The NYU clinic also operates day programs in rural areas 5 hours from the city. Dr. Khan recently evaluated a 12-year-old girl with significant anxiety and low mood, both of which had worsened.
“She would not have been able to access care otherwise,” said Dr. Khan. And for rural patients who do not have access to broadband or smartphones, audio visits “have been immensely helpful,” she said.
Dr. Khan, Dr. Geller, and Dr. Yellowlees have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The American Psychiatric Association (APA) is calling on Congress to permanently lift restrictions that have allowed unfettered delivery of telehealth services during the COVID-19 pandemic, which experts say has been a boon to patients and physicians alike.
“We ask Congress to extend the telehealth waiver authority under COVID-19 beyond the emergency and to study its impact while doing so,” said APA President Jeffrey Geller, MD, in a May 27 video briefing with congressional staff and reporters.
The APA is also seeking to make permanent certain waivers granted by the Centers for Medicare & Medicaid Services on April 30, including elimination of geographic restrictions on behavioral health and allowing patients be seen at home, said Dr. Geller.
The APA also is asking for the elimination of the rule that requires clinicians to have an initial face-to-face meeting with patients before they can prescribe controlled substances, Dr. Geller said. The Drug Enforcement Administration waived that requirement, known as the Ryan Haight Act, on March 17 for the duration of the national emergency.
Telemedicine has supporters on both sides of the aisle in Congress, including Rep. Paul Tonko (D-N.Y.) who said at the APA briefing he would fight to make the waivers permanent.
“The expanded use of telehealth has enormous potential during normal times as well, especially in behavioral health,” said Mr. Tonko. “I am pushing fiercely for these current flexibilities to be extended for a reasonable time after the public health emergency so that we can have time to evaluate which should be made permanent,” he said.
Dr. Geller, other clinicians, and advocates in the briefing praised CMS for facilitating telepsychiatry for Medicare. That follows in the footsteps of most private insurers, who have also relaxed requirements into the summer, according to the Medical Group Management Association.
Game changer
The Medicare waivers “have dramatically changed the entire scene for someone like myself as a clinician to allow me to see my patients in a much easier way,” said Peter Yellowlees, MBBS, MD, chief wellness officer, University of California Davis Health. Within 2 weeks in March, the health system converted almost all of its regular outpatient visits to telemedicine, he said.
Dr. Yellowlees added government still needs to address, what he called, outdated HIPAA regulations that ban certain technologies.
“It makes no sense that I can talk to someone on an iPhone, but the moment I talk to them on FaceTime, it’s illegal,” said Dr. Yellowlees, a former president of the American Telemedicine Association.
Dr. Geller said that “psychiatric care provided by telehealth is as effective as in-person psychiatric services,” adding that “some patients prefer telepsychiatry because of its convenience and as a means of reducing stigma associated with seeking help for mental health.”
Shabana Khan, MD, a child psychiatrist and director of telepsychiatry at New York University Langone Health, said audio and video conferencing are helping address a shortage and maldistribution of child and adolescent psychiatrists.
Americans’ mental health is suffering during the pandemic. The U.S. Census Bureau recently released data showing that half of those surveyed reported depressed mood and that one-third are reporting anxiety, depression, or both, as reported by the Washington Post.
“At this very time that anxiety, depression, substance use, and other mental health problems are rising, our nation’s already strained mental health system is really being pushed to the brink,” said Jodi Kwarciany, manager for mental health policy for the National Alliance on Mental Illness, during the briefing.
Telemedicine can help “by connecting people to providers at the time and the place and using the technology that works best for them,” she said, adding that NAMI would press policymakers to address barriers to access.
The clinicians on the briefing said they’ve observed that some patients are more comfortable with video or audio interactions than with in-person visits.
Increased access to care
Telepsychiatry seems to be convincing some to reconsider therapy, since they can do it at home, said Dr. Yellowlees. he said.
For instance, he said, he has been able to consult by phone and video with several patients who receive care through the Indian Health Service who had not be able to get into the physical clinic.
Dr. Yellowlees said video sessions also may encourage patients to be more, not less, talkative. “Video is actually counterintuitively a very intimate experience,” he said, in part because of the perceived distance and people’s tendency to be less inhibited on technology platforms.“It’s less embarrassing,” he said. “If you’ve got really dramatic, difficult, traumatic things to talk about, it’s slightly easier to talk to someone who’s slightly further apart from you on video,” said Dr. Yellowlees.
“Individuals who have a significant amount of anxiety may actually feel more comfortable with the distance that this technology affords,” agreed Dr. Khan. She said telemedicine had made sessions more comfortable for some of her patients with autism spectrum disorder.
Dr. Geller said audio and video have been important to his practice during the pandemic. One of his patients never leaves the house and does not use computers. “He spends his time sequestered at home listening to records on his record player,” said Dr. Geller. But he’s been amenable to phone sessions. “What I’ve found with him, and I’ve found with several other patients, is that they actually talk more easily when they’re not face to face,” he said.
Far fewer no-shows
Another plus for his New England–based practice during the last few months: patients have not been anxious about missing sessions because of the weather. The clinicians all noted that telepsychiatry seemed to reduce missed visits.
Dr. Yellowlees said that no-show rates had decreased by half at UC Davis. “That means no significant loss of income,” during the pandemic, he said.
“The no-show rate is incredibly low, particularly because when you call the patients and they don’t remember they had an appointment, you have the appointment anyway, most of the time,” said Dr. Geller.
For Dr. Khan, being able to conduct audio and video sessions during the pandemic has meant keeping up continuity of care.
As a result of the pandemic, many college students in New York City had to go home – often to another state. The waivers granted by New York’s Medicaid program and other insurers have allowed Dr. Khan to continue care for these patients.
The NYU clinic also operates day programs in rural areas 5 hours from the city. Dr. Khan recently evaluated a 12-year-old girl with significant anxiety and low mood, both of which had worsened.
“She would not have been able to access care otherwise,” said Dr. Khan. And for rural patients who do not have access to broadband or smartphones, audio visits “have been immensely helpful,” she said.
Dr. Khan, Dr. Geller, and Dr. Yellowlees have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Testing the limits of medical technology
On March 9 my team was given a directive by the chief medical officer of our health system. It seemed like an impossible task, involving the mobilization of people, processes, and technology at a scale and speed we had never before achieved. It turned out getting this done was impossible. In spite of our best efforts, we failed to meet the deadline – it actually took us 3 days. Still, by March 12, we had opened the doors on the first community testing site in our area and gained the attention of local and national news outlets for our accomplishment.
Now more than 2 months later, I’m quite proud of what our team was able to achieve for the health system, but I’m still quite frustrated at the state of COVID-19 testing nationwide – there’s simply not enough available, and there is tremendous variability in the reliability of the tests. In this column, we’d like to highlight some of the challenges we’ve faced and reflect on how the shortcomings of modern technology have once again proven that medicine is both a science and an art.
Our dangerous lack of preparation
Prior to the coronavirus pandemic, I had never considered surgical masks, face shields, and nasal swabs to be critical components of medical technology. My opinion quickly changed after opening our drive-through COVID-19 site. I now have a much greater appreciation for the importance of personal protective equipment and basic testing supplies.
I was shocked by how difficult obtaining it has been during the past few months. It seems that no one anticipated the possibility of a pandemic on this grand a scale, so stockpiles of equipment were depleted quickly and couldn’t be replenished. Also, most manufacturing occurs outside the United States, which creates additional barriers to controlling the supply chain. One need not look far to find stories of widespread price-gouging, black market racketeering, and even hijackings that have stood in the way of accessing the necessary supplies. Sadly, the lack of equipment is far from the only challenge we’ve faced. In some cases, it has been a mistrust of results that has prevented widespread testing and mitigation.
The risks of flying blind
When President Trump touted the introduction of a rapid COVID-19 test at the end of March, many people were excited. Promising positive results in as few as 5 minutes, the assay was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration in order to expedite its availability in the market. According to the FDA’s website, an EUA allows “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions.” This rapid (though untested) approval was all that many health care providers needed to hear – immediately hospitals and physicians scrambled to get their hands on the testing devices. Unfortunately, on May 14th, the FDA issued a press release that raised concerns about that same test because it seemed to be reporting a high number of false-negative results. Just as quickly as the devices had been adopted, health care providers began backing away from them in favor of other assays, and a serious truth about COVID-19 testing was revealed: In many ways, we’re flying blind.
Laboratory manufacturers have been working overtime to create assays for SARS-CoV-2 (the coronavirus that causes COVID-19) and have used different technologies for detection. The most commonly used are polymerase chain reaction (PCR) tests. In these assays, viral RNA is converted to DNA by reverse transcriptase, then amplified through the addition of primers that enable detection. PCR technology has been available for years and is a reliable method for identifying DNA and RNA, but the required heating and cooling process takes time and results can take several hours to return. To address this and expedite testing, other methods of detection have been tried, such as the loop-mediated isothermal amplification (LAMP) technique employed by the rapid assay mentioned above. Regardless of methodology, all laboratory tests have one thing in common: None of them is perfect.
Every assay has a different level of reliability. When screening for a disease such as COVID-19, we are particularly interested in a test’s sensitivity (that is, it’s ability to detect disease); we’d love such a screening test to be 100% sensitive and thereby not miss a single case. In truth, no test’s sensitivity is 100%, and in this particular case even the best assays only score around 98%. This means that out of every 100 patients with COVID-19 who are evaluated, two might test negative for the virus. In a pandemic this can have dire consequences, so health care providers – unable to fully trust their instruments – must employ clinical acumen and years of experience to navigate these cloudy skies. We are hopeful that additional tools will complement our current methods, but with new assays also come new questions.
Is anyone safe?
We receive regular questions from physicians about the value of antibody testing, but it’s not yet clear how best to respond. While the assays seem to be reliable, the utility of the results are still ill defined. Antibodies to SARS-CoV-2 (both IgG and IgM) appear to peak about 2-3 weeks after symptom onset, but we don’t yet know if the presence of those antibodies confers long-term immunity. Therefore, patients should not use the information to change their masking or social-distancing practices, nor should they presume that they are safe from becoming reinfected with COVID-19. While new research looks promising, there are still too many unknowns to be able to confidently reassure providers or patients of the true value of antibody testing. This underscores our final point: Medicine remains an art.
As we are regularly reminded, we’ll never fully anticipate the challenges or barriers to success, and technology will never replace the value of clinical judgment and human experience. While the situation is unsettling in many ways, we are reassured and encouraged by the role we still get to play in keeping our patients healthy in this health care crisis, and we’ll continue to do so through whatever the future holds.
Dr. Notte is a family physician and chief medical officer of Abington Lansdale (Pa.) Hospital - Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
On March 9 my team was given a directive by the chief medical officer of our health system. It seemed like an impossible task, involving the mobilization of people, processes, and technology at a scale and speed we had never before achieved. It turned out getting this done was impossible. In spite of our best efforts, we failed to meet the deadline – it actually took us 3 days. Still, by March 12, we had opened the doors on the first community testing site in our area and gained the attention of local and national news outlets for our accomplishment.
Now more than 2 months later, I’m quite proud of what our team was able to achieve for the health system, but I’m still quite frustrated at the state of COVID-19 testing nationwide – there’s simply not enough available, and there is tremendous variability in the reliability of the tests. In this column, we’d like to highlight some of the challenges we’ve faced and reflect on how the shortcomings of modern technology have once again proven that medicine is both a science and an art.
Our dangerous lack of preparation
Prior to the coronavirus pandemic, I had never considered surgical masks, face shields, and nasal swabs to be critical components of medical technology. My opinion quickly changed after opening our drive-through COVID-19 site. I now have a much greater appreciation for the importance of personal protective equipment and basic testing supplies.
I was shocked by how difficult obtaining it has been during the past few months. It seems that no one anticipated the possibility of a pandemic on this grand a scale, so stockpiles of equipment were depleted quickly and couldn’t be replenished. Also, most manufacturing occurs outside the United States, which creates additional barriers to controlling the supply chain. One need not look far to find stories of widespread price-gouging, black market racketeering, and even hijackings that have stood in the way of accessing the necessary supplies. Sadly, the lack of equipment is far from the only challenge we’ve faced. In some cases, it has been a mistrust of results that has prevented widespread testing and mitigation.
The risks of flying blind
When President Trump touted the introduction of a rapid COVID-19 test at the end of March, many people were excited. Promising positive results in as few as 5 minutes, the assay was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration in order to expedite its availability in the market. According to the FDA’s website, an EUA allows “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions.” This rapid (though untested) approval was all that many health care providers needed to hear – immediately hospitals and physicians scrambled to get their hands on the testing devices. Unfortunately, on May 14th, the FDA issued a press release that raised concerns about that same test because it seemed to be reporting a high number of false-negative results. Just as quickly as the devices had been adopted, health care providers began backing away from them in favor of other assays, and a serious truth about COVID-19 testing was revealed: In many ways, we’re flying blind.
Laboratory manufacturers have been working overtime to create assays for SARS-CoV-2 (the coronavirus that causes COVID-19) and have used different technologies for detection. The most commonly used are polymerase chain reaction (PCR) tests. In these assays, viral RNA is converted to DNA by reverse transcriptase, then amplified through the addition of primers that enable detection. PCR technology has been available for years and is a reliable method for identifying DNA and RNA, but the required heating and cooling process takes time and results can take several hours to return. To address this and expedite testing, other methods of detection have been tried, such as the loop-mediated isothermal amplification (LAMP) technique employed by the rapid assay mentioned above. Regardless of methodology, all laboratory tests have one thing in common: None of them is perfect.
Every assay has a different level of reliability. When screening for a disease such as COVID-19, we are particularly interested in a test’s sensitivity (that is, it’s ability to detect disease); we’d love such a screening test to be 100% sensitive and thereby not miss a single case. In truth, no test’s sensitivity is 100%, and in this particular case even the best assays only score around 98%. This means that out of every 100 patients with COVID-19 who are evaluated, two might test negative for the virus. In a pandemic this can have dire consequences, so health care providers – unable to fully trust their instruments – must employ clinical acumen and years of experience to navigate these cloudy skies. We are hopeful that additional tools will complement our current methods, but with new assays also come new questions.
Is anyone safe?
We receive regular questions from physicians about the value of antibody testing, but it’s not yet clear how best to respond. While the assays seem to be reliable, the utility of the results are still ill defined. Antibodies to SARS-CoV-2 (both IgG and IgM) appear to peak about 2-3 weeks after symptom onset, but we don’t yet know if the presence of those antibodies confers long-term immunity. Therefore, patients should not use the information to change their masking or social-distancing practices, nor should they presume that they are safe from becoming reinfected with COVID-19. While new research looks promising, there are still too many unknowns to be able to confidently reassure providers or patients of the true value of antibody testing. This underscores our final point: Medicine remains an art.
As we are regularly reminded, we’ll never fully anticipate the challenges or barriers to success, and technology will never replace the value of clinical judgment and human experience. While the situation is unsettling in many ways, we are reassured and encouraged by the role we still get to play in keeping our patients healthy in this health care crisis, and we’ll continue to do so through whatever the future holds.
Dr. Notte is a family physician and chief medical officer of Abington Lansdale (Pa.) Hospital - Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
On March 9 my team was given a directive by the chief medical officer of our health system. It seemed like an impossible task, involving the mobilization of people, processes, and technology at a scale and speed we had never before achieved. It turned out getting this done was impossible. In spite of our best efforts, we failed to meet the deadline – it actually took us 3 days. Still, by March 12, we had opened the doors on the first community testing site in our area and gained the attention of local and national news outlets for our accomplishment.
Now more than 2 months later, I’m quite proud of what our team was able to achieve for the health system, but I’m still quite frustrated at the state of COVID-19 testing nationwide – there’s simply not enough available, and there is tremendous variability in the reliability of the tests. In this column, we’d like to highlight some of the challenges we’ve faced and reflect on how the shortcomings of modern technology have once again proven that medicine is both a science and an art.
Our dangerous lack of preparation
Prior to the coronavirus pandemic, I had never considered surgical masks, face shields, and nasal swabs to be critical components of medical technology. My opinion quickly changed after opening our drive-through COVID-19 site. I now have a much greater appreciation for the importance of personal protective equipment and basic testing supplies.
I was shocked by how difficult obtaining it has been during the past few months. It seems that no one anticipated the possibility of a pandemic on this grand a scale, so stockpiles of equipment were depleted quickly and couldn’t be replenished. Also, most manufacturing occurs outside the United States, which creates additional barriers to controlling the supply chain. One need not look far to find stories of widespread price-gouging, black market racketeering, and even hijackings that have stood in the way of accessing the necessary supplies. Sadly, the lack of equipment is far from the only challenge we’ve faced. In some cases, it has been a mistrust of results that has prevented widespread testing and mitigation.
The risks of flying blind
When President Trump touted the introduction of a rapid COVID-19 test at the end of March, many people were excited. Promising positive results in as few as 5 minutes, the assay was granted an Emergency Use Authorization (EUA) by the Food and Drug Administration in order to expedite its availability in the market. According to the FDA’s website, an EUA allows “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions.” This rapid (though untested) approval was all that many health care providers needed to hear – immediately hospitals and physicians scrambled to get their hands on the testing devices. Unfortunately, on May 14th, the FDA issued a press release that raised concerns about that same test because it seemed to be reporting a high number of false-negative results. Just as quickly as the devices had been adopted, health care providers began backing away from them in favor of other assays, and a serious truth about COVID-19 testing was revealed: In many ways, we’re flying blind.
Laboratory manufacturers have been working overtime to create assays for SARS-CoV-2 (the coronavirus that causes COVID-19) and have used different technologies for detection. The most commonly used are polymerase chain reaction (PCR) tests. In these assays, viral RNA is converted to DNA by reverse transcriptase, then amplified through the addition of primers that enable detection. PCR technology has been available for years and is a reliable method for identifying DNA and RNA, but the required heating and cooling process takes time and results can take several hours to return. To address this and expedite testing, other methods of detection have been tried, such as the loop-mediated isothermal amplification (LAMP) technique employed by the rapid assay mentioned above. Regardless of methodology, all laboratory tests have one thing in common: None of them is perfect.
Every assay has a different level of reliability. When screening for a disease such as COVID-19, we are particularly interested in a test’s sensitivity (that is, it’s ability to detect disease); we’d love such a screening test to be 100% sensitive and thereby not miss a single case. In truth, no test’s sensitivity is 100%, and in this particular case even the best assays only score around 98%. This means that out of every 100 patients with COVID-19 who are evaluated, two might test negative for the virus. In a pandemic this can have dire consequences, so health care providers – unable to fully trust their instruments – must employ clinical acumen and years of experience to navigate these cloudy skies. We are hopeful that additional tools will complement our current methods, but with new assays also come new questions.
Is anyone safe?
We receive regular questions from physicians about the value of antibody testing, but it’s not yet clear how best to respond. While the assays seem to be reliable, the utility of the results are still ill defined. Antibodies to SARS-CoV-2 (both IgG and IgM) appear to peak about 2-3 weeks after symptom onset, but we don’t yet know if the presence of those antibodies confers long-term immunity. Therefore, patients should not use the information to change their masking or social-distancing practices, nor should they presume that they are safe from becoming reinfected with COVID-19. While new research looks promising, there are still too many unknowns to be able to confidently reassure providers or patients of the true value of antibody testing. This underscores our final point: Medicine remains an art.
As we are regularly reminded, we’ll never fully anticipate the challenges or barriers to success, and technology will never replace the value of clinical judgment and human experience. While the situation is unsettling in many ways, we are reassured and encouraged by the role we still get to play in keeping our patients healthy in this health care crisis, and we’ll continue to do so through whatever the future holds.
Dr. Notte is a family physician and chief medical officer of Abington Lansdale (Pa.) Hospital - Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. They have no conflicts related to the content of this piece.
Scientific doubt tempers COVID-19 vaccine optimism
US government and industry projections that a COVID-19 vaccine will be ready by this fall or even January would take compressing what usually takes at least a decade into months, with little room for error or safety surprises.
“If all the cards fall into the right place and all the stars are aligned, you definitely could get a vaccine by December or January,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said last week.
But Fauci said a more realistic timeline is still 12 to 18 months, and experts interviewed by Medscape Medical News agree. They say that although recent developments are encouraging, history and scientific reason say the day when a COVID-19 vaccine is widely available will not come this year and may not come by the end of 2021.
The encouraging signals come primarily from two recent announcements: the $1.2 billion United States backing last week of one vaccine platform and the announcement on May 18 that the first human trials of another have produced some positive phase 1 results.
Recent developments
On May 21, the US Department of Health and Human Services (HHS) under “Operation Warp Speed” announced that the US will give AstraZeneca $1.2 billion “to make available at least 300 million doses of a coronavirus vaccine called AZD1222, with the first doses delivered as early as October 2020.”
On May 18, the Massachusetts-based biotechnology company Moderna announced that phase 1 clinical results showed that its vaccine candidate, which uses a new messenger RNA (mRNA) technology, appeared safe. Eight participants in the human trials were able to produce neutralizing antibodies that researchers believe are important in developing protection from the virus.
Moderna Chief Medical Officer Tal Zaks, MD, PhD told CNN that if the vaccine candidate does well in phase 2, “it could be ready by January 2021.”
The two candidates are among 10 in clinical trials for the SARS-CoV-2 virus, according to the World Health Organization (WHO). The AstraZeneca/ AZD1222 candidate (also called ChAdOx1 nCoV-19, in collaboration with the University of Oxford) has entered phase 2/3.
Moderna’s candidate and another being developed in Beijing, China, are in phase 2, WHO reports. As of yesterday, 115 other candidates are in preclinical evaluation.
Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News it’s important to realize that, in the case of the $1.2 billion US investment, “what they’re talking about is manufacturing.”
The idea, she said, is to pay AstraZeneca up front so that manufacturing can start before it is known whether the vaccine candidate is safe or effective, the reverse of how the clinical trial process usually works.
That way, if the candidate is deemed safe and effective, time is not lost by then deciding how to make it and distribute it.
By the end of this year, she said, “Maybe we will have many vaccines made and stored in a refrigerator somewhere. But between now and December, there’s absolutely no way you can show efficacy of the vaccine at the same time you confirm that it’s safe.”
“Take these things with a grain of salt”
Animal testing for the AstraZeneca candidate, made in partnership with the University of Oxford in the United Kingdom, has yielded lackluster results, according to results on the preprint server BioRxiv, which have not been peer-reviewed.
“The results were not bad, but they were not gangbusters,” Bottazzi said. The results show the vaccine offered only partial protection.
“Partial protection is better than no protection,” she noted. “You have to take these things with a grain of salt. We don’t know what’s going to happen in humans.”
As for the Moderna candidate, Bottazzi said, “the good news is they found an appropriate safety profile. But from an eight-person group to make the extrapolation that they have efficacy — it’s unrealistic.”
Nicole Lurie, MD, MSPH, is senior adviser to the CEO for the Coalition for Epidemic Preparedness Innovation (CEPI), a nongovernmental organization funded by the Wellcome Trust, the Bill and Melinda Gates Foundation, the European Commission, and eight countries (Australia, Belgium, Canada, Ethiopia, Germany, Japan, Norway, and the United Kingdom) charged with supporting development of vaccines for pathogens on WHO’s priority list.
She and her colleagues write in a paper published online in the New England Journal of Medicine on March 30 that “it typically takes multiple candidates and many years to produce a licensed vaccine.”
The fastest time for developing a vaccine to date is 4 years, for the mumps vaccine, licensed in 1967.
As to whether she would expect a rollout of any vaccine by the end of the year, Lurie told Medscape Medical News, “If everything goes according to plan in every way, shape or form, well then maybe you can get there. But I wouldn’t hold my breath.”
Lurie and her colleagues write that “it’s far from certain that these new platforms will be scalable or that existing capacity can provide sufficient quantities of vaccine fast enough.”
On a call with reporters today, leaders of some of the words largest pharmaceutical companies said that one of the key bottlenecks is the sheer number of vials needed in order to distribute billions of doses of a successful vaccine.
Pfizer CEO Albert Bourla, DVM, PhD, said, “Typically we are producing vaccines in single-dose vials. We are exploring with governments right now if it would be more convenient if there were 5-dose vials or 10-dose vials. I think we can resolve a significant part of the bottleneck.”
Despite the challenges, experts interviewed for this article agree that it will be possible to make a vaccine for COVID-19. They don’t expect attempts to meet the same complications that HIV researchers have seen over decades as the virus continues to confound with mutations.
Fred Ledley, MD, director of the Center for Integration of Science and Industry at Bentley University in Waltham, Massachusetts, told Medscape Medical News, “There doesn’t appear to be anything terribly diabolical about this virus. The mutation rate doesn’t appear to be anything like HIV. It appears to have some big, ugly proteins on the surface, which is good for vaccines — proteins with a lot of physical features look distinguishable from healthy cells. Signs all point to that it should be possible to make a vaccine.”
History raises safety concerns
However, Ledley said, “The idea of doing it in 6 months is largely unrealistic.”
He says 18 months is more realistic, primarily because of the sheer number of people that would have to be enrolled in a phase 3 study to truly test whether the endpoints are being met.
Vaccines are given to healthy volunteers. If safety signals arise, they may not be apparent until massive numbers of people are tested in phase 3.
“You’re never going to see the rates cut to 0%, but to see the difference between 10 people getting sick and seven people getting sick, takes very, very large numbers,” Ledley said. “There’s no way that can be done in 6 months. You’re talking about tens of thousands of people enrolled.”
He notes at this point it’s unclear what the endpoints will be and what the safety thresholds will be after consideration of risks and benefit.
Another big question for Ledley: “We don’t know what type of immunity we need to protect us against the virus. Do you just need the antibodies in your blood or do you need cells that are primed to attack the virus? Is it more of a chemical clearance or do the cells need to physically go in and digest the virus?”
History also points to the need for rigorous safety precautions that scientists fear could be compromised as trial phases overlap and processes are run in parallel instead of one step at a time.
An early batch of the Salk vaccine for polio in 1955, for example, turned out to be contaminated and caused paralysis in some children and 10 deaths, he points out.
CEPI’s Lurie adds that early candidates for another coronavirus, severe acute respiratory syndrome (SARS), “caused a reaction in the lungs that was very dangerous” before development was halted.
She also pointed to previous findings that a vaccine for dengue fever could worsen the disease in some people through a phenomenon called antibody-dependent enhancement.
Lurie and colleagues write in their paper that “it’s critical that vaccines also be developed using the tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
Live attenuated vaccine
Raul Andino, PhD, a virologist at the University of California San Francisco, is among the scientists working with a tried-and-true method — a live attenuated vaccine — and he told Medscape Medical News he’s predicting it will take 2 years to develop.
He said it is cheaper to produce because scientists just have to learn how to grow the virus. Because the technology is already proven, a live attenuated vaccine could be rapidly produced on a worldwide scale.
The hope is also that a live attenuated vaccine would be given once in a lifetime and therefore be more affordable, especially in poorer countries.
“While a Moderna vaccine might be good for Europe and the United States,” he said, “It’s not going to be good for Africa, India, Brazil.”
Andino said, “I would bet money” that the front-runner vaccines so far will not be one-time vaccines.
He points out that most of the vaccine candidates are trying to protect people from disease. While there’s nothing wrong with that, he said, “In my opinion that is the lower-hanging fruit.”
“In my mind we need something that interrupts the chain of transmission and induces protection,” Andino said, important for developing herd immunity.
The reason this type of approach takes longer is because you are introducing a weakened form of the virus to the body and you have to make sure it doesn’t cause disease, not just in a small test population, but in populations who may be more susceptible to the disease, Andino said.
A call for unified strategies
Universities, countries, international consortiums, and public-private partnerships are all racing to find several safe and effective vaccines as no one entity will likely be able to provide the global solution.
Some of the efforts involve overlap of entities but with different focuses.
Along with “Operation Warp Speed” and CEPI, other collaborations include Gavi the Vaccine Alliance, whose core partners include WHO, UNICEF, the World Bank, and the Gates Foundation; and “Accelerating Therapeutic Interventions and Vaccines (ACTIV) partnership,” led by the National Institutes of Health.
Industry partners in ACTIV (18 biopharmaceutical companies), according to a May 18 article published online in the Journal of the American Medical Association, have said they will contribute their respective clinical trial capacities, regardless of which agent is studied.
Some, however, have called for more streamlining of efforts.
“Ideally we’d be working together,” Lurie told Medscape Medical News.
“I’m hopeful we will find ways to collaborate scientifically,” she said. “The US government’s responsibility is to make doses for the US. CEPI’s responsibility is to make doses for the world. A big focus of CEPI is to make sure we have manufacturing capacity outside of the US so those doses can be available to the world and they don’t get seized by wealthy countries.”
Bottazzi, Ledley, Lurie, and Andino report no relevant financial relationships.
This article first appeared on Medscape.com.
US government and industry projections that a COVID-19 vaccine will be ready by this fall or even January would take compressing what usually takes at least a decade into months, with little room for error or safety surprises.
“If all the cards fall into the right place and all the stars are aligned, you definitely could get a vaccine by December or January,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said last week.
But Fauci said a more realistic timeline is still 12 to 18 months, and experts interviewed by Medscape Medical News agree. They say that although recent developments are encouraging, history and scientific reason say the day when a COVID-19 vaccine is widely available will not come this year and may not come by the end of 2021.
The encouraging signals come primarily from two recent announcements: the $1.2 billion United States backing last week of one vaccine platform and the announcement on May 18 that the first human trials of another have produced some positive phase 1 results.
Recent developments
On May 21, the US Department of Health and Human Services (HHS) under “Operation Warp Speed” announced that the US will give AstraZeneca $1.2 billion “to make available at least 300 million doses of a coronavirus vaccine called AZD1222, with the first doses delivered as early as October 2020.”
On May 18, the Massachusetts-based biotechnology company Moderna announced that phase 1 clinical results showed that its vaccine candidate, which uses a new messenger RNA (mRNA) technology, appeared safe. Eight participants in the human trials were able to produce neutralizing antibodies that researchers believe are important in developing protection from the virus.
Moderna Chief Medical Officer Tal Zaks, MD, PhD told CNN that if the vaccine candidate does well in phase 2, “it could be ready by January 2021.”
The two candidates are among 10 in clinical trials for the SARS-CoV-2 virus, according to the World Health Organization (WHO). The AstraZeneca/ AZD1222 candidate (also called ChAdOx1 nCoV-19, in collaboration with the University of Oxford) has entered phase 2/3.
Moderna’s candidate and another being developed in Beijing, China, are in phase 2, WHO reports. As of yesterday, 115 other candidates are in preclinical evaluation.
Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News it’s important to realize that, in the case of the $1.2 billion US investment, “what they’re talking about is manufacturing.”
The idea, she said, is to pay AstraZeneca up front so that manufacturing can start before it is known whether the vaccine candidate is safe or effective, the reverse of how the clinical trial process usually works.
That way, if the candidate is deemed safe and effective, time is not lost by then deciding how to make it and distribute it.
By the end of this year, she said, “Maybe we will have many vaccines made and stored in a refrigerator somewhere. But between now and December, there’s absolutely no way you can show efficacy of the vaccine at the same time you confirm that it’s safe.”
“Take these things with a grain of salt”
Animal testing for the AstraZeneca candidate, made in partnership with the University of Oxford in the United Kingdom, has yielded lackluster results, according to results on the preprint server BioRxiv, which have not been peer-reviewed.
“The results were not bad, but they were not gangbusters,” Bottazzi said. The results show the vaccine offered only partial protection.
“Partial protection is better than no protection,” she noted. “You have to take these things with a grain of salt. We don’t know what’s going to happen in humans.”
As for the Moderna candidate, Bottazzi said, “the good news is they found an appropriate safety profile. But from an eight-person group to make the extrapolation that they have efficacy — it’s unrealistic.”
Nicole Lurie, MD, MSPH, is senior adviser to the CEO for the Coalition for Epidemic Preparedness Innovation (CEPI), a nongovernmental organization funded by the Wellcome Trust, the Bill and Melinda Gates Foundation, the European Commission, and eight countries (Australia, Belgium, Canada, Ethiopia, Germany, Japan, Norway, and the United Kingdom) charged with supporting development of vaccines for pathogens on WHO’s priority list.
She and her colleagues write in a paper published online in the New England Journal of Medicine on March 30 that “it typically takes multiple candidates and many years to produce a licensed vaccine.”
The fastest time for developing a vaccine to date is 4 years, for the mumps vaccine, licensed in 1967.
As to whether she would expect a rollout of any vaccine by the end of the year, Lurie told Medscape Medical News, “If everything goes according to plan in every way, shape or form, well then maybe you can get there. But I wouldn’t hold my breath.”
Lurie and her colleagues write that “it’s far from certain that these new platforms will be scalable or that existing capacity can provide sufficient quantities of vaccine fast enough.”
On a call with reporters today, leaders of some of the words largest pharmaceutical companies said that one of the key bottlenecks is the sheer number of vials needed in order to distribute billions of doses of a successful vaccine.
Pfizer CEO Albert Bourla, DVM, PhD, said, “Typically we are producing vaccines in single-dose vials. We are exploring with governments right now if it would be more convenient if there were 5-dose vials or 10-dose vials. I think we can resolve a significant part of the bottleneck.”
Despite the challenges, experts interviewed for this article agree that it will be possible to make a vaccine for COVID-19. They don’t expect attempts to meet the same complications that HIV researchers have seen over decades as the virus continues to confound with mutations.
Fred Ledley, MD, director of the Center for Integration of Science and Industry at Bentley University in Waltham, Massachusetts, told Medscape Medical News, “There doesn’t appear to be anything terribly diabolical about this virus. The mutation rate doesn’t appear to be anything like HIV. It appears to have some big, ugly proteins on the surface, which is good for vaccines — proteins with a lot of physical features look distinguishable from healthy cells. Signs all point to that it should be possible to make a vaccine.”
History raises safety concerns
However, Ledley said, “The idea of doing it in 6 months is largely unrealistic.”
He says 18 months is more realistic, primarily because of the sheer number of people that would have to be enrolled in a phase 3 study to truly test whether the endpoints are being met.
Vaccines are given to healthy volunteers. If safety signals arise, they may not be apparent until massive numbers of people are tested in phase 3.
“You’re never going to see the rates cut to 0%, but to see the difference between 10 people getting sick and seven people getting sick, takes very, very large numbers,” Ledley said. “There’s no way that can be done in 6 months. You’re talking about tens of thousands of people enrolled.”
He notes at this point it’s unclear what the endpoints will be and what the safety thresholds will be after consideration of risks and benefit.
Another big question for Ledley: “We don’t know what type of immunity we need to protect us against the virus. Do you just need the antibodies in your blood or do you need cells that are primed to attack the virus? Is it more of a chemical clearance or do the cells need to physically go in and digest the virus?”
History also points to the need for rigorous safety precautions that scientists fear could be compromised as trial phases overlap and processes are run in parallel instead of one step at a time.
An early batch of the Salk vaccine for polio in 1955, for example, turned out to be contaminated and caused paralysis in some children and 10 deaths, he points out.
CEPI’s Lurie adds that early candidates for another coronavirus, severe acute respiratory syndrome (SARS), “caused a reaction in the lungs that was very dangerous” before development was halted.
She also pointed to previous findings that a vaccine for dengue fever could worsen the disease in some people through a phenomenon called antibody-dependent enhancement.
Lurie and colleagues write in their paper that “it’s critical that vaccines also be developed using the tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
Live attenuated vaccine
Raul Andino, PhD, a virologist at the University of California San Francisco, is among the scientists working with a tried-and-true method — a live attenuated vaccine — and he told Medscape Medical News he’s predicting it will take 2 years to develop.
He said it is cheaper to produce because scientists just have to learn how to grow the virus. Because the technology is already proven, a live attenuated vaccine could be rapidly produced on a worldwide scale.
The hope is also that a live attenuated vaccine would be given once in a lifetime and therefore be more affordable, especially in poorer countries.
“While a Moderna vaccine might be good for Europe and the United States,” he said, “It’s not going to be good for Africa, India, Brazil.”
Andino said, “I would bet money” that the front-runner vaccines so far will not be one-time vaccines.
He points out that most of the vaccine candidates are trying to protect people from disease. While there’s nothing wrong with that, he said, “In my opinion that is the lower-hanging fruit.”
“In my mind we need something that interrupts the chain of transmission and induces protection,” Andino said, important for developing herd immunity.
The reason this type of approach takes longer is because you are introducing a weakened form of the virus to the body and you have to make sure it doesn’t cause disease, not just in a small test population, but in populations who may be more susceptible to the disease, Andino said.
A call for unified strategies
Universities, countries, international consortiums, and public-private partnerships are all racing to find several safe and effective vaccines as no one entity will likely be able to provide the global solution.
Some of the efforts involve overlap of entities but with different focuses.
Along with “Operation Warp Speed” and CEPI, other collaborations include Gavi the Vaccine Alliance, whose core partners include WHO, UNICEF, the World Bank, and the Gates Foundation; and “Accelerating Therapeutic Interventions and Vaccines (ACTIV) partnership,” led by the National Institutes of Health.
Industry partners in ACTIV (18 biopharmaceutical companies), according to a May 18 article published online in the Journal of the American Medical Association, have said they will contribute their respective clinical trial capacities, regardless of which agent is studied.
Some, however, have called for more streamlining of efforts.
“Ideally we’d be working together,” Lurie told Medscape Medical News.
“I’m hopeful we will find ways to collaborate scientifically,” she said. “The US government’s responsibility is to make doses for the US. CEPI’s responsibility is to make doses for the world. A big focus of CEPI is to make sure we have manufacturing capacity outside of the US so those doses can be available to the world and they don’t get seized by wealthy countries.”
Bottazzi, Ledley, Lurie, and Andino report no relevant financial relationships.
This article first appeared on Medscape.com.
US government and industry projections that a COVID-19 vaccine will be ready by this fall or even January would take compressing what usually takes at least a decade into months, with little room for error or safety surprises.
“If all the cards fall into the right place and all the stars are aligned, you definitely could get a vaccine by December or January,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said last week.
But Fauci said a more realistic timeline is still 12 to 18 months, and experts interviewed by Medscape Medical News agree. They say that although recent developments are encouraging, history and scientific reason say the day when a COVID-19 vaccine is widely available will not come this year and may not come by the end of 2021.
The encouraging signals come primarily from two recent announcements: the $1.2 billion United States backing last week of one vaccine platform and the announcement on May 18 that the first human trials of another have produced some positive phase 1 results.
Recent developments
On May 21, the US Department of Health and Human Services (HHS) under “Operation Warp Speed” announced that the US will give AstraZeneca $1.2 billion “to make available at least 300 million doses of a coronavirus vaccine called AZD1222, with the first doses delivered as early as October 2020.”
On May 18, the Massachusetts-based biotechnology company Moderna announced that phase 1 clinical results showed that its vaccine candidate, which uses a new messenger RNA (mRNA) technology, appeared safe. Eight participants in the human trials were able to produce neutralizing antibodies that researchers believe are important in developing protection from the virus.
Moderna Chief Medical Officer Tal Zaks, MD, PhD told CNN that if the vaccine candidate does well in phase 2, “it could be ready by January 2021.”
The two candidates are among 10 in clinical trials for the SARS-CoV-2 virus, according to the World Health Organization (WHO). The AstraZeneca/ AZD1222 candidate (also called ChAdOx1 nCoV-19, in collaboration with the University of Oxford) has entered phase 2/3.
Moderna’s candidate and another being developed in Beijing, China, are in phase 2, WHO reports. As of yesterday, 115 other candidates are in preclinical evaluation.
Maria Elena Bottazzi, PhD, associate dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, told Medscape Medical News it’s important to realize that, in the case of the $1.2 billion US investment, “what they’re talking about is manufacturing.”
The idea, she said, is to pay AstraZeneca up front so that manufacturing can start before it is known whether the vaccine candidate is safe or effective, the reverse of how the clinical trial process usually works.
That way, if the candidate is deemed safe and effective, time is not lost by then deciding how to make it and distribute it.
By the end of this year, she said, “Maybe we will have many vaccines made and stored in a refrigerator somewhere. But between now and December, there’s absolutely no way you can show efficacy of the vaccine at the same time you confirm that it’s safe.”
“Take these things with a grain of salt”
Animal testing for the AstraZeneca candidate, made in partnership with the University of Oxford in the United Kingdom, has yielded lackluster results, according to results on the preprint server BioRxiv, which have not been peer-reviewed.
“The results were not bad, but they were not gangbusters,” Bottazzi said. The results show the vaccine offered only partial protection.
“Partial protection is better than no protection,” she noted. “You have to take these things with a grain of salt. We don’t know what’s going to happen in humans.”
As for the Moderna candidate, Bottazzi said, “the good news is they found an appropriate safety profile. But from an eight-person group to make the extrapolation that they have efficacy — it’s unrealistic.”
Nicole Lurie, MD, MSPH, is senior adviser to the CEO for the Coalition for Epidemic Preparedness Innovation (CEPI), a nongovernmental organization funded by the Wellcome Trust, the Bill and Melinda Gates Foundation, the European Commission, and eight countries (Australia, Belgium, Canada, Ethiopia, Germany, Japan, Norway, and the United Kingdom) charged with supporting development of vaccines for pathogens on WHO’s priority list.
She and her colleagues write in a paper published online in the New England Journal of Medicine on March 30 that “it typically takes multiple candidates and many years to produce a licensed vaccine.”
The fastest time for developing a vaccine to date is 4 years, for the mumps vaccine, licensed in 1967.
As to whether she would expect a rollout of any vaccine by the end of the year, Lurie told Medscape Medical News, “If everything goes according to plan in every way, shape or form, well then maybe you can get there. But I wouldn’t hold my breath.”
Lurie and her colleagues write that “it’s far from certain that these new platforms will be scalable or that existing capacity can provide sufficient quantities of vaccine fast enough.”
On a call with reporters today, leaders of some of the words largest pharmaceutical companies said that one of the key bottlenecks is the sheer number of vials needed in order to distribute billions of doses of a successful vaccine.
Pfizer CEO Albert Bourla, DVM, PhD, said, “Typically we are producing vaccines in single-dose vials. We are exploring with governments right now if it would be more convenient if there were 5-dose vials or 10-dose vials. I think we can resolve a significant part of the bottleneck.”
Despite the challenges, experts interviewed for this article agree that it will be possible to make a vaccine for COVID-19. They don’t expect attempts to meet the same complications that HIV researchers have seen over decades as the virus continues to confound with mutations.
Fred Ledley, MD, director of the Center for Integration of Science and Industry at Bentley University in Waltham, Massachusetts, told Medscape Medical News, “There doesn’t appear to be anything terribly diabolical about this virus. The mutation rate doesn’t appear to be anything like HIV. It appears to have some big, ugly proteins on the surface, which is good for vaccines — proteins with a lot of physical features look distinguishable from healthy cells. Signs all point to that it should be possible to make a vaccine.”
History raises safety concerns
However, Ledley said, “The idea of doing it in 6 months is largely unrealistic.”
He says 18 months is more realistic, primarily because of the sheer number of people that would have to be enrolled in a phase 3 study to truly test whether the endpoints are being met.
Vaccines are given to healthy volunteers. If safety signals arise, they may not be apparent until massive numbers of people are tested in phase 3.
“You’re never going to see the rates cut to 0%, but to see the difference between 10 people getting sick and seven people getting sick, takes very, very large numbers,” Ledley said. “There’s no way that can be done in 6 months. You’re talking about tens of thousands of people enrolled.”
He notes at this point it’s unclear what the endpoints will be and what the safety thresholds will be after consideration of risks and benefit.
Another big question for Ledley: “We don’t know what type of immunity we need to protect us against the virus. Do you just need the antibodies in your blood or do you need cells that are primed to attack the virus? Is it more of a chemical clearance or do the cells need to physically go in and digest the virus?”
History also points to the need for rigorous safety precautions that scientists fear could be compromised as trial phases overlap and processes are run in parallel instead of one step at a time.
An early batch of the Salk vaccine for polio in 1955, for example, turned out to be contaminated and caused paralysis in some children and 10 deaths, he points out.
CEPI’s Lurie adds that early candidates for another coronavirus, severe acute respiratory syndrome (SARS), “caused a reaction in the lungs that was very dangerous” before development was halted.
She also pointed to previous findings that a vaccine for dengue fever could worsen the disease in some people through a phenomenon called antibody-dependent enhancement.
Lurie and colleagues write in their paper that “it’s critical that vaccines also be developed using the tried-and-true methods, even if they may take longer to enter clinical trials or to result in large numbers of doses.”
Live attenuated vaccine
Raul Andino, PhD, a virologist at the University of California San Francisco, is among the scientists working with a tried-and-true method — a live attenuated vaccine — and he told Medscape Medical News he’s predicting it will take 2 years to develop.
He said it is cheaper to produce because scientists just have to learn how to grow the virus. Because the technology is already proven, a live attenuated vaccine could be rapidly produced on a worldwide scale.
The hope is also that a live attenuated vaccine would be given once in a lifetime and therefore be more affordable, especially in poorer countries.
“While a Moderna vaccine might be good for Europe and the United States,” he said, “It’s not going to be good for Africa, India, Brazil.”
Andino said, “I would bet money” that the front-runner vaccines so far will not be one-time vaccines.
He points out that most of the vaccine candidates are trying to protect people from disease. While there’s nothing wrong with that, he said, “In my opinion that is the lower-hanging fruit.”
“In my mind we need something that interrupts the chain of transmission and induces protection,” Andino said, important for developing herd immunity.
The reason this type of approach takes longer is because you are introducing a weakened form of the virus to the body and you have to make sure it doesn’t cause disease, not just in a small test population, but in populations who may be more susceptible to the disease, Andino said.
A call for unified strategies
Universities, countries, international consortiums, and public-private partnerships are all racing to find several safe and effective vaccines as no one entity will likely be able to provide the global solution.
Some of the efforts involve overlap of entities but with different focuses.
Along with “Operation Warp Speed” and CEPI, other collaborations include Gavi the Vaccine Alliance, whose core partners include WHO, UNICEF, the World Bank, and the Gates Foundation; and “Accelerating Therapeutic Interventions and Vaccines (ACTIV) partnership,” led by the National Institutes of Health.
Industry partners in ACTIV (18 biopharmaceutical companies), according to a May 18 article published online in the Journal of the American Medical Association, have said they will contribute their respective clinical trial capacities, regardless of which agent is studied.
Some, however, have called for more streamlining of efforts.
“Ideally we’d be working together,” Lurie told Medscape Medical News.
“I’m hopeful we will find ways to collaborate scientifically,” she said. “The US government’s responsibility is to make doses for the US. CEPI’s responsibility is to make doses for the world. A big focus of CEPI is to make sure we have manufacturing capacity outside of the US so those doses can be available to the world and they don’t get seized by wealthy countries.”
Bottazzi, Ledley, Lurie, and Andino report no relevant financial relationships.
This article first appeared on Medscape.com.
COVID-19: Putting distance between projection and reality
When it comes to COVID-19, studies show that social distancing flattened the curve.
Cumulative hospitalizations in four states with stay-at-home orders were well short of the projected exponential growth curves, Soumya Sen, PhD, of the University of Minnesota, Minneapolis, and associates reported May 27 in a research letter in JAMA. All states were observed through April 28.
The deviations between observed cases and worst-case projections in the four states – Colorado, Minnesota, Ohio, and Virginia – all began within 8-10 days of the stay-at-home orders. In Minnesota, 17 days after the order, there were 361 cumulative hospitalizations, compared with a projection of 988 had no such action been taken. In Virginia, the corresponding numbers were 1,048 observed and 2,335 projected, they reported.
“Observed hospitalizations consistently fell outside of the 95% prediction bands of the projected exponential growth curve,” Dr. Sen and associates noted.
In a separate Canadian study measuring COVID-19 patients occupying ICU beds in Ontario and deaths among those cases, hospitals “would have rapidly exceeded ICU capacity and observed substantially higher mortality” without any physical distancing intervention, Ashleigh R. Tuite, PhD, MPH, of the University of Toronto and associates wrote May 27 in a letter in Annals of Internal Medicine.
Their model, based on a 70% reduction in physical contacts for March 19–May 3, projected 2.0 cases per 100,000 population with physical distancing and 37.4 per 100,000 without. Deaths among those ICU patients were projected at 2.5 per 100,000 with distancing and 12.7 per 100,000 without intervention, they reported.
“Our modeling also shows the challenges associated with relaxation of physical distancing measures without a concomitant increase in other public health measures. Specifically, when the number of contacts between persons returns to more than 50% of normal, we expect disease activity to resurge rapidly and ICUs to quickly reach capacity,” they wrote.
The study published in JAMA used publicly available data from the University of Minnesota COVID-19 Hospitalization Project, which is partially funded by the University of Minnesota Office of Academic Clinical Affairs and United Health Foundation.
SOURCES: Sen S et al. JAMA. 2020 May 27. doi: 10.1001/jama.2020.9176; Tuite AR et al. Ann Intern Med. 2020 May 27. doi: 10.7326/M20-2945.
When it comes to COVID-19, studies show that social distancing flattened the curve.
Cumulative hospitalizations in four states with stay-at-home orders were well short of the projected exponential growth curves, Soumya Sen, PhD, of the University of Minnesota, Minneapolis, and associates reported May 27 in a research letter in JAMA. All states were observed through April 28.
The deviations between observed cases and worst-case projections in the four states – Colorado, Minnesota, Ohio, and Virginia – all began within 8-10 days of the stay-at-home orders. In Minnesota, 17 days after the order, there were 361 cumulative hospitalizations, compared with a projection of 988 had no such action been taken. In Virginia, the corresponding numbers were 1,048 observed and 2,335 projected, they reported.
“Observed hospitalizations consistently fell outside of the 95% prediction bands of the projected exponential growth curve,” Dr. Sen and associates noted.
In a separate Canadian study measuring COVID-19 patients occupying ICU beds in Ontario and deaths among those cases, hospitals “would have rapidly exceeded ICU capacity and observed substantially higher mortality” without any physical distancing intervention, Ashleigh R. Tuite, PhD, MPH, of the University of Toronto and associates wrote May 27 in a letter in Annals of Internal Medicine.
Their model, based on a 70% reduction in physical contacts for March 19–May 3, projected 2.0 cases per 100,000 population with physical distancing and 37.4 per 100,000 without. Deaths among those ICU patients were projected at 2.5 per 100,000 with distancing and 12.7 per 100,000 without intervention, they reported.
“Our modeling also shows the challenges associated with relaxation of physical distancing measures without a concomitant increase in other public health measures. Specifically, when the number of contacts between persons returns to more than 50% of normal, we expect disease activity to resurge rapidly and ICUs to quickly reach capacity,” they wrote.
The study published in JAMA used publicly available data from the University of Minnesota COVID-19 Hospitalization Project, which is partially funded by the University of Minnesota Office of Academic Clinical Affairs and United Health Foundation.
SOURCES: Sen S et al. JAMA. 2020 May 27. doi: 10.1001/jama.2020.9176; Tuite AR et al. Ann Intern Med. 2020 May 27. doi: 10.7326/M20-2945.
When it comes to COVID-19, studies show that social distancing flattened the curve.
Cumulative hospitalizations in four states with stay-at-home orders were well short of the projected exponential growth curves, Soumya Sen, PhD, of the University of Minnesota, Minneapolis, and associates reported May 27 in a research letter in JAMA. All states were observed through April 28.
The deviations between observed cases and worst-case projections in the four states – Colorado, Minnesota, Ohio, and Virginia – all began within 8-10 days of the stay-at-home orders. In Minnesota, 17 days after the order, there were 361 cumulative hospitalizations, compared with a projection of 988 had no such action been taken. In Virginia, the corresponding numbers were 1,048 observed and 2,335 projected, they reported.
“Observed hospitalizations consistently fell outside of the 95% prediction bands of the projected exponential growth curve,” Dr. Sen and associates noted.
In a separate Canadian study measuring COVID-19 patients occupying ICU beds in Ontario and deaths among those cases, hospitals “would have rapidly exceeded ICU capacity and observed substantially higher mortality” without any physical distancing intervention, Ashleigh R. Tuite, PhD, MPH, of the University of Toronto and associates wrote May 27 in a letter in Annals of Internal Medicine.
Their model, based on a 70% reduction in physical contacts for March 19–May 3, projected 2.0 cases per 100,000 population with physical distancing and 37.4 per 100,000 without. Deaths among those ICU patients were projected at 2.5 per 100,000 with distancing and 12.7 per 100,000 without intervention, they reported.
“Our modeling also shows the challenges associated with relaxation of physical distancing measures without a concomitant increase in other public health measures. Specifically, when the number of contacts between persons returns to more than 50% of normal, we expect disease activity to resurge rapidly and ICUs to quickly reach capacity,” they wrote.
The study published in JAMA used publicly available data from the University of Minnesota COVID-19 Hospitalization Project, which is partially funded by the University of Minnesota Office of Academic Clinical Affairs and United Health Foundation.
SOURCES: Sen S et al. JAMA. 2020 May 27. doi: 10.1001/jama.2020.9176; Tuite AR et al. Ann Intern Med. 2020 May 27. doi: 10.7326/M20-2945.
New York City inpatient detox unit keeps running: Here’s how
Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.
I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.
At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.
Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.
Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.
Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.
Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.
Early in the process a huddle team was instituted with daily briefing of staff lasting 30 minutes or less. This team consists of physicians, nurses, a physician assistant, a social worker, and a counselor. In addition to discussing treatment plans for the patient, they deliberate on the public health information from the hospital’s COVID-19 command center, New York State Department of Health, the Office of Mental Health, and the Centers for Disease Control and Prevention concerning the latest evidence-based information. These discussions have helped us modify our policies and practices.
We instituted a no visiting rule during a short hospital stay of 5-7 days, and this was initiated weeks in advance of many institutions, including nursing homes with vulnerable populations. Our admitting criteria was reviewed to allow for admission of only those patients who absolutely needed inpatient substance use disorder treatment, including patients with severe withdrawal symptoms and signs, comorbidities, or neuropsychiatric manifestations that made them unsafe for outpatient or home detoxification. Others were triaged to the outpatient services which was amply supported with telemedicine. Rooms and designated areas of the building were earmarked as places for isolation/quarantine if suspected COVID-19 cases were identified pending testing. To assess patients’ risk of COVID-19, we do point-of-care nasopharyngeal swab testing with polymerase chain reaction.
Regarding face masks, patients and staff were fitted with ones early in the process. Additionally, staff were trained on the importance of face mask use and how to ensure you have a tight seal around the mouth and nose and were provided with other appropriate personal protective equipment. Concerning social distancing, we reduced the patient population capacity for the unit down to 50% and offered only single room admissions. Social distancing was encouraged in the unit, including in the television and recreation room and dining room, and during small treatment groups of less than six individuals. Daily temperature checks with noncontact handheld thermometers were enforced for staff and anyone coming into the life recovery center.
Patients are continuously being educated on the presentations of COVID-19 and encouraged to report any symptoms. Any staff feeling sick or having symptoms are encouraged to stay home. Rigorous and continuous cleaning of surfaces, especially of areas subjected to common use, is done frequently by the hospital housekeeping and environmental crew and is the order of the day.
Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.
Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.
I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.
At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.
Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.
Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.
Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.
Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.
Early in the process a huddle team was instituted with daily briefing of staff lasting 30 minutes or less. This team consists of physicians, nurses, a physician assistant, a social worker, and a counselor. In addition to discussing treatment plans for the patient, they deliberate on the public health information from the hospital’s COVID-19 command center, New York State Department of Health, the Office of Mental Health, and the Centers for Disease Control and Prevention concerning the latest evidence-based information. These discussions have helped us modify our policies and practices.
We instituted a no visiting rule during a short hospital stay of 5-7 days, and this was initiated weeks in advance of many institutions, including nursing homes with vulnerable populations. Our admitting criteria was reviewed to allow for admission of only those patients who absolutely needed inpatient substance use disorder treatment, including patients with severe withdrawal symptoms and signs, comorbidities, or neuropsychiatric manifestations that made them unsafe for outpatient or home detoxification. Others were triaged to the outpatient services which was amply supported with telemedicine. Rooms and designated areas of the building were earmarked as places for isolation/quarantine if suspected COVID-19 cases were identified pending testing. To assess patients’ risk of COVID-19, we do point-of-care nasopharyngeal swab testing with polymerase chain reaction.
Regarding face masks, patients and staff were fitted with ones early in the process. Additionally, staff were trained on the importance of face mask use and how to ensure you have a tight seal around the mouth and nose and were provided with other appropriate personal protective equipment. Concerning social distancing, we reduced the patient population capacity for the unit down to 50% and offered only single room admissions. Social distancing was encouraged in the unit, including in the television and recreation room and dining room, and during small treatment groups of less than six individuals. Daily temperature checks with noncontact handheld thermometers were enforced for staff and anyone coming into the life recovery center.
Patients are continuously being educated on the presentations of COVID-19 and encouraged to report any symptoms. Any staff feeling sick or having symptoms are encouraged to stay home. Rigorous and continuous cleaning of surfaces, especially of areas subjected to common use, is done frequently by the hospital housekeeping and environmental crew and is the order of the day.
Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.
Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.
I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.
At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.
Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.
Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.
Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.
Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.
Early in the process a huddle team was instituted with daily briefing of staff lasting 30 minutes or less. This team consists of physicians, nurses, a physician assistant, a social worker, and a counselor. In addition to discussing treatment plans for the patient, they deliberate on the public health information from the hospital’s COVID-19 command center, New York State Department of Health, the Office of Mental Health, and the Centers for Disease Control and Prevention concerning the latest evidence-based information. These discussions have helped us modify our policies and practices.
We instituted a no visiting rule during a short hospital stay of 5-7 days, and this was initiated weeks in advance of many institutions, including nursing homes with vulnerable populations. Our admitting criteria was reviewed to allow for admission of only those patients who absolutely needed inpatient substance use disorder treatment, including patients with severe withdrawal symptoms and signs, comorbidities, or neuropsychiatric manifestations that made them unsafe for outpatient or home detoxification. Others were triaged to the outpatient services which was amply supported with telemedicine. Rooms and designated areas of the building were earmarked as places for isolation/quarantine if suspected COVID-19 cases were identified pending testing. To assess patients’ risk of COVID-19, we do point-of-care nasopharyngeal swab testing with polymerase chain reaction.
Regarding face masks, patients and staff were fitted with ones early in the process. Additionally, staff were trained on the importance of face mask use and how to ensure you have a tight seal around the mouth and nose and were provided with other appropriate personal protective equipment. Concerning social distancing, we reduced the patient population capacity for the unit down to 50% and offered only single room admissions. Social distancing was encouraged in the unit, including in the television and recreation room and dining room, and during small treatment groups of less than six individuals. Daily temperature checks with noncontact handheld thermometers were enforced for staff and anyone coming into the life recovery center.
Patients are continuously being educated on the presentations of COVID-19 and encouraged to report any symptoms. Any staff feeling sick or having symptoms are encouraged to stay home. Rigorous and continuous cleaning of surfaces, especially of areas subjected to common use, is done frequently by the hospital housekeeping and environmental crew and is the order of the day.
Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.
SARS-CoV-2 infection rate 16% in asymptomatic pregnant women at delivery
Among women with a planned delivery in a New York City health system during the first half of April, the rate of asymptomatic SARS-CoV-2 infection was 16%, according to a study published in Obstetrics & Gynecology. Among the patients’ designated support persons, the asymptomatic carrier rate was 10%.
“If universal testing of pregnant patients in a high prevalence area is not performed, health care workers will be inadvertently exposed to COVID-19, unless universal precautions with personal protective equipment are taken,” wrote the researchers affiliated with the department of obstetrics, gynecology, and reproductive medicine at Icahn School of Medicine at Mount Sinai, New York.
Angela Bianco, MD, and colleagues conducted an observational study of women who were scheduled for a planned delivery within the Mount Sinai Health System between April 4 and April 15, 2020. Patients and their designated support person completed a telephone screen and underwent COVID-19 testing the day before a scheduled delivery. If support persons screened positive during the telephone interview about COVID-19 symptoms, they could not attend the birth, and patients could contact a different support person to be screened and tested. “All patients and their support persons were informed of their SARS-CoV-2 test results before admission,” the investigators wrote. “Those who tested positive were counseled regarding symptomatology that should prompt medical attention.”
In all, researchers screened 158 patients with a planned delivery, and 155 agreed to undergo COVID-19 testing. Of the 155 women tested, 24 (16%) tested positive for SARS CoV-2 infection. Among 146 support persons who had a negative interview screen and underwent SARS-CoV-2 testing, 14 (10%) tested positive for SARS-CoV-2 infection.
Test results were substantially concordant among patient and support person pairs. “Among patients who tested positive for COVID-19 infection and had a support person present, 11 of 19 (58%) support persons also tested positive for COVID-19 infection,” the authors reported. “Among patients who tested negative for COVID-19 infection and had a support person present, only 3 of 127 (2.4%) support persons tested positive for COVID-19 infection.”
Telephone screening did not identify any of the COVID-19–positive cases. Of the 24 patients with SARS-CoV-2 infection, none of their newborns tested positive at birth.
“Universal testing ... provides a mechanism for more accurate counseling of patients regarding issues such as newborn skin-to-skin contact and breastfeeding,” noted Dr. Bianco and colleagues. At their institution, parents with COVID-19 are instructed to wear a mask and practice proper hand hygiene when caring for their newborns.
Kristina Adams Waldorf, MD, said in an interview that the study by Bianco et al. underscores the high rate of asymptomatic or mildly symptomatic COVID-19 infections detected with universal screening in a hospital at the U.S. epicenter of the pandemic. “Each state and hospital will need to evaluate their own data to determine the value of universal screening for their patient population. In rural parts of America that have yet to see cases, universal screening may not make sense, but these areas are likely to be few and far between. The rest of America will need to quickly get on board with universal screening to protect their labor and delivery staff.”
Testing the partner was a strength of the study. “It is reassuring that when a pregnant woman tested negative for SARS-CoV-2, the rate was very, very low (2.4%) that her partner would test positive. However, it was disconcerting that telephone screening for common symptoms associated with COVID-19 was not very helpful in identifying cases,” said Dr. Waldorf, a professor of obstetrics and gynecology at the University of Washington, Seattle. She was not involved in the study by Bianco et al.
One study author receives payment from the American Board of Obstetrics and Gynecology for serving as a board examiner, receives payment from UpToDate, and serves as an expert witness in malpractice and products liability cases. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.
SOURCE: Bianco A et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003985.
Among women with a planned delivery in a New York City health system during the first half of April, the rate of asymptomatic SARS-CoV-2 infection was 16%, according to a study published in Obstetrics & Gynecology. Among the patients’ designated support persons, the asymptomatic carrier rate was 10%.
“If universal testing of pregnant patients in a high prevalence area is not performed, health care workers will be inadvertently exposed to COVID-19, unless universal precautions with personal protective equipment are taken,” wrote the researchers affiliated with the department of obstetrics, gynecology, and reproductive medicine at Icahn School of Medicine at Mount Sinai, New York.
Angela Bianco, MD, and colleagues conducted an observational study of women who were scheduled for a planned delivery within the Mount Sinai Health System between April 4 and April 15, 2020. Patients and their designated support person completed a telephone screen and underwent COVID-19 testing the day before a scheduled delivery. If support persons screened positive during the telephone interview about COVID-19 symptoms, they could not attend the birth, and patients could contact a different support person to be screened and tested. “All patients and their support persons were informed of their SARS-CoV-2 test results before admission,” the investigators wrote. “Those who tested positive were counseled regarding symptomatology that should prompt medical attention.”
In all, researchers screened 158 patients with a planned delivery, and 155 agreed to undergo COVID-19 testing. Of the 155 women tested, 24 (16%) tested positive for SARS CoV-2 infection. Among 146 support persons who had a negative interview screen and underwent SARS-CoV-2 testing, 14 (10%) tested positive for SARS-CoV-2 infection.
Test results were substantially concordant among patient and support person pairs. “Among patients who tested positive for COVID-19 infection and had a support person present, 11 of 19 (58%) support persons also tested positive for COVID-19 infection,” the authors reported. “Among patients who tested negative for COVID-19 infection and had a support person present, only 3 of 127 (2.4%) support persons tested positive for COVID-19 infection.”
Telephone screening did not identify any of the COVID-19–positive cases. Of the 24 patients with SARS-CoV-2 infection, none of their newborns tested positive at birth.
“Universal testing ... provides a mechanism for more accurate counseling of patients regarding issues such as newborn skin-to-skin contact and breastfeeding,” noted Dr. Bianco and colleagues. At their institution, parents with COVID-19 are instructed to wear a mask and practice proper hand hygiene when caring for their newborns.
Kristina Adams Waldorf, MD, said in an interview that the study by Bianco et al. underscores the high rate of asymptomatic or mildly symptomatic COVID-19 infections detected with universal screening in a hospital at the U.S. epicenter of the pandemic. “Each state and hospital will need to evaluate their own data to determine the value of universal screening for their patient population. In rural parts of America that have yet to see cases, universal screening may not make sense, but these areas are likely to be few and far between. The rest of America will need to quickly get on board with universal screening to protect their labor and delivery staff.”
Testing the partner was a strength of the study. “It is reassuring that when a pregnant woman tested negative for SARS-CoV-2, the rate was very, very low (2.4%) that her partner would test positive. However, it was disconcerting that telephone screening for common symptoms associated with COVID-19 was not very helpful in identifying cases,” said Dr. Waldorf, a professor of obstetrics and gynecology at the University of Washington, Seattle. She was not involved in the study by Bianco et al.
One study author receives payment from the American Board of Obstetrics and Gynecology for serving as a board examiner, receives payment from UpToDate, and serves as an expert witness in malpractice and products liability cases. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.
SOURCE: Bianco A et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003985.
Among women with a planned delivery in a New York City health system during the first half of April, the rate of asymptomatic SARS-CoV-2 infection was 16%, according to a study published in Obstetrics & Gynecology. Among the patients’ designated support persons, the asymptomatic carrier rate was 10%.
“If universal testing of pregnant patients in a high prevalence area is not performed, health care workers will be inadvertently exposed to COVID-19, unless universal precautions with personal protective equipment are taken,” wrote the researchers affiliated with the department of obstetrics, gynecology, and reproductive medicine at Icahn School of Medicine at Mount Sinai, New York.
Angela Bianco, MD, and colleagues conducted an observational study of women who were scheduled for a planned delivery within the Mount Sinai Health System between April 4 and April 15, 2020. Patients and their designated support person completed a telephone screen and underwent COVID-19 testing the day before a scheduled delivery. If support persons screened positive during the telephone interview about COVID-19 symptoms, they could not attend the birth, and patients could contact a different support person to be screened and tested. “All patients and their support persons were informed of their SARS-CoV-2 test results before admission,” the investigators wrote. “Those who tested positive were counseled regarding symptomatology that should prompt medical attention.”
In all, researchers screened 158 patients with a planned delivery, and 155 agreed to undergo COVID-19 testing. Of the 155 women tested, 24 (16%) tested positive for SARS CoV-2 infection. Among 146 support persons who had a negative interview screen and underwent SARS-CoV-2 testing, 14 (10%) tested positive for SARS-CoV-2 infection.
Test results were substantially concordant among patient and support person pairs. “Among patients who tested positive for COVID-19 infection and had a support person present, 11 of 19 (58%) support persons also tested positive for COVID-19 infection,” the authors reported. “Among patients who tested negative for COVID-19 infection and had a support person present, only 3 of 127 (2.4%) support persons tested positive for COVID-19 infection.”
Telephone screening did not identify any of the COVID-19–positive cases. Of the 24 patients with SARS-CoV-2 infection, none of their newborns tested positive at birth.
“Universal testing ... provides a mechanism for more accurate counseling of patients regarding issues such as newborn skin-to-skin contact and breastfeeding,” noted Dr. Bianco and colleagues. At their institution, parents with COVID-19 are instructed to wear a mask and practice proper hand hygiene when caring for their newborns.
Kristina Adams Waldorf, MD, said in an interview that the study by Bianco et al. underscores the high rate of asymptomatic or mildly symptomatic COVID-19 infections detected with universal screening in a hospital at the U.S. epicenter of the pandemic. “Each state and hospital will need to evaluate their own data to determine the value of universal screening for their patient population. In rural parts of America that have yet to see cases, universal screening may not make sense, but these areas are likely to be few and far between. The rest of America will need to quickly get on board with universal screening to protect their labor and delivery staff.”
Testing the partner was a strength of the study. “It is reassuring that when a pregnant woman tested negative for SARS-CoV-2, the rate was very, very low (2.4%) that her partner would test positive. However, it was disconcerting that telephone screening for common symptoms associated with COVID-19 was not very helpful in identifying cases,” said Dr. Waldorf, a professor of obstetrics and gynecology at the University of Washington, Seattle. She was not involved in the study by Bianco et al.
One study author receives payment from the American Board of Obstetrics and Gynecology for serving as a board examiner, receives payment from UpToDate, and serves as an expert witness in malpractice and products liability cases. The other authors did not report any potential conflicts of interest. Dr. Waldorf said she had no relevant financial disclosures.
SOURCE: Bianco A et al. Obstet Gynecol. 2020 May 19. doi: 10.1097/AOG.0000000000003985.
FROM OBSTETRICS & GYNECOLOGY
A long road to recovery: Lung rehab needed after COVID-19
If one word describes Eladio (“Lad”) Braganza, age 77, it’s “tenacious.” For 28 days, he clung to life on a ventilator in a Seattle ICU. Now – after a 46-day hospitalization for SARS-CoV-2 infection – he’s making progress in inpatient rehab, determined to regain function.
“We were not sure if he was going to make it through his first night in the hospital, and for a while after that. We were really prepared that he would not survive his ventilator time,” his daughter, Maria Braganza, said in an interview just 5 days after her father had been transferred to inpatient rehab.
In many ways, Mr. Braganza’s experience is typical of seriously ill COVID-19 patients. Many go from walking and talking to being on a ventilator within 10 hours or less. Mr. Braganza was admitted to the hospital on March 21 and was intubated that day. To keep him on the ventilator, he was heavily sedated and unconscious at times. In the ICU, he experienced bouts of low blood pressure, a pattern of shock that occurs in COVID-19 patients and that does not always respond to fluids.
Doctors have quickly learned to treat these patients aggressively. Many patients in the ICU with COVID-19 develop an inflamed, atypical form of acute respiratory distress syndrome (ARDS), in which the lung’s compliance, or stiffness, does not match the severity of hypoxia. These patients require high levels of oxygen and high ventilator settings. Many develop pneumothorax, or collapsed lungs, because of the high pressures needed to deliver oxygen and the prolonged time on ventilation.
“The vast majority of COVID patients in the ICU have lung disease that is quite severe, much more severe than I have seen in my 20 years of doing this,” said critical care specialist Anna Nolan, MD, of the department of medicine at New York University.
After about 2 weeks, some of these patients can come off the ventilator, or they may undergo a tracheostomy, a hole in the neck through which a tube is placed to deliver oxygen. By this time, many have developed ICU-acquired weakness and muscle wasting. Some may be so debilitated that they cannot walk. Even the respiratory muscles that help them breathe may have weakened as a result of the ventilator doing the work for them.
These patients “get sick very fast, and it takes a long time for them to heal. What’s not really well appreciated is how much rehab and how much recovery time these patients are going to need,” said David Chong, MD. He is medical director of the ICU at New York–Presbyterian Hospital/Columbia University Medical Center, and he has been on the front lines during the COVID-19 surge in New York City.
The road to recovery
Regardless of the cause, many people who have a prolonged stint in the ICU face an even longer convalescence. Still-unanswered questions concern whether recovery time will be longer for those with COVID-19, compared with other illnesses, and whether some of the damage may be permanent. A number of small studies in Hong Kong and China, as well as studies of severe acute respiratory syndrome patients’ recoveries, have promoted speculation about possible long-lasting damage to lungs and other organs from COVID-19.
Yet some of these reports have left out important details about ARDS in COVID-19 patients who also may be most at risk for long-lasting damage. To clear up some of the confusion, the Pulmonary Fibrosis Foundation said on April 6 that some but not all of COVID-19 patients who develop ARDS may go on to develop lung fibrosis – scarring of the lungs – which may be permanent.
“Post-ARDS fibrosis typically is not progressive, but nonetheless can be severe and limiting. The recovery period for post-ARDS fibrosis is approximately 1 year and the residual deficits persist, but generally do not progress,” the foundation noted.
Emerging research on lung damage in COVID-19
Because the pandemic is only a few months in, it’s unclear as yet what the long-term consequences of severe COVID-19 may be. But emerging data are enabling researchers to venture an educated guess about what may happen in the months and years ahead.
The key to understanding the data is knowing that ARDS is a syndrome – the end product of a variety of diseases or insults to the lung. Under the microscope, lung damage from ARDS associated with COVID-19 is indistinguishable from lung damage resulting from other causes, such as vaping, sepsis, or shock caused by a motor vehicle accident, said Sanjay Mukhopadhyay, MD, director of pulmonary pathology at Cleveland Clinic.
Dr. Mukhopadhyay, who specializes in lung pathology, performed one of the first complete autopsies of a COVID-19 patient in the United States. In most autopsy series published to date, he said, the most common lung finding in patients who have died from COVID-19 is diffuse alveolar damage (DAD), a pattern of lung injury seen in ARDS from many other causes.
In DAD, the walls of the alveoli – thinly lined air sacs that facilitate gas exchange in the lung – develop a pink, hyaline membrane composed of damaged cells and plasma proteins that leak from capillaries in the wall of the alveolus. This hyaline membrane gets plastered against the wall of the alveolus and interferes with diffusion of oxygen into the body.
“We know what happens in ARDS from other causes. If you follow people who have been on a ventilator long term, some of their respiratory function goes back to normal,” Dr. Mukhopadhyay said. “But there are other people in whom some degree of respiratory impairment lingers. In these patients, we think the DAD progresses to an organizing stage.”
Organizing pneumonia refers to a family of diseases in which fibroblasts (cells involved in wound healing) arrive and form scar tissue that forms hyaline membranes and fibrin balls (tough proteins) that fill up the alveoli, making gas exchange very difficult.
Also called BOOP (bronchiolitis obliterans organizing pneumonia), this condition is sensitive to steroids. Early aggressive steroid treatment can prevent long-term lung damage. Without steroids, damage can become permanent. A variant of this condition is termed acute fibrinous and organizing pneumonia (AFOP), which is also sensitive to steroids. A report from France demonstrates AFOP in some patients who have died from COVID-19.
The trick is identifying who is developing BOOP and who is not, and beyond that, who might be most amenable to treatment. Use of steroids for patients with certain other problems, such as a bacterial infection on top of COVID-19, could be harmful. David H. Chong, MD, and colleagues at Columbia University Irving Medical Center, New York, are investigating this to determine which COVID-19 patients may benefit from early steroid therapy.
“It’s not clear if there is a predominant histologic type or if we are catching people at different phases of their disease, and therefore we’re seeing different lung pathology,” Dr. Chong said.
He thinks that many patients with severe COVID-19 probably will not develop this pattern of lung scarring. “We’re speculating that lung damage from severe COVID-19 is probably going to behave more like lung damage from regular ARDS, which is often reversible. We think the vast majority of these patients probably have DAD that is similar to most patients with ARDS from other etiologies,” Dr. Chong said.
That would be consistent with information from China. In an April interview with Chinese domestic media, Zhong Nanshan, MD, a pulmonologist at the head of China’s COVID-19 task force, stated that he expects that the lungs in most patients with COVID-19 will gradually recover. He was responding to a widely publicized small study that found evidence of residual lung abnormalities at hospital discharge in most patients (94%, 66/70) who suffered from COVID-19 pneumonia in Wuhan, China, from January to February 2020.
Tough research conditions
Experts say that follow-up in this Chinese study and others to date has not been nearly long enough to allow predictions about lasting lung damage in COVID-19.
They also highlight the tough conditions in which researchers are working. Few autopsies have been performed so far – autopsies take time, extra precautions must be taken to avoid spread of COVID-19, and many patients and families do not consent to an autopsy. Furthermore, autopsy data from patients who died of COVID-19 may not extrapolate to survivors.
“I would not hang my hat on any of the limited data I have seen on autopsies,” said Lina Miyakawa, MD, a critical care and pulmonary medicine specialist at Mount Sinai Hospital in New York City.
“Even though we have answers about how the lungs are damaged at the end stage, this does not elucidate any answers about the earlier lung damage from this disease,” she continued. “It would be informative to have pathological data from the early or transitional phase, to see if that may translate into a treatment modality for COVID-19 patients.”
The problem is that these patients often experience a large amount of sloughing of airway cells, along with mucous plugging (collections of mucous that can block airflow and collapse alveoli). Bronchoscopy, which is used to view the inside of the lungs and sometimes to retrieve biopsy specimens for microscopic evaluation, is too risky for many COVID-19 patients.
In addition, few CT data exist for severely ill COVID-19 patients, who can be so unstable that to transport them to undergo a CT scan can be dangerous, not to mention the concern regarding infection control.
Even if sufficient data did exist, findings from chest x-rays, CTs, pathology studies, and lung function tests do not always match up. A patient who has lung abnormalities on CT may not necessarily have clinically impaired lung function or abnormal pathologic findings, according to Ali Gholamrezanezhad, MD, an emergency radiologist who is with the department of clinical radiology at the University of Southern California, Los Angeles.
Together with colleagues at USC, Dr. Gholamrezanezhad has started a long-term study of patients who were hospitalized with COVID-19. The researchers will follow patients for at least 1 year and will use chest x-ray, chest CT, and exercise testing to evaluate lung recovery over time.
“In the acute phase, we have acute inflammation called ground glass opacities, which usually happen bilaterally in COVID-19. That is totally reversible damage that can return to normal with no scarring,” Dr. Gholamrezanezhad said.
On the basis of data from survivors of other severe pneumonias, such as Middle East respiratory syndrome, SARS-CoV-1 infection, and H1N1 influenza, Gholamrezanezhad thinks that most survivors of COVID-19 will be able to return to work and normal life, although some may show residual lung dysfunction. Age, underlying medical conditions, smoking, length of hospital stay, severity of illness, and quality of treatment may all play a role in how well these people recover.
The lung has a remarkable capacity to recover, he added. Critical illness can destroy type one pneumocytes — the cells that line the alveoli in the lung — but over time, these cells grow back and reline the lungs. When they do, they can also help repair the lungs.
On top of that, the lung has a large functional reserve, and when one section becomes damaged, the rest of the lung can compensate.
However, for some people, total maximum exercise capacity may be affected, he commented.
Mukhopadhyay said: “My feeling is you will get reversal to normal in some patients and you will get long-term fibrosis from ARDS in some survivors. The question is, how many will have complete resolution and how many will have fibrosis? To know the answer, we will need a lot more data than we have now.”
Convalescence of COVID-19 Patients
Like many who become seriously ill with COVID-19, Braganza had underlying medical problems. Before becoming ill, he had had a heart attack and stroke. He walked with a walker and had some age-related memory problems.
Five days after transfer to inpatient rehab, Braganza was walking up and down the hallway using a walker. He was still shaking off the effects of being heavily sedated for so long, and he experienced periods of confusion. When he first came off the ventilator, he mixed up days and nights. Sometimes he did not remember being so sick. A former software engineer, Braganza usually had no problem using technology, but he has had to relearn how to use his phone and connect his iPad to Wi-Fi.
“He is still struggling quite a bit with remembering how to do basic things,” Maria Braganza said. “He has times of being really depressed because he feels like he’s not making progress.”
Doctors are taking note and starting to think about what lies ahead for ICU survivors of COVID-19. They worry about the potential for disease recurrence as well as readmission for other problems, such as other infections and hip fractures.
“As COVID-19 survivors begin to recover, there will be a large burden of chronic critical illness. We expect a significant need for rehabilitation in most ICU survivors of COVID-19,” said Steve Lubinsky, MD, medical director of respiratory care at New York University Langone Tisch Hospital.
Thinking about her father, Maria Braganza brings an extra dimension to these concerns. She thinks about depression, loneliness, and social isolation among older survivors of COVID-19. These problems existed long before the pandemic, but COVID-19 has magnified them.
The rehab staff estimates that Mr. Braganza will spend 10-14 days in their program, but discharge home creates a conundrum. Before becoming ill, Mr. Braganza lived in an independent senior living facility. Now, because of social distancing, he will no longer be able to hang out and have meals with his friends.
“Dad’s already feeling really lonely in the hospital. If we stay on a semipermanent lockdown, will he be able to see the people he loves?” Maria Braganza said. “Even though somebody is older, they have a lot to give and a lot of experience. They just need a little extra to be able to have that life.”
Dr. Nolan, Dr. Chong, Dr. Mukhopadhyay, Dr. Miyakawa, Dr. Gholamrezanezhad, and Dr. Lubinsky report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
If one word describes Eladio (“Lad”) Braganza, age 77, it’s “tenacious.” For 28 days, he clung to life on a ventilator in a Seattle ICU. Now – after a 46-day hospitalization for SARS-CoV-2 infection – he’s making progress in inpatient rehab, determined to regain function.
“We were not sure if he was going to make it through his first night in the hospital, and for a while after that. We were really prepared that he would not survive his ventilator time,” his daughter, Maria Braganza, said in an interview just 5 days after her father had been transferred to inpatient rehab.
In many ways, Mr. Braganza’s experience is typical of seriously ill COVID-19 patients. Many go from walking and talking to being on a ventilator within 10 hours or less. Mr. Braganza was admitted to the hospital on March 21 and was intubated that day. To keep him on the ventilator, he was heavily sedated and unconscious at times. In the ICU, he experienced bouts of low blood pressure, a pattern of shock that occurs in COVID-19 patients and that does not always respond to fluids.
Doctors have quickly learned to treat these patients aggressively. Many patients in the ICU with COVID-19 develop an inflamed, atypical form of acute respiratory distress syndrome (ARDS), in which the lung’s compliance, or stiffness, does not match the severity of hypoxia. These patients require high levels of oxygen and high ventilator settings. Many develop pneumothorax, or collapsed lungs, because of the high pressures needed to deliver oxygen and the prolonged time on ventilation.
“The vast majority of COVID patients in the ICU have lung disease that is quite severe, much more severe than I have seen in my 20 years of doing this,” said critical care specialist Anna Nolan, MD, of the department of medicine at New York University.
After about 2 weeks, some of these patients can come off the ventilator, or they may undergo a tracheostomy, a hole in the neck through which a tube is placed to deliver oxygen. By this time, many have developed ICU-acquired weakness and muscle wasting. Some may be so debilitated that they cannot walk. Even the respiratory muscles that help them breathe may have weakened as a result of the ventilator doing the work for them.
These patients “get sick very fast, and it takes a long time for them to heal. What’s not really well appreciated is how much rehab and how much recovery time these patients are going to need,” said David Chong, MD. He is medical director of the ICU at New York–Presbyterian Hospital/Columbia University Medical Center, and he has been on the front lines during the COVID-19 surge in New York City.
The road to recovery
Regardless of the cause, many people who have a prolonged stint in the ICU face an even longer convalescence. Still-unanswered questions concern whether recovery time will be longer for those with COVID-19, compared with other illnesses, and whether some of the damage may be permanent. A number of small studies in Hong Kong and China, as well as studies of severe acute respiratory syndrome patients’ recoveries, have promoted speculation about possible long-lasting damage to lungs and other organs from COVID-19.
Yet some of these reports have left out important details about ARDS in COVID-19 patients who also may be most at risk for long-lasting damage. To clear up some of the confusion, the Pulmonary Fibrosis Foundation said on April 6 that some but not all of COVID-19 patients who develop ARDS may go on to develop lung fibrosis – scarring of the lungs – which may be permanent.
“Post-ARDS fibrosis typically is not progressive, but nonetheless can be severe and limiting. The recovery period for post-ARDS fibrosis is approximately 1 year and the residual deficits persist, but generally do not progress,” the foundation noted.
Emerging research on lung damage in COVID-19
Because the pandemic is only a few months in, it’s unclear as yet what the long-term consequences of severe COVID-19 may be. But emerging data are enabling researchers to venture an educated guess about what may happen in the months and years ahead.
The key to understanding the data is knowing that ARDS is a syndrome – the end product of a variety of diseases or insults to the lung. Under the microscope, lung damage from ARDS associated with COVID-19 is indistinguishable from lung damage resulting from other causes, such as vaping, sepsis, or shock caused by a motor vehicle accident, said Sanjay Mukhopadhyay, MD, director of pulmonary pathology at Cleveland Clinic.
Dr. Mukhopadhyay, who specializes in lung pathology, performed one of the first complete autopsies of a COVID-19 patient in the United States. In most autopsy series published to date, he said, the most common lung finding in patients who have died from COVID-19 is diffuse alveolar damage (DAD), a pattern of lung injury seen in ARDS from many other causes.
In DAD, the walls of the alveoli – thinly lined air sacs that facilitate gas exchange in the lung – develop a pink, hyaline membrane composed of damaged cells and plasma proteins that leak from capillaries in the wall of the alveolus. This hyaline membrane gets plastered against the wall of the alveolus and interferes with diffusion of oxygen into the body.
“We know what happens in ARDS from other causes. If you follow people who have been on a ventilator long term, some of their respiratory function goes back to normal,” Dr. Mukhopadhyay said. “But there are other people in whom some degree of respiratory impairment lingers. In these patients, we think the DAD progresses to an organizing stage.”
Organizing pneumonia refers to a family of diseases in which fibroblasts (cells involved in wound healing) arrive and form scar tissue that forms hyaline membranes and fibrin balls (tough proteins) that fill up the alveoli, making gas exchange very difficult.
Also called BOOP (bronchiolitis obliterans organizing pneumonia), this condition is sensitive to steroids. Early aggressive steroid treatment can prevent long-term lung damage. Without steroids, damage can become permanent. A variant of this condition is termed acute fibrinous and organizing pneumonia (AFOP), which is also sensitive to steroids. A report from France demonstrates AFOP in some patients who have died from COVID-19.
The trick is identifying who is developing BOOP and who is not, and beyond that, who might be most amenable to treatment. Use of steroids for patients with certain other problems, such as a bacterial infection on top of COVID-19, could be harmful. David H. Chong, MD, and colleagues at Columbia University Irving Medical Center, New York, are investigating this to determine which COVID-19 patients may benefit from early steroid therapy.
“It’s not clear if there is a predominant histologic type or if we are catching people at different phases of their disease, and therefore we’re seeing different lung pathology,” Dr. Chong said.
He thinks that many patients with severe COVID-19 probably will not develop this pattern of lung scarring. “We’re speculating that lung damage from severe COVID-19 is probably going to behave more like lung damage from regular ARDS, which is often reversible. We think the vast majority of these patients probably have DAD that is similar to most patients with ARDS from other etiologies,” Dr. Chong said.
That would be consistent with information from China. In an April interview with Chinese domestic media, Zhong Nanshan, MD, a pulmonologist at the head of China’s COVID-19 task force, stated that he expects that the lungs in most patients with COVID-19 will gradually recover. He was responding to a widely publicized small study that found evidence of residual lung abnormalities at hospital discharge in most patients (94%, 66/70) who suffered from COVID-19 pneumonia in Wuhan, China, from January to February 2020.
Tough research conditions
Experts say that follow-up in this Chinese study and others to date has not been nearly long enough to allow predictions about lasting lung damage in COVID-19.
They also highlight the tough conditions in which researchers are working. Few autopsies have been performed so far – autopsies take time, extra precautions must be taken to avoid spread of COVID-19, and many patients and families do not consent to an autopsy. Furthermore, autopsy data from patients who died of COVID-19 may not extrapolate to survivors.
“I would not hang my hat on any of the limited data I have seen on autopsies,” said Lina Miyakawa, MD, a critical care and pulmonary medicine specialist at Mount Sinai Hospital in New York City.
“Even though we have answers about how the lungs are damaged at the end stage, this does not elucidate any answers about the earlier lung damage from this disease,” she continued. “It would be informative to have pathological data from the early or transitional phase, to see if that may translate into a treatment modality for COVID-19 patients.”
The problem is that these patients often experience a large amount of sloughing of airway cells, along with mucous plugging (collections of mucous that can block airflow and collapse alveoli). Bronchoscopy, which is used to view the inside of the lungs and sometimes to retrieve biopsy specimens for microscopic evaluation, is too risky for many COVID-19 patients.
In addition, few CT data exist for severely ill COVID-19 patients, who can be so unstable that to transport them to undergo a CT scan can be dangerous, not to mention the concern regarding infection control.
Even if sufficient data did exist, findings from chest x-rays, CTs, pathology studies, and lung function tests do not always match up. A patient who has lung abnormalities on CT may not necessarily have clinically impaired lung function or abnormal pathologic findings, according to Ali Gholamrezanezhad, MD, an emergency radiologist who is with the department of clinical radiology at the University of Southern California, Los Angeles.
Together with colleagues at USC, Dr. Gholamrezanezhad has started a long-term study of patients who were hospitalized with COVID-19. The researchers will follow patients for at least 1 year and will use chest x-ray, chest CT, and exercise testing to evaluate lung recovery over time.
“In the acute phase, we have acute inflammation called ground glass opacities, which usually happen bilaterally in COVID-19. That is totally reversible damage that can return to normal with no scarring,” Dr. Gholamrezanezhad said.
On the basis of data from survivors of other severe pneumonias, such as Middle East respiratory syndrome, SARS-CoV-1 infection, and H1N1 influenza, Gholamrezanezhad thinks that most survivors of COVID-19 will be able to return to work and normal life, although some may show residual lung dysfunction. Age, underlying medical conditions, smoking, length of hospital stay, severity of illness, and quality of treatment may all play a role in how well these people recover.
The lung has a remarkable capacity to recover, he added. Critical illness can destroy type one pneumocytes — the cells that line the alveoli in the lung — but over time, these cells grow back and reline the lungs. When they do, they can also help repair the lungs.
On top of that, the lung has a large functional reserve, and when one section becomes damaged, the rest of the lung can compensate.
However, for some people, total maximum exercise capacity may be affected, he commented.
Mukhopadhyay said: “My feeling is you will get reversal to normal in some patients and you will get long-term fibrosis from ARDS in some survivors. The question is, how many will have complete resolution and how many will have fibrosis? To know the answer, we will need a lot more data than we have now.”
Convalescence of COVID-19 Patients
Like many who become seriously ill with COVID-19, Braganza had underlying medical problems. Before becoming ill, he had had a heart attack and stroke. He walked with a walker and had some age-related memory problems.
Five days after transfer to inpatient rehab, Braganza was walking up and down the hallway using a walker. He was still shaking off the effects of being heavily sedated for so long, and he experienced periods of confusion. When he first came off the ventilator, he mixed up days and nights. Sometimes he did not remember being so sick. A former software engineer, Braganza usually had no problem using technology, but he has had to relearn how to use his phone and connect his iPad to Wi-Fi.
“He is still struggling quite a bit with remembering how to do basic things,” Maria Braganza said. “He has times of being really depressed because he feels like he’s not making progress.”
Doctors are taking note and starting to think about what lies ahead for ICU survivors of COVID-19. They worry about the potential for disease recurrence as well as readmission for other problems, such as other infections and hip fractures.
“As COVID-19 survivors begin to recover, there will be a large burden of chronic critical illness. We expect a significant need for rehabilitation in most ICU survivors of COVID-19,” said Steve Lubinsky, MD, medical director of respiratory care at New York University Langone Tisch Hospital.
Thinking about her father, Maria Braganza brings an extra dimension to these concerns. She thinks about depression, loneliness, and social isolation among older survivors of COVID-19. These problems existed long before the pandemic, but COVID-19 has magnified them.
The rehab staff estimates that Mr. Braganza will spend 10-14 days in their program, but discharge home creates a conundrum. Before becoming ill, Mr. Braganza lived in an independent senior living facility. Now, because of social distancing, he will no longer be able to hang out and have meals with his friends.
“Dad’s already feeling really lonely in the hospital. If we stay on a semipermanent lockdown, will he be able to see the people he loves?” Maria Braganza said. “Even though somebody is older, they have a lot to give and a lot of experience. They just need a little extra to be able to have that life.”
Dr. Nolan, Dr. Chong, Dr. Mukhopadhyay, Dr. Miyakawa, Dr. Gholamrezanezhad, and Dr. Lubinsky report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
If one word describes Eladio (“Lad”) Braganza, age 77, it’s “tenacious.” For 28 days, he clung to life on a ventilator in a Seattle ICU. Now – after a 46-day hospitalization for SARS-CoV-2 infection – he’s making progress in inpatient rehab, determined to regain function.
“We were not sure if he was going to make it through his first night in the hospital, and for a while after that. We were really prepared that he would not survive his ventilator time,” his daughter, Maria Braganza, said in an interview just 5 days after her father had been transferred to inpatient rehab.
In many ways, Mr. Braganza’s experience is typical of seriously ill COVID-19 patients. Many go from walking and talking to being on a ventilator within 10 hours or less. Mr. Braganza was admitted to the hospital on March 21 and was intubated that day. To keep him on the ventilator, he was heavily sedated and unconscious at times. In the ICU, he experienced bouts of low blood pressure, a pattern of shock that occurs in COVID-19 patients and that does not always respond to fluids.
Doctors have quickly learned to treat these patients aggressively. Many patients in the ICU with COVID-19 develop an inflamed, atypical form of acute respiratory distress syndrome (ARDS), in which the lung’s compliance, or stiffness, does not match the severity of hypoxia. These patients require high levels of oxygen and high ventilator settings. Many develop pneumothorax, or collapsed lungs, because of the high pressures needed to deliver oxygen and the prolonged time on ventilation.
“The vast majority of COVID patients in the ICU have lung disease that is quite severe, much more severe than I have seen in my 20 years of doing this,” said critical care specialist Anna Nolan, MD, of the department of medicine at New York University.
After about 2 weeks, some of these patients can come off the ventilator, or they may undergo a tracheostomy, a hole in the neck through which a tube is placed to deliver oxygen. By this time, many have developed ICU-acquired weakness and muscle wasting. Some may be so debilitated that they cannot walk. Even the respiratory muscles that help them breathe may have weakened as a result of the ventilator doing the work for them.
These patients “get sick very fast, and it takes a long time for them to heal. What’s not really well appreciated is how much rehab and how much recovery time these patients are going to need,” said David Chong, MD. He is medical director of the ICU at New York–Presbyterian Hospital/Columbia University Medical Center, and he has been on the front lines during the COVID-19 surge in New York City.
The road to recovery
Regardless of the cause, many people who have a prolonged stint in the ICU face an even longer convalescence. Still-unanswered questions concern whether recovery time will be longer for those with COVID-19, compared with other illnesses, and whether some of the damage may be permanent. A number of small studies in Hong Kong and China, as well as studies of severe acute respiratory syndrome patients’ recoveries, have promoted speculation about possible long-lasting damage to lungs and other organs from COVID-19.
Yet some of these reports have left out important details about ARDS in COVID-19 patients who also may be most at risk for long-lasting damage. To clear up some of the confusion, the Pulmonary Fibrosis Foundation said on April 6 that some but not all of COVID-19 patients who develop ARDS may go on to develop lung fibrosis – scarring of the lungs – which may be permanent.
“Post-ARDS fibrosis typically is not progressive, but nonetheless can be severe and limiting. The recovery period for post-ARDS fibrosis is approximately 1 year and the residual deficits persist, but generally do not progress,” the foundation noted.
Emerging research on lung damage in COVID-19
Because the pandemic is only a few months in, it’s unclear as yet what the long-term consequences of severe COVID-19 may be. But emerging data are enabling researchers to venture an educated guess about what may happen in the months and years ahead.
The key to understanding the data is knowing that ARDS is a syndrome – the end product of a variety of diseases or insults to the lung. Under the microscope, lung damage from ARDS associated with COVID-19 is indistinguishable from lung damage resulting from other causes, such as vaping, sepsis, or shock caused by a motor vehicle accident, said Sanjay Mukhopadhyay, MD, director of pulmonary pathology at Cleveland Clinic.
Dr. Mukhopadhyay, who specializes in lung pathology, performed one of the first complete autopsies of a COVID-19 patient in the United States. In most autopsy series published to date, he said, the most common lung finding in patients who have died from COVID-19 is diffuse alveolar damage (DAD), a pattern of lung injury seen in ARDS from many other causes.
In DAD, the walls of the alveoli – thinly lined air sacs that facilitate gas exchange in the lung – develop a pink, hyaline membrane composed of damaged cells and plasma proteins that leak from capillaries in the wall of the alveolus. This hyaline membrane gets plastered against the wall of the alveolus and interferes with diffusion of oxygen into the body.
“We know what happens in ARDS from other causes. If you follow people who have been on a ventilator long term, some of their respiratory function goes back to normal,” Dr. Mukhopadhyay said. “But there are other people in whom some degree of respiratory impairment lingers. In these patients, we think the DAD progresses to an organizing stage.”
Organizing pneumonia refers to a family of diseases in which fibroblasts (cells involved in wound healing) arrive and form scar tissue that forms hyaline membranes and fibrin balls (tough proteins) that fill up the alveoli, making gas exchange very difficult.
Also called BOOP (bronchiolitis obliterans organizing pneumonia), this condition is sensitive to steroids. Early aggressive steroid treatment can prevent long-term lung damage. Without steroids, damage can become permanent. A variant of this condition is termed acute fibrinous and organizing pneumonia (AFOP), which is also sensitive to steroids. A report from France demonstrates AFOP in some patients who have died from COVID-19.
The trick is identifying who is developing BOOP and who is not, and beyond that, who might be most amenable to treatment. Use of steroids for patients with certain other problems, such as a bacterial infection on top of COVID-19, could be harmful. David H. Chong, MD, and colleagues at Columbia University Irving Medical Center, New York, are investigating this to determine which COVID-19 patients may benefit from early steroid therapy.
“It’s not clear if there is a predominant histologic type or if we are catching people at different phases of their disease, and therefore we’re seeing different lung pathology,” Dr. Chong said.
He thinks that many patients with severe COVID-19 probably will not develop this pattern of lung scarring. “We’re speculating that lung damage from severe COVID-19 is probably going to behave more like lung damage from regular ARDS, which is often reversible. We think the vast majority of these patients probably have DAD that is similar to most patients with ARDS from other etiologies,” Dr. Chong said.
That would be consistent with information from China. In an April interview with Chinese domestic media, Zhong Nanshan, MD, a pulmonologist at the head of China’s COVID-19 task force, stated that he expects that the lungs in most patients with COVID-19 will gradually recover. He was responding to a widely publicized small study that found evidence of residual lung abnormalities at hospital discharge in most patients (94%, 66/70) who suffered from COVID-19 pneumonia in Wuhan, China, from January to February 2020.
Tough research conditions
Experts say that follow-up in this Chinese study and others to date has not been nearly long enough to allow predictions about lasting lung damage in COVID-19.
They also highlight the tough conditions in which researchers are working. Few autopsies have been performed so far – autopsies take time, extra precautions must be taken to avoid spread of COVID-19, and many patients and families do not consent to an autopsy. Furthermore, autopsy data from patients who died of COVID-19 may not extrapolate to survivors.
“I would not hang my hat on any of the limited data I have seen on autopsies,” said Lina Miyakawa, MD, a critical care and pulmonary medicine specialist at Mount Sinai Hospital in New York City.
“Even though we have answers about how the lungs are damaged at the end stage, this does not elucidate any answers about the earlier lung damage from this disease,” she continued. “It would be informative to have pathological data from the early or transitional phase, to see if that may translate into a treatment modality for COVID-19 patients.”
The problem is that these patients often experience a large amount of sloughing of airway cells, along with mucous plugging (collections of mucous that can block airflow and collapse alveoli). Bronchoscopy, which is used to view the inside of the lungs and sometimes to retrieve biopsy specimens for microscopic evaluation, is too risky for many COVID-19 patients.
In addition, few CT data exist for severely ill COVID-19 patients, who can be so unstable that to transport them to undergo a CT scan can be dangerous, not to mention the concern regarding infection control.
Even if sufficient data did exist, findings from chest x-rays, CTs, pathology studies, and lung function tests do not always match up. A patient who has lung abnormalities on CT may not necessarily have clinically impaired lung function or abnormal pathologic findings, according to Ali Gholamrezanezhad, MD, an emergency radiologist who is with the department of clinical radiology at the University of Southern California, Los Angeles.
Together with colleagues at USC, Dr. Gholamrezanezhad has started a long-term study of patients who were hospitalized with COVID-19. The researchers will follow patients for at least 1 year and will use chest x-ray, chest CT, and exercise testing to evaluate lung recovery over time.
“In the acute phase, we have acute inflammation called ground glass opacities, which usually happen bilaterally in COVID-19. That is totally reversible damage that can return to normal with no scarring,” Dr. Gholamrezanezhad said.
On the basis of data from survivors of other severe pneumonias, such as Middle East respiratory syndrome, SARS-CoV-1 infection, and H1N1 influenza, Gholamrezanezhad thinks that most survivors of COVID-19 will be able to return to work and normal life, although some may show residual lung dysfunction. Age, underlying medical conditions, smoking, length of hospital stay, severity of illness, and quality of treatment may all play a role in how well these people recover.
The lung has a remarkable capacity to recover, he added. Critical illness can destroy type one pneumocytes — the cells that line the alveoli in the lung — but over time, these cells grow back and reline the lungs. When they do, they can also help repair the lungs.
On top of that, the lung has a large functional reserve, and when one section becomes damaged, the rest of the lung can compensate.
However, for some people, total maximum exercise capacity may be affected, he commented.
Mukhopadhyay said: “My feeling is you will get reversal to normal in some patients and you will get long-term fibrosis from ARDS in some survivors. The question is, how many will have complete resolution and how many will have fibrosis? To know the answer, we will need a lot more data than we have now.”
Convalescence of COVID-19 Patients
Like many who become seriously ill with COVID-19, Braganza had underlying medical problems. Before becoming ill, he had had a heart attack and stroke. He walked with a walker and had some age-related memory problems.
Five days after transfer to inpatient rehab, Braganza was walking up and down the hallway using a walker. He was still shaking off the effects of being heavily sedated for so long, and he experienced periods of confusion. When he first came off the ventilator, he mixed up days and nights. Sometimes he did not remember being so sick. A former software engineer, Braganza usually had no problem using technology, but he has had to relearn how to use his phone and connect his iPad to Wi-Fi.
“He is still struggling quite a bit with remembering how to do basic things,” Maria Braganza said. “He has times of being really depressed because he feels like he’s not making progress.”
Doctors are taking note and starting to think about what lies ahead for ICU survivors of COVID-19. They worry about the potential for disease recurrence as well as readmission for other problems, such as other infections and hip fractures.
“As COVID-19 survivors begin to recover, there will be a large burden of chronic critical illness. We expect a significant need for rehabilitation in most ICU survivors of COVID-19,” said Steve Lubinsky, MD, medical director of respiratory care at New York University Langone Tisch Hospital.
Thinking about her father, Maria Braganza brings an extra dimension to these concerns. She thinks about depression, loneliness, and social isolation among older survivors of COVID-19. These problems existed long before the pandemic, but COVID-19 has magnified them.
The rehab staff estimates that Mr. Braganza will spend 10-14 days in their program, but discharge home creates a conundrum. Before becoming ill, Mr. Braganza lived in an independent senior living facility. Now, because of social distancing, he will no longer be able to hang out and have meals with his friends.
“Dad’s already feeling really lonely in the hospital. If we stay on a semipermanent lockdown, will he be able to see the people he loves?” Maria Braganza said. “Even though somebody is older, they have a lot to give and a lot of experience. They just need a little extra to be able to have that life.”
Dr. Nolan, Dr. Chong, Dr. Mukhopadhyay, Dr. Miyakawa, Dr. Gholamrezanezhad, and Dr. Lubinsky report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘The story unfolding is worrisome’ for diabetes and COVID-19
The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.
“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.
Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.
Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”
Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.
“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
Although rapidly collected, data “offer important clues”
Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.
Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.
“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”
Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”
Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.
“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
Existing insulin use linked to COVID-19 death risk
One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.
Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).
“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.
Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
Remote glucose monitoring a novel tool for COVID-19 isolation
Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.
Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.
“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.
“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.
Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”
Key question: Does glycemic management make a difference?
With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.
They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.
In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.
And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”
Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”
“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
More on obesity and COVID-19, this time from China
Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.
An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m2) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.
A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
Emerging from the crisis: Protect the vulnerable, increase knowledge base
As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.
Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”
Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.
“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.
Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.
Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”
Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.
“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
Although rapidly collected, data “offer important clues”
Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.
Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.
“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”
Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”
Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.
“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
Existing insulin use linked to COVID-19 death risk
One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.
Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).
“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.
Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
Remote glucose monitoring a novel tool for COVID-19 isolation
Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.
Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.
“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.
“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.
Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”
Key question: Does glycemic management make a difference?
With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.
They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.
In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.
And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”
Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”
“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
More on obesity and COVID-19, this time from China
Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.
An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m2) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.
A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
Emerging from the crisis: Protect the vulnerable, increase knowledge base
As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.
Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”
Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
The American Diabetes Association has dedicated a whole section of its journal, Diabetes Care, to the topic of “Diabetes and COVID-19,” publishing a range of articles with new data to help guide physicians in caring for patients.
“Certain groups are more vulnerable to COVID-19, notably older people and those with underlying medical conditions. Because diabetes is one of the conditions associated with high risk, the diabetes community urgently needs to know more about COVID-19 and its effects on people with diabetes,” an introductory commentary noted.
Entitled “COVID-19 in people with diabetes: Urgently needed lessons from early reports,” the commentary is penned by the journal’s editor-in-chief, Matthew Riddle, MD, of Oregon Health & Science University, Portland, and colleagues.
Also writing in the same issue, William T. Cefalu, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) noted it is known that the SARS-CoV-2 virus enters cells via the angiotensin-converting enzyme 2 (ACE-2) receptor. The ACE-2 receptor is known to be in the lungs and upper respiratory tract, “but we also know that it is expressed in other tissues such as heart, small and large intestines, and pancreas,” they wrote, and also “in the kidney.”
Hence, there are emerging reports of acute kidney injury resulting from COVID-19, as well as the impact on many other endocrine/metabolic and gastrointestinal outcomes.
“Pilot clinical studies (observational and interventional) are needed that will support the understanding or treatment of COVID-19–related diseases within the mission of the NIDDK,” they stated.
Although rapidly collected, data “offer important clues”
Some of the new ground covered in the journal articles includes an analysis of COVID-19 outcomes by type of glucose-lowering medication; remote glucose monitoring in hospitalized patients with COVID-19; a suggested approach to cardiovascular risk management in the COVID-19 era, as already reported by Medscape Medical News; and the diagnosis and management of gestational diabetes during the pandemic.
Other articles provide new data for previously reported phenomena, including obesity as a risk factor for worse COVID-19 outcomes and the role of inpatient glycemic control on COVID-19 outcomes.
“The data reported in these articles were rapidly collected and analyzed, in most cases under urgent and stressful conditions,” Dr. Riddle and colleagues cautioned. “Thus, some of the analyses are understandably limited due to missing data, incomplete follow-up, and inability to identify infected but asymptomatic patients.”
Even so, they wrote, some points are clear. “The consistency of findings in these rapidly published reports is reassuring in terms of scientific validity, but the story unfolding is worrisome.”
Specifically, while diabetes does not appear to increase the likelihood of SARS-CoV-2 infection, progression to severe illness is more likely in people with diabetes and COVID-19: They are two to three times as likely to require intensive care, and to die, compared with those infected but without diabetes.
“Neither the mechanisms underlying the increased risk nor the best interventions to limit it have yet been defined, but the studies in this collection of articles offer important clues,” Dr. Riddle and colleagues wrote.
Existing insulin use linked to COVID-19 death risk
One of the articles is a retrospective study of 904 hospitalized COVID-19 patients by Yuchen Chen, MD, of the Huazhong University of Science and Technology, Wuhan, China, and colleagues.
Among the 136 patients with diabetes, risk factors for mortality included older age (adjusted odds ratio, 1.09 per year increase; P = .001) elevated C-reactive protein (aOR, 1.12; P = .043), and insulin use (aOR, 3.58; P = .009).
“Attention needs to be paid to patients with diabetes and COVID-19 who use insulin,” the Chinese authors wrote. “Whether this was due to effects of insulin itself or to characteristics of the patients for whom it was prescribed is not clear,” Dr. Riddle and colleagues noted.
Dr. Chen and colleagues also found no difference in clinical outcomes between those diabetes patients with COVID-19 who were taking an ACE inhibitor or angiotensin II type I receptor blocker, compared with those who did not, which supports existing recommendations to continue use of this type of medication.
Remote glucose monitoring a novel tool for COVID-19 isolation
Another publication, by Gilat Shehav-Zaltzman of Sheba Medical Center, Tel Hashomer, Israel, and colleagues, describes the use of remote continuous glucose monitoring (CGM) in two hospitalized COVID-19 patients who were in isolation – one with type 1 diabetes and the other with type 2 diabetes – treated with basal-bolus insulin.
Using Medtronic CGM systems, the hospital staff was able to view patients’ real-time data uploaded to the Web from computer terminals in virus-free areas outside the patients’ rooms. The hospital’s endocrinology team had trained the intensive care staff on how to replace the sensors weekly and calibrate them twice daily.
“Converting a personal CGM system originally designed for diabetes self-management to team-based, real-time remote glucose monitoring offers a novel tool for inpatient diabetes control in COVID-19 isolation facilities,” the authors wrote.
“Such a solution in addition to ongoing remotely monitored clinical parameters (such as pulse rate, electrocardiogram, and oxygen saturation) adds to quality of diabetes care while minimizing risk of staff exposure and burden,” they observed.
Dr. Riddle and colleagues concurred: “Newer methods of remotely monitoring glucose patterns could be uniquely helpful.”
Key question: Does glycemic management make a difference?
With regard to the important issue of in-hospital control of glucose, Celestino Sardu, MD, PhD, of the University of Campania Luigi Vanvitelli, Naples, Italy, and colleagues reported on 59 patients hospitalized with confirmed COVID-19 and moderately severe pneumonia.
They were categorized as normoglycemic (n = 34) or hyperglycemic (n = 25), as well as with or without diabetes, on the basis of a diagnosis preceding the current illness. Of the 25 patients with hyperglycemia, 15 patients were treated with insulin infusion and 10 patients were not.
In a risk-adjusted analysis, both patients with hyperglycemia and patients with diabetes had a higher risk of severe disease than did those without diabetes and with normoglycemia. Patients with hyperglycemia treated with insulin infusion had a lower risk of severe disease than did patients who didn’t receive an insulin infusion.
And although they noted limitations, the authors wrote, “Our data evidenced that optimal glucose control in the immediate postadmission period for almost 18 days was associated with a significant reduction of inflammatory cytokines and procoagulative status.”
Dr. Riddle and colleagues wrote that the findings of this unrandomized comparison were interpreted “as suggesting that insulin infusion may improve outcomes.”
“If the benefits of seeking excellent glycemic control by this means are confirmed, close monitoring of glucose levels will be essential.”
More on obesity and COVID-19, this time from China
Because it has become increasingly clear that obesity is a risk factor for severe COVID-19, new data from China – where this was less apparent initially – support observations in Europe and the United States.
An article by Qingxian Cai, PhD, of Southern University of Science and Technology, Shenzhen, Guangdong, China, and colleagues looks at this. They found that, among 383 hospitalized patients with COVID-19, the 41 patients with obesity (defined as a body mass index ≥ 28 kg/m2) were significantly more likely to progress to severe disease compared with the 203 patients classified as having normal weight (BMI, 18.5-23.9), with an odds ratio of 3.4.
A similar finding comes from Feng Gao, MD, PhD, of the First Affiliated Hospital of Wenzhou (China) Medical University and colleagues, who studied 75 patients hospitalized with confirmed COVID-19 and obesity (defined as a BMI > 25 in this Asian population) to 75 patients without obesity matched by age and sex. After adjustment for clinical characteristics including the presence of diabetes, those with obesity had a threefold greater risk of progression to severe or critical COVID-19 status, with a nearly linear relationship.
Emerging from the crisis: Protect the vulnerable, increase knowledge base
As the research community emerges from the crisis, “there should be renewed efforts for multidisciplinary research ... aimed at greatly increasing the knowledge base to understand how ... the current COVID-19 threat” affects “both healthy people and people with chronic diseases and conditions,” Dr. Cefalu and colleagues concluded in their commentary.
Dr. Riddle and coauthors agreed: “We will enter a longer interval in which we must continue to support the most vulnerable populations – especially older people, those with diabetes or obesity, and those who lack the resources to limit day-to-day exposure to infection. We hope a growing sense of community will help in this task.”
Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from AstraZeneca, Eli Lilly, and Novo Nordisk, and honoraria for consulting from Adocia, AstraZeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Sanofi, and Theracos. Dr. Cefalu has reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.