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The benefits of continuous positive airway pressure therapy for patients with obstructive sleep apnea are well documented, but it only works if patients can adhere to the therapy.

A large national study of older Medicare patients with obstructive sleep apnea (OSA) has identified lower socioeconomic status and comorbidities as independent risk factors for nonadherence to continuous positive airway pressure (CPAP) therapy.

“[The] present results represent the largest study to date of rates and predictors of CPAP adherence among older adults in the United States. In our national sample of Medicare beneficiaries, adherence rates were generally lower than previously reported in smaller, clinic-based studies,” Emerson M. Wickwire, PhD, of the Sleep Disorders Center and division of pulmonary and critical care medicine at the University of Maryland, Baltimore, and colleagues wrote in Sleep.

Dr. Wickwire and colleagues estimated CPAP machine adherence using a 5% sample of Medicare claims data, identifying 3,229 Medicare beneficiaries with OSA who began CPAP therapy between 2009 and 2011. Individuals in the sample were aged at least 65 years with a new diagnosis of OSA, 88.1% of beneficiaries were white, and 52.3% were male.

The researchers applied objective adherence criteria set by the Centers for Medicare & Medicaid Services, which defines CPAP adherence as a patient using CPAP for at least 4 hours on 70% of nights, or CPAP use for 21 of 30 consecutive days within 90 days after beginning therapy.

Using CPAP machine charges as a measure of who adhered to therapy, they found 1,420 of 3,229 individuals (44%) achieved adherence under these criteria, which included making 13 monthly payments during their CPAP machine’s “rent-to-own” period. Partial adherence was found in 997 individuals (30.9%) who made between 4-12 payments on their CPAP machine, while 812 individuals (25.2%) made 4 payments or fewer on their CPAP machines, which the researchers classified as nonadherence. Nonadherers tended to be slightly younger (mean, 72.5 years vs. 79.2 years; P < .001) and had a higher number of comorbidities (35.2% vs. 30.4%; P = .002), compared with individuals with high adherence. Anxiety (odds ratio, 1.34; 95% confidence interval, 1.12-1.61), anemia (OR, 1.16; 95% CI, 1.02-1.32), fibromyalgia (OR, 1.19; 95% CI, 1.03-1.38), traumatic brain injury (OR, 1.58; 95% CI, 1.21-2.07), and Medicaid eligibility (OR, 1.48; 95% CI, 1.24-1.75) were all independently associated with lower CPAP adherence. Medicaid eligibility was considered an indicator of lower socioeconomic status.

Krishna M. Sundar, MD, FCCP, director at the Sleep-Wake Center in the University of Utah pulmonary division in Salt Lake City and CHEST Physician editorial board member, said in an interview that studies have shown early signs of adherence within the first few weeks are an important indicator of overall adherence to CPAP therapy. However, the use of CPAP machine payments in the study by Dr. Wickwire and colleagues was a novel way to track adherence.

Some of the issues with nonadherence may be related to challenges in using the technology, but it is the clinician’s role to communicate with patients about the effectiveness of CPAP and identifying reasons for nonadherence while also attempting to tease out the subtle socioeconomic factors related to nonadherence, Dr. Sundar noted. “We need to alter our practice to make sure that we communicate with these patients and better understand what are the social factors in getting the CPAP or utilizing CPAP, and also following these patients more closely, especially in the first month of starting CPAP therapy.

“Just because somebody has severe sleep apnea and other comorbid conditions does not mean that they’re going to wear the CPAP,” he said. “So, the fact that socioeconomic factors play an equal if not more important role in terms of predicting CPAP adherence. That is an important takeaway.”

Octavian C. Ioachimescu, MD, FCCP, of Emory University, Atlanta, and the Atlanta Veteran Affairs Administration and CHEST Physician editorial board member, said in an interview that the study raises a major question of what is next. “What can we offer to these patients, and what is the real-world compliance to that ‘next-best’ modality?” Dr. Ioachimescu said. “What are the outcomes of these individuals in the point-of-care environment, or ‘real world?’ ”

The analysis by the authors adds the perspective of a “real-world depiction of clinical care for patients with OSA,” Dr. Ioachimescu said. “One major lesson of such an analysis is that the health care goal setting that is referential to initial, randomized, well-controlled studies on highly selected patient populations need to be reassessed periodically from the point of view of actual results in the clinics.”

Clinicians may need to borrow ideas from other therapeutic fields to help improve patient adherence, he said. “[W]e may be able to develop and implement in the future peer involvement, behavioral and cognitive approaches, motivational enhancement interventions, as well as elements of acceptance and commitment techniques, all in the larger context of more integrated and in the same time individualized approaches to therapy.”

The investigators concluded that, “relative to Medicare-only beneficiaries, those eligible for both Medicare and Medicaid were significantly less likely to adhere to CPAP. Future research should seek to develop a deeper understanding of the mechanisms through which [socioeconomic status] and other social determinants impact patient experience throughout the OSA diagnostic and treatment process, including receiving, acclimating, and adhering to CPAP therapy.”

Dr. Sundar concurred with this assessment and said more research is needed on factors impacting adherence such as poverty, homelessness, and home support systems. “It’s not just coordinating with the patient. Clearly, more work is needed in understanding the social aspects of CPAP adherence.”

This study was funded in part by an investigator-initiated grant provided by ResMed to Dr. Wickmire’s institution, the University of Maryland, Baltimore. Dr. Wickmire reported being a scientific consultant to DayZz, Eisai, Merck, and Purdue and holds shares in WellTap. Dr. Oldstone is a ResMed employee and shareholder. Dr. Sundar reported being a cofounder of Hypnoscure, which creates software for population management of sleep apnea, and an investigator in trials where ResMed and Respironics devices were used. Dr. Ioachimescu reported no relevant financial disclosures.

SOURCE: Wickwire EM et al. Sleep. 2020 Jun 23. doi: 10.1093/sleep/zsaa122.

The benefits of continuous positive airway pressure therapy for patients with obstructive sleep apnea are well documented, but it only works if patients can adhere to the therapy.

A large national study of older Medicare patients with obstructive sleep apnea (OSA) has identified lower socioeconomic status and comorbidities as independent risk factors for nonadherence to continuous positive airway pressure (CPAP) therapy.

“[The] present results represent the largest study to date of rates and predictors of CPAP adherence among older adults in the United States. In our national sample of Medicare beneficiaries, adherence rates were generally lower than previously reported in smaller, clinic-based studies,” Emerson M. Wickwire, PhD, of the Sleep Disorders Center and division of pulmonary and critical care medicine at the University of Maryland, Baltimore, and colleagues wrote in Sleep.

Dr. Wickwire and colleagues estimated CPAP machine adherence using a 5% sample of Medicare claims data, identifying 3,229 Medicare beneficiaries with OSA who began CPAP therapy between 2009 and 2011. Individuals in the sample were aged at least 65 years with a new diagnosis of OSA, 88.1% of beneficiaries were white, and 52.3% were male.

The researchers applied objective adherence criteria set by the Centers for Medicare & Medicaid Services, which defines CPAP adherence as a patient using CPAP for at least 4 hours on 70% of nights, or CPAP use for 21 of 30 consecutive days within 90 days after beginning therapy.

Using CPAP machine charges as a measure of who adhered to therapy, they found 1,420 of 3,229 individuals (44%) achieved adherence under these criteria, which included making 13 monthly payments during their CPAP machine’s “rent-to-own” period. Partial adherence was found in 997 individuals (30.9%) who made between 4-12 payments on their CPAP machine, while 812 individuals (25.2%) made 4 payments or fewer on their CPAP machines, which the researchers classified as nonadherence. Nonadherers tended to be slightly younger (mean, 72.5 years vs. 79.2 years; P < .001) and had a higher number of comorbidities (35.2% vs. 30.4%; P = .002), compared with individuals with high adherence. Anxiety (odds ratio, 1.34; 95% confidence interval, 1.12-1.61), anemia (OR, 1.16; 95% CI, 1.02-1.32), fibromyalgia (OR, 1.19; 95% CI, 1.03-1.38), traumatic brain injury (OR, 1.58; 95% CI, 1.21-2.07), and Medicaid eligibility (OR, 1.48; 95% CI, 1.24-1.75) were all independently associated with lower CPAP adherence. Medicaid eligibility was considered an indicator of lower socioeconomic status.

Krishna M. Sundar, MD, FCCP, director at the Sleep-Wake Center in the University of Utah pulmonary division in Salt Lake City and CHEST Physician editorial board member, said in an interview that studies have shown early signs of adherence within the first few weeks are an important indicator of overall adherence to CPAP therapy. However, the use of CPAP machine payments in the study by Dr. Wickwire and colleagues was a novel way to track adherence.

Some of the issues with nonadherence may be related to challenges in using the technology, but it is the clinician’s role to communicate with patients about the effectiveness of CPAP and identifying reasons for nonadherence while also attempting to tease out the subtle socioeconomic factors related to nonadherence, Dr. Sundar noted. “We need to alter our practice to make sure that we communicate with these patients and better understand what are the social factors in getting the CPAP or utilizing CPAP, and also following these patients more closely, especially in the first month of starting CPAP therapy.

“Just because somebody has severe sleep apnea and other comorbid conditions does not mean that they’re going to wear the CPAP,” he said. “So, the fact that socioeconomic factors play an equal if not more important role in terms of predicting CPAP adherence. That is an important takeaway.”

Octavian C. Ioachimescu, MD, FCCP, of Emory University, Atlanta, and the Atlanta Veteran Affairs Administration and CHEST Physician editorial board member, said in an interview that the study raises a major question of what is next. “What can we offer to these patients, and what is the real-world compliance to that ‘next-best’ modality?” Dr. Ioachimescu said. “What are the outcomes of these individuals in the point-of-care environment, or ‘real world?’ ”

The analysis by the authors adds the perspective of a “real-world depiction of clinical care for patients with OSA,” Dr. Ioachimescu said. “One major lesson of such an analysis is that the health care goal setting that is referential to initial, randomized, well-controlled studies on highly selected patient populations need to be reassessed periodically from the point of view of actual results in the clinics.”

Clinicians may need to borrow ideas from other therapeutic fields to help improve patient adherence, he said. “[W]e may be able to develop and implement in the future peer involvement, behavioral and cognitive approaches, motivational enhancement interventions, as well as elements of acceptance and commitment techniques, all in the larger context of more integrated and in the same time individualized approaches to therapy.”

The investigators concluded that, “relative to Medicare-only beneficiaries, those eligible for both Medicare and Medicaid were significantly less likely to adhere to CPAP. Future research should seek to develop a deeper understanding of the mechanisms through which [socioeconomic status] and other social determinants impact patient experience throughout the OSA diagnostic and treatment process, including receiving, acclimating, and adhering to CPAP therapy.”

Dr. Sundar concurred with this assessment and said more research is needed on factors impacting adherence such as poverty, homelessness, and home support systems. “It’s not just coordinating with the patient. Clearly, more work is needed in understanding the social aspects of CPAP adherence.”

This study was funded in part by an investigator-initiated grant provided by ResMed to Dr. Wickmire’s institution, the University of Maryland, Baltimore. Dr. Wickmire reported being a scientific consultant to DayZz, Eisai, Merck, and Purdue and holds shares in WellTap. Dr. Oldstone is a ResMed employee and shareholder. Dr. Sundar reported being a cofounder of Hypnoscure, which creates software for population management of sleep apnea, and an investigator in trials where ResMed and Respironics devices were used. Dr. Ioachimescu reported no relevant financial disclosures.

SOURCE: Wickwire EM et al. Sleep. 2020 Jun 23. doi: 10.1093/sleep/zsaa122.

The benefits of continuous positive airway pressure therapy for patients with obstructive sleep apnea are well documented, but it only works if patients can adhere to the therapy.

A large national study of older Medicare patients with obstructive sleep apnea (OSA) has identified lower socioeconomic status and comorbidities as independent risk factors for nonadherence to continuous positive airway pressure (CPAP) therapy.

“[The] present results represent the largest study to date of rates and predictors of CPAP adherence among older adults in the United States. In our national sample of Medicare beneficiaries, adherence rates were generally lower than previously reported in smaller, clinic-based studies,” Emerson M. Wickwire, PhD, of the Sleep Disorders Center and division of pulmonary and critical care medicine at the University of Maryland, Baltimore, and colleagues wrote in Sleep.

Dr. Wickwire and colleagues estimated CPAP machine adherence using a 5% sample of Medicare claims data, identifying 3,229 Medicare beneficiaries with OSA who began CPAP therapy between 2009 and 2011. Individuals in the sample were aged at least 65 years with a new diagnosis of OSA, 88.1% of beneficiaries were white, and 52.3% were male.

The researchers applied objective adherence criteria set by the Centers for Medicare & Medicaid Services, which defines CPAP adherence as a patient using CPAP for at least 4 hours on 70% of nights, or CPAP use for 21 of 30 consecutive days within 90 days after beginning therapy.

Using CPAP machine charges as a measure of who adhered to therapy, they found 1,420 of 3,229 individuals (44%) achieved adherence under these criteria, which included making 13 monthly payments during their CPAP machine’s “rent-to-own” period. Partial adherence was found in 997 individuals (30.9%) who made between 4-12 payments on their CPAP machine, while 812 individuals (25.2%) made 4 payments or fewer on their CPAP machines, which the researchers classified as nonadherence. Nonadherers tended to be slightly younger (mean, 72.5 years vs. 79.2 years; P < .001) and had a higher number of comorbidities (35.2% vs. 30.4%; P = .002), compared with individuals with high adherence. Anxiety (odds ratio, 1.34; 95% confidence interval, 1.12-1.61), anemia (OR, 1.16; 95% CI, 1.02-1.32), fibromyalgia (OR, 1.19; 95% CI, 1.03-1.38), traumatic brain injury (OR, 1.58; 95% CI, 1.21-2.07), and Medicaid eligibility (OR, 1.48; 95% CI, 1.24-1.75) were all independently associated with lower CPAP adherence. Medicaid eligibility was considered an indicator of lower socioeconomic status.

Krishna M. Sundar, MD, FCCP, director at the Sleep-Wake Center in the University of Utah pulmonary division in Salt Lake City and CHEST Physician editorial board member, said in an interview that studies have shown early signs of adherence within the first few weeks are an important indicator of overall adherence to CPAP therapy. However, the use of CPAP machine payments in the study by Dr. Wickwire and colleagues was a novel way to track adherence.

Some of the issues with nonadherence may be related to challenges in using the technology, but it is the clinician’s role to communicate with patients about the effectiveness of CPAP and identifying reasons for nonadherence while also attempting to tease out the subtle socioeconomic factors related to nonadherence, Dr. Sundar noted. “We need to alter our practice to make sure that we communicate with these patients and better understand what are the social factors in getting the CPAP or utilizing CPAP, and also following these patients more closely, especially in the first month of starting CPAP therapy.

“Just because somebody has severe sleep apnea and other comorbid conditions does not mean that they’re going to wear the CPAP,” he said. “So, the fact that socioeconomic factors play an equal if not more important role in terms of predicting CPAP adherence. That is an important takeaway.”

Octavian C. Ioachimescu, MD, FCCP, of Emory University, Atlanta, and the Atlanta Veteran Affairs Administration and CHEST Physician editorial board member, said in an interview that the study raises a major question of what is next. “What can we offer to these patients, and what is the real-world compliance to that ‘next-best’ modality?” Dr. Ioachimescu said. “What are the outcomes of these individuals in the point-of-care environment, or ‘real world?’ ”

The analysis by the authors adds the perspective of a “real-world depiction of clinical care for patients with OSA,” Dr. Ioachimescu said. “One major lesson of such an analysis is that the health care goal setting that is referential to initial, randomized, well-controlled studies on highly selected patient populations need to be reassessed periodically from the point of view of actual results in the clinics.”

Clinicians may need to borrow ideas from other therapeutic fields to help improve patient adherence, he said. “[W]e may be able to develop and implement in the future peer involvement, behavioral and cognitive approaches, motivational enhancement interventions, as well as elements of acceptance and commitment techniques, all in the larger context of more integrated and in the same time individualized approaches to therapy.”

The investigators concluded that, “relative to Medicare-only beneficiaries, those eligible for both Medicare and Medicaid were significantly less likely to adhere to CPAP. Future research should seek to develop a deeper understanding of the mechanisms through which [socioeconomic status] and other social determinants impact patient experience throughout the OSA diagnostic and treatment process, including receiving, acclimating, and adhering to CPAP therapy.”

Dr. Sundar concurred with this assessment and said more research is needed on factors impacting adherence such as poverty, homelessness, and home support systems. “It’s not just coordinating with the patient. Clearly, more work is needed in understanding the social aspects of CPAP adherence.”

This study was funded in part by an investigator-initiated grant provided by ResMed to Dr. Wickmire’s institution, the University of Maryland, Baltimore. Dr. Wickmire reported being a scientific consultant to DayZz, Eisai, Merck, and Purdue and holds shares in WellTap. Dr. Oldstone is a ResMed employee and shareholder. Dr. Sundar reported being a cofounder of Hypnoscure, which creates software for population management of sleep apnea, and an investigator in trials where ResMed and Respironics devices were used. Dr. Ioachimescu reported no relevant financial disclosures.

SOURCE: Wickwire EM et al. Sleep. 2020 Jun 23. doi: 10.1093/sleep/zsaa122.

A phase 1/2 trial of a vaccine against SARS-CoV-2 being developed by the University of Oxford has found that the vaccine is safe, causes few side effects, and induces strong immune responses.

The early stage results, published in The Lancet, found that the candidate vaccine, known as ChAdOx1 nCoV-19, provoked a T-cell response peaking 14 days after vaccination, and an antibody response within 28 days.

Andrew Pollard, chief investigator on the study, and professor of pediatric infection and immunity at Oxford University, described the results as “encouraging”. He told a briefing convened by the Science Media Centre on Monday that it was “a really important milestone on the path to the development of the vaccine”.

In the Commons, the Health Secretary, Matt Hancock, hailed the results for taking us “one step closer to finding a vaccine that can potentially save lives, all around the world”.

The trial, which has so far involved 1,077 healthy adults, caused minor side effects when compared with a control group given a meningitis vaccine. Fatigue and headache were the most commonly reported reactions.

However, there were no serious adverse events from the vaccine, the researchers said.
 

‘Still a long way to go’

Sarah Gilbert, lead researcher of the vaccine development program, and professor of vaccinology at Oxford, cautioned that there was still a long way to go before the team could confirm that the vaccine could protect against developing COVID-19.

“The difficulty that we have, and that all vaccine developers have in trying to make a vaccine against this particular virus, is that we don’t know how strong that immune response needs to be,” she said.

“So, we can’t say just by looking at immune responses whether this is going to protect people or not. And the only way we’re going to find out is by doing the large phase 3 trials and wait for people to be infected as part of that trial before we know if the vaccine can work.”

The authors noted some limitations to their findings. They said more research was needed to confirm their results in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations.

A notable result of the trial was that participants given a second dose of the vaccine appeared to display a stronger immune response, a finding that had influenced plans to “look at two dose regimes as well as one dose regimes in the phase 3 trial”, Prof Adrian Hill, director of Oxford’s Jenner Institute, confirmed.

ChAdOx1 nCoV-19 is made from a weakened version of an adenovirus that causes infections in chimpanzees. The virus has been genetically modified so that it cannot grow in humans.

On Monday, the government announced that it had struck a deal with AstraZeneca for access to 100 million doses of the Oxford vaccine, in addition to millions of doses of other promising candidate vaccines.
 

Expert reaction to the findings

The Medical Research Council helped to fund the trial. Executive Chair Professor Fiona Watt commented: “It is truly remarkable how fast this vaccine has progressed, with our support, through early clinical trials, and it is very encouraging that it shows no safety concerns and evokes strong immune responses.

“There is a lot that we don’t yet know about immunity to the virus that causes COVID-19. However, it seems that both antibody and T cell immunity are important, and this vaccine triggers both responses. The much anticipated next milestone will be the results of the larger trials that are happening now to find out if the vaccine will protect people from the virus.”

Jonathan Ball, professor of molecular virology at the University of Nottingham, told the SMC: “The results of the Oxford chimp adenovirus vaccine candidate show that the vaccine is able to generate antibodies and T cells in humans and these persisted for several weeks. Whilst encouraging there is still a long way to go before we can herald the arrival of a successful coronavirus vaccine.

“It is unclear whether the levels of immunity can protect against infection – that’s what the larger ongoing phase III trials are designed to test. Nor do we know if this vaccine can protect those most vulnerable to severe COVID-19 disease.”

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, commented: “For the vaccine to be really useful, we not only need the larger studies conducted where COVID-19 is still occurring at a high rate, but we need to be reasonably sure that the protection lasts for a considerable time.”

He said it was also vital that people older than 55 were included in later trials.

Richard Torbett, chief executive of the Association of the British Pharmaceutical Industry, said: “Developing a vaccine is an incredibly difficult challenge; the fact that there are multiple candidates in development is hopefully a sign that the hard work will ultimately pay off.

“But we must be patient. Proving that a vaccine is safe and effective is a long process and we could still be many months away.”

This article first appeared on Medscape.com.

A phase 1/2 trial of a vaccine against SARS-CoV-2 being developed by the University of Oxford has found that the vaccine is safe, causes few side effects, and induces strong immune responses.

The early stage results, published in The Lancet, found that the candidate vaccine, known as ChAdOx1 nCoV-19, provoked a T-cell response peaking 14 days after vaccination, and an antibody response within 28 days.

Andrew Pollard, chief investigator on the study, and professor of pediatric infection and immunity at Oxford University, described the results as “encouraging”. He told a briefing convened by the Science Media Centre on Monday that it was “a really important milestone on the path to the development of the vaccine”.

In the Commons, the Health Secretary, Matt Hancock, hailed the results for taking us “one step closer to finding a vaccine that can potentially save lives, all around the world”.

The trial, which has so far involved 1,077 healthy adults, caused minor side effects when compared with a control group given a meningitis vaccine. Fatigue and headache were the most commonly reported reactions.

However, there were no serious adverse events from the vaccine, the researchers said.
 

‘Still a long way to go’

Sarah Gilbert, lead researcher of the vaccine development program, and professor of vaccinology at Oxford, cautioned that there was still a long way to go before the team could confirm that the vaccine could protect against developing COVID-19.

“The difficulty that we have, and that all vaccine developers have in trying to make a vaccine against this particular virus, is that we don’t know how strong that immune response needs to be,” she said.

“So, we can’t say just by looking at immune responses whether this is going to protect people or not. And the only way we’re going to find out is by doing the large phase 3 trials and wait for people to be infected as part of that trial before we know if the vaccine can work.”

The authors noted some limitations to their findings. They said more research was needed to confirm their results in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations.

A notable result of the trial was that participants given a second dose of the vaccine appeared to display a stronger immune response, a finding that had influenced plans to “look at two dose regimes as well as one dose regimes in the phase 3 trial”, Prof Adrian Hill, director of Oxford’s Jenner Institute, confirmed.

ChAdOx1 nCoV-19 is made from a weakened version of an adenovirus that causes infections in chimpanzees. The virus has been genetically modified so that it cannot grow in humans.

On Monday, the government announced that it had struck a deal with AstraZeneca for access to 100 million doses of the Oxford vaccine, in addition to millions of doses of other promising candidate vaccines.
 

Expert reaction to the findings

The Medical Research Council helped to fund the trial. Executive Chair Professor Fiona Watt commented: “It is truly remarkable how fast this vaccine has progressed, with our support, through early clinical trials, and it is very encouraging that it shows no safety concerns and evokes strong immune responses.

“There is a lot that we don’t yet know about immunity to the virus that causes COVID-19. However, it seems that both antibody and T cell immunity are important, and this vaccine triggers both responses. The much anticipated next milestone will be the results of the larger trials that are happening now to find out if the vaccine will protect people from the virus.”

Jonathan Ball, professor of molecular virology at the University of Nottingham, told the SMC: “The results of the Oxford chimp adenovirus vaccine candidate show that the vaccine is able to generate antibodies and T cells in humans and these persisted for several weeks. Whilst encouraging there is still a long way to go before we can herald the arrival of a successful coronavirus vaccine.

“It is unclear whether the levels of immunity can protect against infection – that’s what the larger ongoing phase III trials are designed to test. Nor do we know if this vaccine can protect those most vulnerable to severe COVID-19 disease.”

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, commented: “For the vaccine to be really useful, we not only need the larger studies conducted where COVID-19 is still occurring at a high rate, but we need to be reasonably sure that the protection lasts for a considerable time.”

He said it was also vital that people older than 55 were included in later trials.

Richard Torbett, chief executive of the Association of the British Pharmaceutical Industry, said: “Developing a vaccine is an incredibly difficult challenge; the fact that there are multiple candidates in development is hopefully a sign that the hard work will ultimately pay off.

“But we must be patient. Proving that a vaccine is safe and effective is a long process and we could still be many months away.”

This article first appeared on Medscape.com.

A phase 1/2 trial of a vaccine against SARS-CoV-2 being developed by the University of Oxford has found that the vaccine is safe, causes few side effects, and induces strong immune responses.

The early stage results, published in The Lancet, found that the candidate vaccine, known as ChAdOx1 nCoV-19, provoked a T-cell response peaking 14 days after vaccination, and an antibody response within 28 days.

Andrew Pollard, chief investigator on the study, and professor of pediatric infection and immunity at Oxford University, described the results as “encouraging”. He told a briefing convened by the Science Media Centre on Monday that it was “a really important milestone on the path to the development of the vaccine”.

In the Commons, the Health Secretary, Matt Hancock, hailed the results for taking us “one step closer to finding a vaccine that can potentially save lives, all around the world”.

The trial, which has so far involved 1,077 healthy adults, caused minor side effects when compared with a control group given a meningitis vaccine. Fatigue and headache were the most commonly reported reactions.

However, there were no serious adverse events from the vaccine, the researchers said.
 

‘Still a long way to go’

Sarah Gilbert, lead researcher of the vaccine development program, and professor of vaccinology at Oxford, cautioned that there was still a long way to go before the team could confirm that the vaccine could protect against developing COVID-19.

“The difficulty that we have, and that all vaccine developers have in trying to make a vaccine against this particular virus, is that we don’t know how strong that immune response needs to be,” she said.

“So, we can’t say just by looking at immune responses whether this is going to protect people or not. And the only way we’re going to find out is by doing the large phase 3 trials and wait for people to be infected as part of that trial before we know if the vaccine can work.”

The authors noted some limitations to their findings. They said more research was needed to confirm their results in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations.

A notable result of the trial was that participants given a second dose of the vaccine appeared to display a stronger immune response, a finding that had influenced plans to “look at two dose regimes as well as one dose regimes in the phase 3 trial”, Prof Adrian Hill, director of Oxford’s Jenner Institute, confirmed.

ChAdOx1 nCoV-19 is made from a weakened version of an adenovirus that causes infections in chimpanzees. The virus has been genetically modified so that it cannot grow in humans.

On Monday, the government announced that it had struck a deal with AstraZeneca for access to 100 million doses of the Oxford vaccine, in addition to millions of doses of other promising candidate vaccines.
 

Expert reaction to the findings

The Medical Research Council helped to fund the trial. Executive Chair Professor Fiona Watt commented: “It is truly remarkable how fast this vaccine has progressed, with our support, through early clinical trials, and it is very encouraging that it shows no safety concerns and evokes strong immune responses.

“There is a lot that we don’t yet know about immunity to the virus that causes COVID-19. However, it seems that both antibody and T cell immunity are important, and this vaccine triggers both responses. The much anticipated next milestone will be the results of the larger trials that are happening now to find out if the vaccine will protect people from the virus.”

Jonathan Ball, professor of molecular virology at the University of Nottingham, told the SMC: “The results of the Oxford chimp adenovirus vaccine candidate show that the vaccine is able to generate antibodies and T cells in humans and these persisted for several weeks. Whilst encouraging there is still a long way to go before we can herald the arrival of a successful coronavirus vaccine.

“It is unclear whether the levels of immunity can protect against infection – that’s what the larger ongoing phase III trials are designed to test. Nor do we know if this vaccine can protect those most vulnerable to severe COVID-19 disease.”

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, commented: “For the vaccine to be really useful, we not only need the larger studies conducted where COVID-19 is still occurring at a high rate, but we need to be reasonably sure that the protection lasts for a considerable time.”

He said it was also vital that people older than 55 were included in later trials.

Richard Torbett, chief executive of the Association of the British Pharmaceutical Industry, said: “Developing a vaccine is an incredibly difficult challenge; the fact that there are multiple candidates in development is hopefully a sign that the hard work will ultimately pay off.

“But we must be patient. Proving that a vaccine is safe and effective is a long process and we could still be many months away.”

This article first appeared on Medscape.com.

Every person who received Moderna’s COVID-19 vaccine, mRNA-1273, developed an immune response to the virus that causes it, the company says in a news release.

Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.

The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.

A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.

The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.

The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.

In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.

Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.

The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older

Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.

This article first appeared on WebMD.com.

Every person who received Moderna’s COVID-19 vaccine, mRNA-1273, developed an immune response to the virus that causes it, the company says in a news release.

Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.

The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.

A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.

The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.

The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.

In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.

Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.

The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older

Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.

This article first appeared on WebMD.com.

Every person who received Moderna’s COVID-19 vaccine, mRNA-1273, developed an immune response to the virus that causes it, the company says in a news release.

Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.

The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.

A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.

The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.

The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.

In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.

Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.

The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older

Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.

This article first appeared on WebMD.com.

Israel Shippy doesn’t remember much about having COVID-19 – or the unusual autoimmune disease it triggered – other than being groggy and uncomfortable for a bunch of days. He’s a 5-year-old boy and would much rather talk about cartoons or the ideas for inventions that constantly pop into his head.

“Hold your horses, I think I know what I’m gonna make,” he said, holding up a finger in the middle of a conversation. “I’m gonna make something that lights up and attaches to things with glue, so if you don’t have a flashlight, you can just use it!”

In New York, at least 237 kids, including Israel, appear to have Multisystem Inflammatory Syndrome in Children (MIS-C). And state officials continue to track the syndrome, but the Centers for Disease Control and Prevention did not respond to repeated requests for information on how many children nationwide have been diagnosed so far with MIS-C.

A study published June 29 in the New England Journal of Medicine reported on 186 patients in 26 states who had been diagnosed with MIS-C. A researcher writing in the same issue added reports from other countries, finding that about 1,000 children worldwide have been diagnosed with MIS-C.
 

Tracking the long-term health effects of MIS-C

Israel is friendly and energetic, but he’s also really good at sitting still. During a recent checkup at the Children’s Hospital at Montefiore, New York, he had no complaints about all the stickers and wires a health aide attached to him for an EKG. And when Marc Foca, MD, an infectious disease specialist, came by to listen to his heart and lungs, and prod his abdomen, Israel barely seemed to notice.

There were still some tests pending, but overall, Dr. Foca said, “Israel looks like a totally healthy 5-year-old.”

“Stay safe!” Israel called out, as Dr. Foca left. It’s his new sign-off, instead of goodbye. His mother, Janelle Moholland, explained Israel came up with it himself. And she’s also hoping that, after a harrowing couple of weeks in early May, Israel himself will “stay safe.”

That’s why they’ve been returning to Montefiore for the periodic checkups, even though Israel seems to have recovered fully from both COVID-19 and MIS-C.

MIS-C is relatively rare, and it apparently responds well to treatment, but it is new enough – and mysterious enough – that doctors here want to make sure the children who recover don’t experience any related health complications in the future.

“We’ve seen these kids get really sick, and get better and recover and go home, yet we don’t know what the long-term outcomes are,” said Nadine Choueiter, MD, a pediatric cardiologist at Montefiore. “So that’s why we will be seeing them.”

When Israel first got sick at the end of April, his illness didn’t exactly look like COVID-19. He had persistent high fevers, with his temperature reaching 104° F – but no problems breathing. He wasn’t eating. He was barely drinking. He wasn’t using the bathroom. He had abdominal pains. His eyes were red.

They went to the ED a couple of times and visited an urgent care center, but the doctors sent them home without testing him for the coronavirus. Ms. Moholland, 29, said she felt powerless.

“There was nothing I could do but make him comfortable,” she said. “I literally had to just trust in a higher power and just hope that He would come through for us. It taught me a lot about patience and faith.”

As Israel grew sicker, and they still had no answers, Ms. Moholland grew frustrated. “I wish his pediatrician and [the ED and urgent care staff] had done what they were supposed to do and given him a test” when Israel first got sick, Ms. Moholland said. “What harm would it have done? He suffered for about 10 or 11 days that could have been avoided.”

In a later interview, she talked with NPR about how COVID-19 has disproportionately affected the African American community because of a combination of underlying health conditions and lack of access to good health care. She said she felt she, too, had fallen victim to those disparities.

“It affects me, personally, because I am African American, but you just never know,” she said. “It’s hard. We’re living in uncertain times – very uncertain times.”

Finally, the Children’s Hospital at Montefiore admitted Israel – and the test she’d been trying to get for days confirmed he had the virus.

“I was literally in tears, like begging them not to discharge me because I knew he was not fine,” she recalled.

Israel was in shock, and by the time he got to the hospital, doctors were on the lookout for MIS-C, so they recognized his symptoms – which were distinct from most people with COVID-19.

Doctors gave Israel fluids and intravenous immunoglobulin, a substance obtained from donated human plasma, which is used to treat deficiencies in the immune system.

Immunoglobulin has been effective in children like Israel because MIS-C appears to be caused by an immune overreaction to the initial coronavirus infection, according to Dr. Choueiter.

“The immune system starts attacking the body itself, including the arteries of the heart,” she said.

In some MIS-C cases – though not Israel’s – the attack occurs in the coronary arteries, inflaming and dilating them. That also happens in a different syndrome affecting children, Kawasaki disease. About 5% of Kawasaki patients experience aneurysms – which can fatally rupture blood vessels – after the initial condition subsides.

Dr. Choueiter and colleagues want to make sure MIS-C patients don’t face similar risks. So far, they’re cautiously optimistic.

“We have not seen any new decrease in heart function or any new coronary artery dilations,” she said. “When we check their blood, their inflammatory markers are back to normal. For the parents, the child is back to baseline, and it’s as if this illness is a nightmare that’s long gone.”
 

For a Pennsylvania teen, the MIS-C diagnosis came much later

Not every child who develops MIS-C tests positive for the coronavirus, though many will test positive for antibodies to the coronavirus, indicating they had been infected previously. That was the case with Andrew Lis, a boy from Pennsylvania who was the first MIS-C patient seen at the Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del.

Andrew had been a healthy 14-year-old boy before he got sick. He and his twin brother love sports and video games. He said the first symptom was a bad headache. He developed a fever the next day, then constipation and intense stomach pain.

“It was terrible,” Andrew said. “It was unbearable. I couldn’t really move a lot.”

His mother, Ingrid Lis, said they were thinking appendicitis, not coronavirus, at first. In fact, she hesitated to take Andrew to the hospital, for fear of exposing him to the virus. But after Andrew stopped eating because of his headache and stomach discomfort, “I knew I couldn’t keep him home anymore,” Mrs. Lis said.

Andrew was admitted to the hospital April 12, but that was before reports of the mysterious syndrome had started trickling out of Europe.

Over about 5 days in the pediatric ICU, Andrew’s condition deteriorated rapidly, as doctors struggled to figure out what was wrong. Puzzled, they tried treatments for scarlet fever, strep throat, and toxic shock syndrome. Andrew’s body broke out in rashes, then his heart began failing and he was put on a ventilator. Andrew’s father, Ed Lis, said doctors told the family to brace for the worst: “We’ve got a healthy kid who a few days ago was just having these sort of strange symptoms. And now they’re telling us that we could lose him.”

Though Andrew’s symptoms were atypical for Kawasaki disease, doctors decided to give him the standard treatment for that condition – administering intravenous immunoglobulin, the same treatment Israel Shippy received.

“Within the 24 hours of the infusion, he was a different person,” Mrs. Lis said. Andrew was removed from the ventilator, and his appetite eventually returned. “That’s when we knew that we had turned that corner.”

It wasn’t until after Andrew’s discharge that his doctors learned about MIS-C from colleagues in Europe. They recommended the whole family be tested for antibodies to the coronavirus. Although Andrew tested positive, the rest of the family – both parents, Andrew’s twin brother and two older siblings – all tested negative. Andrew’s mother is still not sure how he was exposed since the family had been observing a strict lockdown since mid-March. Both she and her husband were working remotely from home, and she says they all wore masks and were conscientious about hand-washing when they ventured out for groceries. She thinks Andrew must have been exposed at least a month before his illness began.

And she’s puzzled why the rest of her close-knit family wasn’t infected as well. “We are a Latino family,” Mrs. Lis said. “We are very used to being together, clustering in the same room.” Even when Andrew was sick, she says, all six of them huddled in his bedroom to comfort him.

Meanwhile, Andrew has made a quick recovery. Not long after his discharge in April, he turned 15 and resumed an exercise routine involving running, push-ups, and sit-ups. A few weeks later, an ECG showed Andrew’s heart was “perfect,” Mr. Lis said. Still, doctors have asked Andrew to follow up with a cardiologist every 3 months.
 

An eye on the long-term effects

The medical team at Montefiore is tracking the 40 children they have already treated and discharged. With kids showing few symptoms in the immediate aftermath, Dr. Choueiter hopes the long-term trajectory after MIS-C will be similar to what happens after Kawasaki disease.

“Usually children who have had coronary artery dilations [from Kawasaki disease] that have resolved within the first 6 weeks of the illness do well long-term,” said Dr. Choueiter, who runs the Kawasaki disease program at Montefiore.

The Montefiore team is asking patients affected by MIS-C to return for a checkup 1 week after discharge, then after 1 month, 3 months, 6 months, and a year. They will be evaluated by pediatric cardiologists, hematologists, rheumatologists and infectious disease specialists.

Montefiore and other children’s hospitals around the country are sharing information. Dr. Choueiter wants to establish an even longer-term monitoring program for MIS-C, comparable with registries that exist for other diseases.

Ms. Moholland is glad the hospital is being vigilant.

“The uncertainty of not knowing whether it could come back in his future is a little unsettling,” she said. “But I am hopeful.”

This story is part of a partnership that includes WNYC, NPR, and Kaiser Health News. A version of this article originally appeared on Kaiser Health News.

Israel Shippy doesn’t remember much about having COVID-19 – or the unusual autoimmune disease it triggered – other than being groggy and uncomfortable for a bunch of days. He’s a 5-year-old boy and would much rather talk about cartoons or the ideas for inventions that constantly pop into his head.

“Hold your horses, I think I know what I’m gonna make,” he said, holding up a finger in the middle of a conversation. “I’m gonna make something that lights up and attaches to things with glue, so if you don’t have a flashlight, you can just use it!”

In New York, at least 237 kids, including Israel, appear to have Multisystem Inflammatory Syndrome in Children (MIS-C). And state officials continue to track the syndrome, but the Centers for Disease Control and Prevention did not respond to repeated requests for information on how many children nationwide have been diagnosed so far with MIS-C.

A study published June 29 in the New England Journal of Medicine reported on 186 patients in 26 states who had been diagnosed with MIS-C. A researcher writing in the same issue added reports from other countries, finding that about 1,000 children worldwide have been diagnosed with MIS-C.
 

Tracking the long-term health effects of MIS-C

Israel is friendly and energetic, but he’s also really good at sitting still. During a recent checkup at the Children’s Hospital at Montefiore, New York, he had no complaints about all the stickers and wires a health aide attached to him for an EKG. And when Marc Foca, MD, an infectious disease specialist, came by to listen to his heart and lungs, and prod his abdomen, Israel barely seemed to notice.

There were still some tests pending, but overall, Dr. Foca said, “Israel looks like a totally healthy 5-year-old.”

“Stay safe!” Israel called out, as Dr. Foca left. It’s his new sign-off, instead of goodbye. His mother, Janelle Moholland, explained Israel came up with it himself. And she’s also hoping that, after a harrowing couple of weeks in early May, Israel himself will “stay safe.”

That’s why they’ve been returning to Montefiore for the periodic checkups, even though Israel seems to have recovered fully from both COVID-19 and MIS-C.

MIS-C is relatively rare, and it apparently responds well to treatment, but it is new enough – and mysterious enough – that doctors here want to make sure the children who recover don’t experience any related health complications in the future.

“We’ve seen these kids get really sick, and get better and recover and go home, yet we don’t know what the long-term outcomes are,” said Nadine Choueiter, MD, a pediatric cardiologist at Montefiore. “So that’s why we will be seeing them.”

When Israel first got sick at the end of April, his illness didn’t exactly look like COVID-19. He had persistent high fevers, with his temperature reaching 104° F – but no problems breathing. He wasn’t eating. He was barely drinking. He wasn’t using the bathroom. He had abdominal pains. His eyes were red.

They went to the ED a couple of times and visited an urgent care center, but the doctors sent them home without testing him for the coronavirus. Ms. Moholland, 29, said she felt powerless.

“There was nothing I could do but make him comfortable,” she said. “I literally had to just trust in a higher power and just hope that He would come through for us. It taught me a lot about patience and faith.”

As Israel grew sicker, and they still had no answers, Ms. Moholland grew frustrated. “I wish his pediatrician and [the ED and urgent care staff] had done what they were supposed to do and given him a test” when Israel first got sick, Ms. Moholland said. “What harm would it have done? He suffered for about 10 or 11 days that could have been avoided.”

In a later interview, she talked with NPR about how COVID-19 has disproportionately affected the African American community because of a combination of underlying health conditions and lack of access to good health care. She said she felt she, too, had fallen victim to those disparities.

“It affects me, personally, because I am African American, but you just never know,” she said. “It’s hard. We’re living in uncertain times – very uncertain times.”

Finally, the Children’s Hospital at Montefiore admitted Israel – and the test she’d been trying to get for days confirmed he had the virus.

“I was literally in tears, like begging them not to discharge me because I knew he was not fine,” she recalled.

Israel was in shock, and by the time he got to the hospital, doctors were on the lookout for MIS-C, so they recognized his symptoms – which were distinct from most people with COVID-19.

Doctors gave Israel fluids and intravenous immunoglobulin, a substance obtained from donated human plasma, which is used to treat deficiencies in the immune system.

Immunoglobulin has been effective in children like Israel because MIS-C appears to be caused by an immune overreaction to the initial coronavirus infection, according to Dr. Choueiter.

“The immune system starts attacking the body itself, including the arteries of the heart,” she said.

In some MIS-C cases – though not Israel’s – the attack occurs in the coronary arteries, inflaming and dilating them. That also happens in a different syndrome affecting children, Kawasaki disease. About 5% of Kawasaki patients experience aneurysms – which can fatally rupture blood vessels – after the initial condition subsides.

Dr. Choueiter and colleagues want to make sure MIS-C patients don’t face similar risks. So far, they’re cautiously optimistic.

“We have not seen any new decrease in heart function or any new coronary artery dilations,” she said. “When we check their blood, their inflammatory markers are back to normal. For the parents, the child is back to baseline, and it’s as if this illness is a nightmare that’s long gone.”
 

For a Pennsylvania teen, the MIS-C diagnosis came much later

Not every child who develops MIS-C tests positive for the coronavirus, though many will test positive for antibodies to the coronavirus, indicating they had been infected previously. That was the case with Andrew Lis, a boy from Pennsylvania who was the first MIS-C patient seen at the Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del.

Andrew had been a healthy 14-year-old boy before he got sick. He and his twin brother love sports and video games. He said the first symptom was a bad headache. He developed a fever the next day, then constipation and intense stomach pain.

“It was terrible,” Andrew said. “It was unbearable. I couldn’t really move a lot.”

His mother, Ingrid Lis, said they were thinking appendicitis, not coronavirus, at first. In fact, she hesitated to take Andrew to the hospital, for fear of exposing him to the virus. But after Andrew stopped eating because of his headache and stomach discomfort, “I knew I couldn’t keep him home anymore,” Mrs. Lis said.

Andrew was admitted to the hospital April 12, but that was before reports of the mysterious syndrome had started trickling out of Europe.

Over about 5 days in the pediatric ICU, Andrew’s condition deteriorated rapidly, as doctors struggled to figure out what was wrong. Puzzled, they tried treatments for scarlet fever, strep throat, and toxic shock syndrome. Andrew’s body broke out in rashes, then his heart began failing and he was put on a ventilator. Andrew’s father, Ed Lis, said doctors told the family to brace for the worst: “We’ve got a healthy kid who a few days ago was just having these sort of strange symptoms. And now they’re telling us that we could lose him.”

Though Andrew’s symptoms were atypical for Kawasaki disease, doctors decided to give him the standard treatment for that condition – administering intravenous immunoglobulin, the same treatment Israel Shippy received.

“Within the 24 hours of the infusion, he was a different person,” Mrs. Lis said. Andrew was removed from the ventilator, and his appetite eventually returned. “That’s when we knew that we had turned that corner.”

It wasn’t until after Andrew’s discharge that his doctors learned about MIS-C from colleagues in Europe. They recommended the whole family be tested for antibodies to the coronavirus. Although Andrew tested positive, the rest of the family – both parents, Andrew’s twin brother and two older siblings – all tested negative. Andrew’s mother is still not sure how he was exposed since the family had been observing a strict lockdown since mid-March. Both she and her husband were working remotely from home, and she says they all wore masks and were conscientious about hand-washing when they ventured out for groceries. She thinks Andrew must have been exposed at least a month before his illness began.

And she’s puzzled why the rest of her close-knit family wasn’t infected as well. “We are a Latino family,” Mrs. Lis said. “We are very used to being together, clustering in the same room.” Even when Andrew was sick, she says, all six of them huddled in his bedroom to comfort him.

Meanwhile, Andrew has made a quick recovery. Not long after his discharge in April, he turned 15 and resumed an exercise routine involving running, push-ups, and sit-ups. A few weeks later, an ECG showed Andrew’s heart was “perfect,” Mr. Lis said. Still, doctors have asked Andrew to follow up with a cardiologist every 3 months.
 

An eye on the long-term effects

The medical team at Montefiore is tracking the 40 children they have already treated and discharged. With kids showing few symptoms in the immediate aftermath, Dr. Choueiter hopes the long-term trajectory after MIS-C will be similar to what happens after Kawasaki disease.

“Usually children who have had coronary artery dilations [from Kawasaki disease] that have resolved within the first 6 weeks of the illness do well long-term,” said Dr. Choueiter, who runs the Kawasaki disease program at Montefiore.

The Montefiore team is asking patients affected by MIS-C to return for a checkup 1 week after discharge, then after 1 month, 3 months, 6 months, and a year. They will be evaluated by pediatric cardiologists, hematologists, rheumatologists and infectious disease specialists.

Montefiore and other children’s hospitals around the country are sharing information. Dr. Choueiter wants to establish an even longer-term monitoring program for MIS-C, comparable with registries that exist for other diseases.

Ms. Moholland is glad the hospital is being vigilant.

“The uncertainty of not knowing whether it could come back in his future is a little unsettling,” she said. “But I am hopeful.”

This story is part of a partnership that includes WNYC, NPR, and Kaiser Health News. A version of this article originally appeared on Kaiser Health News.

Israel Shippy doesn’t remember much about having COVID-19 – or the unusual autoimmune disease it triggered – other than being groggy and uncomfortable for a bunch of days. He’s a 5-year-old boy and would much rather talk about cartoons or the ideas for inventions that constantly pop into his head.

“Hold your horses, I think I know what I’m gonna make,” he said, holding up a finger in the middle of a conversation. “I’m gonna make something that lights up and attaches to things with glue, so if you don’t have a flashlight, you can just use it!”

In New York, at least 237 kids, including Israel, appear to have Multisystem Inflammatory Syndrome in Children (MIS-C). And state officials continue to track the syndrome, but the Centers for Disease Control and Prevention did not respond to repeated requests for information on how many children nationwide have been diagnosed so far with MIS-C.

A study published June 29 in the New England Journal of Medicine reported on 186 patients in 26 states who had been diagnosed with MIS-C. A researcher writing in the same issue added reports from other countries, finding that about 1,000 children worldwide have been diagnosed with MIS-C.
 

Tracking the long-term health effects of MIS-C

Israel is friendly and energetic, but he’s also really good at sitting still. During a recent checkup at the Children’s Hospital at Montefiore, New York, he had no complaints about all the stickers and wires a health aide attached to him for an EKG. And when Marc Foca, MD, an infectious disease specialist, came by to listen to his heart and lungs, and prod his abdomen, Israel barely seemed to notice.

There were still some tests pending, but overall, Dr. Foca said, “Israel looks like a totally healthy 5-year-old.”

“Stay safe!” Israel called out, as Dr. Foca left. It’s his new sign-off, instead of goodbye. His mother, Janelle Moholland, explained Israel came up with it himself. And she’s also hoping that, after a harrowing couple of weeks in early May, Israel himself will “stay safe.”

That’s why they’ve been returning to Montefiore for the periodic checkups, even though Israel seems to have recovered fully from both COVID-19 and MIS-C.

MIS-C is relatively rare, and it apparently responds well to treatment, but it is new enough – and mysterious enough – that doctors here want to make sure the children who recover don’t experience any related health complications in the future.

“We’ve seen these kids get really sick, and get better and recover and go home, yet we don’t know what the long-term outcomes are,” said Nadine Choueiter, MD, a pediatric cardiologist at Montefiore. “So that’s why we will be seeing them.”

When Israel first got sick at the end of April, his illness didn’t exactly look like COVID-19. He had persistent high fevers, with his temperature reaching 104° F – but no problems breathing. He wasn’t eating. He was barely drinking. He wasn’t using the bathroom. He had abdominal pains. His eyes were red.

They went to the ED a couple of times and visited an urgent care center, but the doctors sent them home without testing him for the coronavirus. Ms. Moholland, 29, said she felt powerless.

“There was nothing I could do but make him comfortable,” she said. “I literally had to just trust in a higher power and just hope that He would come through for us. It taught me a lot about patience and faith.”

As Israel grew sicker, and they still had no answers, Ms. Moholland grew frustrated. “I wish his pediatrician and [the ED and urgent care staff] had done what they were supposed to do and given him a test” when Israel first got sick, Ms. Moholland said. “What harm would it have done? He suffered for about 10 or 11 days that could have been avoided.”

In a later interview, she talked with NPR about how COVID-19 has disproportionately affected the African American community because of a combination of underlying health conditions and lack of access to good health care. She said she felt she, too, had fallen victim to those disparities.

“It affects me, personally, because I am African American, but you just never know,” she said. “It’s hard. We’re living in uncertain times – very uncertain times.”

Finally, the Children’s Hospital at Montefiore admitted Israel – and the test she’d been trying to get for days confirmed he had the virus.

“I was literally in tears, like begging them not to discharge me because I knew he was not fine,” she recalled.

Israel was in shock, and by the time he got to the hospital, doctors were on the lookout for MIS-C, so they recognized his symptoms – which were distinct from most people with COVID-19.

Doctors gave Israel fluids and intravenous immunoglobulin, a substance obtained from donated human plasma, which is used to treat deficiencies in the immune system.

Immunoglobulin has been effective in children like Israel because MIS-C appears to be caused by an immune overreaction to the initial coronavirus infection, according to Dr. Choueiter.

“The immune system starts attacking the body itself, including the arteries of the heart,” she said.

In some MIS-C cases – though not Israel’s – the attack occurs in the coronary arteries, inflaming and dilating them. That also happens in a different syndrome affecting children, Kawasaki disease. About 5% of Kawasaki patients experience aneurysms – which can fatally rupture blood vessels – after the initial condition subsides.

Dr. Choueiter and colleagues want to make sure MIS-C patients don’t face similar risks. So far, they’re cautiously optimistic.

“We have not seen any new decrease in heart function or any new coronary artery dilations,” she said. “When we check their blood, their inflammatory markers are back to normal. For the parents, the child is back to baseline, and it’s as if this illness is a nightmare that’s long gone.”
 

For a Pennsylvania teen, the MIS-C diagnosis came much later

Not every child who develops MIS-C tests positive for the coronavirus, though many will test positive for antibodies to the coronavirus, indicating they had been infected previously. That was the case with Andrew Lis, a boy from Pennsylvania who was the first MIS-C patient seen at the Nemours/Alfred I. duPont Hospital for Children in Wilmington, Del.

Andrew had been a healthy 14-year-old boy before he got sick. He and his twin brother love sports and video games. He said the first symptom was a bad headache. He developed a fever the next day, then constipation and intense stomach pain.

“It was terrible,” Andrew said. “It was unbearable. I couldn’t really move a lot.”

His mother, Ingrid Lis, said they were thinking appendicitis, not coronavirus, at first. In fact, she hesitated to take Andrew to the hospital, for fear of exposing him to the virus. But after Andrew stopped eating because of his headache and stomach discomfort, “I knew I couldn’t keep him home anymore,” Mrs. Lis said.

Andrew was admitted to the hospital April 12, but that was before reports of the mysterious syndrome had started trickling out of Europe.

Over about 5 days in the pediatric ICU, Andrew’s condition deteriorated rapidly, as doctors struggled to figure out what was wrong. Puzzled, they tried treatments for scarlet fever, strep throat, and toxic shock syndrome. Andrew’s body broke out in rashes, then his heart began failing and he was put on a ventilator. Andrew’s father, Ed Lis, said doctors told the family to brace for the worst: “We’ve got a healthy kid who a few days ago was just having these sort of strange symptoms. And now they’re telling us that we could lose him.”

Though Andrew’s symptoms were atypical for Kawasaki disease, doctors decided to give him the standard treatment for that condition – administering intravenous immunoglobulin, the same treatment Israel Shippy received.

“Within the 24 hours of the infusion, he was a different person,” Mrs. Lis said. Andrew was removed from the ventilator, and his appetite eventually returned. “That’s when we knew that we had turned that corner.”

It wasn’t until after Andrew’s discharge that his doctors learned about MIS-C from colleagues in Europe. They recommended the whole family be tested for antibodies to the coronavirus. Although Andrew tested positive, the rest of the family – both parents, Andrew’s twin brother and two older siblings – all tested negative. Andrew’s mother is still not sure how he was exposed since the family had been observing a strict lockdown since mid-March. Both she and her husband were working remotely from home, and she says they all wore masks and were conscientious about hand-washing when they ventured out for groceries. She thinks Andrew must have been exposed at least a month before his illness began.

And she’s puzzled why the rest of her close-knit family wasn’t infected as well. “We are a Latino family,” Mrs. Lis said. “We are very used to being together, clustering in the same room.” Even when Andrew was sick, she says, all six of them huddled in his bedroom to comfort him.

Meanwhile, Andrew has made a quick recovery. Not long after his discharge in April, he turned 15 and resumed an exercise routine involving running, push-ups, and sit-ups. A few weeks later, an ECG showed Andrew’s heart was “perfect,” Mr. Lis said. Still, doctors have asked Andrew to follow up with a cardiologist every 3 months.
 

An eye on the long-term effects

The medical team at Montefiore is tracking the 40 children they have already treated and discharged. With kids showing few symptoms in the immediate aftermath, Dr. Choueiter hopes the long-term trajectory after MIS-C will be similar to what happens after Kawasaki disease.

“Usually children who have had coronary artery dilations [from Kawasaki disease] that have resolved within the first 6 weeks of the illness do well long-term,” said Dr. Choueiter, who runs the Kawasaki disease program at Montefiore.

The Montefiore team is asking patients affected by MIS-C to return for a checkup 1 week after discharge, then after 1 month, 3 months, 6 months, and a year. They will be evaluated by pediatric cardiologists, hematologists, rheumatologists and infectious disease specialists.

Montefiore and other children’s hospitals around the country are sharing information. Dr. Choueiter wants to establish an even longer-term monitoring program for MIS-C, comparable with registries that exist for other diseases.

Ms. Moholland is glad the hospital is being vigilant.

“The uncertainty of not knowing whether it could come back in his future is a little unsettling,” she said. “But I am hopeful.”

This story is part of a partnership that includes WNYC, NPR, and Kaiser Health News. A version of this article originally appeared on Kaiser Health News.

As COVID-19 cases mounted in Texas in late June, a local Houston news station shadowed Joseph Varon, MD, making rounds in the intensive care unit at United Memorial Medical Center in Houston. An unseen newscaster tells viewers that Varon credits his success against COVID-19 so far to an experimental and “controversial” drug protocol consisting of vitamins, steroids, and blood thinners.

“This is war. There’s no time to double-blind anything,” Varon tells the camera. “This is working. And if it’s working, I’m going to keep on doing it.”

Varon is one of 10 physicians behind the protocol known as MATH+, which in media interviews and congressional testimony they say has worked to treat COVID-19 patients and save lives in their intensive care units across the country. But response to the protocol among other critical care physicians is mixed, with several physicians, in interviews with Medscape Medical News, urging caution because the benefits and relative risks of the combined medications have not been tested in randomized control trials.

From the earliest days of the pandemic, there’s been tension between the need for rigorous scientific study to understand a novel disease, which takes time, and the need to treat seriously ill patients immediately. Some treatments, like hydroxychloroquine, were promoted without randomized clinical trial data and then later were shown to be ineffective or even potentially harmful when tested.

“This pandemic has shown us there’s lots of ideas out there and they need to be tested and a theoretical basis is insufficient,” says Daniel Kaul, MD, a professor of infectious disease at the University of Michigan in Ann Arbor. The ups and downs with hydroxychloroquine offer a sobering example, he says. “I would argue we have an ethical obligation to do randomized controlled trials to see if our treatments work.”
 

Creating MATH+

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

Over a few weeks, the protocol evolved as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action, swapping in methylprednisolone and adding the anticoagulant heparin.

When Marik and colleagues created the protocol in early March, many healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients. The MATH+ physicians decided they needed to spread a different message, and began publicizing the protocol with a website and a small communications team.

Marik says they tried to get their protocol in front of healthcare organizations – including the WHO, the Centers for Disease Control and Prevention, and the National Institutes of Health – but received no response. Marik went on Newt Gingrich’s podcast to discuss the protocol in the hopes it would make its way to the White House.

Senator Ron Johnson of Wisconsin saw the protocol and invited Pierre Kory, MD, MPA, who practices in Johnson’s home state, to testify remotely in front of the Senate Homeland Security Committee. Kory is a pulmonary critical care specialist about to start a new job at Aurora St. Luke’s Medical Center in Milwaukee.

In his testimony, Kory shared his positive experience using the protocol to treat patients and expressed his dismay that national healthcare organizations came out against the use of corticosteroids for COVID-19 from the early days of the pandemic based on what he called a “tragic error in analysis of medical data.” Although an analysis by national organizations suggested corticosteroids might be dangerous in COVID-19 patients, one of his colleagues came to the opposite conclusion, he said. But these organizations advised supportive care only, and against steroids. “We think that is a fatal and tragic flaw,” Kory said.

“The problem with the protocol early on was that it was heresy,” says Kory, referring to the protocol’s inclusion of corticosteroids before official treatment guidelines. During the height of the pandemic in New York this spring, Kory spent 5 weeks working in the ICU at Mount Sinai Beth Israel in Manhattan. Seeing patients flounder on supportive care, Kory says he used MATH+ successfully during his time in New York, using escalating and pulse doses of corticosteroids to stabilize rapidly deteriorating patients.

The website’s home page initially included an invitation for visitors to donate money to support “getting word of this effective treatment protocol out to physicians and hospitals around the world.” After Medscape Medical News brought up the donation prompt in questions, the physicians decided to remove all calls for donations from the website and social media, communications representative Betsy Ashton said. “Critics are misinterpreting this as some kind of fund-raising operation, when that could hardly be the case,” Ashton said in an email. “They are horrified that anyone would impugn their motives.”

Donations paid for the website designer, webmaster, and her work, Ashton said, and the physicians now have donors who will support publicizing the protocol without online calls for donations. “We have no commercial or vested interest,” Marik said. “I’m not going to make a single cent out of this and it’s obviously very time-consuming.”
 

The basis for the protocol

The protocol is based on common sense, an understanding of scientific literature, and an understanding of COVID-19, Marik says. The website includes links to past research trials and observational studies examining ascorbic acid and thiamine in critically ill patients and early looks at anticoagulants in COVID-19 patients.

They chose methylprednisolone as their corticosteroid based on the expertise of group member G. Umberto Meduri, MD, professor of medicine at the University of Tennessee Health Science Center in Memphis, Tennessee, who had found the steroid effective in treating acute respiratory distress syndrome. On the MATH+ website, the physicians link to multiple observational studies posted on preprint servers in April and May that suggest methylprednisolone helped COVID-19 patients.

“What’s happened with time is all the elements have been validated by scientific studies, which makes this so cool,” says Marik. The RECOVERY Trial results in particular validated the push to use corticosteroids in COVID-19 patients, he says. But that study used a different steroid, dexamethasone, in much smaller doses than what MATH+ recommends. Revised guidance from the Infectious Diseases Society of America recommends dexamethasone for severely ill patients, but says methylprednisolone and prednisone can be used as substitutes at equivalent doses.

Marik and Kory say that mortality rates for COVID-19 patients at their respective hospitals decreased after they began using the protocol. The physicians have been collecting observational data on their patients, but have not yet published any, and do not plan to conduct a randomized trial.

Several physicians who were not involved in the creation of the protocol say the evidence the physicians cite is not robust enough to warrant the promotion of MATH+ and call for randomized controlled trials. Coming up with a protocol is fine, says Kaul, but “you have to do the hard work of doing a randomized control trial to determine if those drugs given in those combinations work or not.”

“When I looked at it, I thought it was actually not very evidence based,” says Michelle Gong, MD, chief of the Division of Critical Care Medicine at Montefiore Health System in New York City. “It is not something I would recommend for my doctors to do outside of a clinical trial.”

The protocol authors push back against the necessity and feasibility of randomized control trials.

There is no time for a randomized control trial right now, says Jose Iglesias, DO, associate professor at Hackensack Meridian School of Medicine at Seton Hall and critical care specialist at Community Medical Center and Jersey Shore University Medical Center in New Jersey. “Time is limited. We’re busy bedside clinicians taking care of patients, and patients who are dying.”

Marik argues there is not equipoise: It wouldn’t be ethical to randomize patients in a placebo group when the physicians are confident the steroids will help. And the protocol is personalized for each patient, making the standardization required for a randomized control trial incredibly difficult, he says. He also cites “the people who are unwilling to accept our results and just think it’s too good to be true.”

Hugh Cassiere, MD, director of critical care medicine at Northwell Health’s North Shore University Hospital in Manhasset, New York, said he finds it “very disturbing that this is being propagated.” In the context of a pandemic in which physicians from other specialties are helping out colleagues in ICUs and might follow the protocol uncritically, he worries, “this could potentially lead to harm.”

“I understand the intention; everybody wants to do something, these patients are so sick and the crisis so sharp that we all want to do something to make patients better,” Gong said. “But as physicians taking care of patients we need to make sure we separate the noise from the evidence.”
 

Peer review

The physicians who reviewed MATH+ for Medscape Medical News differed on which parts of the protocol they support and which parts they would change.

Dexamethasone should be the corticosteroid of choice over methylprednisolone, says Cassiere, because it has now been proven effective in the randomized RECOVERY Trial, which also tested dosing and a timetable for treatment.

But Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, thinks methylprednisolone may be effective, and that even higher doses over longer periods of time may stave off recurring pneumonia, based on his experience using the steroid to treat COVID-19 patients in New York.

“What I really like about this protocol is, these guys are very smart, they recommend the need to treat multiple different things at the same time,” says Parnia. COVID-19 is a complex condition, he notes: If physicians are only focused on solving one problem, like hypoxia, patients could still be dying from blood clots.

Despite general concerns about the protocol, Cassiere says he was excited about the inclusion of heparin. Given the extreme levels of clotting seen in COVID-19 patients, he would have included specific D-dimer levels to guide treatment and explored antiplatelet therapies like aspirin. Gong, however, cautioned that she had seen her patients on anticoagulants develop gastrointestinal bleeding, and reiterated the need for clinical evidence. (At least one clinical trial is currently testing the risks and benefits of heparin as an antithrombotic therapy for COVID-19 patients.)

Perhaps the most divisive part of the protocol is the inclusion of ascorbic acid. “That’s the civil war,” says Kory. “It’s the most polarizing medicine.” The authors of the MATH+ protocol were close colleagues before COVID-19 in part because of a mutual research interest in ascorbic acid, he says. Other physicians, including Cassiere, are extremely skeptical that ascorbic acid has any effect, citing recently published studies in the Journal of the American Medical Association that found ascorbic acid ineffective for treating sepsis.

The MATH+ creators say they are working on a literature review of the research behind the protocol, and they plan to write up the observational impacts of the protocol. Marik says he’s not optimistic about getting the findings published in a high-impact journal given the observational nature of the research; the relatively small number of patients treated at hospitals using the protocol (140 patients at Marik’s hospital in Virginia and 180 at Varon’s in Houston, according to Marik); and the vast number of COVID-19 papers being submitted to scientific journals right now.

“This is not a remedy with expensive designer drugs,” Marik said. “No one has any interest in treating patients with cheap, safe, readily available drugs.”

“I hope they’re right if they’re saying this combination of medicines dramatically decreases mortality,” says Taison Bell, MD, director of the medical intensive care unit and assistant professor of medicine at UVA Health in Charlottesville, Virginia.

But physicians have hurt patients in the past with medications they hoped would work, he says. “We have to make sure we’re balancing the risk and the harm with that benefit, and the only way to protect patients from those biases is by doing a randomized controlled trial.”

This article first appeared on Medscape.com.

As COVID-19 cases mounted in Texas in late June, a local Houston news station shadowed Joseph Varon, MD, making rounds in the intensive care unit at United Memorial Medical Center in Houston. An unseen newscaster tells viewers that Varon credits his success against COVID-19 so far to an experimental and “controversial” drug protocol consisting of vitamins, steroids, and blood thinners.

“This is war. There’s no time to double-blind anything,” Varon tells the camera. “This is working. And if it’s working, I’m going to keep on doing it.”

Varon is one of 10 physicians behind the protocol known as MATH+, which in media interviews and congressional testimony they say has worked to treat COVID-19 patients and save lives in their intensive care units across the country. But response to the protocol among other critical care physicians is mixed, with several physicians, in interviews with Medscape Medical News, urging caution because the benefits and relative risks of the combined medications have not been tested in randomized control trials.

From the earliest days of the pandemic, there’s been tension between the need for rigorous scientific study to understand a novel disease, which takes time, and the need to treat seriously ill patients immediately. Some treatments, like hydroxychloroquine, were promoted without randomized clinical trial data and then later were shown to be ineffective or even potentially harmful when tested.

“This pandemic has shown us there’s lots of ideas out there and they need to be tested and a theoretical basis is insufficient,” says Daniel Kaul, MD, a professor of infectious disease at the University of Michigan in Ann Arbor. The ups and downs with hydroxychloroquine offer a sobering example, he says. “I would argue we have an ethical obligation to do randomized controlled trials to see if our treatments work.”
 

Creating MATH+

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

Over a few weeks, the protocol evolved as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action, swapping in methylprednisolone and adding the anticoagulant heparin.

When Marik and colleagues created the protocol in early March, many healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients. The MATH+ physicians decided they needed to spread a different message, and began publicizing the protocol with a website and a small communications team.

Marik says they tried to get their protocol in front of healthcare organizations – including the WHO, the Centers for Disease Control and Prevention, and the National Institutes of Health – but received no response. Marik went on Newt Gingrich’s podcast to discuss the protocol in the hopes it would make its way to the White House.

Senator Ron Johnson of Wisconsin saw the protocol and invited Pierre Kory, MD, MPA, who practices in Johnson’s home state, to testify remotely in front of the Senate Homeland Security Committee. Kory is a pulmonary critical care specialist about to start a new job at Aurora St. Luke’s Medical Center in Milwaukee.

In his testimony, Kory shared his positive experience using the protocol to treat patients and expressed his dismay that national healthcare organizations came out against the use of corticosteroids for COVID-19 from the early days of the pandemic based on what he called a “tragic error in analysis of medical data.” Although an analysis by national organizations suggested corticosteroids might be dangerous in COVID-19 patients, one of his colleagues came to the opposite conclusion, he said. But these organizations advised supportive care only, and against steroids. “We think that is a fatal and tragic flaw,” Kory said.

“The problem with the protocol early on was that it was heresy,” says Kory, referring to the protocol’s inclusion of corticosteroids before official treatment guidelines. During the height of the pandemic in New York this spring, Kory spent 5 weeks working in the ICU at Mount Sinai Beth Israel in Manhattan. Seeing patients flounder on supportive care, Kory says he used MATH+ successfully during his time in New York, using escalating and pulse doses of corticosteroids to stabilize rapidly deteriorating patients.

The website’s home page initially included an invitation for visitors to donate money to support “getting word of this effective treatment protocol out to physicians and hospitals around the world.” After Medscape Medical News brought up the donation prompt in questions, the physicians decided to remove all calls for donations from the website and social media, communications representative Betsy Ashton said. “Critics are misinterpreting this as some kind of fund-raising operation, when that could hardly be the case,” Ashton said in an email. “They are horrified that anyone would impugn their motives.”

Donations paid for the website designer, webmaster, and her work, Ashton said, and the physicians now have donors who will support publicizing the protocol without online calls for donations. “We have no commercial or vested interest,” Marik said. “I’m not going to make a single cent out of this and it’s obviously very time-consuming.”
 

The basis for the protocol

The protocol is based on common sense, an understanding of scientific literature, and an understanding of COVID-19, Marik says. The website includes links to past research trials and observational studies examining ascorbic acid and thiamine in critically ill patients and early looks at anticoagulants in COVID-19 patients.

They chose methylprednisolone as their corticosteroid based on the expertise of group member G. Umberto Meduri, MD, professor of medicine at the University of Tennessee Health Science Center in Memphis, Tennessee, who had found the steroid effective in treating acute respiratory distress syndrome. On the MATH+ website, the physicians link to multiple observational studies posted on preprint servers in April and May that suggest methylprednisolone helped COVID-19 patients.

“What’s happened with time is all the elements have been validated by scientific studies, which makes this so cool,” says Marik. The RECOVERY Trial results in particular validated the push to use corticosteroids in COVID-19 patients, he says. But that study used a different steroid, dexamethasone, in much smaller doses than what MATH+ recommends. Revised guidance from the Infectious Diseases Society of America recommends dexamethasone for severely ill patients, but says methylprednisolone and prednisone can be used as substitutes at equivalent doses.

Marik and Kory say that mortality rates for COVID-19 patients at their respective hospitals decreased after they began using the protocol. The physicians have been collecting observational data on their patients, but have not yet published any, and do not plan to conduct a randomized trial.

Several physicians who were not involved in the creation of the protocol say the evidence the physicians cite is not robust enough to warrant the promotion of MATH+ and call for randomized controlled trials. Coming up with a protocol is fine, says Kaul, but “you have to do the hard work of doing a randomized control trial to determine if those drugs given in those combinations work or not.”

“When I looked at it, I thought it was actually not very evidence based,” says Michelle Gong, MD, chief of the Division of Critical Care Medicine at Montefiore Health System in New York City. “It is not something I would recommend for my doctors to do outside of a clinical trial.”

The protocol authors push back against the necessity and feasibility of randomized control trials.

There is no time for a randomized control trial right now, says Jose Iglesias, DO, associate professor at Hackensack Meridian School of Medicine at Seton Hall and critical care specialist at Community Medical Center and Jersey Shore University Medical Center in New Jersey. “Time is limited. We’re busy bedside clinicians taking care of patients, and patients who are dying.”

Marik argues there is not equipoise: It wouldn’t be ethical to randomize patients in a placebo group when the physicians are confident the steroids will help. And the protocol is personalized for each patient, making the standardization required for a randomized control trial incredibly difficult, he says. He also cites “the people who are unwilling to accept our results and just think it’s too good to be true.”

Hugh Cassiere, MD, director of critical care medicine at Northwell Health’s North Shore University Hospital in Manhasset, New York, said he finds it “very disturbing that this is being propagated.” In the context of a pandemic in which physicians from other specialties are helping out colleagues in ICUs and might follow the protocol uncritically, he worries, “this could potentially lead to harm.”

“I understand the intention; everybody wants to do something, these patients are so sick and the crisis so sharp that we all want to do something to make patients better,” Gong said. “But as physicians taking care of patients we need to make sure we separate the noise from the evidence.”
 

Peer review

The physicians who reviewed MATH+ for Medscape Medical News differed on which parts of the protocol they support and which parts they would change.

Dexamethasone should be the corticosteroid of choice over methylprednisolone, says Cassiere, because it has now been proven effective in the randomized RECOVERY Trial, which also tested dosing and a timetable for treatment.

But Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, thinks methylprednisolone may be effective, and that even higher doses over longer periods of time may stave off recurring pneumonia, based on his experience using the steroid to treat COVID-19 patients in New York.

“What I really like about this protocol is, these guys are very smart, they recommend the need to treat multiple different things at the same time,” says Parnia. COVID-19 is a complex condition, he notes: If physicians are only focused on solving one problem, like hypoxia, patients could still be dying from blood clots.

Despite general concerns about the protocol, Cassiere says he was excited about the inclusion of heparin. Given the extreme levels of clotting seen in COVID-19 patients, he would have included specific D-dimer levels to guide treatment and explored antiplatelet therapies like aspirin. Gong, however, cautioned that she had seen her patients on anticoagulants develop gastrointestinal bleeding, and reiterated the need for clinical evidence. (At least one clinical trial is currently testing the risks and benefits of heparin as an antithrombotic therapy for COVID-19 patients.)

Perhaps the most divisive part of the protocol is the inclusion of ascorbic acid. “That’s the civil war,” says Kory. “It’s the most polarizing medicine.” The authors of the MATH+ protocol were close colleagues before COVID-19 in part because of a mutual research interest in ascorbic acid, he says. Other physicians, including Cassiere, are extremely skeptical that ascorbic acid has any effect, citing recently published studies in the Journal of the American Medical Association that found ascorbic acid ineffective for treating sepsis.

The MATH+ creators say they are working on a literature review of the research behind the protocol, and they plan to write up the observational impacts of the protocol. Marik says he’s not optimistic about getting the findings published in a high-impact journal given the observational nature of the research; the relatively small number of patients treated at hospitals using the protocol (140 patients at Marik’s hospital in Virginia and 180 at Varon’s in Houston, according to Marik); and the vast number of COVID-19 papers being submitted to scientific journals right now.

“This is not a remedy with expensive designer drugs,” Marik said. “No one has any interest in treating patients with cheap, safe, readily available drugs.”

“I hope they’re right if they’re saying this combination of medicines dramatically decreases mortality,” says Taison Bell, MD, director of the medical intensive care unit and assistant professor of medicine at UVA Health in Charlottesville, Virginia.

But physicians have hurt patients in the past with medications they hoped would work, he says. “We have to make sure we’re balancing the risk and the harm with that benefit, and the only way to protect patients from those biases is by doing a randomized controlled trial.”

This article first appeared on Medscape.com.

As COVID-19 cases mounted in Texas in late June, a local Houston news station shadowed Joseph Varon, MD, making rounds in the intensive care unit at United Memorial Medical Center in Houston. An unseen newscaster tells viewers that Varon credits his success against COVID-19 so far to an experimental and “controversial” drug protocol consisting of vitamins, steroids, and blood thinners.

“This is war. There’s no time to double-blind anything,” Varon tells the camera. “This is working. And if it’s working, I’m going to keep on doing it.”

Varon is one of 10 physicians behind the protocol known as MATH+, which in media interviews and congressional testimony they say has worked to treat COVID-19 patients and save lives in their intensive care units across the country. But response to the protocol among other critical care physicians is mixed, with several physicians, in interviews with Medscape Medical News, urging caution because the benefits and relative risks of the combined medications have not been tested in randomized control trials.

From the earliest days of the pandemic, there’s been tension between the need for rigorous scientific study to understand a novel disease, which takes time, and the need to treat seriously ill patients immediately. Some treatments, like hydroxychloroquine, were promoted without randomized clinical trial data and then later were shown to be ineffective or even potentially harmful when tested.

“This pandemic has shown us there’s lots of ideas out there and they need to be tested and a theoretical basis is insufficient,” says Daniel Kaul, MD, a professor of infectious disease at the University of Michigan in Ann Arbor. The ups and downs with hydroxychloroquine offer a sobering example, he says. “I would argue we have an ethical obligation to do randomized controlled trials to see if our treatments work.”
 

Creating MATH+

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

Over a few weeks, the protocol evolved as Marik, chief of the division of pulmonary and critical care medicine at Eastern Virginia Medical School in Norfolk, emailed with a small group of colleagues about treatments and their observations of SARS-CoV-2 in action, swapping in methylprednisolone and adding the anticoagulant heparin.

When Marik and colleagues created the protocol in early March, many healthcare organizations like the World Health Organization (WHO) were advising against steroids for COVID-19 patients. The MATH+ physicians decided they needed to spread a different message, and began publicizing the protocol with a website and a small communications team.

Marik says they tried to get their protocol in front of healthcare organizations – including the WHO, the Centers for Disease Control and Prevention, and the National Institutes of Health – but received no response. Marik went on Newt Gingrich’s podcast to discuss the protocol in the hopes it would make its way to the White House.

Senator Ron Johnson of Wisconsin saw the protocol and invited Pierre Kory, MD, MPA, who practices in Johnson’s home state, to testify remotely in front of the Senate Homeland Security Committee. Kory is a pulmonary critical care specialist about to start a new job at Aurora St. Luke’s Medical Center in Milwaukee.

In his testimony, Kory shared his positive experience using the protocol to treat patients and expressed his dismay that national healthcare organizations came out against the use of corticosteroids for COVID-19 from the early days of the pandemic based on what he called a “tragic error in analysis of medical data.” Although an analysis by national organizations suggested corticosteroids might be dangerous in COVID-19 patients, one of his colleagues came to the opposite conclusion, he said. But these organizations advised supportive care only, and against steroids. “We think that is a fatal and tragic flaw,” Kory said.

“The problem with the protocol early on was that it was heresy,” says Kory, referring to the protocol’s inclusion of corticosteroids before official treatment guidelines. During the height of the pandemic in New York this spring, Kory spent 5 weeks working in the ICU at Mount Sinai Beth Israel in Manhattan. Seeing patients flounder on supportive care, Kory says he used MATH+ successfully during his time in New York, using escalating and pulse doses of corticosteroids to stabilize rapidly deteriorating patients.

The website’s home page initially included an invitation for visitors to donate money to support “getting word of this effective treatment protocol out to physicians and hospitals around the world.” After Medscape Medical News brought up the donation prompt in questions, the physicians decided to remove all calls for donations from the website and social media, communications representative Betsy Ashton said. “Critics are misinterpreting this as some kind of fund-raising operation, when that could hardly be the case,” Ashton said in an email. “They are horrified that anyone would impugn their motives.”

Donations paid for the website designer, webmaster, and her work, Ashton said, and the physicians now have donors who will support publicizing the protocol without online calls for donations. “We have no commercial or vested interest,” Marik said. “I’m not going to make a single cent out of this and it’s obviously very time-consuming.”
 

The basis for the protocol

The protocol is based on common sense, an understanding of scientific literature, and an understanding of COVID-19, Marik says. The website includes links to past research trials and observational studies examining ascorbic acid and thiamine in critically ill patients and early looks at anticoagulants in COVID-19 patients.

They chose methylprednisolone as their corticosteroid based on the expertise of group member G. Umberto Meduri, MD, professor of medicine at the University of Tennessee Health Science Center in Memphis, Tennessee, who had found the steroid effective in treating acute respiratory distress syndrome. On the MATH+ website, the physicians link to multiple observational studies posted on preprint servers in April and May that suggest methylprednisolone helped COVID-19 patients.

“What’s happened with time is all the elements have been validated by scientific studies, which makes this so cool,” says Marik. The RECOVERY Trial results in particular validated the push to use corticosteroids in COVID-19 patients, he says. But that study used a different steroid, dexamethasone, in much smaller doses than what MATH+ recommends. Revised guidance from the Infectious Diseases Society of America recommends dexamethasone for severely ill patients, but says methylprednisolone and prednisone can be used as substitutes at equivalent doses.

Marik and Kory say that mortality rates for COVID-19 patients at their respective hospitals decreased after they began using the protocol. The physicians have been collecting observational data on their patients, but have not yet published any, and do not plan to conduct a randomized trial.

Several physicians who were not involved in the creation of the protocol say the evidence the physicians cite is not robust enough to warrant the promotion of MATH+ and call for randomized controlled trials. Coming up with a protocol is fine, says Kaul, but “you have to do the hard work of doing a randomized control trial to determine if those drugs given in those combinations work or not.”

“When I looked at it, I thought it was actually not very evidence based,” says Michelle Gong, MD, chief of the Division of Critical Care Medicine at Montefiore Health System in New York City. “It is not something I would recommend for my doctors to do outside of a clinical trial.”

The protocol authors push back against the necessity and feasibility of randomized control trials.

There is no time for a randomized control trial right now, says Jose Iglesias, DO, associate professor at Hackensack Meridian School of Medicine at Seton Hall and critical care specialist at Community Medical Center and Jersey Shore University Medical Center in New Jersey. “Time is limited. We’re busy bedside clinicians taking care of patients, and patients who are dying.”

Marik argues there is not equipoise: It wouldn’t be ethical to randomize patients in a placebo group when the physicians are confident the steroids will help. And the protocol is personalized for each patient, making the standardization required for a randomized control trial incredibly difficult, he says. He also cites “the people who are unwilling to accept our results and just think it’s too good to be true.”

Hugh Cassiere, MD, director of critical care medicine at Northwell Health’s North Shore University Hospital in Manhasset, New York, said he finds it “very disturbing that this is being propagated.” In the context of a pandemic in which physicians from other specialties are helping out colleagues in ICUs and might follow the protocol uncritically, he worries, “this could potentially lead to harm.”

“I understand the intention; everybody wants to do something, these patients are so sick and the crisis so sharp that we all want to do something to make patients better,” Gong said. “But as physicians taking care of patients we need to make sure we separate the noise from the evidence.”
 

Peer review

The physicians who reviewed MATH+ for Medscape Medical News differed on which parts of the protocol they support and which parts they would change.

Dexamethasone should be the corticosteroid of choice over methylprednisolone, says Cassiere, because it has now been proven effective in the randomized RECOVERY Trial, which also tested dosing and a timetable for treatment.

But Sam Parnia, MD, PhD, associate professor of medicine and director of critical care and resuscitation research at NYU Langone, thinks methylprednisolone may be effective, and that even higher doses over longer periods of time may stave off recurring pneumonia, based on his experience using the steroid to treat COVID-19 patients in New York.

“What I really like about this protocol is, these guys are very smart, they recommend the need to treat multiple different things at the same time,” says Parnia. COVID-19 is a complex condition, he notes: If physicians are only focused on solving one problem, like hypoxia, patients could still be dying from blood clots.

Despite general concerns about the protocol, Cassiere says he was excited about the inclusion of heparin. Given the extreme levels of clotting seen in COVID-19 patients, he would have included specific D-dimer levels to guide treatment and explored antiplatelet therapies like aspirin. Gong, however, cautioned that she had seen her patients on anticoagulants develop gastrointestinal bleeding, and reiterated the need for clinical evidence. (At least one clinical trial is currently testing the risks and benefits of heparin as an antithrombotic therapy for COVID-19 patients.)

Perhaps the most divisive part of the protocol is the inclusion of ascorbic acid. “That’s the civil war,” says Kory. “It’s the most polarizing medicine.” The authors of the MATH+ protocol were close colleagues before COVID-19 in part because of a mutual research interest in ascorbic acid, he says. Other physicians, including Cassiere, are extremely skeptical that ascorbic acid has any effect, citing recently published studies in the Journal of the American Medical Association that found ascorbic acid ineffective for treating sepsis.

The MATH+ creators say they are working on a literature review of the research behind the protocol, and they plan to write up the observational impacts of the protocol. Marik says he’s not optimistic about getting the findings published in a high-impact journal given the observational nature of the research; the relatively small number of patients treated at hospitals using the protocol (140 patients at Marik’s hospital in Virginia and 180 at Varon’s in Houston, according to Marik); and the vast number of COVID-19 papers being submitted to scientific journals right now.

“This is not a remedy with expensive designer drugs,” Marik said. “No one has any interest in treating patients with cheap, safe, readily available drugs.”

“I hope they’re right if they’re saying this combination of medicines dramatically decreases mortality,” says Taison Bell, MD, director of the medical intensive care unit and assistant professor of medicine at UVA Health in Charlottesville, Virginia.

But physicians have hurt patients in the past with medications they hoped would work, he says. “We have to make sure we’re balancing the risk and the harm with that benefit, and the only way to protect patients from those biases is by doing a randomized controlled trial.”

This article first appeared on Medscape.com.

The conventional treatment mainstays for pemphigus are problematic during the COVID-19 pandemic, and a shift in disease management strategy is in order, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.

First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.

Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.

“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).

The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.

“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.

“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).

Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).

Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.

She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

The conventional treatment mainstays for pemphigus are problematic during the COVID-19 pandemic, and a shift in disease management strategy is in order, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.

First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.

Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.

“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).

The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.

“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.

“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).

Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).

Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.

She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

The conventional treatment mainstays for pemphigus are problematic during the COVID-19 pandemic, and a shift in disease management strategy is in order, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Together with physicians from the Mayo Clinic, Alexandria (Egypt) University, and Tehran (Iran) University, she recently published updated expert guidance for treatment of this severe, potentially fatal mucocutaneous autoimmune blistering disease, in a letter to the editor in the Journal of the American Academy of Dermatology. She presented some of the key recommendations at AAD 2020.

First off, rituximab (Rituxan), the only Food and Drug Administration–approved medication for moderate to severe pemphigus vulgaris and a biologic considered first-line therapy prepandemic, is ill-advised during the COVID-19 era. Its mechanism of benefit is through B-cell depletion. This is an irreversible effect, and reconstitution of B-cell immunity takes 6-12 months. The absence of this immunologic protection for such a long time poses potentially serious problems for pemphigus patients who become infected with SARS-CoV-2.

Also, the opportunity to administer intravenous infusions of the biologic becomes unpredictable during pandemic surges, when limitations on nonemergent medical care may be necessary, noted Dr. Murrell, professor of dermatology at the University of New South Wales and head of dermatology at St. George University Hospital, both in Sydney.

“We have taken the approach of postponing rituximab infusions temporarily, with the aim of delaying peak patient immunosuppression during peak COVID-19 incidence to reduce the risk of adverse outcomes,” Dr. Murrell and coauthors wrote in the letter (J Am Acad Dermatol. 2020 Jun;82[6]:e235-6).

The other traditional go-to therapy for pemphigus is corticosteroids. They’re effective, fast acting, and relatively inexpensive. But their nonselective immunosuppressive action boosts infection risk in general, and more specifically it increases the risk of developing severe forms of COVID-19 should a patient become infected with SARS-CoV-2.

“A basic therapeutic principle with particular importance during the pandemic is that glucocorticoids and steroid-sparing immunosuppressive agents, such as azathioprine and mycophenolate mofetil, should be tapered to the lowest effective dose. In active COVID-19 infection, immunosuppressive steroid-sparing medications should be discontinued when possible, although glucocorticoid cessation often cannot be considered due to risk for adrenal insufficiency,” the authors continued.

“Effective as adjuvant treatment in both pemphigus and COVID-19,intravenous immunoglobulin supports immunity and therefore may be useful in this setting,” they wrote. It’s not immunosuppressive, and, they noted, there’s good-quality evidence from a Japanese randomized, double-blind, controlled trial that a 5-day course of intravenous immunoglobulin is effective therapy for pemphigus (J Am Acad Dermatol. 2009 Apr;60[4]:595-603).

Moreover, intravenous immunoglobulin is also reportedly effective in severe COVID-19 (Open Forum Infect Dis. 2020 Mar 21. doi: 10.1093/ofid/ofaa102.).

Another option is to consider enrolling a patient with moderate or severe pemphigus vulgaris or foliaceus in the ongoing pivotal phase 3, international, double-blind, placebo-controlled PEGASUS trial of rilzabrutinib, a promising oral reversible Bruton tyrosine kinase inhibitor. The medication has a short half-life and a self-limited immunomodulatory effect. Moreover, the trial is set up for remote patient visits on an outpatient basis via teledermatology, so the 65-week study can continue despite the pandemic. Both newly diagnosed and relapsing patients are eligible for the trial, headed by Dr. Murrell. At AAD 2020 she reported encouraging results from a phase 2b trial of rilzabrutinib.

She is a consultant to Principia Biopharma, sponsor of the PEGASUS trial, and has received institutional research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

People who use proton pump inhibitors (PPIs) may be more likely to get COVID-19, researchers say.

In light of this finding, physicians should consider which patients truly need these powerful acid-lowering drugs, said Brennan Spiegel, MD, MSHS, AGAF, professor of medicine and public health at Cedars Sinai Medical Center in Los Angeles, Calif.

“All it means is that we’re going to have a conversation with our patients,” he said in an interview. “We don’t normally have that conversation because we don’t live in an environment with a high risk of enteric infection. But now we’re in a pandemic.”

The study by Dr. Spiegel and his colleagues was published online on July 7 in the American Journal of Gastroenterology.

Use of PPIs has skyrocketed over the past 2 decades. For ambulatory care visits, their use increased from 1.6% in 1998 to 7.6% in 2015. The increase raised questions about overprescription.

Although studies have not borne out many of the other concerns raised about adverse reactions, they have shown that the drugs increase the risk for enteric infections, including infections by SARS-CoV-1, a virus that is related to the COVID-19 virus, SARS-CoV-2, Dr. Spiegel said.

SARS-CoV-2 uses the angiotensin-converting enzyme–2 receptor to invade enterocytes. Dr. Spiegel theorized that an increase in stomach pH above 3 as a result of use of PPIs might allow the virus to enter the GI tract more easily, leading to enteritis, colitis, and systemic spread to other organs, including the lungs. “There is a reason we have acid in our stomachs,” Dr. Spiegel said.

To see how PPI use relates to COVID-19 infections, Dr. Spiegel and his colleagues surveyed online a nationally representative sample of Americans between May 3 and June 24, 2020, as part of a larger survey on gastroenterologic health.

Participants answered questions about gastrointestinal symptoms, current use of PPIs, and COVID-19 test results. They also answered questions about histamine-2 receptor agonists (H₂RAs), also known as H₂ blockers, which are used to treat some of the same conditions as PPIs but that do not reduce stomach acid as much.

The surveying firm, Cint, contacted 264,058 people. Of the 86,602 eligible participants who completed the survey, 53,130 said they had experienced abdominal discomfort, acid reflux, heartburn, or regurgitation. These survey participants were subsequently asked about PPI and H₂RA use.

Of these, 6.4% reported testing positive for SARS-CoV-2. The researchers adjusted for age, sex, race/ethnicity, education, marital status, household income, body mass index, smoking, alcohol consumption, U.S. region, insurance status, and the presence of irritable bowel syndrome, celiac disease, gastroesophageal reflux disease, liver cirrhosis, Crohn’s disease, ulcerative colitis, diabetes, and HIV/AIDS.

After adjusting for these factors, the researchers found that those who took PPIs up to once a day were twice as likely to have had a positive COVID-19 test result than those who did not take the drugs (odds ratio, 2.15; 95% confidence interval, 1.90-2.44).

Those who took PPIs twice a day were almost four times as likely to have tested positive for the disease (OR, 3.67; 95% CI, 2.93-4.60).

By contrast, those taking H₂RA drugs once daily were 15% less likely to report a positive COVID-19 test result (OR, 0.85; 95% CI, 0.74-0.99). Research is currently underway to determine whether H₂RAs might protect against the disease for reasons unrelated to pH balance.

Dr. Spiegel cautioned that the current data show only an association between PPI use and COVID-19 positivity; it cannot prove cause and effect.

Nevertheless, Dr. Spiegel said the findings should encourage physicians to prescribe PPIs only when clearly indicated. “If somebody is not yet on a PPI and you’re considering whether to start them on a PPI, it’s a good idea to consider H₂ blockers,” he said.

People who need a daily dose of a PPI to control a severe condition can safely continue doing so, but such patients should take care to follow standard public health recommendations for avoiding exposure to the virus. These recommendations include wearing a mask, maintaining social distance, and washing hands frequently.

“People who are older, comorbid, or smokers – if they get infected, it could be severe,” he said. “[For] someone like that, it’s reasonable to ask, do we really need to be on twice-daily PPIs? There is good evidence that they are no better off than if they are taking once-daily doses.”

Brian Lacy, MD, PhD, a professor of medicine at the Mayo Clinic in Jacksonville, Fla., agreed that the study should prompt physicians to take a second look at their patients’ PPI prescriptions. “My view is that PPIs are frequently overused, and maybe this is one more piece of data that, if someone is on PPIs, maybe they don’t need to be on this medication.”

On the other hand, the drugs are important for treating conditions such as erosive esophagitis and healing ulcers, he said. The overall risk of contracting COVID-19 is low, so even this finding of a 3.7-fold increased risk should not lead patients or providers to stop taking or prescribing PPIs.

The study also lends support to the idea that the gastrointestinal tract could be involved in SARS-CoV-2 transmission, and it supports warnings about aerosols emitted from flushing toilets and through exhalation, Dr. Spiegel said. There is less evidence of the virus being transmitted through food. “It may not be fecal-oral; it may be fecal-respiratory,” he said.

The study was part of a larger project funded by Ironwood Pharmaceuticals. Dr. Spiegel reported relationships with Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Shire Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals. Dr. Lacy has disclosed no relevant financial relationships.

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

People who use proton pump inhibitors (PPIs) may be more likely to get COVID-19, researchers say.

In light of this finding, physicians should consider which patients truly need these powerful acid-lowering drugs, said Brennan Spiegel, MD, MSHS, AGAF, professor of medicine and public health at Cedars Sinai Medical Center in Los Angeles, Calif.

“All it means is that we’re going to have a conversation with our patients,” he said in an interview. “We don’t normally have that conversation because we don’t live in an environment with a high risk of enteric infection. But now we’re in a pandemic.”

The study by Dr. Spiegel and his colleagues was published online on July 7 in the American Journal of Gastroenterology.

Use of PPIs has skyrocketed over the past 2 decades. For ambulatory care visits, their use increased from 1.6% in 1998 to 7.6% in 2015. The increase raised questions about overprescription.

Although studies have not borne out many of the other concerns raised about adverse reactions, they have shown that the drugs increase the risk for enteric infections, including infections by SARS-CoV-1, a virus that is related to the COVID-19 virus, SARS-CoV-2, Dr. Spiegel said.

SARS-CoV-2 uses the angiotensin-converting enzyme–2 receptor to invade enterocytes. Dr. Spiegel theorized that an increase in stomach pH above 3 as a result of use of PPIs might allow the virus to enter the GI tract more easily, leading to enteritis, colitis, and systemic spread to other organs, including the lungs. “There is a reason we have acid in our stomachs,” Dr. Spiegel said.

To see how PPI use relates to COVID-19 infections, Dr. Spiegel and his colleagues surveyed online a nationally representative sample of Americans between May 3 and June 24, 2020, as part of a larger survey on gastroenterologic health.

Participants answered questions about gastrointestinal symptoms, current use of PPIs, and COVID-19 test results. They also answered questions about histamine-2 receptor agonists (H₂RAs), also known as H₂ blockers, which are used to treat some of the same conditions as PPIs but that do not reduce stomach acid as much.

The surveying firm, Cint, contacted 264,058 people. Of the 86,602 eligible participants who completed the survey, 53,130 said they had experienced abdominal discomfort, acid reflux, heartburn, or regurgitation. These survey participants were subsequently asked about PPI and H₂RA use.

Of these, 6.4% reported testing positive for SARS-CoV-2. The researchers adjusted for age, sex, race/ethnicity, education, marital status, household income, body mass index, smoking, alcohol consumption, U.S. region, insurance status, and the presence of irritable bowel syndrome, celiac disease, gastroesophageal reflux disease, liver cirrhosis, Crohn’s disease, ulcerative colitis, diabetes, and HIV/AIDS.

After adjusting for these factors, the researchers found that those who took PPIs up to once a day were twice as likely to have had a positive COVID-19 test result than those who did not take the drugs (odds ratio, 2.15; 95% confidence interval, 1.90-2.44).

Those who took PPIs twice a day were almost four times as likely to have tested positive for the disease (OR, 3.67; 95% CI, 2.93-4.60).

By contrast, those taking H₂RA drugs once daily were 15% less likely to report a positive COVID-19 test result (OR, 0.85; 95% CI, 0.74-0.99). Research is currently underway to determine whether H₂RAs might protect against the disease for reasons unrelated to pH balance.

Dr. Spiegel cautioned that the current data show only an association between PPI use and COVID-19 positivity; it cannot prove cause and effect.

Nevertheless, Dr. Spiegel said the findings should encourage physicians to prescribe PPIs only when clearly indicated. “If somebody is not yet on a PPI and you’re considering whether to start them on a PPI, it’s a good idea to consider H₂ blockers,” he said.

People who need a daily dose of a PPI to control a severe condition can safely continue doing so, but such patients should take care to follow standard public health recommendations for avoiding exposure to the virus. These recommendations include wearing a mask, maintaining social distance, and washing hands frequently.

“People who are older, comorbid, or smokers – if they get infected, it could be severe,” he said. “[For] someone like that, it’s reasonable to ask, do we really need to be on twice-daily PPIs? There is good evidence that they are no better off than if they are taking once-daily doses.”

Brian Lacy, MD, PhD, a professor of medicine at the Mayo Clinic in Jacksonville, Fla., agreed that the study should prompt physicians to take a second look at their patients’ PPI prescriptions. “My view is that PPIs are frequently overused, and maybe this is one more piece of data that, if someone is on PPIs, maybe they don’t need to be on this medication.”

On the other hand, the drugs are important for treating conditions such as erosive esophagitis and healing ulcers, he said. The overall risk of contracting COVID-19 is low, so even this finding of a 3.7-fold increased risk should not lead patients or providers to stop taking or prescribing PPIs.

The study also lends support to the idea that the gastrointestinal tract could be involved in SARS-CoV-2 transmission, and it supports warnings about aerosols emitted from flushing toilets and through exhalation, Dr. Spiegel said. There is less evidence of the virus being transmitted through food. “It may not be fecal-oral; it may be fecal-respiratory,” he said.

The study was part of a larger project funded by Ironwood Pharmaceuticals. Dr. Spiegel reported relationships with Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Shire Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals. Dr. Lacy has disclosed no relevant financial relationships.

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

People who use proton pump inhibitors (PPIs) may be more likely to get COVID-19, researchers say.

In light of this finding, physicians should consider which patients truly need these powerful acid-lowering drugs, said Brennan Spiegel, MD, MSHS, AGAF, professor of medicine and public health at Cedars Sinai Medical Center in Los Angeles, Calif.

“All it means is that we’re going to have a conversation with our patients,” he said in an interview. “We don’t normally have that conversation because we don’t live in an environment with a high risk of enteric infection. But now we’re in a pandemic.”

The study by Dr. Spiegel and his colleagues was published online on July 7 in the American Journal of Gastroenterology.

Use of PPIs has skyrocketed over the past 2 decades. For ambulatory care visits, their use increased from 1.6% in 1998 to 7.6% in 2015. The increase raised questions about overprescription.

Although studies have not borne out many of the other concerns raised about adverse reactions, they have shown that the drugs increase the risk for enteric infections, including infections by SARS-CoV-1, a virus that is related to the COVID-19 virus, SARS-CoV-2, Dr. Spiegel said.

SARS-CoV-2 uses the angiotensin-converting enzyme–2 receptor to invade enterocytes. Dr. Spiegel theorized that an increase in stomach pH above 3 as a result of use of PPIs might allow the virus to enter the GI tract more easily, leading to enteritis, colitis, and systemic spread to other organs, including the lungs. “There is a reason we have acid in our stomachs,” Dr. Spiegel said.

To see how PPI use relates to COVID-19 infections, Dr. Spiegel and his colleagues surveyed online a nationally representative sample of Americans between May 3 and June 24, 2020, as part of a larger survey on gastroenterologic health.

Participants answered questions about gastrointestinal symptoms, current use of PPIs, and COVID-19 test results. They also answered questions about histamine-2 receptor agonists (H₂RAs), also known as H₂ blockers, which are used to treat some of the same conditions as PPIs but that do not reduce stomach acid as much.

The surveying firm, Cint, contacted 264,058 people. Of the 86,602 eligible participants who completed the survey, 53,130 said they had experienced abdominal discomfort, acid reflux, heartburn, or regurgitation. These survey participants were subsequently asked about PPI and H₂RA use.

Of these, 6.4% reported testing positive for SARS-CoV-2. The researchers adjusted for age, sex, race/ethnicity, education, marital status, household income, body mass index, smoking, alcohol consumption, U.S. region, insurance status, and the presence of irritable bowel syndrome, celiac disease, gastroesophageal reflux disease, liver cirrhosis, Crohn’s disease, ulcerative colitis, diabetes, and HIV/AIDS.

After adjusting for these factors, the researchers found that those who took PPIs up to once a day were twice as likely to have had a positive COVID-19 test result than those who did not take the drugs (odds ratio, 2.15; 95% confidence interval, 1.90-2.44).

Those who took PPIs twice a day were almost four times as likely to have tested positive for the disease (OR, 3.67; 95% CI, 2.93-4.60).

By contrast, those taking H₂RA drugs once daily were 15% less likely to report a positive COVID-19 test result (OR, 0.85; 95% CI, 0.74-0.99). Research is currently underway to determine whether H₂RAs might protect against the disease for reasons unrelated to pH balance.

Dr. Spiegel cautioned that the current data show only an association between PPI use and COVID-19 positivity; it cannot prove cause and effect.

Nevertheless, Dr. Spiegel said the findings should encourage physicians to prescribe PPIs only when clearly indicated. “If somebody is not yet on a PPI and you’re considering whether to start them on a PPI, it’s a good idea to consider H₂ blockers,” he said.

People who need a daily dose of a PPI to control a severe condition can safely continue doing so, but such patients should take care to follow standard public health recommendations for avoiding exposure to the virus. These recommendations include wearing a mask, maintaining social distance, and washing hands frequently.

“People who are older, comorbid, or smokers – if they get infected, it could be severe,” he said. “[For] someone like that, it’s reasonable to ask, do we really need to be on twice-daily PPIs? There is good evidence that they are no better off than if they are taking once-daily doses.”

Brian Lacy, MD, PhD, a professor of medicine at the Mayo Clinic in Jacksonville, Fla., agreed that the study should prompt physicians to take a second look at their patients’ PPI prescriptions. “My view is that PPIs are frequently overused, and maybe this is one more piece of data that, if someone is on PPIs, maybe they don’t need to be on this medication.”

On the other hand, the drugs are important for treating conditions such as erosive esophagitis and healing ulcers, he said. The overall risk of contracting COVID-19 is low, so even this finding of a 3.7-fold increased risk should not lead patients or providers to stop taking or prescribing PPIs.

The study also lends support to the idea that the gastrointestinal tract could be involved in SARS-CoV-2 transmission, and it supports warnings about aerosols emitted from flushing toilets and through exhalation, Dr. Spiegel said. There is less evidence of the virus being transmitted through food. “It may not be fecal-oral; it may be fecal-respiratory,” he said.

The study was part of a larger project funded by Ironwood Pharmaceuticals. Dr. Spiegel reported relationships with Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Shire Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals. Dr. Lacy has disclosed no relevant financial relationships.

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

Microcephaly may be the hallmark of congenital Zika virus syndrome, but neurologic abnormalities also are common in normocephalic children exposed to the virus in utero, according to data from a large pediatric referral center in Rio de Janeiro.

CDC/ Cynthia Goldsmith

The retrospective analysis demonstrated that there is a “spectrum of clinical manifestations” in children with congenital Zika virus syndrome, including those who “had initially been perceived as developing normally based on [head circumference],” Jessica S. Cranston, a medical student at the University of California, Los Angeles, and associates wrote in JAMA Network Open.

Previous studies have described the poor clinical outcomes in Zika virus–exposed infants with microcephaly, but the current analysis evaluated head circumference (HC) as a continuous variable and stratified outcomes according to the presence or absence of microcephaly, they explained.

In the cohort of 215 children referred to Instituto Fernandes Figueira who had laboratory-confirmed antenatal Zika virus exposure, 53 had microcephaly (cephalic perimeter z score of less than –2 standard deviations) and 162 were normocephalic, the investigators said.

The children were evaluated monthly for the first 6 months of life and then every 3 months. Neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition, between 6 months and 3 years of age showed that all of those with microcephaly had abnormal neuromotor findings. All but two of the children with microcephaly had abnormal neuroimaging results, and 38 (72%) had failure to thrive, they reported.

Among the children with normocephaly at birth, 68% had abnormal neurologic findings, including hyperreflexia (27%), abnormal tone (39%), and other congenital neuromotor signs (42%). Results of neuroimaging results, primarily in the form of transfontanelle ultrasonography, were abnormal in 29% of children with normocephaly.

“Infants with a larger birth HC, within the normocephalic range (±2 SDs), had higher overall neurodevelopmental scores on the Bayley-III assessment,” Sarah B. Mulkey, MD, PhD, said in an invited commentary, “whereas infants with a smaller birth HC within the normocephalic range had lower scores in the domains of cognitive and language functions.”

If HC measurements could be combined with early neurologic data such as the results of neuroimaging or a neurological exam, she suggested, it might provide “a practical tool to help determine risk for adverse clinical outcomes in a [Zika virus–]exposed infant at birth that can be widely used in a variety of follow-up settings.”

In nutritional assessments performed for 143 children with normocephaly, 51% had failure to thrive “because of neurologic repercussions leading to poor feeding,” Ms. Cranston and associates wrote, adding that 15 of the 73 (21%) infants with normocephaly and failure to thrive developed secondary microcephaly.

Altogether, 17 of the 162 (10.5%) children with normocephaly developed microcephaly during the follow-up, with the reverse – microcephaly resolving in infants who were microcephalic at birth – occurring in 4 of the 53 (7.5%) affected infants, indicating that “head circumference was not static,” they said.

“The trajectory of head growth is critical,” said Dr. Mulkey of the Prenatal Pediatrics Institute at Children’s National Hospital in Washington. “The neurologic outcome of a child who develops postnatal microcephaly would be very concerning compared with an infant who is born with normocephaly and maintains a steady HC percentile over time.”

HC is just one piece of the puzzle, however, since children with Zika virus syndrome may exhibit “a variety of manifestations and outcomes.” This lack of certainty suggests that “careful monitoring and evaluation of children with suspected exposure is essential for ensuring early detection of possible disabilities and referral to interventional services,” the investigators wrote.

The findings of this study “are both highly statistically significant and clinically significant,”said Kevin T. Powell, MD, PhD, a pediatric hospitalist and clinical ethics consultant living in St. Louis who was not associated with the study.

“While outcomes at birth are dichotomized into those with and without microcephaly, the developmental outcomes measured at 3 years of age are on a spectrum. ... Those with microcephaly tend to be more severely affected, but many infants with small but normal-sized heads are also mild to moderately impacted. The flip side is that 64% of infected babies ended up with average or better development” based on Bayley-III evaluations, said Dr. Powell, who is a member of the Pediatric News editorial advisory board.

The study was funded by grants from the National Institute of Allergy and Infectious Diseases, the National Eye Institute, and the Thrasher Foundation and by awards from Brazil’s National Council of Scientific and Technological Development; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Individual investigators received fees and grants from these and other organizations.

Dr. Mulkey received a contract from the Centers for Disease Control and Prevention for technical expertise for Zika virus studies and received support for Zika studies from the Thrasher Research Fund. Dr. Powell had no relevant financial disclosures.

rfranki@mdedge.com

SOURCE: Cranston JS et al. JAMA Netw Open. 2020 July 7;3(7):e209303.

Microcephaly may be the hallmark of congenital Zika virus syndrome, but neurologic abnormalities also are common in normocephalic children exposed to the virus in utero, according to data from a large pediatric referral center in Rio de Janeiro.

CDC/ Cynthia Goldsmith

The retrospective analysis demonstrated that there is a “spectrum of clinical manifestations” in children with congenital Zika virus syndrome, including those who “had initially been perceived as developing normally based on [head circumference],” Jessica S. Cranston, a medical student at the University of California, Los Angeles, and associates wrote in JAMA Network Open.

Previous studies have described the poor clinical outcomes in Zika virus–exposed infants with microcephaly, but the current analysis evaluated head circumference (HC) as a continuous variable and stratified outcomes according to the presence or absence of microcephaly, they explained.

In the cohort of 215 children referred to Instituto Fernandes Figueira who had laboratory-confirmed antenatal Zika virus exposure, 53 had microcephaly (cephalic perimeter z score of less than –2 standard deviations) and 162 were normocephalic, the investigators said.

The children were evaluated monthly for the first 6 months of life and then every 3 months. Neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition, between 6 months and 3 years of age showed that all of those with microcephaly had abnormal neuromotor findings. All but two of the children with microcephaly had abnormal neuroimaging results, and 38 (72%) had failure to thrive, they reported.

Among the children with normocephaly at birth, 68% had abnormal neurologic findings, including hyperreflexia (27%), abnormal tone (39%), and other congenital neuromotor signs (42%). Results of neuroimaging results, primarily in the form of transfontanelle ultrasonography, were abnormal in 29% of children with normocephaly.

“Infants with a larger birth HC, within the normocephalic range (±2 SDs), had higher overall neurodevelopmental scores on the Bayley-III assessment,” Sarah B. Mulkey, MD, PhD, said in an invited commentary, “whereas infants with a smaller birth HC within the normocephalic range had lower scores in the domains of cognitive and language functions.”

If HC measurements could be combined with early neurologic data such as the results of neuroimaging or a neurological exam, she suggested, it might provide “a practical tool to help determine risk for adverse clinical outcomes in a [Zika virus–]exposed infant at birth that can be widely used in a variety of follow-up settings.”

In nutritional assessments performed for 143 children with normocephaly, 51% had failure to thrive “because of neurologic repercussions leading to poor feeding,” Ms. Cranston and associates wrote, adding that 15 of the 73 (21%) infants with normocephaly and failure to thrive developed secondary microcephaly.

Altogether, 17 of the 162 (10.5%) children with normocephaly developed microcephaly during the follow-up, with the reverse – microcephaly resolving in infants who were microcephalic at birth – occurring in 4 of the 53 (7.5%) affected infants, indicating that “head circumference was not static,” they said.

“The trajectory of head growth is critical,” said Dr. Mulkey of the Prenatal Pediatrics Institute at Children’s National Hospital in Washington. “The neurologic outcome of a child who develops postnatal microcephaly would be very concerning compared with an infant who is born with normocephaly and maintains a steady HC percentile over time.”

HC is just one piece of the puzzle, however, since children with Zika virus syndrome may exhibit “a variety of manifestations and outcomes.” This lack of certainty suggests that “careful monitoring and evaluation of children with suspected exposure is essential for ensuring early detection of possible disabilities and referral to interventional services,” the investigators wrote.

The findings of this study “are both highly statistically significant and clinically significant,”said Kevin T. Powell, MD, PhD, a pediatric hospitalist and clinical ethics consultant living in St. Louis who was not associated with the study.

“While outcomes at birth are dichotomized into those with and without microcephaly, the developmental outcomes measured at 3 years of age are on a spectrum. ... Those with microcephaly tend to be more severely affected, but many infants with small but normal-sized heads are also mild to moderately impacted. The flip side is that 64% of infected babies ended up with average or better development” based on Bayley-III evaluations, said Dr. Powell, who is a member of the Pediatric News editorial advisory board.

The study was funded by grants from the National Institute of Allergy and Infectious Diseases, the National Eye Institute, and the Thrasher Foundation and by awards from Brazil’s National Council of Scientific and Technological Development; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Individual investigators received fees and grants from these and other organizations.

Dr. Mulkey received a contract from the Centers for Disease Control and Prevention for technical expertise for Zika virus studies and received support for Zika studies from the Thrasher Research Fund. Dr. Powell had no relevant financial disclosures.

rfranki@mdedge.com

SOURCE: Cranston JS et al. JAMA Netw Open. 2020 July 7;3(7):e209303.

Microcephaly may be the hallmark of congenital Zika virus syndrome, but neurologic abnormalities also are common in normocephalic children exposed to the virus in utero, according to data from a large pediatric referral center in Rio de Janeiro.

CDC/ Cynthia Goldsmith

The retrospective analysis demonstrated that there is a “spectrum of clinical manifestations” in children with congenital Zika virus syndrome, including those who “had initially been perceived as developing normally based on [head circumference],” Jessica S. Cranston, a medical student at the University of California, Los Angeles, and associates wrote in JAMA Network Open.

Previous studies have described the poor clinical outcomes in Zika virus–exposed infants with microcephaly, but the current analysis evaluated head circumference (HC) as a continuous variable and stratified outcomes according to the presence or absence of microcephaly, they explained.

In the cohort of 215 children referred to Instituto Fernandes Figueira who had laboratory-confirmed antenatal Zika virus exposure, 53 had microcephaly (cephalic perimeter z score of less than –2 standard deviations) and 162 were normocephalic, the investigators said.

The children were evaluated monthly for the first 6 months of life and then every 3 months. Neurodevelopmental evaluation with the Bayley Scales of Infant and Toddler Development, Third Edition, between 6 months and 3 years of age showed that all of those with microcephaly had abnormal neuromotor findings. All but two of the children with microcephaly had abnormal neuroimaging results, and 38 (72%) had failure to thrive, they reported.

Among the children with normocephaly at birth, 68% had abnormal neurologic findings, including hyperreflexia (27%), abnormal tone (39%), and other congenital neuromotor signs (42%). Results of neuroimaging results, primarily in the form of transfontanelle ultrasonography, were abnormal in 29% of children with normocephaly.

“Infants with a larger birth HC, within the normocephalic range (±2 SDs), had higher overall neurodevelopmental scores on the Bayley-III assessment,” Sarah B. Mulkey, MD, PhD, said in an invited commentary, “whereas infants with a smaller birth HC within the normocephalic range had lower scores in the domains of cognitive and language functions.”

If HC measurements could be combined with early neurologic data such as the results of neuroimaging or a neurological exam, she suggested, it might provide “a practical tool to help determine risk for adverse clinical outcomes in a [Zika virus–]exposed infant at birth that can be widely used in a variety of follow-up settings.”

In nutritional assessments performed for 143 children with normocephaly, 51% had failure to thrive “because of neurologic repercussions leading to poor feeding,” Ms. Cranston and associates wrote, adding that 15 of the 73 (21%) infants with normocephaly and failure to thrive developed secondary microcephaly.

Altogether, 17 of the 162 (10.5%) children with normocephaly developed microcephaly during the follow-up, with the reverse – microcephaly resolving in infants who were microcephalic at birth – occurring in 4 of the 53 (7.5%) affected infants, indicating that “head circumference was not static,” they said.

“The trajectory of head growth is critical,” said Dr. Mulkey of the Prenatal Pediatrics Institute at Children’s National Hospital in Washington. “The neurologic outcome of a child who develops postnatal microcephaly would be very concerning compared with an infant who is born with normocephaly and maintains a steady HC percentile over time.”

HC is just one piece of the puzzle, however, since children with Zika virus syndrome may exhibit “a variety of manifestations and outcomes.” This lack of certainty suggests that “careful monitoring and evaluation of children with suspected exposure is essential for ensuring early detection of possible disabilities and referral to interventional services,” the investigators wrote.

The findings of this study “are both highly statistically significant and clinically significant,”said Kevin T. Powell, MD, PhD, a pediatric hospitalist and clinical ethics consultant living in St. Louis who was not associated with the study.

“While outcomes at birth are dichotomized into those with and without microcephaly, the developmental outcomes measured at 3 years of age are on a spectrum. ... Those with microcephaly tend to be more severely affected, but many infants with small but normal-sized heads are also mild to moderately impacted. The flip side is that 64% of infected babies ended up with average or better development” based on Bayley-III evaluations, said Dr. Powell, who is a member of the Pediatric News editorial advisory board.

The study was funded by grants from the National Institute of Allergy and Infectious Diseases, the National Eye Institute, and the Thrasher Foundation and by awards from Brazil’s National Council of Scientific and Technological Development; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro. Individual investigators received fees and grants from these and other organizations.

Dr. Mulkey received a contract from the Centers for Disease Control and Prevention for technical expertise for Zika virus studies and received support for Zika studies from the Thrasher Research Fund. Dr. Powell had no relevant financial disclosures.

rfranki@mdedge.com

SOURCE: Cranston JS et al. JAMA Netw Open. 2020 July 7;3(7):e209303.

Two experts in geriatric diabetes are offering some contemporary practical recommendations for diabetes management in older adults during the COVID-19 pandemic.  

The viewpoint, entitled, “Caring for Older Adults With Diabetes During the COVID-19 Pandemic,” was published online in JAMA Internal Medicine by Medha N. Munshi, MD, director of the geriatrics program at the Joslin Diabetes Center, Boston, and Sarah L. Sy, MD, a geriatrician in the same program.

Adults aged 70 years and older with comorbidities such as diabetes are among those at highest risk for adverse outcomes and mortality due to COVID-19.

At the same time, those who don’t have the illness face major challenges in avoiding it, including disruptions in normal activities and barriers to receiving health care.

Although telemedicine has become much more widely adopted in diabetes management since the pandemic began, older adults may not be as tech savvy, may not have computer or Internet access, and/or may have cognitive dysfunction that precludes its use.

“These unprecedented times pose a great challenge to this heterogeneous population with varying levels of complexity, frailty, and multimorbidity,” Munshi and Sy point out, noting that “clinicians can lessen the load by guiding, reassuring, and supporting them through this pandemic time.”

Because the pandemic could last for several months longer, the authors offer the following advice for clinicians who care for older adults with diabetes.

• Accessibility to health care: When possible, use telemedicine, diabetes care apps, or platforms to obtain data from glucose meters, continuous glucose monitors, and/or pumps. When use of technology isn’t possible, schedule telephone appointments and have the patient or caregiver read the glucose values.
• Multicomplexity and geriatric syndromes: Identify high-risk patients, such as those with or recurrent , and prioritize patient goals. If appropriate, simplify the diabetes treatment plan and reinforce with repeated education and instructions. Glucose goals may need to be liberalized. Advise patients to stay hydrated to minimize the risk of dehydration and falls. Take steps to avoid hypoglycemia, reduce polypharmacy, and consolidate medication doses.
• Burden of diabetes self-care: Bloodwork for can be delayed by a few months. Patients with  can decrease the frequency of blood glucose checks if their glucose levels are generally within acceptable range. Encourage patients to eat healthily with regular meals rather than optimizing the diet for glucose levels, and adjust medications for any changes in diet. Advise safe options for physical activity such as walking inside the home or walking in place for 10 minutes, three times per day, and incorporating strength training, such as with resistance bands. Online exercise programs are another option.
• Psychological stress: Check in with patients and encourage them to stay as connected as possible using technology (phone, video chat, text message), letters, or cards with family, friends, and/or religious communities. Screen for , using either the Geriatric Depression Scale or Patient Health Questionnaire-2, and refer to mental health colleagues if appropriate. Speak or email with caregivers to assess the patient’s mental health state and offer local support resources, if needed.
• Medication and equipment issues: Refill 90-day prescriptions and equipment, and request mail or home (contactless) delivery. Patients should also have backups in case of equipment failures, such as syringes and long-acting insulin in case of pump failure, and test strips/meter for continuous glucose monitor problems.

Munshi and Sy conclude: “Many of the recommendations presented in this article are practical and will continue to be relevant after COVID-19. When this is all over, patients will remember how we made them feel, and how we kept them safe and healthy at home.”

Munshi is a consultant for Sanofi and Lilly. Sy has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Two experts in geriatric diabetes are offering some contemporary practical recommendations for diabetes management in older adults during the COVID-19 pandemic.  

The viewpoint, entitled, “Caring for Older Adults With Diabetes During the COVID-19 Pandemic,” was published online in JAMA Internal Medicine by Medha N. Munshi, MD, director of the geriatrics program at the Joslin Diabetes Center, Boston, and Sarah L. Sy, MD, a geriatrician in the same program.

Adults aged 70 years and older with comorbidities such as diabetes are among those at highest risk for adverse outcomes and mortality due to COVID-19.

At the same time, those who don’t have the illness face major challenges in avoiding it, including disruptions in normal activities and barriers to receiving health care.

Although telemedicine has become much more widely adopted in diabetes management since the pandemic began, older adults may not be as tech savvy, may not have computer or Internet access, and/or may have cognitive dysfunction that precludes its use.

“These unprecedented times pose a great challenge to this heterogeneous population with varying levels of complexity, frailty, and multimorbidity,” Munshi and Sy point out, noting that “clinicians can lessen the load by guiding, reassuring, and supporting them through this pandemic time.”

Because the pandemic could last for several months longer, the authors offer the following advice for clinicians who care for older adults with diabetes.

• Accessibility to health care: When possible, use telemedicine, diabetes care apps, or platforms to obtain data from glucose meters, continuous glucose monitors, and/or pumps. When use of technology isn’t possible, schedule telephone appointments and have the patient or caregiver read the glucose values.
• Multicomplexity and geriatric syndromes: Identify high-risk patients, such as those with or recurrent , and prioritize patient goals. If appropriate, simplify the diabetes treatment plan and reinforce with repeated education and instructions. Glucose goals may need to be liberalized. Advise patients to stay hydrated to minimize the risk of dehydration and falls. Take steps to avoid hypoglycemia, reduce polypharmacy, and consolidate medication doses.
• Burden of diabetes self-care: Bloodwork for can be delayed by a few months. Patients with  can decrease the frequency of blood glucose checks if their glucose levels are generally within acceptable range. Encourage patients to eat healthily with regular meals rather than optimizing the diet for glucose levels, and adjust medications for any changes in diet. Advise safe options for physical activity such as walking inside the home or walking in place for 10 minutes, three times per day, and incorporating strength training, such as with resistance bands. Online exercise programs are another option.
• Psychological stress: Check in with patients and encourage them to stay as connected as possible using technology (phone, video chat, text message), letters, or cards with family, friends, and/or religious communities. Screen for , using either the Geriatric Depression Scale or Patient Health Questionnaire-2, and refer to mental health colleagues if appropriate. Speak or email with caregivers to assess the patient’s mental health state and offer local support resources, if needed.
• Medication and equipment issues: Refill 90-day prescriptions and equipment, and request mail or home (contactless) delivery. Patients should also have backups in case of equipment failures, such as syringes and long-acting insulin in case of pump failure, and test strips/meter for continuous glucose monitor problems.

Munshi and Sy conclude: “Many of the recommendations presented in this article are practical and will continue to be relevant after COVID-19. When this is all over, patients will remember how we made them feel, and how we kept them safe and healthy at home.”

Munshi is a consultant for Sanofi and Lilly. Sy has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Two experts in geriatric diabetes are offering some contemporary practical recommendations for diabetes management in older adults during the COVID-19 pandemic.  

The viewpoint, entitled, “Caring for Older Adults With Diabetes During the COVID-19 Pandemic,” was published online in JAMA Internal Medicine by Medha N. Munshi, MD, director of the geriatrics program at the Joslin Diabetes Center, Boston, and Sarah L. Sy, MD, a geriatrician in the same program.

Adults aged 70 years and older with comorbidities such as diabetes are among those at highest risk for adverse outcomes and mortality due to COVID-19.

At the same time, those who don’t have the illness face major challenges in avoiding it, including disruptions in normal activities and barriers to receiving health care.

Although telemedicine has become much more widely adopted in diabetes management since the pandemic began, older adults may not be as tech savvy, may not have computer or Internet access, and/or may have cognitive dysfunction that precludes its use.

“These unprecedented times pose a great challenge to this heterogeneous population with varying levels of complexity, frailty, and multimorbidity,” Munshi and Sy point out, noting that “clinicians can lessen the load by guiding, reassuring, and supporting them through this pandemic time.”

Because the pandemic could last for several months longer, the authors offer the following advice for clinicians who care for older adults with diabetes.

• Accessibility to health care: When possible, use telemedicine, diabetes care apps, or platforms to obtain data from glucose meters, continuous glucose monitors, and/or pumps. When use of technology isn’t possible, schedule telephone appointments and have the patient or caregiver read the glucose values.
• Multicomplexity and geriatric syndromes: Identify high-risk patients, such as those with or recurrent , and prioritize patient goals. If appropriate, simplify the diabetes treatment plan and reinforce with repeated education and instructions. Glucose goals may need to be liberalized. Advise patients to stay hydrated to minimize the risk of dehydration and falls. Take steps to avoid hypoglycemia, reduce polypharmacy, and consolidate medication doses.
• Burden of diabetes self-care: Bloodwork for can be delayed by a few months. Patients with  can decrease the frequency of blood glucose checks if their glucose levels are generally within acceptable range. Encourage patients to eat healthily with regular meals rather than optimizing the diet for glucose levels, and adjust medications for any changes in diet. Advise safe options for physical activity such as walking inside the home or walking in place for 10 minutes, three times per day, and incorporating strength training, such as with resistance bands. Online exercise programs are another option.
• Psychological stress: Check in with patients and encourage them to stay as connected as possible using technology (phone, video chat, text message), letters, or cards with family, friends, and/or religious communities. Screen for , using either the Geriatric Depression Scale or Patient Health Questionnaire-2, and refer to mental health colleagues if appropriate. Speak or email with caregivers to assess the patient’s mental health state and offer local support resources, if needed.
• Medication and equipment issues: Refill 90-day prescriptions and equipment, and request mail or home (contactless) delivery. Patients should also have backups in case of equipment failures, such as syringes and long-acting insulin in case of pump failure, and test strips/meter for continuous glucose monitor problems.

Munshi and Sy conclude: “Many of the recommendations presented in this article are practical and will continue to be relevant after COVID-19. When this is all over, patients will remember how we made them feel, and how we kept them safe and healthy at home.”

Munshi is a consultant for Sanofi and Lilly. Sy has reported no relevant financial relationships.

This article first appeared on Medscape.com.

Clinicians and researchers have focused on the acute phase of COVID-19 infection, but it’s increasingly clear that some recovered patients discharged from acute care need continued monitoring for long-lasting effects, a study has found.

In a research letter published online July 9 in JAMA, Angelo Carfi, MD, and colleagues from the Gemelli Against COVID-19 Post–Acute Care Study Group in Rome, report that 87.4% of 143 previously hospitalized patients had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge.

Postdischarge assessments of patients who met criteria for SARS-CoV-2 negativity, including a reverse transcriptase–polymerase chain reaction test, were conducted from April 21 to May 29. Among the results:

• Only 12.6% of the 143 patients were completely free of any COVID-19 symptom
• About 32% of patients had one or two symptoms and 55% had three or more
• None had fever or other signs and symptoms of acute illness
• About 53% of patients still had fatigue, 43.4% had dyspnea, 27.3% had joint pain, and had 21.7% chest pain
• About 44% reported worsened quality of life on the EuroQol visual analog scale.

The sample cohort, assessed in a COVID-19 patient service recently established at the Fondazione Policlinico Universitario Agostino Gemelli had a mean age of 56.5 years and 37% were women. The mean length of hospital stay was 13.5 days. During their hospitalization, 72.7% of patients showed evidence of interstitial pneumonia. Noninvasive ventilation was given to 14.7% of patients and 4.9% received invasive ventilation.

The reality of lingering symptoms has led Dr. Carfi’s clinic to schedule a final “wrap-up visit” for patients after full assessment. “On that occasion the doctor prescribes anything necessary to correct the anomalies found during the full evaluation,” Dr. Carfi, a geriatrician at the Gemelli clinic, said in an interview. “These usually include vitamin supplementation and, in selected cases, a new drug prescription such as a blood thinner if necessary.”

Patients can also enroll in a training program in which breathing status is monitored.

In North America, doctors are also addressing the reality that the road to recovery can be a long and upward one, with persistent symptoms worse than those seen with acute influenza infection. “We see patients who were first diagnosed in March or April and still have symptoms in July,” said Zijian Chen, MD, an endocrinologist and medical director of Mount Sinai Health System’s Center for Post-COVID Care in New York.

“Persistent symptoms are much worse for COVID patients than flu patients. Even flu patients who spent time in the intensive care unit recover fully, and we can optimize their breathing before discharge,” Dr. Chen said in an interview.

As in the Italian study, Dr. Chen sees patients with COVID-19 who have ongoing shortness of breath, some requiring supplemental oxygen, or with persistent chest pain on exertion, blood clotting problems, poor concentration, gastrointestinal distress, and reduced muscle strength and impaired grasping power. He doesn’t rule out permanent lung damage in some. “Even asymptomatic individuals already show lung scarring on imaging,” he said.

The Mount Sinai program provides specialized interdisciplinary management that may include CT scans, endoscopy, and drugs such as respiratory medications or anticoagulants. It also offers training to combat the fatigue and deconditioning caused by the infection, symptoms that are not medically treatable but impact quality of life.

“These patients do get better, but I expect they may still have symptoms requiring monitoring after a year,” Dr. Chen said.

The study received no specific funding. Dr. Carfi and colleagues have disclosed no relevant financial relationships. Dr. Chen has disclosed no relevant financial relationships.

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

Clinicians and researchers have focused on the acute phase of COVID-19 infection, but it’s increasingly clear that some recovered patients discharged from acute care need continued monitoring for long-lasting effects, a study has found.

In a research letter published online July 9 in JAMA, Angelo Carfi, MD, and colleagues from the Gemelli Against COVID-19 Post–Acute Care Study Group in Rome, report that 87.4% of 143 previously hospitalized patients had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge.

Postdischarge assessments of patients who met criteria for SARS-CoV-2 negativity, including a reverse transcriptase–polymerase chain reaction test, were conducted from April 21 to May 29. Among the results:

• Only 12.6% of the 143 patients were completely free of any COVID-19 symptom
• About 32% of patients had one or two symptoms and 55% had three or more
• None had fever or other signs and symptoms of acute illness
• About 53% of patients still had fatigue, 43.4% had dyspnea, 27.3% had joint pain, and had 21.7% chest pain
• About 44% reported worsened quality of life on the EuroQol visual analog scale.

The sample cohort, assessed in a COVID-19 patient service recently established at the Fondazione Policlinico Universitario Agostino Gemelli had a mean age of 56.5 years and 37% were women. The mean length of hospital stay was 13.5 days. During their hospitalization, 72.7% of patients showed evidence of interstitial pneumonia. Noninvasive ventilation was given to 14.7% of patients and 4.9% received invasive ventilation.

The reality of lingering symptoms has led Dr. Carfi’s clinic to schedule a final “wrap-up visit” for patients after full assessment. “On that occasion the doctor prescribes anything necessary to correct the anomalies found during the full evaluation,” Dr. Carfi, a geriatrician at the Gemelli clinic, said in an interview. “These usually include vitamin supplementation and, in selected cases, a new drug prescription such as a blood thinner if necessary.”

Patients can also enroll in a training program in which breathing status is monitored.

In North America, doctors are also addressing the reality that the road to recovery can be a long and upward one, with persistent symptoms worse than those seen with acute influenza infection. “We see patients who were first diagnosed in March or April and still have symptoms in July,” said Zijian Chen, MD, an endocrinologist and medical director of Mount Sinai Health System’s Center for Post-COVID Care in New York.

“Persistent symptoms are much worse for COVID patients than flu patients. Even flu patients who spent time in the intensive care unit recover fully, and we can optimize their breathing before discharge,” Dr. Chen said in an interview.

As in the Italian study, Dr. Chen sees patients with COVID-19 who have ongoing shortness of breath, some requiring supplemental oxygen, or with persistent chest pain on exertion, blood clotting problems, poor concentration, gastrointestinal distress, and reduced muscle strength and impaired grasping power. He doesn’t rule out permanent lung damage in some. “Even asymptomatic individuals already show lung scarring on imaging,” he said.

The Mount Sinai program provides specialized interdisciplinary management that may include CT scans, endoscopy, and drugs such as respiratory medications or anticoagulants. It also offers training to combat the fatigue and deconditioning caused by the infection, symptoms that are not medically treatable but impact quality of life.

“These patients do get better, but I expect they may still have symptoms requiring monitoring after a year,” Dr. Chen said.

The study received no specific funding. Dr. Carfi and colleagues have disclosed no relevant financial relationships. Dr. Chen has disclosed no relevant financial relationships.

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

Clinicians and researchers have focused on the acute phase of COVID-19 infection, but it’s increasingly clear that some recovered patients discharged from acute care need continued monitoring for long-lasting effects, a study has found.

In a research letter published online July 9 in JAMA, Angelo Carfi, MD, and colleagues from the Gemelli Against COVID-19 Post–Acute Care Study Group in Rome, report that 87.4% of 143 previously hospitalized patients had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge.

Postdischarge assessments of patients who met criteria for SARS-CoV-2 negativity, including a reverse transcriptase–polymerase chain reaction test, were conducted from April 21 to May 29. Among the results:

• Only 12.6% of the 143 patients were completely free of any COVID-19 symptom
• About 32% of patients had one or two symptoms and 55% had three or more
• None had fever or other signs and symptoms of acute illness
• About 53% of patients still had fatigue, 43.4% had dyspnea, 27.3% had joint pain, and had 21.7% chest pain
• About 44% reported worsened quality of life on the EuroQol visual analog scale.

The sample cohort, assessed in a COVID-19 patient service recently established at the Fondazione Policlinico Universitario Agostino Gemelli had a mean age of 56.5 years and 37% were women. The mean length of hospital stay was 13.5 days. During their hospitalization, 72.7% of patients showed evidence of interstitial pneumonia. Noninvasive ventilation was given to 14.7% of patients and 4.9% received invasive ventilation.

The reality of lingering symptoms has led Dr. Carfi’s clinic to schedule a final “wrap-up visit” for patients after full assessment. “On that occasion the doctor prescribes anything necessary to correct the anomalies found during the full evaluation,” Dr. Carfi, a geriatrician at the Gemelli clinic, said in an interview. “These usually include vitamin supplementation and, in selected cases, a new drug prescription such as a blood thinner if necessary.”

Patients can also enroll in a training program in which breathing status is monitored.

In North America, doctors are also addressing the reality that the road to recovery can be a long and upward one, with persistent symptoms worse than those seen with acute influenza infection. “We see patients who were first diagnosed in March or April and still have symptoms in July,” said Zijian Chen, MD, an endocrinologist and medical director of Mount Sinai Health System’s Center for Post-COVID Care in New York.

“Persistent symptoms are much worse for COVID patients than flu patients. Even flu patients who spent time in the intensive care unit recover fully, and we can optimize their breathing before discharge,” Dr. Chen said in an interview.

As in the Italian study, Dr. Chen sees patients with COVID-19 who have ongoing shortness of breath, some requiring supplemental oxygen, or with persistent chest pain on exertion, blood clotting problems, poor concentration, gastrointestinal distress, and reduced muscle strength and impaired grasping power. He doesn’t rule out permanent lung damage in some. “Even asymptomatic individuals already show lung scarring on imaging,” he said.

The Mount Sinai program provides specialized interdisciplinary management that may include CT scans, endoscopy, and drugs such as respiratory medications or anticoagulants. It also offers training to combat the fatigue and deconditioning caused by the infection, symptoms that are not medically treatable but impact quality of life.

“These patients do get better, but I expect they may still have symptoms requiring monitoring after a year,” Dr. Chen said.

The study received no specific funding. Dr. Carfi and colleagues have disclosed no relevant financial relationships. Dr. Chen has disclosed no relevant financial relationships.

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