Clinician Reviews

When people wear face masks to reduce the spread of the coronavirus, the number of new COVID-19 infections drops by 53%, according to a new study published Nov. 18 in the British Medical Journal.

Social distancing and handwashing were also effective at lowering the number of cases, but wearing masks was the most effective tool against the coronavirus.

“Personal and social measures, including handwashing, mask wearing, and physical distancing are effective at reducing the incidence of COVID-19,” the study authors wrote.

The research team, which included public health and infectious disease specialists in Australia, China, and the U.K., evaluated 72 studies of COVID-19 precautions during the pandemic. They later looked at eight studies that focused on handwashing, mask wearing, and physical distancing.

Among six studies that looked at mask wearing, the researchers found a 53% reduction in COVID-19 cases. In the broader analysis with additional studies, wearing a mask reduced coronavirus transmission, cases, and deaths.

In one study across 200 countries, mandatory mask wearing resulted in nearly 46% fewer negative outcomes from COVID-19. In another study in the U.S., coronavirus transmission was reduced 29% in states where masks were mandatory.

But the research team couldn’t analyze the impact of the type of face mask used, the frequency of mask wearing, or the overall compliance with wearing face masks.

Among five studies that looked at physical distancing, the researchers found a 25% reduction in the rate of COVID-19. A study in the U.S. showed a 12% decrease in coronavirus transmission, while another study in Iran reported a reduction in COVID-19 mortality.

Handwashing interventions also suggested a substantial reduction of COVID-19 cases up to 53%, the researchers wrote. But in adjusted models, the results weren’t statistically significant due to the small number of studies included.

Other studies found significant decreases related to other public health measures, such as quarantines, broad lockdowns, border closures, school closures, business closures, and travel restrictions. Still, the research team couldn’t analyze the overall effectiveness of these measures due to the different ways the studies were conducted.

The study lines up with other research conducted so far during the pandemic, the research team wrote, which indicates that wearing masks and physical distancing can reduce transmission, cases, and deaths.

That said, more studies are needed, particularly now that vaccinations are available and contagious coronavirus variants have become prevalent.

“Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage has been achieved,” they wrote.

“It is likely that further control of the COVID-19 pandemic depends not only on high vaccination coverage and its effectiveness but also on ongoing adherence to effective and sustainable public health measures,” they concluded.

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

When people wear face masks to reduce the spread of the coronavirus, the number of new COVID-19 infections drops by 53%, according to a new study published Nov. 18 in the British Medical Journal.

Social distancing and handwashing were also effective at lowering the number of cases, but wearing masks was the most effective tool against the coronavirus.

“Personal and social measures, including handwashing, mask wearing, and physical distancing are effective at reducing the incidence of COVID-19,” the study authors wrote.

The research team, which included public health and infectious disease specialists in Australia, China, and the U.K., evaluated 72 studies of COVID-19 precautions during the pandemic. They later looked at eight studies that focused on handwashing, mask wearing, and physical distancing.

Among six studies that looked at mask wearing, the researchers found a 53% reduction in COVID-19 cases. In the broader analysis with additional studies, wearing a mask reduced coronavirus transmission, cases, and deaths.

In one study across 200 countries, mandatory mask wearing resulted in nearly 46% fewer negative outcomes from COVID-19. In another study in the U.S., coronavirus transmission was reduced 29% in states where masks were mandatory.

But the research team couldn’t analyze the impact of the type of face mask used, the frequency of mask wearing, or the overall compliance with wearing face masks.

Among five studies that looked at physical distancing, the researchers found a 25% reduction in the rate of COVID-19. A study in the U.S. showed a 12% decrease in coronavirus transmission, while another study in Iran reported a reduction in COVID-19 mortality.

Handwashing interventions also suggested a substantial reduction of COVID-19 cases up to 53%, the researchers wrote. But in adjusted models, the results weren’t statistically significant due to the small number of studies included.

Other studies found significant decreases related to other public health measures, such as quarantines, broad lockdowns, border closures, school closures, business closures, and travel restrictions. Still, the research team couldn’t analyze the overall effectiveness of these measures due to the different ways the studies were conducted.

The study lines up with other research conducted so far during the pandemic, the research team wrote, which indicates that wearing masks and physical distancing can reduce transmission, cases, and deaths.

That said, more studies are needed, particularly now that vaccinations are available and contagious coronavirus variants have become prevalent.

“Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage has been achieved,” they wrote.

“It is likely that further control of the COVID-19 pandemic depends not only on high vaccination coverage and its effectiveness but also on ongoing adherence to effective and sustainable public health measures,” they concluded.

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

When people wear face masks to reduce the spread of the coronavirus, the number of new COVID-19 infections drops by 53%, according to a new study published Nov. 18 in the British Medical Journal.

Social distancing and handwashing were also effective at lowering the number of cases, but wearing masks was the most effective tool against the coronavirus.

“Personal and social measures, including handwashing, mask wearing, and physical distancing are effective at reducing the incidence of COVID-19,” the study authors wrote.

The research team, which included public health and infectious disease specialists in Australia, China, and the U.K., evaluated 72 studies of COVID-19 precautions during the pandemic. They later looked at eight studies that focused on handwashing, mask wearing, and physical distancing.

Among six studies that looked at mask wearing, the researchers found a 53% reduction in COVID-19 cases. In the broader analysis with additional studies, wearing a mask reduced coronavirus transmission, cases, and deaths.

In one study across 200 countries, mandatory mask wearing resulted in nearly 46% fewer negative outcomes from COVID-19. In another study in the U.S., coronavirus transmission was reduced 29% in states where masks were mandatory.

But the research team couldn’t analyze the impact of the type of face mask used, the frequency of mask wearing, or the overall compliance with wearing face masks.

Among five studies that looked at physical distancing, the researchers found a 25% reduction in the rate of COVID-19. A study in the U.S. showed a 12% decrease in coronavirus transmission, while another study in Iran reported a reduction in COVID-19 mortality.

Handwashing interventions also suggested a substantial reduction of COVID-19 cases up to 53%, the researchers wrote. But in adjusted models, the results weren’t statistically significant due to the small number of studies included.

Other studies found significant decreases related to other public health measures, such as quarantines, broad lockdowns, border closures, school closures, business closures, and travel restrictions. Still, the research team couldn’t analyze the overall effectiveness of these measures due to the different ways the studies were conducted.

The study lines up with other research conducted so far during the pandemic, the research team wrote, which indicates that wearing masks and physical distancing can reduce transmission, cases, and deaths.

That said, more studies are needed, particularly now that vaccinations are available and contagious coronavirus variants have become prevalent.

“Further research is needed to assess the effectiveness of public health measures after adequate vaccination coverage has been achieved,” they wrote.

“It is likely that further control of the COVID-19 pandemic depends not only on high vaccination coverage and its effectiveness but also on ongoing adherence to effective and sustainable public health measures,” they concluded.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

Mounting evidence suggests selective serotonin reuptake inhibitors (SSRI) are associated with lower COVID-19 severity.

A large analysis of health records shows patients with COVID-19 taking an SSRI were significantly less likely to die of COVID-19 than a matched control group.

Data-driven approach

Investigators analyzed data from the Cerner Real World Data COVID-19 deidentified electronic health records database of 490,373 patients with COVID-19 across 87 health centers, including 3,401 patients who were prescribed SSRIs.

When compared with matched patients with COVID-19 taking SSRIs, patients taking fluoxetine were 28% less likely to die (relative risk, 0.72; 95% CI, 0.54-0.97; adjusted P = .03) and those taking either fluoxetine or fluvoxamine were 26% less likely to die (RR, 0.74; 95% CI, 0.55-0.99; adjusted P = .04) versus those not on these medications.

Patients with COVID-19 taking any kind of SSRI were 8% less likely to die than the matched controls (RR, 0.92; 95% CI, 0.85-0.99; adjusted P = .03).

“We observed a statistically significant reduction in mortality of COVID-19 patients who were already taking SSRIs. This is a demonstration of a data-driven approach for identifying new uses for existing drugs,” Dr. Sirota said in an interview.

“Our study simply shows an association between SSRIs and COVID-19 outcomes and doesn’t investigate the mechanism of action of why the drugs might work. Additional clinical trials need to be carried out before these drugs can be used in patients going forward,” she cautioned.

“There is currently an open-label trial investigating fluoxetine to reduce intubation and death after COVID-19. To our knowledge, there are no phase 3 randomized controlled trials taking place or planned,” study investigator Tomiko Oskotsky, MD, with UCSF, told this news organization.

Urgent need

The current results “confirm and expand on prior findings from observational, preclinical, and clinical studies suggesting that certain SSRI antidepressants, including fluoxetine or fluvoxamine, could be beneficial against COVID-19,” Nicolas Hoertel, MD, PhD, MPH, with Paris University and Corentin-Celton Hospital, France, writes in a linked editorial.

Dr. Hoertel notes that the anti-inflammatory properties of SSRIs may underlie their potential action against COVID-19, and other potential mechanisms may include reduction in platelet aggregation, decreased mast cell degranulation, increased melatonin levels, interference with endolysosomal viral trafficking, and antioxidant activities.

“Because most of the world’s population is currently unvaccinated and the COVID-19 pandemic is still active, effective treatments of COVID-19 – especially those that are easy to use, show good tolerability, can be administered orally, and have widespread availability at low cost to allow their use in resource-poor countries – are urgently needed to reduce COVID-19-related mortality and morbidity,” Dr. Hoertel points out.

“In this context, short-term use of fluoxetine or fluvoxamine, if proven effective, should be considered as a potential means of reaching this goal,” he adds.

The study was supported by the Christopher Hess Research Fund and, in part, by UCSF and the National Institutes of Health. Dr. Sirota has reported serving as a scientific advisor at Aria Pharmaceuticals. Dr. Hoertel has reported being listed as an inventor on a patent application related to methods of treating COVID-19, filed by Assistance Publique-Hopitaux de Paris, and receiving consulting fees and nonfinancial support from Lundbeck.

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

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,¹ the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”²

University of Michigan Institute for Healthcare Policy and Innovation

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index³ is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.⁴ She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Courtesy of Renown Regional Medical Center

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,¹ the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”²

University of Michigan Institute for Healthcare Policy and Innovation

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index³ is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.⁴ She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Courtesy of Renown Regional Medical Center

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,¹ the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”²

University of Michigan Institute for Healthcare Policy and Innovation

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index³ is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.⁴ She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Courtesy of Renown Regional Medical Center

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

I was recently asked to see a 16-year-old, unvaccinated (against COVID-19) adolescent with hypothyroidism and obesity (body mass index 37 kg/m²) seen in the pediatric emergency department with tachycardia, O₂ saturation 96%, urinary tract infection, poor appetite, and nausea. Her chest x-ray had low lung volumes but no infiltrates. She was noted to be dehydrated. Testing for COVID-19 was PCR positive.¹

She was observed overnight, tolerated oral rehydration, and was being readied for discharge. Pediatric Infectious Diseases was called about prescribing remdesivir.

Remdesivir was not indicated as its current use is limited to inpatients with oxygen desaturations less than 94%. Infectious Diseases Society of America guidelines do recommend the use of monoclonal antibodies against the SARS-CoV-2 spike protein for prevention of COVID disease progression in high-risk individuals. Specifically, the IDSA guidelines say, “Among ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab rather than no neutralizing antibody treatment.”

The Food and Drug Administration’s Emergency Use Authorization (EUA) allowed use of specific monoclonal antibodies (casirivimab/imdevimab in combination, bamlanivimab/etesevimab in combination, and sotrovimab alone) for individuals 12 years and above with a minimum weight of 40 kg with high-risk conditions, describing the evidence as moderate certainty.²

Several questions have arisen regarding their use. Which children qualify under the EUA? Are the available monoclonal antibodies effective for SARS-CoV-2 variants? What adverse events were observed? Are there implementation hurdles?

Unlike the EUA for prophylactic use, which targeted unvaccinated individuals and those unlikely to have a good antibody response to vaccine, use of monoclonal antibody for prevention of progression does not have such restrictions. Effectiveness may vary by local variant susceptibility and should be considered in the choice of the most appropriate monoclonal antibody therapy. Reductions in hospitalization and progression to critical disease status were reported from phase 3 studies; reductions were also observed in mortality in some, but not all, studies. Enhanced viral clearance on day 7 was observed with few subjects having persistent high viral load.

Which children qualify under the EUA? Adolescents 12 years and older and over 40 kg are eligible if a high risk condition is present. High-risk conditions include body mass index at the 85th percentile or higher, immunosuppressive disease, or receipt of immunosuppressive therapies, or baseline (pre-COVID infection) medical-related technological dependence such as tracheostomy or positive pressure ventilation. Additional high-risk conditions are neurodevelopmental disorders, sickle cell disease, congenital or acquired heart disease, asthma, or reactive airway or other chronic respiratory disease that requires daily medication for control, diabetes, chronic kidney disease, or pregnancy.³

Are the available monoclonal antibodies effective for SARS-CoV-2 variants? Of course, this is a critical question and relies on knowledge of the dominant variant in a specific geographic location. The CDC data on which variants are susceptible to which monoclonal therapies were updated as of Oct. 21 online (see Table 1). Local departments of public health often will have current data on the dominant variant in the community. Currently, the dominant variant in the United States is Delta and it is anticipated to be susceptible to the three monoclonal treatments authorized under the EUA based on in vitro neutralizing assays.

Implementation challenges

The first challenge is finding a location to infuse the monoclonal antibodies. Although they can be given subcutaneously, the dose is large and little, if any, time is saved as the recommendation is for observation post administration for 1 hour. The challenge we and other centers may face is that the patients are COVID PCR+ and therefore our usual infusion program, which often is occupied by individuals already compromised and at high risk for severe COVID, is an undesirable location. We are planning to use the emergency department to accommodate such patients currently, but even that solution creates challenges for a busy, urban medical center.

Summary

Anti–SARS-CoV-2 monoclonal antibodies are an important part of the therapeutic approach to minimizing disease severity. Clinicians should review high-risk conditions in adolescents who are PCR+ for SARS-CoV-2 and have mild to moderate symptoms. Medical care systems should implement programs to make monoclonal infusions available for such high-risk adolescents.⁴ Obesity and asthma reactive airways or requiring daily medication for control are the two most common conditions that place adolescents with COVID-19 at risk for progression to hospitalization and severe disease in addition to the more traditional immune-compromising conditions and medical fragility.

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide. U.S. Department of Health and Human Services. 2021 Sep 2.

2. Bhimraj A et al. IDSA Guidelines on the Treatment and Management of Patients with COVID-19. Last updated 2021 Nov 9.

3. Anti-SARS-CoV-2 Monoclonal Antibodies. National Institutes of Health’s COVID 19 Treatment Guidelines. Last updated 2021 Oct 19.

4. Spreading the Word on the Benefits of Monoclonal Antibodies for COVID-19, by Hannah R. Buchdahl. CDC Foundation, 2021 Jul 2.

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

With deer hunting season underway or starting in states across the United States, people should wear a mask and gloves when handling deer to prevent coronavirus transmission, experts say.

A recent study by researchers at Penn State University found that more than 80% of the deer sampled during last year’s hunting season in counties across Iowa tested positive for COVID-19. Overall, a third of the deer sampled between September 2020 and January 2021 tested positive.

“The findings suggest that white-tailed deer may be a reservoir for the virus to continually circulate and raise concerns about the emergence of new strains that may prove a threat to wildlife and, possibly, to humans,” the researchers said in a statement.

The deer were likely infected due to “multiple human-to-deer spillover events and deer-to-deer transmission,” they noted.

Studies haven’t shown whether deer have infected humans, but public health experts are recommending that hunters and deer handlers consider possible transmission avenues, The Plain Dealer, a Cleveland newspaper, reported.

To limit deer-to-deer transmission, homeowners and hunters should avoid concentrating deer at backyard feeders or in hunting situations, according to the Ohio Department of Natural Resources Division of Wildlife. The department also urged people to not allow contact between wildlife and domestic animals, including pets and hunting dogs.

Eating venison shouldn’t be a concern if people cook the meat thoroughly, the newspaper reported. Until more is known, people should wear a mask and gloves when handling deer.

In the study, Penn State researchers examined 283 deer between December 2020 and January 2021. They took samples from lymph nodes in the head and neck as part of Iowa’s chronic wasting disease surveillance program.

“This is the first direct evidence of SARS-CoV-2 virus in any free-living species, and our findings have important implications for the ecology and long-term persistence of the virus,” Suresh Kuchipudi, PhD, associate director of the Animal Diagnostics Laboratory at Penn State, said in the statement.

“These include spillover to other free-living or captive animals and potential spillback to human hosts,” he said. “Of course, this highlights that many urgent steps are needed to monitor the spread of the virus in deer and prevent spillback to humans.”

The research team sequenced genomes from all the positive samples and identified 12 coronavirus lineages. The prominent ones corresponded to the same lineages found in humans at the time.

The U.S. Department of Agriculture has also inspected 480 samples this year from white-tailed deer in Illinois, Michigan, New York, and Pennsylvania. Researchers detected virus antibodies in 33% of samples, according to a statement from the department. The department has confirmed the virus in deer in Ohio as well.

Health officials have recommended that hunters also take precautions while around other people by getting vaccinated and wearing a mask, according to WMTV in Wisconsin.

“If someone comes to deer camp and they have COVID and other folks aren’t vaccinated, in that enclosed space with the laughing and good times that are had, the likelihood that those other hunters would be infected is pretty high,” Jeff Pothof, MD, an emergency medicine doctor at UW Health, told the news outlet.

“I think the biggest risk to deer hunters is going to be other hunters, not so much the deer,” he said.

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

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a 2-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a 2-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

Patients with immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease and rheumatic conditions, have a reduced serologic response to a 2-dose vaccination regimen with mRNA COVID-19 vaccines, according to the findings of a meta-analysis.

“These results suggest that IMID patients receiving mRNA vaccines should complete the vaccine series without delay and support the strategy of providing a third dose of the vaccine,” wrote study authors Atsushi Sakuraba, MD, of the University of Chicago Medicine, and colleagues in Gastroenterology.

During the COVID-19 pandemic, concerns were raised about the susceptibility of patients with pre-existing conditions to infection with the novel coronavirus, the authors noted. Likewise, ongoing concerns have centered on the risk of worse COVID-19–related outcomes among patients with IMIDs who are treated with immunosuppressive agents.

Since the onset of the pandemic, several registries have been established to gauge the incidence and prognosis of COVID-19 in patients with IMID, including the Surveillance Epidemiology of Coronavirus Under Research Exclusion (SECURE)–Inflammatory Bowel Disease (IBD) registry and the COVID-19 Global Rheumatology Alliance 75 (C19-GRA), which includes patients with rheumatic diseases.

Authorization of COVID-19 mRNA vaccines provided hope that the COVID-19 pandemic could soon come to an end given the overwhelming safety and efficacy data supporting the use of these vaccines for preventing hospitalization and death. Despite these data, little is known regarding the efficacy of mRNA COVID-19 vaccines in patients with IMIDs and/or patients treated with immunosuppressive therapies, as these patients were excluded from the regulatory vaccine studies.

The study by Dr. Sakuraba and colleagues was a meta-analysis of 25 observational studies that reported serologic response rates to COVID-19 vaccination in a pooled cohort of 5,360 patients with IMIDs. Data regarding the reference population, medications, vaccination, and proportion of patients who achieved a serologic response were extracted from the observational studies and included in the meta-analysis.

In the analyzed studies, serologic response was evaluated separately after one or two vaccine doses. The researchers also examined the post-vaccine serologic response rate in patients with IMIDs versus controls without IMIDs.

A total of 23 studies used the BNT162b2 or mRNA-1273 vaccines, while 3 studies reported that 50% to 75.9% of patients received the AZD1222 vaccine. Some studies also included patients who received other COVID-19 vaccines, including CoronaVac, BBV152, and Ad26.COV2.S.

While 6 studies assessed serologic response to COVID-19 after just 1 dose, 20 studies assessed the post-vaccination serologic response following 2 doses. In most cases, researchers evaluated serologic response at 2 to 3 weeks after the first dose. After the second vaccine dose, most studies examined serologic response at 1 to 3 weeks.

The serologic response after 1 dose of the mRNA vaccines was 73.2% (95% CI 65.7-79.5). In a multivariate meta-regression analysis, the researchers found that a significantly greater proportion of patients with IMIDs who took anti-tumor necrosis factor (anti-TNF) therapies had a lower serologic response rate (coefficient, –2.60; 95% CI –4.49 to –0.72; P =.0069). The investigators indicated this “likely contributed to the difference in serologic response rates and overall heterogeneity.”

Studies with patients with IBD reported a lower serologic response rate compared with studies that included patients with rheumatoid arthritis (49.2% vs. 65.0%, respectively), which the investigators explained was likely reflective of the increased use of anti-TNF agents in patients with IBD.

After 2 doses of the mRNA vaccines, the pooled serologic response was 83.4% (95% CI, 76.8%-88.4%). Multivariate meta-regression found that a significantly greater proportion of patients who took anti-CD20 treatments had a lower serologic response (coefficient, -6.08; 95% CI -9.40 to -2.76; P <.001). The investigators found that older age was significantly associated with lower serologic response after 2 doses (coefficient, -0.044; 95% CI -0.083 to -0.0050; P =.027).

For the non-mRNA COVID-19 vaccines, the rates of serologic response after 2 doses were 93.5% with AZD1222, 22.9% with CoronaVac, and 55.6% with BBV152.

Compared with controls without IMIDs, those with IMIDs were significantly less likely to achieve a serologic response following 2 mRNA vaccine doses (odds ratio, 0.086; 95% CI 0.036-0.206; P <.001). The investigators noted that there were not enough studies to examine and compare serologic response rates to adenoviral or inactivated vaccines between patients and controls.

In terms of limitations, the researchers wrote that additional studies examining humoral and cellular immunity to COVID-19 vaccines are needed to determine vaccine efficacy and durability in patients with IMIDs. Additionally, there is a need for studies with larger patient populations to determine serologic response to COVID-19 vaccines in the broader IMID population.

The researchers reported no funding for the study and no relevant conflicts of interest with the pharmaceutical industry.

While a squamous cell carcinoma presenting this way is perhaps more common, this nonhealing draining papule over a sternal scar was actually a sternocutaneous fistula (SCF). Examination revealed multiple bound down pits along the sternotomy scar. Very gentle probing of the papule in consideration of biopsy revealed a wire foreign body—the end of a sternotomy wire. A culture of yellow discharge ultimately grew Staphylococcus aureus.

SCF is a rare, and sometimes devastating, complication of cardiac surgery that occurred in 0.23% of cases at 1-year in a single center study of 12,297 patients over 9 years.¹ As in this case, it may also present distantly from the time of surgery. The risk of SCF increases with smoking, previous sternal wound infection, renal failure, and use of bone wax during surgery.¹

As soon as there was concern for SCF as a possible diagnosis, the patient was referred to, and quickly evaluated by, Cardiothoracic Surgery. Ultrasound and computed tomography imaging did not reveal any osteomyelitis or deep mediastinal disease. He was treated with debridement and removal of the sternotomy wire. At the 1-year follow-up, he had no further episodes of skin infection in the area.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

While a squamous cell carcinoma presenting this way is perhaps more common, this nonhealing draining papule over a sternal scar was actually a sternocutaneous fistula (SCF). Examination revealed multiple bound down pits along the sternotomy scar. Very gentle probing of the papule in consideration of biopsy revealed a wire foreign body—the end of a sternotomy wire. A culture of yellow discharge ultimately grew Staphylococcus aureus.

SCF is a rare, and sometimes devastating, complication of cardiac surgery that occurred in 0.23% of cases at 1-year in a single center study of 12,297 patients over 9 years.¹ As in this case, it may also present distantly from the time of surgery. The risk of SCF increases with smoking, previous sternal wound infection, renal failure, and use of bone wax during surgery.¹

As soon as there was concern for SCF as a possible diagnosis, the patient was referred to, and quickly evaluated by, Cardiothoracic Surgery. Ultrasound and computed tomography imaging did not reveal any osteomyelitis or deep mediastinal disease. He was treated with debridement and removal of the sternotomy wire. At the 1-year follow-up, he had no further episodes of skin infection in the area.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

While a squamous cell carcinoma presenting this way is perhaps more common, this nonhealing draining papule over a sternal scar was actually a sternocutaneous fistula (SCF). Examination revealed multiple bound down pits along the sternotomy scar. Very gentle probing of the papule in consideration of biopsy revealed a wire foreign body—the end of a sternotomy wire. A culture of yellow discharge ultimately grew Staphylococcus aureus.

SCF is a rare, and sometimes devastating, complication of cardiac surgery that occurred in 0.23% of cases at 1-year in a single center study of 12,297 patients over 9 years.¹ As in this case, it may also present distantly from the time of surgery. The risk of SCF increases with smoking, previous sternal wound infection, renal failure, and use of bone wax during surgery.¹

As soon as there was concern for SCF as a possible diagnosis, the patient was referred to, and quickly evaluated by, Cardiothoracic Surgery. Ultrasound and computed tomography imaging did not reveal any osteomyelitis or deep mediastinal disease. He was treated with debridement and removal of the sternotomy wire. At the 1-year follow-up, he had no further episodes of skin infection in the area.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

It sounds like a fairy tale steeped in HIV stigma: A woman wakes up one morning and, poof, the HIV she’s been living with for 8 years is gone. But for a 30-year-old Argentinian woman from the aptly named village of Esperanza, that’s close to the truth, according to an article published in Annals of Internal Medicine.

The woman, the so-called Esperanza Patient, appears to be the second person whose immune system cleared the virus without the use of stem cell transplantation. The first was Loreen Willenberg, a California woman who, after living with HIV for 27 years, no longer had replicating HIV in her system. That case was reported last year.

“That’s the beauty of this name, right? Esperanza,” said Xu Yu, MD, principal investigator of the Ragon Institute of Massachusetts General Hospital, the Massachusetts Institute of Technology, and Harvard University, Boston, referring to the Spanish word for “hope.” “This makes us hopeful that a natural cure of HIV is actually possible.”

Two other people appear to have cleared HIV, but only after full replacement of the immune system via stem cell transplantation – the Berlin Patient, Timothy Ray Brown, and the London Patient. Another man, from Brazil, appeared to have an undetectable viral load after receiving intensified antiretroviral treatment plus supplemental vitamin B3.
 

The rarest of the rare

The Esperanza Patient is among a rare group of people living with HIV called elite controllers. These people’s immune systems can control HIV without antiretrovirals. Most elite controllers’ immune systems, however, can’t mount the immune attack necessary to eliminate all replicating HIV from their systems. Instead, their immune systems control the virus without affecting the reservoirs where HIV continues to make copies of itself and can spread.

The Esperanza Patient and Ms. Willenberg, however, appear to be the rarest of the rare. Their own immune systems seem not only to have stopped HIV replication outside of reservoirs but also to have stormed those reservoirs and killed all virus that might have continued to replicate.

The two women are connected in another way: At an HIV conference in 2019, Dr. Yu was presenting data on Ms. Willenberg’s case. At that conference, she met Natalia Laufer, MD, PhD, associate researcher at the Instituto de Investigaciones Biomédicas en Retrovirs y SIDA at the University of Buenos Aires. Dr. Laufer had been studying the Esperanza Patient at the time and asked Dr. Yu whether she and her team at the Ragon Institute could help her sequence the patient’s HIV genome to see whether, indeed, the virus had been spontaneously cleared from the patient’s system.

So that’s what the pair did, in collaboration with several other researchers into cures for HIV. The Esperanza Patient first acquired HIV in 2013, but in the 8 years that followed, results of 10 conventional viral load tests indicated the virus was undetectable (that is, below the level of quantification for standard technology). During that time, the woman’s boyfriend, from whom she had acquired HIV, died of AIDS-defining illnesses. She subsequently married and had a baby. Both her partner and baby are HIV negative. She only received HIV treatment for 6 months while she was pregnant.
 

A fossil record of HIV

Yet, there was still HIV in the woman’s system. Dr. Laufer and Dr. Yu wanted to know whether that HIV was transmissible or whether it was a relic from when HIV was still replicating and was now defective and incapable of replicating. They performed extensive genome sequencing on nearly 1.2 billion cells that Dr. Laufer had taken from the patient’s blood in 2017, 2018, 2019, and 2020, an additional 503 million cells that were from the placenta of the baby she gave birth to in 2020, and 150 million resting CD4 T cells. Proviral sequencing was undertaken of the full DNA of the HIV to detect whether the virus was still intact. The DNA was then analyzed by use of an algorithm and was tested for mutations. The investigators tested the patient’s CD4 cells to determine whether the cells still harbored any latent HIV.

In this way, they conducted a full viral workup using tests that are far more sensitive than the viral load tests the woman had undergone in the clinic. The investigators then assessed the patient’s immune system to see what the various cells of the immune system could tell them about how well her natural immune system could identify and kill HIV. They isolated the Esperanza Patient’s immune cells and subjected those cells to HIV in the lab to see whether the cells could detect and eliminate the virus.

And just to be safe, they checked to make sure there were no antiretroviral drugs in the patient’s system.

What they found was that without treatment, her CD4 count hovered around 1,000 cells – a sign of a functioning immune system. DNA sequences revealed large chunks of missing DNA, and one sequence had an immune-induced hypermutation. In total, seven proviruses were found, but none were capable of replicating. The CD4 cells they evaluated showed no evidence of latent HIV.

In other words, they had uncovered a fossil record.

“These HIV-1 DNA products clearly indicate that this person was infected with HIV-1 in the past and that active cycles of viral replication had occurred at one point,” Dr. Yu and colleagues write in their recent article.

What may be more useful to researchers looking to turn this spontaneous cure into treatment for millions of people living with active HIV was the evidence that the woman’s immune system had trained itself to attack HIV through a number of genetic mutations. What they found, the researchers write, was evidence of “an incomplete seroconversion” – that is, when the patient was acquiring HIV, the infection was stopped in its tracks.

Yet, Dr. Yu and colleagues say that they can’t prove that the woman is fully cured of HIV.

“Although this might sound unsatisfying, it reflects an intrinsic limitation of scientific research,” they write. “Scientific concepts can never be proved through empirical data collection; they can only be disproved.”
 

There are more out there

Are these women the only ones to have spontaneously cleared HIV? That’s the question, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Just like they can’t disprove that the women cured themselves, they can’t prove that she and Ms. Willenberg are the only two people to have experienced this cure.

“We’re all struggling with this,” Dr. Dieffenbach told this news organization. “The goal is to get enough of these people so maybe there’s a road map to how to induce, trigger, change immunity. But this could well be a unique event at the time of initiation of infection. We just don’t know.”

What is needed, Dr. Yu said, is for clinicians to reach out to them regarding cases that could mimic the cases of Ms. Willenberg and the Esperanza Patient. Elaborate testing could then be conducted to see whether these cases are similar to those of Ms. Willenberg and the Esperanza Patient.

“We do think there are more out there,” Dr. Yu said in an interview.

Asked whether we’re still far away from applying these one-off cures to the millions of people taking HIV treatment daily, Dr. Yu responded, “We might be close. That’s the beauty of scientific discovery. We don’t know, but that’s why we need more engagement of the community and care providers to help us.”

The research was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. Dr. Yu and Dr. Dieffenbach have reported no relevant financial relationships.

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

It sounds like a fairy tale steeped in HIV stigma: A woman wakes up one morning and, poof, the HIV she’s been living with for 8 years is gone. But for a 30-year-old Argentinian woman from the aptly named village of Esperanza, that’s close to the truth, according to an article published in Annals of Internal Medicine.

The woman, the so-called Esperanza Patient, appears to be the second person whose immune system cleared the virus without the use of stem cell transplantation. The first was Loreen Willenberg, a California woman who, after living with HIV for 27 years, no longer had replicating HIV in her system. That case was reported last year.

“That’s the beauty of this name, right? Esperanza,” said Xu Yu, MD, principal investigator of the Ragon Institute of Massachusetts General Hospital, the Massachusetts Institute of Technology, and Harvard University, Boston, referring to the Spanish word for “hope.” “This makes us hopeful that a natural cure of HIV is actually possible.”

Two other people appear to have cleared HIV, but only after full replacement of the immune system via stem cell transplantation – the Berlin Patient, Timothy Ray Brown, and the London Patient. Another man, from Brazil, appeared to have an undetectable viral load after receiving intensified antiretroviral treatment plus supplemental vitamin B3.
 

The rarest of the rare

The Esperanza Patient is among a rare group of people living with HIV called elite controllers. These people’s immune systems can control HIV without antiretrovirals. Most elite controllers’ immune systems, however, can’t mount the immune attack necessary to eliminate all replicating HIV from their systems. Instead, their immune systems control the virus without affecting the reservoirs where HIV continues to make copies of itself and can spread.

The Esperanza Patient and Ms. Willenberg, however, appear to be the rarest of the rare. Their own immune systems seem not only to have stopped HIV replication outside of reservoirs but also to have stormed those reservoirs and killed all virus that might have continued to replicate.

The two women are connected in another way: At an HIV conference in 2019, Dr. Yu was presenting data on Ms. Willenberg’s case. At that conference, she met Natalia Laufer, MD, PhD, associate researcher at the Instituto de Investigaciones Biomédicas en Retrovirs y SIDA at the University of Buenos Aires. Dr. Laufer had been studying the Esperanza Patient at the time and asked Dr. Yu whether she and her team at the Ragon Institute could help her sequence the patient’s HIV genome to see whether, indeed, the virus had been spontaneously cleared from the patient’s system.

So that’s what the pair did, in collaboration with several other researchers into cures for HIV. The Esperanza Patient first acquired HIV in 2013, but in the 8 years that followed, results of 10 conventional viral load tests indicated the virus was undetectable (that is, below the level of quantification for standard technology). During that time, the woman’s boyfriend, from whom she had acquired HIV, died of AIDS-defining illnesses. She subsequently married and had a baby. Both her partner and baby are HIV negative. She only received HIV treatment for 6 months while she was pregnant.
 

A fossil record of HIV

Yet, there was still HIV in the woman’s system. Dr. Laufer and Dr. Yu wanted to know whether that HIV was transmissible or whether it was a relic from when HIV was still replicating and was now defective and incapable of replicating. They performed extensive genome sequencing on nearly 1.2 billion cells that Dr. Laufer had taken from the patient’s blood in 2017, 2018, 2019, and 2020, an additional 503 million cells that were from the placenta of the baby she gave birth to in 2020, and 150 million resting CD4 T cells. Proviral sequencing was undertaken of the full DNA of the HIV to detect whether the virus was still intact. The DNA was then analyzed by use of an algorithm and was tested for mutations. The investigators tested the patient’s CD4 cells to determine whether the cells still harbored any latent HIV.

In this way, they conducted a full viral workup using tests that are far more sensitive than the viral load tests the woman had undergone in the clinic. The investigators then assessed the patient’s immune system to see what the various cells of the immune system could tell them about how well her natural immune system could identify and kill HIV. They isolated the Esperanza Patient’s immune cells and subjected those cells to HIV in the lab to see whether the cells could detect and eliminate the virus.

And just to be safe, they checked to make sure there were no antiretroviral drugs in the patient’s system.

What they found was that without treatment, her CD4 count hovered around 1,000 cells – a sign of a functioning immune system. DNA sequences revealed large chunks of missing DNA, and one sequence had an immune-induced hypermutation. In total, seven proviruses were found, but none were capable of replicating. The CD4 cells they evaluated showed no evidence of latent HIV.

In other words, they had uncovered a fossil record.

“These HIV-1 DNA products clearly indicate that this person was infected with HIV-1 in the past and that active cycles of viral replication had occurred at one point,” Dr. Yu and colleagues write in their recent article.

What may be more useful to researchers looking to turn this spontaneous cure into treatment for millions of people living with active HIV was the evidence that the woman’s immune system had trained itself to attack HIV through a number of genetic mutations. What they found, the researchers write, was evidence of “an incomplete seroconversion” – that is, when the patient was acquiring HIV, the infection was stopped in its tracks.

Yet, Dr. Yu and colleagues say that they can’t prove that the woman is fully cured of HIV.

“Although this might sound unsatisfying, it reflects an intrinsic limitation of scientific research,” they write. “Scientific concepts can never be proved through empirical data collection; they can only be disproved.”
 

There are more out there

Are these women the only ones to have spontaneously cleared HIV? That’s the question, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Just like they can’t disprove that the women cured themselves, they can’t prove that she and Ms. Willenberg are the only two people to have experienced this cure.

“We’re all struggling with this,” Dr. Dieffenbach told this news organization. “The goal is to get enough of these people so maybe there’s a road map to how to induce, trigger, change immunity. But this could well be a unique event at the time of initiation of infection. We just don’t know.”

What is needed, Dr. Yu said, is for clinicians to reach out to them regarding cases that could mimic the cases of Ms. Willenberg and the Esperanza Patient. Elaborate testing could then be conducted to see whether these cases are similar to those of Ms. Willenberg and the Esperanza Patient.

“We do think there are more out there,” Dr. Yu said in an interview.

Asked whether we’re still far away from applying these one-off cures to the millions of people taking HIV treatment daily, Dr. Yu responded, “We might be close. That’s the beauty of scientific discovery. We don’t know, but that’s why we need more engagement of the community and care providers to help us.”

The research was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. Dr. Yu and Dr. Dieffenbach have reported no relevant financial relationships.

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

It sounds like a fairy tale steeped in HIV stigma: A woman wakes up one morning and, poof, the HIV she’s been living with for 8 years is gone. But for a 30-year-old Argentinian woman from the aptly named village of Esperanza, that’s close to the truth, according to an article published in Annals of Internal Medicine.

The woman, the so-called Esperanza Patient, appears to be the second person whose immune system cleared the virus without the use of stem cell transplantation. The first was Loreen Willenberg, a California woman who, after living with HIV for 27 years, no longer had replicating HIV in her system. That case was reported last year.

“That’s the beauty of this name, right? Esperanza,” said Xu Yu, MD, principal investigator of the Ragon Institute of Massachusetts General Hospital, the Massachusetts Institute of Technology, and Harvard University, Boston, referring to the Spanish word for “hope.” “This makes us hopeful that a natural cure of HIV is actually possible.”

Two other people appear to have cleared HIV, but only after full replacement of the immune system via stem cell transplantation – the Berlin Patient, Timothy Ray Brown, and the London Patient. Another man, from Brazil, appeared to have an undetectable viral load after receiving intensified antiretroviral treatment plus supplemental vitamin B3.
 

The rarest of the rare

The Esperanza Patient is among a rare group of people living with HIV called elite controllers. These people’s immune systems can control HIV without antiretrovirals. Most elite controllers’ immune systems, however, can’t mount the immune attack necessary to eliminate all replicating HIV from their systems. Instead, their immune systems control the virus without affecting the reservoirs where HIV continues to make copies of itself and can spread.

The Esperanza Patient and Ms. Willenberg, however, appear to be the rarest of the rare. Their own immune systems seem not only to have stopped HIV replication outside of reservoirs but also to have stormed those reservoirs and killed all virus that might have continued to replicate.

The two women are connected in another way: At an HIV conference in 2019, Dr. Yu was presenting data on Ms. Willenberg’s case. At that conference, she met Natalia Laufer, MD, PhD, associate researcher at the Instituto de Investigaciones Biomédicas en Retrovirs y SIDA at the University of Buenos Aires. Dr. Laufer had been studying the Esperanza Patient at the time and asked Dr. Yu whether she and her team at the Ragon Institute could help her sequence the patient’s HIV genome to see whether, indeed, the virus had been spontaneously cleared from the patient’s system.

So that’s what the pair did, in collaboration with several other researchers into cures for HIV. The Esperanza Patient first acquired HIV in 2013, but in the 8 years that followed, results of 10 conventional viral load tests indicated the virus was undetectable (that is, below the level of quantification for standard technology). During that time, the woman’s boyfriend, from whom she had acquired HIV, died of AIDS-defining illnesses. She subsequently married and had a baby. Both her partner and baby are HIV negative. She only received HIV treatment for 6 months while she was pregnant.
 

A fossil record of HIV

Yet, there was still HIV in the woman’s system. Dr. Laufer and Dr. Yu wanted to know whether that HIV was transmissible or whether it was a relic from when HIV was still replicating and was now defective and incapable of replicating. They performed extensive genome sequencing on nearly 1.2 billion cells that Dr. Laufer had taken from the patient’s blood in 2017, 2018, 2019, and 2020, an additional 503 million cells that were from the placenta of the baby she gave birth to in 2020, and 150 million resting CD4 T cells. Proviral sequencing was undertaken of the full DNA of the HIV to detect whether the virus was still intact. The DNA was then analyzed by use of an algorithm and was tested for mutations. The investigators tested the patient’s CD4 cells to determine whether the cells still harbored any latent HIV.

In this way, they conducted a full viral workup using tests that are far more sensitive than the viral load tests the woman had undergone in the clinic. The investigators then assessed the patient’s immune system to see what the various cells of the immune system could tell them about how well her natural immune system could identify and kill HIV. They isolated the Esperanza Patient’s immune cells and subjected those cells to HIV in the lab to see whether the cells could detect and eliminate the virus.

And just to be safe, they checked to make sure there were no antiretroviral drugs in the patient’s system.

What they found was that without treatment, her CD4 count hovered around 1,000 cells – a sign of a functioning immune system. DNA sequences revealed large chunks of missing DNA, and one sequence had an immune-induced hypermutation. In total, seven proviruses were found, but none were capable of replicating. The CD4 cells they evaluated showed no evidence of latent HIV.

In other words, they had uncovered a fossil record.

“These HIV-1 DNA products clearly indicate that this person was infected with HIV-1 in the past and that active cycles of viral replication had occurred at one point,” Dr. Yu and colleagues write in their recent article.

What may be more useful to researchers looking to turn this spontaneous cure into treatment for millions of people living with active HIV was the evidence that the woman’s immune system had trained itself to attack HIV through a number of genetic mutations. What they found, the researchers write, was evidence of “an incomplete seroconversion” – that is, when the patient was acquiring HIV, the infection was stopped in its tracks.

Yet, Dr. Yu and colleagues say that they can’t prove that the woman is fully cured of HIV.

“Although this might sound unsatisfying, it reflects an intrinsic limitation of scientific research,” they write. “Scientific concepts can never be proved through empirical data collection; they can only be disproved.”
 

There are more out there

Are these women the only ones to have spontaneously cleared HIV? That’s the question, said Carl Dieffenbach, PhD, director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Just like they can’t disprove that the women cured themselves, they can’t prove that she and Ms. Willenberg are the only two people to have experienced this cure.

“We’re all struggling with this,” Dr. Dieffenbach told this news organization. “The goal is to get enough of these people so maybe there’s a road map to how to induce, trigger, change immunity. But this could well be a unique event at the time of initiation of infection. We just don’t know.”

What is needed, Dr. Yu said, is for clinicians to reach out to them regarding cases that could mimic the cases of Ms. Willenberg and the Esperanza Patient. Elaborate testing could then be conducted to see whether these cases are similar to those of Ms. Willenberg and the Esperanza Patient.

“We do think there are more out there,” Dr. Yu said in an interview.

Asked whether we’re still far away from applying these one-off cures to the millions of people taking HIV treatment daily, Dr. Yu responded, “We might be close. That’s the beauty of scientific discovery. We don’t know, but that’s why we need more engagement of the community and care providers to help us.”

The research was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. Dr. Yu and Dr. Dieffenbach have reported no relevant financial relationships.

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

Drinking coffee or tea is associated with reduced risk for stroke and dementia, with the biggest benefit associated with consuming both beverages, new research suggests.

amenic181/Getty Images

Investigators found that individuals who drank two to three cups of coffee and two to three cups of tea per day had a 30% decrease in incidence of stroke and a 28% lower risk for dementia compared with those who did not.

“From a public health perspective, because regular tea and coffee drinkers comprise such a large proportion of the population and because these beverages tend to be consumed habitually throughout adult life, even small potential health benefits or risks associated with tea and coffee intake may have important public health implications,” the investigators wrote.

The study was published online Nov. 16 in PLOS Medicine.
 

Synergistic effect?

Whereas earlier studies have shown significant health benefits from moderate coffee and tea intake separately, few have examined the effect of drinking both.

Researchers enrolled 365,682 participants from the UK Biobank for the analysis of coffee and tea consumption and stroke and dementia risk and 13,352 participants for the analysis of poststroke dementia.

During a median follow-up of 11.4 years, 2.8% of participants experienced a stroke and 1.4% developed dementia.

After adjustment for confounders, stroke risk was 10% lower in those who drank a half-cup to a cup of coffee per day (P < .001) and 8% lower in those who had more than two cups a day (P = .009). Tea drinkers who had more than two cups a day saw a 16% reduction in stroke (P < .001).

Those who drank both coffee and tea during the day saw the greatest benefit. Drinking two to three cups of coffee and two to three cups of tea lowered stroke risk by 32% (P < .001) and dementia risk by 28% (P = .002).

Drinking both beverages offered significantly greater benefits than drinking just coffee or tea alone, with an 11% lower risk for stroke (P < .001), an 8% lower risk for dementia (P = .001), and 18% lower risk for vascular dementia (P = .001).

Among those participants who experienced a stroke during the follow-up period, drinking two to three cups of coffee was associated with 20% lower risk for poststroke dementia (P = .044), and for those who drank both coffee and tea (half to one cup of coffee and two to three cups of tea per day) the risk for poststroke dementia was lowered by 50% (P =.006).

There was no significant association between coffee and tea consumption and risk for hemorrhagic stroke or Alzheimer’s disease.

The study was funded by the National Natural Science Foundation of China. The authors have disclosed no relevant financial relationships.

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

Drinking coffee or tea is associated with reduced risk for stroke and dementia, with the biggest benefit associated with consuming both beverages, new research suggests.

amenic181/Getty Images

Investigators found that individuals who drank two to three cups of coffee and two to three cups of tea per day had a 30% decrease in incidence of stroke and a 28% lower risk for dementia compared with those who did not.

“From a public health perspective, because regular tea and coffee drinkers comprise such a large proportion of the population and because these beverages tend to be consumed habitually throughout adult life, even small potential health benefits or risks associated with tea and coffee intake may have important public health implications,” the investigators wrote.

The study was published online Nov. 16 in PLOS Medicine.
 

Synergistic effect?

Whereas earlier studies have shown significant health benefits from moderate coffee and tea intake separately, few have examined the effect of drinking both.

Researchers enrolled 365,682 participants from the UK Biobank for the analysis of coffee and tea consumption and stroke and dementia risk and 13,352 participants for the analysis of poststroke dementia.

During a median follow-up of 11.4 years, 2.8% of participants experienced a stroke and 1.4% developed dementia.

After adjustment for confounders, stroke risk was 10% lower in those who drank a half-cup to a cup of coffee per day (P < .001) and 8% lower in those who had more than two cups a day (P = .009). Tea drinkers who had more than two cups a day saw a 16% reduction in stroke (P < .001).

Those who drank both coffee and tea during the day saw the greatest benefit. Drinking two to three cups of coffee and two to three cups of tea lowered stroke risk by 32% (P < .001) and dementia risk by 28% (P = .002).

Drinking both beverages offered significantly greater benefits than drinking just coffee or tea alone, with an 11% lower risk for stroke (P < .001), an 8% lower risk for dementia (P = .001), and 18% lower risk for vascular dementia (P = .001).

Among those participants who experienced a stroke during the follow-up period, drinking two to three cups of coffee was associated with 20% lower risk for poststroke dementia (P = .044), and for those who drank both coffee and tea (half to one cup of coffee and two to three cups of tea per day) the risk for poststroke dementia was lowered by 50% (P =.006).

There was no significant association between coffee and tea consumption and risk for hemorrhagic stroke or Alzheimer’s disease.

The study was funded by the National Natural Science Foundation of China. The authors have disclosed no relevant financial relationships.

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

Drinking coffee or tea is associated with reduced risk for stroke and dementia, with the biggest benefit associated with consuming both beverages, new research suggests.

amenic181/Getty Images

Investigators found that individuals who drank two to three cups of coffee and two to three cups of tea per day had a 30% decrease in incidence of stroke and a 28% lower risk for dementia compared with those who did not.

“From a public health perspective, because regular tea and coffee drinkers comprise such a large proportion of the population and because these beverages tend to be consumed habitually throughout adult life, even small potential health benefits or risks associated with tea and coffee intake may have important public health implications,” the investigators wrote.

The study was published online Nov. 16 in PLOS Medicine.
 

Synergistic effect?

Whereas earlier studies have shown significant health benefits from moderate coffee and tea intake separately, few have examined the effect of drinking both.

Researchers enrolled 365,682 participants from the UK Biobank for the analysis of coffee and tea consumption and stroke and dementia risk and 13,352 participants for the analysis of poststroke dementia.

During a median follow-up of 11.4 years, 2.8% of participants experienced a stroke and 1.4% developed dementia.

After adjustment for confounders, stroke risk was 10% lower in those who drank a half-cup to a cup of coffee per day (P < .001) and 8% lower in those who had more than two cups a day (P = .009). Tea drinkers who had more than two cups a day saw a 16% reduction in stroke (P < .001).

Those who drank both coffee and tea during the day saw the greatest benefit. Drinking two to three cups of coffee and two to three cups of tea lowered stroke risk by 32% (P < .001) and dementia risk by 28% (P = .002).

Drinking both beverages offered significantly greater benefits than drinking just coffee or tea alone, with an 11% lower risk for stroke (P < .001), an 8% lower risk for dementia (P = .001), and 18% lower risk for vascular dementia (P = .001).

Among those participants who experienced a stroke during the follow-up period, drinking two to three cups of coffee was associated with 20% lower risk for poststroke dementia (P = .044), and for those who drank both coffee and tea (half to one cup of coffee and two to three cups of tea per day) the risk for poststroke dementia was lowered by 50% (P =.006).

There was no significant association between coffee and tea consumption and risk for hemorrhagic stroke or Alzheimer’s disease.

The study was funded by the National Natural Science Foundation of China. The authors have disclosed no relevant financial relationships.

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

Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.