Clinical

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.

After initial promising interim results on Nov. 9, Pfizer and BioNTech today announced that their mRNA vaccine, in development to prevent COVID-19, is 95% effective.

Final analysis of the randomized, phase 3 study of more than 43,000 people yielded 170 confirmed cases of COVID-19 – with 162 positive cases in the placebo group versus 8 in the BNT162b2 vaccine group.

Researchers reported 10 severe cases of COVID-19 in the trial, 9 of which occurred in the placebo group.

The study was ethnically diverse, and results were consistent across gender and age groups, with a 94% efficacy reported among participants aged older than 65 years.

Pfizer plans to file for an emergency-use authorization with the Food and Drug Administration “within days,” having now met all the FDA data endpoints, according to a news release from the two companies.

The vaccine was well tolerated with no serious safety concerns, the company stated. Two grade 3 adverse events were reported – fatigue in 3.8% of participants and headache in 2%.

The 95% efficacy places the Pfizer vaccine in the same neighborhood as the interim results of the Moderna vaccine, reported at 94.5%. Both products are two-dose mRNA vaccines.

As of Nov. 13, of 43,661 total participants in the Pfizer vaccine phase 3 trial, 41,135 received a second dose. The final results are based on two outcomes measured 7 days after the second dose: vaccine efficacy in people without prior SARS-CoV-2 infection as well as a secondary outcome in people both with and without prior SARS-CoV-2 infection.

The 95% vaccine efficacy was statistically significant, compared with placebo (P < .0001).
 

‘Historic 8-month journey’

The BNT162b2 vaccine candidate is a joint effort between Pfizer and BioNTech. “The study results mark an important step in this historic 8-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” Albert Bourla, DVM, PhD, Pfizer chairman and CEO, said in a statement. “With hundreds of thousands of people around the globe infected every day, we urgently need to get a safe and effective vaccine to the world.”

Ugur Sahin, MD, PhD, cofounder and CEO of BioNTech, added, “we are grateful that the first global trial to reach the final efficacy analysis mark indicates that a high rate of protection against COVID-19 can be achieved very fast after the first 30-mcg dose, underscoring the power of BNT162 in providing early protection.”

The two companies expect to produce up to 50 million vaccine doses in 2020 for global distribution. Projections for 2021 include up to 1.3 billion doses.

The companies also designed temperature-controlled thermal shipping containers with dry ice to maintain the required, approximate –70° C (–94° F) conditions. Clinicians can use the containers as temporary storage units for up to 15 days by replacing the dry ice.

This article first appeared on Medscape.com.

A “hospital at home” (HaH) program at Atrium Health, a large integrated delivery system in the Southeast, expanded its hospital capacity during the early phase of the COVID-19 pandemic by providing hospital-level acute care to COVID-19 patients at home, according to a new study in Annals of Internal Medicine.

“Virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond,” wrote Kranthi Sitammagari, MD, from the Atrium Health Hospitalist Group, Monroe, N.C., and colleagues.

Whereas most previous HaH programs have relied on visiting nurses and physicians, the new study uses telemedicine to connect with patients. Advocate Health Care researchers published the only other study using the telemedicine-powered model in 2015.

The new Atrium Health study evaluated 1,477 patients who received care in the HaH program between March 23 and May 7 of this year after having been diagnosed with COVID-19. The program provided home monitoring and hospital-level care in a home-based virtual observation unit (VOU) and a virtual acute care unit (VACU).

Patients were tested for the virus in Atrium emergency departments, primary care clinics, urgent care centers, and external testing sites. Those who tested positive were invited to be cared for either in the VOU, if they had mild to moderate symptoms, or in the VACU, if they were sick enough to be admitted to the hospital.
 

Patients hop onboard

Nearly all COVID-positive patients tested in these sites agreed to be admitted to the hospital at home, coauthor Stephanie Murphy, DO, medical director of the Atrium Health HaH program, said in an interview.

Patients with moderate symptoms were glad to be monitored at home, she said. When they got to the point where the nurse supervising their care felt they needed escalation to acute care, they were asked whether they wanted to continue to be cared for at home. Most opted to stay home rather than be admitted to the hospital, where their loved ones couldn’t visit them.

Low-acuity patients in the VOU received daily telemonitoring by a nurse to identify disease progression and escalate care as needed. For those who required more care and were admitted to the VACU, a team of paramedics and registered nurses (RNs; mobile clinicians) visited the patient’s home within 24 hours, setting up a hospital bed, other necessary medical equipment, videoconferencing gear, and a remote-monitoring kit that included a blood pressure cuff, a pulse oximeter, and a thermometer.

Dedicated hospitalists and nurses managed patients with 24/7 coverage and monitoring, bringing in other specialties as needed for virtual consults. Mobile clinician and virtual provider visits continued daily until a patient’s condition improved to the point where they could be deescalated back to the VOU. After that, patients received mobile app-driven symptom monitoring and telephone follow-up with a nurse until they got better.
 

Few patients go to hospital

Overall, patients had a median length of stay of 11 days in the VOU or the VACU or both. The vast majority, 1,293 patients (88%), received care in the VOU only. In that cohort, just 40 patients (3%) required hospitalization in an Atrium facility. Sixteen of those patients spent time in an ICU, seven required ventilator support, and two died in the hospital.

A total of 184 patients (12%) were admitted to the VACU. Twenty-one (11%) required intravenous fluids, 16 (9%) received antibiotics, 40 (22%) required inhaler or nebulizer treatments, 41 (22%) used supplemental oxygen, and 24 (13%) were admitted to a conventional hospital. Of the latter patients, 10 were admitted to an ICU, one required a ventilator, and none died in the hospital.

Dr. Sitammagari, a hospitalist and comedical director for quality at Atrium Health, told this news organization that, overall, the outcomes for patients in the system’s HaH were comparable to those seen in the literature among other COVID-19 cohorts.
 

Augmenting hospital capacity

The authors note that treating the 160 VACU patients within the HaH saved hospital beds for other patients. The HaH maintained a consistent census of between 20 and 30 patients for the first 6 weeks as COVID-19 cases spread.

Since last spring, Dr. Murphy said, the Atrium HaH’s daily census has grown to between 30 and 45 patients. “We could absorb 50 patients if our hospitals required it.”

How much capacity does that add to Atrium Health? While there are 50 hospitals in the health system, the HaH was set up mainly to care for COVID-19 patients who would otherwise have been admitted to the 10 acute-care hospitals in the Charlotte, N.C., area. In the 4 weeks ending Nov. 16, these facilities carried an average daily census of around 160 COVID-19 patients, Dr. Murphy noted. “During that time, the Atrium Health HaH has carried, on average, about 20%-25% of that census.”

If the pandemic were to overwhelm area hospitals, she added, “the structure would support flexing up our staffing and supplies to expand to crisis capacity,” which could be up to 200 patients a day.

For the nurses who make most of the phone calls to patients, patients average about 12 to 15 per RN, Dr. Murphy said, and there’s one mobile clinician for every six to nine patients. That’s pretty consistent with the staffing on med-surg floors in hospitals, she said.

The physicians in the program include hospitalists dedicated to telemedicine and some doctors who can’t work in the regular hospital because they’re immunocompromised. The physicians round virtually, covering 12-17 HaH patients per day, according to Dr. Murphy.
 

Prior planning paid off

Unlike some other health care systems that have launched HaH programs with the aid of outside vendors, Atrium Health developed its own HaH and brought it online just 2 weeks after deciding to launch the program. Atrium was able to do this, Dr. Sitammagari explained, because before the pandemic its hospitalist program was already developing an HaH model to improve the care of high-risk patients after hospital discharge to prevent readmission.

While Atrium’s electronic health record system wasn’t designed for hospital at home, its health information technology department and clinicians collaborated in rewriting some of the workflows and order sets in the EHR. For example, they set up a nursing questionnaire to administer after VACU admission, and they created another form for automatic admission to the HaH after a patient tested positive for COVID-19. Atrium staff also modified a patient-doctor communications app to help clinicians monitor HaH patients, Dr. Murphy noted.

Other hospital systems have gotten up to speed on HaH pretty quickly by using platforms supplied by outside vendors. Adventist Health in Los Angeles, for example, started admitting patients to its hospital at home just a month after approaching a vendor called Medically Home.
 

COVID vs. non-COVID patients

Atrium’s decision to focus its HaH effort on COVID-19 patients is unusual among the small but growing number of health systems that have adopted the HaH model to increase their capacity. (Atrium is now transferring some hospitalized patients with other conditions to its HaH, but is still focusing mainly on COVID-19 in its HaH program.)

Bruce Leff, MD, a professor of health policy and management at Johns Hopkins Bloomberg School of Public Health, Baltimore, a leading expert on the HaH model, agrees that it can increase hospital capacity significantly.

Dr. Leff praised the Atrium Health study. “It proves that within an integrated delivery system you can quickly deploy and implement a virtual hospital in the specific-use case of COVID, and help patients and help the system at scale,” he said. “They took a bunch of people into the virtual observation unit and thereby kept people from overwhelming their [emergency department] and treated those people safely at home.”

Dr. Leff had no problem with Atrium’s focus on patients with COVID-19 rather than other conditions. “My guess is that they have the ability to take what they developed and apply it to other conditions. Once you have the ability to do acute care at home, you can do a lot at home.”

The biggest barrier to the spread of hospital at home remains the lack of insurer coverage. Dr. Murphy said that health plans are covering virtual physician consultations with patients in the HaH, as well as some other bits and pieces, but not the entire episode of acute care.

Dr. Leff believes that this will start changing soon. COVID-19 has altered the attitudes of physicians and hospitals toward telehealth, he noted, “and it has moved policy makers and payers to start thinking about the new models – home-based care in general and hospital at home in particular. For the first time in 25 years, payers are starting to get interested.”

Most of the authors are employees of Atrium Health. In addition, one coauthor reports being the cofounder of a digital health company, iEnroll, and receiving grants from The Heineman Foundation. Dr. Leff is an advisor to Medically Home, which provides support to hospital at home programs.

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

A “hospital at home” (HaH) program at Atrium Health, a large integrated delivery system in the Southeast, expanded its hospital capacity during the early phase of the COVID-19 pandemic by providing hospital-level acute care to COVID-19 patients at home, according to a new study in Annals of Internal Medicine.

“Virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond,” wrote Kranthi Sitammagari, MD, from the Atrium Health Hospitalist Group, Monroe, N.C., and colleagues.

Whereas most previous HaH programs have relied on visiting nurses and physicians, the new study uses telemedicine to connect with patients. Advocate Health Care researchers published the only other study using the telemedicine-powered model in 2015.

The new Atrium Health study evaluated 1,477 patients who received care in the HaH program between March 23 and May 7 of this year after having been diagnosed with COVID-19. The program provided home monitoring and hospital-level care in a home-based virtual observation unit (VOU) and a virtual acute care unit (VACU).

Patients were tested for the virus in Atrium emergency departments, primary care clinics, urgent care centers, and external testing sites. Those who tested positive were invited to be cared for either in the VOU, if they had mild to moderate symptoms, or in the VACU, if they were sick enough to be admitted to the hospital.
 

Patients hop onboard

Nearly all COVID-positive patients tested in these sites agreed to be admitted to the hospital at home, coauthor Stephanie Murphy, DO, medical director of the Atrium Health HaH program, said in an interview.

Patients with moderate symptoms were glad to be monitored at home, she said. When they got to the point where the nurse supervising their care felt they needed escalation to acute care, they were asked whether they wanted to continue to be cared for at home. Most opted to stay home rather than be admitted to the hospital, where their loved ones couldn’t visit them.

Low-acuity patients in the VOU received daily telemonitoring by a nurse to identify disease progression and escalate care as needed. For those who required more care and were admitted to the VACU, a team of paramedics and registered nurses (RNs; mobile clinicians) visited the patient’s home within 24 hours, setting up a hospital bed, other necessary medical equipment, videoconferencing gear, and a remote-monitoring kit that included a blood pressure cuff, a pulse oximeter, and a thermometer.

Dedicated hospitalists and nurses managed patients with 24/7 coverage and monitoring, bringing in other specialties as needed for virtual consults. Mobile clinician and virtual provider visits continued daily until a patient’s condition improved to the point where they could be deescalated back to the VOU. After that, patients received mobile app-driven symptom monitoring and telephone follow-up with a nurse until they got better.
 

Few patients go to hospital

Overall, patients had a median length of stay of 11 days in the VOU or the VACU or both. The vast majority, 1,293 patients (88%), received care in the VOU only. In that cohort, just 40 patients (3%) required hospitalization in an Atrium facility. Sixteen of those patients spent time in an ICU, seven required ventilator support, and two died in the hospital.

A total of 184 patients (12%) were admitted to the VACU. Twenty-one (11%) required intravenous fluids, 16 (9%) received antibiotics, 40 (22%) required inhaler or nebulizer treatments, 41 (22%) used supplemental oxygen, and 24 (13%) were admitted to a conventional hospital. Of the latter patients, 10 were admitted to an ICU, one required a ventilator, and none died in the hospital.

Dr. Sitammagari, a hospitalist and comedical director for quality at Atrium Health, told this news organization that, overall, the outcomes for patients in the system’s HaH were comparable to those seen in the literature among other COVID-19 cohorts.
 

Augmenting hospital capacity

The authors note that treating the 160 VACU patients within the HaH saved hospital beds for other patients. The HaH maintained a consistent census of between 20 and 30 patients for the first 6 weeks as COVID-19 cases spread.

Since last spring, Dr. Murphy said, the Atrium HaH’s daily census has grown to between 30 and 45 patients. “We could absorb 50 patients if our hospitals required it.”

How much capacity does that add to Atrium Health? While there are 50 hospitals in the health system, the HaH was set up mainly to care for COVID-19 patients who would otherwise have been admitted to the 10 acute-care hospitals in the Charlotte, N.C., area. In the 4 weeks ending Nov. 16, these facilities carried an average daily census of around 160 COVID-19 patients, Dr. Murphy noted. “During that time, the Atrium Health HaH has carried, on average, about 20%-25% of that census.”

If the pandemic were to overwhelm area hospitals, she added, “the structure would support flexing up our staffing and supplies to expand to crisis capacity,” which could be up to 200 patients a day.

For the nurses who make most of the phone calls to patients, patients average about 12 to 15 per RN, Dr. Murphy said, and there’s one mobile clinician for every six to nine patients. That’s pretty consistent with the staffing on med-surg floors in hospitals, she said.

The physicians in the program include hospitalists dedicated to telemedicine and some doctors who can’t work in the regular hospital because they’re immunocompromised. The physicians round virtually, covering 12-17 HaH patients per day, according to Dr. Murphy.
 

Prior planning paid off

Unlike some other health care systems that have launched HaH programs with the aid of outside vendors, Atrium Health developed its own HaH and brought it online just 2 weeks after deciding to launch the program. Atrium was able to do this, Dr. Sitammagari explained, because before the pandemic its hospitalist program was already developing an HaH model to improve the care of high-risk patients after hospital discharge to prevent readmission.

While Atrium’s electronic health record system wasn’t designed for hospital at home, its health information technology department and clinicians collaborated in rewriting some of the workflows and order sets in the EHR. For example, they set up a nursing questionnaire to administer after VACU admission, and they created another form for automatic admission to the HaH after a patient tested positive for COVID-19. Atrium staff also modified a patient-doctor communications app to help clinicians monitor HaH patients, Dr. Murphy noted.

Other hospital systems have gotten up to speed on HaH pretty quickly by using platforms supplied by outside vendors. Adventist Health in Los Angeles, for example, started admitting patients to its hospital at home just a month after approaching a vendor called Medically Home.
 

COVID vs. non-COVID patients

Atrium’s decision to focus its HaH effort on COVID-19 patients is unusual among the small but growing number of health systems that have adopted the HaH model to increase their capacity. (Atrium is now transferring some hospitalized patients with other conditions to its HaH, but is still focusing mainly on COVID-19 in its HaH program.)

Bruce Leff, MD, a professor of health policy and management at Johns Hopkins Bloomberg School of Public Health, Baltimore, a leading expert on the HaH model, agrees that it can increase hospital capacity significantly.

Dr. Leff praised the Atrium Health study. “It proves that within an integrated delivery system you can quickly deploy and implement a virtual hospital in the specific-use case of COVID, and help patients and help the system at scale,” he said. “They took a bunch of people into the virtual observation unit and thereby kept people from overwhelming their [emergency department] and treated those people safely at home.”

Dr. Leff had no problem with Atrium’s focus on patients with COVID-19 rather than other conditions. “My guess is that they have the ability to take what they developed and apply it to other conditions. Once you have the ability to do acute care at home, you can do a lot at home.”

The biggest barrier to the spread of hospital at home remains the lack of insurer coverage. Dr. Murphy said that health plans are covering virtual physician consultations with patients in the HaH, as well as some other bits and pieces, but not the entire episode of acute care.

Dr. Leff believes that this will start changing soon. COVID-19 has altered the attitudes of physicians and hospitals toward telehealth, he noted, “and it has moved policy makers and payers to start thinking about the new models – home-based care in general and hospital at home in particular. For the first time in 25 years, payers are starting to get interested.”

Most of the authors are employees of Atrium Health. In addition, one coauthor reports being the cofounder of a digital health company, iEnroll, and receiving grants from The Heineman Foundation. Dr. Leff is an advisor to Medically Home, which provides support to hospital at home programs.

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

A “hospital at home” (HaH) program at Atrium Health, a large integrated delivery system in the Southeast, expanded its hospital capacity during the early phase of the COVID-19 pandemic by providing hospital-level acute care to COVID-19 patients at home, according to a new study in Annals of Internal Medicine.

“Virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond,” wrote Kranthi Sitammagari, MD, from the Atrium Health Hospitalist Group, Monroe, N.C., and colleagues.

Whereas most previous HaH programs have relied on visiting nurses and physicians, the new study uses telemedicine to connect with patients. Advocate Health Care researchers published the only other study using the telemedicine-powered model in 2015.

The new Atrium Health study evaluated 1,477 patients who received care in the HaH program between March 23 and May 7 of this year after having been diagnosed with COVID-19. The program provided home monitoring and hospital-level care in a home-based virtual observation unit (VOU) and a virtual acute care unit (VACU).

Patients were tested for the virus in Atrium emergency departments, primary care clinics, urgent care centers, and external testing sites. Those who tested positive were invited to be cared for either in the VOU, if they had mild to moderate symptoms, or in the VACU, if they were sick enough to be admitted to the hospital.
 

Patients hop onboard

Nearly all COVID-positive patients tested in these sites agreed to be admitted to the hospital at home, coauthor Stephanie Murphy, DO, medical director of the Atrium Health HaH program, said in an interview.

Patients with moderate symptoms were glad to be monitored at home, she said. When they got to the point where the nurse supervising their care felt they needed escalation to acute care, they were asked whether they wanted to continue to be cared for at home. Most opted to stay home rather than be admitted to the hospital, where their loved ones couldn’t visit them.

Low-acuity patients in the VOU received daily telemonitoring by a nurse to identify disease progression and escalate care as needed. For those who required more care and were admitted to the VACU, a team of paramedics and registered nurses (RNs; mobile clinicians) visited the patient’s home within 24 hours, setting up a hospital bed, other necessary medical equipment, videoconferencing gear, and a remote-monitoring kit that included a blood pressure cuff, a pulse oximeter, and a thermometer.

Dedicated hospitalists and nurses managed patients with 24/7 coverage and monitoring, bringing in other specialties as needed for virtual consults. Mobile clinician and virtual provider visits continued daily until a patient’s condition improved to the point where they could be deescalated back to the VOU. After that, patients received mobile app-driven symptom monitoring and telephone follow-up with a nurse until they got better.
 

Few patients go to hospital

Overall, patients had a median length of stay of 11 days in the VOU or the VACU or both. The vast majority, 1,293 patients (88%), received care in the VOU only. In that cohort, just 40 patients (3%) required hospitalization in an Atrium facility. Sixteen of those patients spent time in an ICU, seven required ventilator support, and two died in the hospital.

A total of 184 patients (12%) were admitted to the VACU. Twenty-one (11%) required intravenous fluids, 16 (9%) received antibiotics, 40 (22%) required inhaler or nebulizer treatments, 41 (22%) used supplemental oxygen, and 24 (13%) were admitted to a conventional hospital. Of the latter patients, 10 were admitted to an ICU, one required a ventilator, and none died in the hospital.

Dr. Sitammagari, a hospitalist and comedical director for quality at Atrium Health, told this news organization that, overall, the outcomes for patients in the system’s HaH were comparable to those seen in the literature among other COVID-19 cohorts.
 

Augmenting hospital capacity

The authors note that treating the 160 VACU patients within the HaH saved hospital beds for other patients. The HaH maintained a consistent census of between 20 and 30 patients for the first 6 weeks as COVID-19 cases spread.

Since last spring, Dr. Murphy said, the Atrium HaH’s daily census has grown to between 30 and 45 patients. “We could absorb 50 patients if our hospitals required it.”

How much capacity does that add to Atrium Health? While there are 50 hospitals in the health system, the HaH was set up mainly to care for COVID-19 patients who would otherwise have been admitted to the 10 acute-care hospitals in the Charlotte, N.C., area. In the 4 weeks ending Nov. 16, these facilities carried an average daily census of around 160 COVID-19 patients, Dr. Murphy noted. “During that time, the Atrium Health HaH has carried, on average, about 20%-25% of that census.”

If the pandemic were to overwhelm area hospitals, she added, “the structure would support flexing up our staffing and supplies to expand to crisis capacity,” which could be up to 200 patients a day.

For the nurses who make most of the phone calls to patients, patients average about 12 to 15 per RN, Dr. Murphy said, and there’s one mobile clinician for every six to nine patients. That’s pretty consistent with the staffing on med-surg floors in hospitals, she said.

The physicians in the program include hospitalists dedicated to telemedicine and some doctors who can’t work in the regular hospital because they’re immunocompromised. The physicians round virtually, covering 12-17 HaH patients per day, according to Dr. Murphy.
 

Prior planning paid off

Unlike some other health care systems that have launched HaH programs with the aid of outside vendors, Atrium Health developed its own HaH and brought it online just 2 weeks after deciding to launch the program. Atrium was able to do this, Dr. Sitammagari explained, because before the pandemic its hospitalist program was already developing an HaH model to improve the care of high-risk patients after hospital discharge to prevent readmission.

While Atrium’s electronic health record system wasn’t designed for hospital at home, its health information technology department and clinicians collaborated in rewriting some of the workflows and order sets in the EHR. For example, they set up a nursing questionnaire to administer after VACU admission, and they created another form for automatic admission to the HaH after a patient tested positive for COVID-19. Atrium staff also modified a patient-doctor communications app to help clinicians monitor HaH patients, Dr. Murphy noted.

Other hospital systems have gotten up to speed on HaH pretty quickly by using platforms supplied by outside vendors. Adventist Health in Los Angeles, for example, started admitting patients to its hospital at home just a month after approaching a vendor called Medically Home.
 

COVID vs. non-COVID patients

Atrium’s decision to focus its HaH effort on COVID-19 patients is unusual among the small but growing number of health systems that have adopted the HaH model to increase their capacity. (Atrium is now transferring some hospitalized patients with other conditions to its HaH, but is still focusing mainly on COVID-19 in its HaH program.)

Bruce Leff, MD, a professor of health policy and management at Johns Hopkins Bloomberg School of Public Health, Baltimore, a leading expert on the HaH model, agrees that it can increase hospital capacity significantly.

Dr. Leff praised the Atrium Health study. “It proves that within an integrated delivery system you can quickly deploy and implement a virtual hospital in the specific-use case of COVID, and help patients and help the system at scale,” he said. “They took a bunch of people into the virtual observation unit and thereby kept people from overwhelming their [emergency department] and treated those people safely at home.”

Dr. Leff had no problem with Atrium’s focus on patients with COVID-19 rather than other conditions. “My guess is that they have the ability to take what they developed and apply it to other conditions. Once you have the ability to do acute care at home, you can do a lot at home.”

The biggest barrier to the spread of hospital at home remains the lack of insurer coverage. Dr. Murphy said that health plans are covering virtual physician consultations with patients in the HaH, as well as some other bits and pieces, but not the entire episode of acute care.

Dr. Leff believes that this will start changing soon. COVID-19 has altered the attitudes of physicians and hospitals toward telehealth, he noted, “and it has moved policy makers and payers to start thinking about the new models – home-based care in general and hospital at home in particular. For the first time in 25 years, payers are starting to get interested.”

Most of the authors are employees of Atrium Health. In addition, one coauthor reports being the cofounder of a digital health company, iEnroll, and receiving grants from The Heineman Foundation. Dr. Leff is an advisor to Medically Home, which provides support to hospital at home programs.

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

“An increasing number of older adults are using multiple medicines, and it is important that the benefits are outweighing the risks,” said Nikesh Parekh, MBBS, MPH, lead author of a recent study of a new predictive tool. The study was done in the context of the World Health Organization campaign to halve the incidence of medication-related harm (MRH) by 2022 – reducing MRH following hospital discharge was identified as a priority area.

This works allows clinicians to calculate the risk of a patient suffering MRH post-discharge requiring health care, said Dr. Parekh, a research fellow at Brighton and Sussex Medical School in Great Britain. “This enables practitioners and policy makers to target interventions to reduce MRH at those with highest risk. This should support the delivery of cost-effective care. The knowledge of individual risk can also prompt clinicians to reconsider any high-risk medicines that they intend on prescribing at discharge.”

This is the first prediction tool to calculate individual patient risk of serious MRH post-discharge, he added.The high readmission rate for older adults is often an avoidable pressure for hospitalists, particularly where MRH is the underlying cause. “The prediction tool has the potential to significantly reduce this burden for hospitalists/patients by identifying those individuals at high risk upon discharge and ensuring that monitoring and additional support is provided to them in the community with their medications,” Dr. Parekh said.

This electronic tool could be integrated into the electronic discharge summaries so that the information can be shared with primary care clinicians in a straightforward way. “The risk score should be calculated automatically by a self-population of the tool’s fields from information that exists on the patient within the electronic discharge system.”The tool now needs to be externally validated through testing in new settings to assess its validity and reliability in new populations. “If the tool is found to be usable by hospitalists and demonstrates reasonable predictive accuracy, then it should be implemented widely to reduce the incidence of MRH,” Dr. Parekh said.
 

Reference

1. Parekh N, et al. Medication-related harm in older adults following hospital discharge: development and validation of a prediction tool. BMJ Qual Saf. Published Online First 2019 Sept 16. doi: 10.1136/bmjqs-2019-009587.

“An increasing number of older adults are using multiple medicines, and it is important that the benefits are outweighing the risks,” said Nikesh Parekh, MBBS, MPH, lead author of a recent study of a new predictive tool. The study was done in the context of the World Health Organization campaign to halve the incidence of medication-related harm (MRH) by 2022 – reducing MRH following hospital discharge was identified as a priority area.

This works allows clinicians to calculate the risk of a patient suffering MRH post-discharge requiring health care, said Dr. Parekh, a research fellow at Brighton and Sussex Medical School in Great Britain. “This enables practitioners and policy makers to target interventions to reduce MRH at those with highest risk. This should support the delivery of cost-effective care. The knowledge of individual risk can also prompt clinicians to reconsider any high-risk medicines that they intend on prescribing at discharge.”

This is the first prediction tool to calculate individual patient risk of serious MRH post-discharge, he added.The high readmission rate for older adults is often an avoidable pressure for hospitalists, particularly where MRH is the underlying cause. “The prediction tool has the potential to significantly reduce this burden for hospitalists/patients by identifying those individuals at high risk upon discharge and ensuring that monitoring and additional support is provided to them in the community with their medications,” Dr. Parekh said.

This electronic tool could be integrated into the electronic discharge summaries so that the information can be shared with primary care clinicians in a straightforward way. “The risk score should be calculated automatically by a self-population of the tool’s fields from information that exists on the patient within the electronic discharge system.”The tool now needs to be externally validated through testing in new settings to assess its validity and reliability in new populations. “If the tool is found to be usable by hospitalists and demonstrates reasonable predictive accuracy, then it should be implemented widely to reduce the incidence of MRH,” Dr. Parekh said.
 

Reference

1. Parekh N, et al. Medication-related harm in older adults following hospital discharge: development and validation of a prediction tool. BMJ Qual Saf. Published Online First 2019 Sept 16. doi: 10.1136/bmjqs-2019-009587.

“An increasing number of older adults are using multiple medicines, and it is important that the benefits are outweighing the risks,” said Nikesh Parekh, MBBS, MPH, lead author of a recent study of a new predictive tool. The study was done in the context of the World Health Organization campaign to halve the incidence of medication-related harm (MRH) by 2022 – reducing MRH following hospital discharge was identified as a priority area.

This works allows clinicians to calculate the risk of a patient suffering MRH post-discharge requiring health care, said Dr. Parekh, a research fellow at Brighton and Sussex Medical School in Great Britain. “This enables practitioners and policy makers to target interventions to reduce MRH at those with highest risk. This should support the delivery of cost-effective care. The knowledge of individual risk can also prompt clinicians to reconsider any high-risk medicines that they intend on prescribing at discharge.”

This is the first prediction tool to calculate individual patient risk of serious MRH post-discharge, he added.The high readmission rate for older adults is often an avoidable pressure for hospitalists, particularly where MRH is the underlying cause. “The prediction tool has the potential to significantly reduce this burden for hospitalists/patients by identifying those individuals at high risk upon discharge and ensuring that monitoring and additional support is provided to them in the community with their medications,” Dr. Parekh said.

This electronic tool could be integrated into the electronic discharge summaries so that the information can be shared with primary care clinicians in a straightforward way. “The risk score should be calculated automatically by a self-population of the tool’s fields from information that exists on the patient within the electronic discharge system.”The tool now needs to be externally validated through testing in new settings to assess its validity and reliability in new populations. “If the tool is found to be usable by hospitalists and demonstrates reasonable predictive accuracy, then it should be implemented widely to reduce the incidence of MRH,” Dr. Parekh said.
 

Reference

1. Parekh N, et al. Medication-related harm in older adults following hospital discharge: development and validation of a prediction tool. BMJ Qual Saf. Published Online First 2019 Sept 16. doi: 10.1136/bmjqs-2019-009587.

An international autopsy study of 21 patients who died from COVID-19 has shown the presence of multifocal lymphocytic myocarditis in three patients (14%). In an additional six patients, focally increased interstitial T-lymphocytes within the myocardium were noted, with only focal or no myocyte injury.

However, increased interstitial macrophage infiltration, possibly related to cytokine infiltration, was seen in 86% of patients.

“One way to think about this is that, if these patients were having biopsies and not autopsies, there would be myocardial injury in the patients with myocarditis, even after they recovered. But with interstitial macrophages, there may or may not be any injury,” said cardiovascular pathologist James R. Stone, MD, PhD, Massachusetts General Hospital, Boston.

Dr. Stone and colleagues from Mass General, two hospitals in Italy, the University of Amsterdam, and the Mayo Clinic in Rochester, Minn., conducted the autopsies in March and April. The results were published in the October 14 issue of the European Heart Journal.

Their technique was rigorous: a median of 20 full-thickness blocks of myocardium were examined histologically (range, 5-29 blocks).

The presence of myocarditis, defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analyzed by immunohistochemistry.

“I think one of the take-homes from this study is that you have to do a thorough sampling of the heart in order to exclude myocardial injury. You cannot exclude myocarditis with just a biopsy or two,” said Dr. Stone in an interview.

“We looked at multiple different sections of tissue preserved in paraffin for every case and found only 14% had myocarditis. The vast majority of autopsies done on patients dying from COVID-19 have short-changed the autopsy and not been done in a way to exclude myocarditis,” he added.

For all patients, COVID-19 was the underlying cause of death, but the mechanisms of death were acute respiratory distress syndrome in 15, viral pneumonia in 4, cardiogenic shock in 1, and cardiac arrest in 1. Seven patients had a history of cardiovascular disease, including atrial fibrillation in four, coronary artery disease in three, left ventricular hypertrophy in one, and previous valve replacement in one. A total of 16 had hypertension, 7 had diabetes mellitus, and 1 had chronic obstructive pulmonary disease. In four cases, mild pericarditis was present. Acute myocyte injury in the right ventricle, most probably from strain or overload, was also present in four cases.

A nonsignificant trend was seen toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. There were no reports of disrupted coronary artery plaques, coronary artery aneurysms, or large pulmonary emboli.

Macrophage infiltration rather than myocarditis, myocardial injury?

The study sheds more light on previous cardiac magnetic resonance (CMR) imaging findings that have suggested that many patients who recover from COVID-19 show signs suggestive of myocarditis. These earlier studies include a recent one in competitive athletes and the earlier Puntmann and colleagues study of relatively young COVID-19 patients, which showed ongoing myocardial involvement in a majority of patients.

“It would not surprise me if some or all of the cardiac MR changes seen in some of these recent imaging studies are due to the macrophages,” said Dr. Stone.

“What we saw was not a routine pathology by any means. It was a huge amount of macrophages, higher that what we saw in SARS and more similar to a study published in 2007 that looked at patients with bacterial sepsis,” said Dr. Stone.

In an older study of SARS patients, 35% had the virus detected in myocardial tissue by polymerase chain reaction. In that subset, the degree of myocardial macrophage infiltrate was comparable to that seen in 86% of the COVID-19 cases described in this series.

Another possibility is that the macrophage infiltration reflects underlying disease rather than COVID-19. All but one of the patients had known underlying medical conditions associated with cardiac remodeling, said Nikolaos G. Frangogiannis, MD, a cardiologist who studies the mechanisms of cardiac injury, repair, and remodeling.

Frangogiannis, from Albert Einstein College of Medicine, New York, wrote an editorial that accompanied the autopsy study.

“The problem with this finding of increased macrophage infiltration is that it’s very hard to interpret because as we age, and especially in a less healthy population, the numbers and the density of macrophages in the heart increase, so it’s impossible to interpret as an effect of the infection itself unless you have an appropriate control population that matches the same characteristics, which is almost impossible to ask for,” he said.

“I’ve observed since the beginning of the pandemic that there seemed to be some people who wanted every single case to be myocarditis and others who had a bias toward not wanting COVID-19 to be a cause of myocarditis. I think what we’re seeing is it’s not either/or for anything with this virus, it’s a bit of everything,” said Dr. Stone.

Dr. Stone and Dr. Frangogiannis reported no conflict of interest.
 

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

An international autopsy study of 21 patients who died from COVID-19 has shown the presence of multifocal lymphocytic myocarditis in three patients (14%). In an additional six patients, focally increased interstitial T-lymphocytes within the myocardium were noted, with only focal or no myocyte injury.

However, increased interstitial macrophage infiltration, possibly related to cytokine infiltration, was seen in 86% of patients.

“One way to think about this is that, if these patients were having biopsies and not autopsies, there would be myocardial injury in the patients with myocarditis, even after they recovered. But with interstitial macrophages, there may or may not be any injury,” said cardiovascular pathologist James R. Stone, MD, PhD, Massachusetts General Hospital, Boston.

Dr. Stone and colleagues from Mass General, two hospitals in Italy, the University of Amsterdam, and the Mayo Clinic in Rochester, Minn., conducted the autopsies in March and April. The results were published in the October 14 issue of the European Heart Journal.

Their technique was rigorous: a median of 20 full-thickness blocks of myocardium were examined histologically (range, 5-29 blocks).

The presence of myocarditis, defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analyzed by immunohistochemistry.

“I think one of the take-homes from this study is that you have to do a thorough sampling of the heart in order to exclude myocardial injury. You cannot exclude myocarditis with just a biopsy or two,” said Dr. Stone in an interview.

“We looked at multiple different sections of tissue preserved in paraffin for every case and found only 14% had myocarditis. The vast majority of autopsies done on patients dying from COVID-19 have short-changed the autopsy and not been done in a way to exclude myocarditis,” he added.

For all patients, COVID-19 was the underlying cause of death, but the mechanisms of death were acute respiratory distress syndrome in 15, viral pneumonia in 4, cardiogenic shock in 1, and cardiac arrest in 1. Seven patients had a history of cardiovascular disease, including atrial fibrillation in four, coronary artery disease in three, left ventricular hypertrophy in one, and previous valve replacement in one. A total of 16 had hypertension, 7 had diabetes mellitus, and 1 had chronic obstructive pulmonary disease. In four cases, mild pericarditis was present. Acute myocyte injury in the right ventricle, most probably from strain or overload, was also present in four cases.

A nonsignificant trend was seen toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. There were no reports of disrupted coronary artery plaques, coronary artery aneurysms, or large pulmonary emboli.

Macrophage infiltration rather than myocarditis, myocardial injury?

The study sheds more light on previous cardiac magnetic resonance (CMR) imaging findings that have suggested that many patients who recover from COVID-19 show signs suggestive of myocarditis. These earlier studies include a recent one in competitive athletes and the earlier Puntmann and colleagues study of relatively young COVID-19 patients, which showed ongoing myocardial involvement in a majority of patients.

“It would not surprise me if some or all of the cardiac MR changes seen in some of these recent imaging studies are due to the macrophages,” said Dr. Stone.

“What we saw was not a routine pathology by any means. It was a huge amount of macrophages, higher that what we saw in SARS and more similar to a study published in 2007 that looked at patients with bacterial sepsis,” said Dr. Stone.

In an older study of SARS patients, 35% had the virus detected in myocardial tissue by polymerase chain reaction. In that subset, the degree of myocardial macrophage infiltrate was comparable to that seen in 86% of the COVID-19 cases described in this series.

Another possibility is that the macrophage infiltration reflects underlying disease rather than COVID-19. All but one of the patients had known underlying medical conditions associated with cardiac remodeling, said Nikolaos G. Frangogiannis, MD, a cardiologist who studies the mechanisms of cardiac injury, repair, and remodeling.

Frangogiannis, from Albert Einstein College of Medicine, New York, wrote an editorial that accompanied the autopsy study.

“The problem with this finding of increased macrophage infiltration is that it’s very hard to interpret because as we age, and especially in a less healthy population, the numbers and the density of macrophages in the heart increase, so it’s impossible to interpret as an effect of the infection itself unless you have an appropriate control population that matches the same characteristics, which is almost impossible to ask for,” he said.

“I’ve observed since the beginning of the pandemic that there seemed to be some people who wanted every single case to be myocarditis and others who had a bias toward not wanting COVID-19 to be a cause of myocarditis. I think what we’re seeing is it’s not either/or for anything with this virus, it’s a bit of everything,” said Dr. Stone.

Dr. Stone and Dr. Frangogiannis reported no conflict of interest.
 

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

An international autopsy study of 21 patients who died from COVID-19 has shown the presence of multifocal lymphocytic myocarditis in three patients (14%). In an additional six patients, focally increased interstitial T-lymphocytes within the myocardium were noted, with only focal or no myocyte injury.

However, increased interstitial macrophage infiltration, possibly related to cytokine infiltration, was seen in 86% of patients.

“One way to think about this is that, if these patients were having biopsies and not autopsies, there would be myocardial injury in the patients with myocarditis, even after they recovered. But with interstitial macrophages, there may or may not be any injury,” said cardiovascular pathologist James R. Stone, MD, PhD, Massachusetts General Hospital, Boston.

Dr. Stone and colleagues from Mass General, two hospitals in Italy, the University of Amsterdam, and the Mayo Clinic in Rochester, Minn., conducted the autopsies in March and April. The results were published in the October 14 issue of the European Heart Journal.

Their technique was rigorous: a median of 20 full-thickness blocks of myocardium were examined histologically (range, 5-29 blocks).

The presence of myocarditis, defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analyzed by immunohistochemistry.

“I think one of the take-homes from this study is that you have to do a thorough sampling of the heart in order to exclude myocardial injury. You cannot exclude myocarditis with just a biopsy or two,” said Dr. Stone in an interview.

“We looked at multiple different sections of tissue preserved in paraffin for every case and found only 14% had myocarditis. The vast majority of autopsies done on patients dying from COVID-19 have short-changed the autopsy and not been done in a way to exclude myocarditis,” he added.

For all patients, COVID-19 was the underlying cause of death, but the mechanisms of death were acute respiratory distress syndrome in 15, viral pneumonia in 4, cardiogenic shock in 1, and cardiac arrest in 1. Seven patients had a history of cardiovascular disease, including atrial fibrillation in four, coronary artery disease in three, left ventricular hypertrophy in one, and previous valve replacement in one. A total of 16 had hypertension, 7 had diabetes mellitus, and 1 had chronic obstructive pulmonary disease. In four cases, mild pericarditis was present. Acute myocyte injury in the right ventricle, most probably from strain or overload, was also present in four cases.

A nonsignificant trend was seen toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. There were no reports of disrupted coronary artery plaques, coronary artery aneurysms, or large pulmonary emboli.

Macrophage infiltration rather than myocarditis, myocardial injury?

The study sheds more light on previous cardiac magnetic resonance (CMR) imaging findings that have suggested that many patients who recover from COVID-19 show signs suggestive of myocarditis. These earlier studies include a recent one in competitive athletes and the earlier Puntmann and colleagues study of relatively young COVID-19 patients, which showed ongoing myocardial involvement in a majority of patients.

“It would not surprise me if some or all of the cardiac MR changes seen in some of these recent imaging studies are due to the macrophages,” said Dr. Stone.

“What we saw was not a routine pathology by any means. It was a huge amount of macrophages, higher that what we saw in SARS and more similar to a study published in 2007 that looked at patients with bacterial sepsis,” said Dr. Stone.

In an older study of SARS patients, 35% had the virus detected in myocardial tissue by polymerase chain reaction. In that subset, the degree of myocardial macrophage infiltrate was comparable to that seen in 86% of the COVID-19 cases described in this series.

Another possibility is that the macrophage infiltration reflects underlying disease rather than COVID-19. All but one of the patients had known underlying medical conditions associated with cardiac remodeling, said Nikolaos G. Frangogiannis, MD, a cardiologist who studies the mechanisms of cardiac injury, repair, and remodeling.

Frangogiannis, from Albert Einstein College of Medicine, New York, wrote an editorial that accompanied the autopsy study.

“The problem with this finding of increased macrophage infiltration is that it’s very hard to interpret because as we age, and especially in a less healthy population, the numbers and the density of macrophages in the heart increase, so it’s impossible to interpret as an effect of the infection itself unless you have an appropriate control population that matches the same characteristics, which is almost impossible to ask for,” he said.

“I’ve observed since the beginning of the pandemic that there seemed to be some people who wanted every single case to be myocarditis and others who had a bias toward not wanting COVID-19 to be a cause of myocarditis. I think what we’re seeing is it’s not either/or for anything with this virus, it’s a bit of everything,” said Dr. Stone.

Dr. Stone and Dr. Frangogiannis reported no conflict of interest.
 

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

There is a link between liver injury and a tendency toward excessive clotting in patients with COVID-19, and the organ’s own blood vessels could be responsible, new research shows.

Cells that line the liver’s blood vessels produce high levels of factor VIII, a coagulation factor, when they are exposed to interleukin-6, an inflammatory molecule associated with COVID-19.

These findings “center the liver in global coagulopathy of COVID-19 and define a mechanism for increased coagulation factor levels that may be treatment targets,” said investigator Matthew McConnell, MD, from the Yale University, New Haven, Conn.

The effect of IL-6 on the liver sinusoidal endothelial cells lining the liver blood vessels creates a prothrombotic environment that includes the release of factor VIII, said Dr. McConnell, who presented the results at the virtual annual meeting of the American Association for the Study of Liver Diseases.

These associations offer insights into why COVID-19 patients with underlying liver disease can experience “devastating complications” related to improper blood vessel function in the organ, he added.

For their study, Dr. McConnell and colleagues analyzed data on ALT and hypercoagulability from 68 adults treated at the Yale–New Haven Hospital. The liver and coagulation tests were administered within 5 days of each other.

The team set the ALT cutoff for liver injury at three times the upper limit of normal. Patients with two or more parameters indicating excessive clotting were considered to have a hypercoagulable profile, which Dr. McConnell called “a signature clinical finding of COVID-19 infection.”

Patients with high levels of ALT also experienced elevations in clotting-related factors, such as fibrinogen levels and the activity of factor VIII and factor II. Furthermore, liver injury was significantly associated with hypercoagulability (P < .05).

Because COVID-19 is linked to the proinflammatory IL-6, the investigators examined how this cytokine and its receptor affect human liver sinusoidal cells. Cells exposed to IL-6 and its receptor pumped out factor VIII at levels that were significantly higher than in unexposed cells (P < .01). Exposed cells also produced significantly more von Willebrand factor (P < .05), another prothrombotic molecule, and showed increased expression of genes that induce the expression of factor VIII.

“As we learn more about COVID-19, we find that it is as much a coagulatory as a respiratory disease,” said Tien Dong, MD, PhD, from the University of California, Los Angeles, who was not involved in the study.

These findings are in line with a lot of other COVID-19-related research that suggests a link between hepatocyte injury and clotting disorders, he added.

One important factor is existing liver disease, said Dr. Dong. “If you have COVID-19 on top of that, you’re probably at risk of developing acute liver injury from the infection itself.”

That said, it’s still a good idea to check liver function in patients with COVID-19 and no known liver disease, he advised. Staying on top of these measures will keep the odds of long-term problems “a lot lower.”

There is utility in the findings beyond COVID-19, said Dr. McConnell. They provide “insights into complications of critical illness, in general, in the liver blood vessels” of patients with underlying liver disease.

Dr. McConnell and Dr. Dong have disclosed no relevant financial relationships.

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

There is a link between liver injury and a tendency toward excessive clotting in patients with COVID-19, and the organ’s own blood vessels could be responsible, new research shows.

Cells that line the liver’s blood vessels produce high levels of factor VIII, a coagulation factor, when they are exposed to interleukin-6, an inflammatory molecule associated with COVID-19.

These findings “center the liver in global coagulopathy of COVID-19 and define a mechanism for increased coagulation factor levels that may be treatment targets,” said investigator Matthew McConnell, MD, from the Yale University, New Haven, Conn.

The effect of IL-6 on the liver sinusoidal endothelial cells lining the liver blood vessels creates a prothrombotic environment that includes the release of factor VIII, said Dr. McConnell, who presented the results at the virtual annual meeting of the American Association for the Study of Liver Diseases.

These associations offer insights into why COVID-19 patients with underlying liver disease can experience “devastating complications” related to improper blood vessel function in the organ, he added.

For their study, Dr. McConnell and colleagues analyzed data on ALT and hypercoagulability from 68 adults treated at the Yale–New Haven Hospital. The liver and coagulation tests were administered within 5 days of each other.

The team set the ALT cutoff for liver injury at three times the upper limit of normal. Patients with two or more parameters indicating excessive clotting were considered to have a hypercoagulable profile, which Dr. McConnell called “a signature clinical finding of COVID-19 infection.”

Patients with high levels of ALT also experienced elevations in clotting-related factors, such as fibrinogen levels and the activity of factor VIII and factor II. Furthermore, liver injury was significantly associated with hypercoagulability (P < .05).

Because COVID-19 is linked to the proinflammatory IL-6, the investigators examined how this cytokine and its receptor affect human liver sinusoidal cells. Cells exposed to IL-6 and its receptor pumped out factor VIII at levels that were significantly higher than in unexposed cells (P < .01). Exposed cells also produced significantly more von Willebrand factor (P < .05), another prothrombotic molecule, and showed increased expression of genes that induce the expression of factor VIII.

“As we learn more about COVID-19, we find that it is as much a coagulatory as a respiratory disease,” said Tien Dong, MD, PhD, from the University of California, Los Angeles, who was not involved in the study.

These findings are in line with a lot of other COVID-19-related research that suggests a link between hepatocyte injury and clotting disorders, he added.

One important factor is existing liver disease, said Dr. Dong. “If you have COVID-19 on top of that, you’re probably at risk of developing acute liver injury from the infection itself.”

That said, it’s still a good idea to check liver function in patients with COVID-19 and no known liver disease, he advised. Staying on top of these measures will keep the odds of long-term problems “a lot lower.”

There is utility in the findings beyond COVID-19, said Dr. McConnell. They provide “insights into complications of critical illness, in general, in the liver blood vessels” of patients with underlying liver disease.

Dr. McConnell and Dr. Dong have disclosed no relevant financial relationships.

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

There is a link between liver injury and a tendency toward excessive clotting in patients with COVID-19, and the organ’s own blood vessels could be responsible, new research shows.

Cells that line the liver’s blood vessels produce high levels of factor VIII, a coagulation factor, when they are exposed to interleukin-6, an inflammatory molecule associated with COVID-19.

These findings “center the liver in global coagulopathy of COVID-19 and define a mechanism for increased coagulation factor levels that may be treatment targets,” said investigator Matthew McConnell, MD, from the Yale University, New Haven, Conn.

The effect of IL-6 on the liver sinusoidal endothelial cells lining the liver blood vessels creates a prothrombotic environment that includes the release of factor VIII, said Dr. McConnell, who presented the results at the virtual annual meeting of the American Association for the Study of Liver Diseases.

These associations offer insights into why COVID-19 patients with underlying liver disease can experience “devastating complications” related to improper blood vessel function in the organ, he added.

For their study, Dr. McConnell and colleagues analyzed data on ALT and hypercoagulability from 68 adults treated at the Yale–New Haven Hospital. The liver and coagulation tests were administered within 5 days of each other.

The team set the ALT cutoff for liver injury at three times the upper limit of normal. Patients with two or more parameters indicating excessive clotting were considered to have a hypercoagulable profile, which Dr. McConnell called “a signature clinical finding of COVID-19 infection.”

Patients with high levels of ALT also experienced elevations in clotting-related factors, such as fibrinogen levels and the activity of factor VIII and factor II. Furthermore, liver injury was significantly associated with hypercoagulability (P < .05).

Because COVID-19 is linked to the proinflammatory IL-6, the investigators examined how this cytokine and its receptor affect human liver sinusoidal cells. Cells exposed to IL-6 and its receptor pumped out factor VIII at levels that were significantly higher than in unexposed cells (P < .01). Exposed cells also produced significantly more von Willebrand factor (P < .05), another prothrombotic molecule, and showed increased expression of genes that induce the expression of factor VIII.

“As we learn more about COVID-19, we find that it is as much a coagulatory as a respiratory disease,” said Tien Dong, MD, PhD, from the University of California, Los Angeles, who was not involved in the study.

These findings are in line with a lot of other COVID-19-related research that suggests a link between hepatocyte injury and clotting disorders, he added.

One important factor is existing liver disease, said Dr. Dong. “If you have COVID-19 on top of that, you’re probably at risk of developing acute liver injury from the infection itself.”

That said, it’s still a good idea to check liver function in patients with COVID-19 and no known liver disease, he advised. Staying on top of these measures will keep the odds of long-term problems “a lot lower.”

There is utility in the findings beyond COVID-19, said Dr. McConnell. They provide “insights into complications of critical illness, in general, in the liver blood vessels” of patients with underlying liver disease.

Dr. McConnell and Dr. Dong have disclosed no relevant financial relationships.

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

More patients are surviving critical illnesses requiring ICU care but many emerge with physical debility that may or may not eventually resolve.

Over the past decade, functional status deterioration after critical illness has become more common and of greater magnitude, despite concurrent efforts to reduce post–intensive care syndrome, based on a retrospective analysis of more than 100,000 patients.

Almost one-third of patients who survived nonsurgical ICU admission had evidence of functional status decline, reported lead author Nicholas E. Ingraham, MD, of the University of Minnesota, Minneapolis, and colleagues.

“Increasing capacity and decreasing mortality have created an evolving and diverse population of ICU survivors,” the investigators wrote in Critical Care Medicine. “Today’s survivors of critical illness are increasingly burdened by extensive physical and psychological comorbidities, often resulting in reduced quality of life.”

To determine trends in post–intensive care syndrome from 2008 to 2016, Dr. Ingraham and colleagues analyzed data from the Cerner Acute Physiology and Chronic Health Evaluation outcomes database, a national prospective cohort. Out of 202,786 adult patients admitted to the ICU, 129,917 were eligible for the study. Patients were excluded because of surgical admission, death, lack of functional status documentation, or inadequate hospital size or duration of participation. The final dataset had a median age of 63 years, with a slight predominance of male patients (54.0%). Most patients (80.9%) were White.

The primary outcome was defined as presence or absence of functional status deterioration, based on functional status at admission versus time of discharge. The secondary outcome was magnitude of deterioration over time.

The analysis, which controlled for age and severity of illness, revealed concerning trends for both outcomes.

Across the entire cohort 38,116 patients (29.3%) had functional status deterioration, with a 15% increase in prevalence over the course of the decade that spanned all disease categories (prevalence rate ratio, 1.15; 95% confidence interval, 1.13-1.17; P < .001). The magnitude of functional status decline also increased by 4% (odds ratio, 1.04; P < .001), with all but nonsurgical trauma patients showing greater deterioration over time.

“However, despite the decreasing magnitude of functional status deterioration in nonsurgical trauma, many admission diagnoses in this category remain in the top quartile of higher risk for functional status deterioration,” the investigators noted.

Functional status decline was most common among patients with head and polytrauma (OR, 3.39), followed closely by chest and spine trauma (OR, 3.38), and spine trauma (OR, 3.19). The top quartile of categories for prevalence of deterioration included nonsurgical trauma, neurologic, pulmonary, and gastrointestinal diseases.

Functional status decline was least common among patients diagnosed with diabetic ketoacidosis (OR, 0.27) or asthma (OR, 0.35).

“We believe our study provides important information that can be used in beginning to identify patients at high risk of functional status decline,” the investigators concluded. “Improving the identification of these patients and targeting appropriate interventions to mitigate this decline will be important directions for future studies in this area.”

According to David L. Bowton, MD, FCCP, professor emeritus, section on critical care, Wake Forest Baptist Health, Winston-Salem, N.C., the findings show just how common functional decline is after critical illness, and may actually underestimate prevalence.

“Because the authors employed a course evaluation tool employing only three categories of ability/disability and abstracted the level of disability from the medical record, they likely underestimated the frequency of clinically important, though not detected, disability at the time of hospital discharge,” Dr. Bowton said. “The study did not address cognitive impairment which can be detected in half of patients at 3 months following critical illness, and which significantly affects patients’ quality of life (Am J Respir Crit Care Med. 2020;202[2]:193-201).”

Dr. Bowton suggested that evidence-based methods of preventing post–intensive care syndrome are limited.

“Current efforts to improve post-ICU functional and cognitive outcomes suffer from the lack of proven effective interventions (Crit Care Med. 2019;47[11]:1607-18),” he said. “Observational data indicates that compliance with the ABCDEF bundle decreases the duration and incidence of delirium, ICU length of stay, duration of mechanical ventilation, and mortality (Crit Care Med. 2019;47[1]:3-14). However, the implications of these improvements on postdischarge functional outcomes are unknown as area the relative importance of individual elements of the bundle. Early mobility and patient and family diaries appear to improve functional status at discharge and postdischarge anxiety and depression, though the evidence supporting this is thin.”

Appropriate intervention may be especially challenging during the COVID-19 pandemic, he added.

“The impact of COVID on ICU staffing adequacy and stress is significant and the impact on quality bundle compliance and the availability of support services is currently not clear, but likely to be detrimental, especially to support services such as physical therapy that are already commonly understaffed,” Dr. Bowton said.

The study was supported by grants from the University of Minnesota’s Critical Care Research and Programmatic Development Program; the National Heart, Lung, and Blood Institute; and the University of Minnesota Clinical and Translational Science via the National Center for Advancing Translational Sciences. The investigators reported financial relationships with no other relevant organizations. Dr. Bowton reported no conflicts of interest.

SOURCE: Ingraham NE et al. Crit Care Med. 2020 Nov. doi: 10.1097/CCM.0000000000004524.

More patients are surviving critical illnesses requiring ICU care but many emerge with physical debility that may or may not eventually resolve.

Over the past decade, functional status deterioration after critical illness has become more common and of greater magnitude, despite concurrent efforts to reduce post–intensive care syndrome, based on a retrospective analysis of more than 100,000 patients.

Almost one-third of patients who survived nonsurgical ICU admission had evidence of functional status decline, reported lead author Nicholas E. Ingraham, MD, of the University of Minnesota, Minneapolis, and colleagues.

“Increasing capacity and decreasing mortality have created an evolving and diverse population of ICU survivors,” the investigators wrote in Critical Care Medicine. “Today’s survivors of critical illness are increasingly burdened by extensive physical and psychological comorbidities, often resulting in reduced quality of life.”

To determine trends in post–intensive care syndrome from 2008 to 2016, Dr. Ingraham and colleagues analyzed data from the Cerner Acute Physiology and Chronic Health Evaluation outcomes database, a national prospective cohort. Out of 202,786 adult patients admitted to the ICU, 129,917 were eligible for the study. Patients were excluded because of surgical admission, death, lack of functional status documentation, or inadequate hospital size or duration of participation. The final dataset had a median age of 63 years, with a slight predominance of male patients (54.0%). Most patients (80.9%) were White.

The primary outcome was defined as presence or absence of functional status deterioration, based on functional status at admission versus time of discharge. The secondary outcome was magnitude of deterioration over time.

The analysis, which controlled for age and severity of illness, revealed concerning trends for both outcomes.

Across the entire cohort 38,116 patients (29.3%) had functional status deterioration, with a 15% increase in prevalence over the course of the decade that spanned all disease categories (prevalence rate ratio, 1.15; 95% confidence interval, 1.13-1.17; P < .001). The magnitude of functional status decline also increased by 4% (odds ratio, 1.04; P < .001), with all but nonsurgical trauma patients showing greater deterioration over time.

“However, despite the decreasing magnitude of functional status deterioration in nonsurgical trauma, many admission diagnoses in this category remain in the top quartile of higher risk for functional status deterioration,” the investigators noted.

Functional status decline was most common among patients with head and polytrauma (OR, 3.39), followed closely by chest and spine trauma (OR, 3.38), and spine trauma (OR, 3.19). The top quartile of categories for prevalence of deterioration included nonsurgical trauma, neurologic, pulmonary, and gastrointestinal diseases.

Functional status decline was least common among patients diagnosed with diabetic ketoacidosis (OR, 0.27) or asthma (OR, 0.35).

“We believe our study provides important information that can be used in beginning to identify patients at high risk of functional status decline,” the investigators concluded. “Improving the identification of these patients and targeting appropriate interventions to mitigate this decline will be important directions for future studies in this area.”

According to David L. Bowton, MD, FCCP, professor emeritus, section on critical care, Wake Forest Baptist Health, Winston-Salem, N.C., the findings show just how common functional decline is after critical illness, and may actually underestimate prevalence.

“Because the authors employed a course evaluation tool employing only three categories of ability/disability and abstracted the level of disability from the medical record, they likely underestimated the frequency of clinically important, though not detected, disability at the time of hospital discharge,” Dr. Bowton said. “The study did not address cognitive impairment which can be detected in half of patients at 3 months following critical illness, and which significantly affects patients’ quality of life (Am J Respir Crit Care Med. 2020;202[2]:193-201).”

Dr. Bowton suggested that evidence-based methods of preventing post–intensive care syndrome are limited.

“Current efforts to improve post-ICU functional and cognitive outcomes suffer from the lack of proven effective interventions (Crit Care Med. 2019;47[11]:1607-18),” he said. “Observational data indicates that compliance with the ABCDEF bundle decreases the duration and incidence of delirium, ICU length of stay, duration of mechanical ventilation, and mortality (Crit Care Med. 2019;47[1]:3-14). However, the implications of these improvements on postdischarge functional outcomes are unknown as area the relative importance of individual elements of the bundle. Early mobility and patient and family diaries appear to improve functional status at discharge and postdischarge anxiety and depression, though the evidence supporting this is thin.”

Appropriate intervention may be especially challenging during the COVID-19 pandemic, he added.

“The impact of COVID on ICU staffing adequacy and stress is significant and the impact on quality bundle compliance and the availability of support services is currently not clear, but likely to be detrimental, especially to support services such as physical therapy that are already commonly understaffed,” Dr. Bowton said.

The study was supported by grants from the University of Minnesota’s Critical Care Research and Programmatic Development Program; the National Heart, Lung, and Blood Institute; and the University of Minnesota Clinical and Translational Science via the National Center for Advancing Translational Sciences. The investigators reported financial relationships with no other relevant organizations. Dr. Bowton reported no conflicts of interest.

SOURCE: Ingraham NE et al. Crit Care Med. 2020 Nov. doi: 10.1097/CCM.0000000000004524.

More patients are surviving critical illnesses requiring ICU care but many emerge with physical debility that may or may not eventually resolve.

Over the past decade, functional status deterioration after critical illness has become more common and of greater magnitude, despite concurrent efforts to reduce post–intensive care syndrome, based on a retrospective analysis of more than 100,000 patients.

Almost one-third of patients who survived nonsurgical ICU admission had evidence of functional status decline, reported lead author Nicholas E. Ingraham, MD, of the University of Minnesota, Minneapolis, and colleagues.

“Increasing capacity and decreasing mortality have created an evolving and diverse population of ICU survivors,” the investigators wrote in Critical Care Medicine. “Today’s survivors of critical illness are increasingly burdened by extensive physical and psychological comorbidities, often resulting in reduced quality of life.”

To determine trends in post–intensive care syndrome from 2008 to 2016, Dr. Ingraham and colleagues analyzed data from the Cerner Acute Physiology and Chronic Health Evaluation outcomes database, a national prospective cohort. Out of 202,786 adult patients admitted to the ICU, 129,917 were eligible for the study. Patients were excluded because of surgical admission, death, lack of functional status documentation, or inadequate hospital size or duration of participation. The final dataset had a median age of 63 years, with a slight predominance of male patients (54.0%). Most patients (80.9%) were White.

The primary outcome was defined as presence or absence of functional status deterioration, based on functional status at admission versus time of discharge. The secondary outcome was magnitude of deterioration over time.

The analysis, which controlled for age and severity of illness, revealed concerning trends for both outcomes.

Across the entire cohort 38,116 patients (29.3%) had functional status deterioration, with a 15% increase in prevalence over the course of the decade that spanned all disease categories (prevalence rate ratio, 1.15; 95% confidence interval, 1.13-1.17; P < .001). The magnitude of functional status decline also increased by 4% (odds ratio, 1.04; P < .001), with all but nonsurgical trauma patients showing greater deterioration over time.

“However, despite the decreasing magnitude of functional status deterioration in nonsurgical trauma, many admission diagnoses in this category remain in the top quartile of higher risk for functional status deterioration,” the investigators noted.

Functional status decline was most common among patients with head and polytrauma (OR, 3.39), followed closely by chest and spine trauma (OR, 3.38), and spine trauma (OR, 3.19). The top quartile of categories for prevalence of deterioration included nonsurgical trauma, neurologic, pulmonary, and gastrointestinal diseases.

Functional status decline was least common among patients diagnosed with diabetic ketoacidosis (OR, 0.27) or asthma (OR, 0.35).

“We believe our study provides important information that can be used in beginning to identify patients at high risk of functional status decline,” the investigators concluded. “Improving the identification of these patients and targeting appropriate interventions to mitigate this decline will be important directions for future studies in this area.”

According to David L. Bowton, MD, FCCP, professor emeritus, section on critical care, Wake Forest Baptist Health, Winston-Salem, N.C., the findings show just how common functional decline is after critical illness, and may actually underestimate prevalence.

“Because the authors employed a course evaluation tool employing only three categories of ability/disability and abstracted the level of disability from the medical record, they likely underestimated the frequency of clinically important, though not detected, disability at the time of hospital discharge,” Dr. Bowton said. “The study did not address cognitive impairment which can be detected in half of patients at 3 months following critical illness, and which significantly affects patients’ quality of life (Am J Respir Crit Care Med. 2020;202[2]:193-201).”

Dr. Bowton suggested that evidence-based methods of preventing post–intensive care syndrome are limited.

“Current efforts to improve post-ICU functional and cognitive outcomes suffer from the lack of proven effective interventions (Crit Care Med. 2019;47[11]:1607-18),” he said. “Observational data indicates that compliance with the ABCDEF bundle decreases the duration and incidence of delirium, ICU length of stay, duration of mechanical ventilation, and mortality (Crit Care Med. 2019;47[1]:3-14). However, the implications of these improvements on postdischarge functional outcomes are unknown as area the relative importance of individual elements of the bundle. Early mobility and patient and family diaries appear to improve functional status at discharge and postdischarge anxiety and depression, though the evidence supporting this is thin.”

Appropriate intervention may be especially challenging during the COVID-19 pandemic, he added.

“The impact of COVID on ICU staffing adequacy and stress is significant and the impact on quality bundle compliance and the availability of support services is currently not clear, but likely to be detrimental, especially to support services such as physical therapy that are already commonly understaffed,” Dr. Bowton said.

The study was supported by grants from the University of Minnesota’s Critical Care Research and Programmatic Development Program; the National Heart, Lung, and Blood Institute; and the University of Minnesota Clinical and Translational Science via the National Center for Advancing Translational Sciences. The investigators reported financial relationships with no other relevant organizations. Dr. Bowton reported no conflicts of interest.

SOURCE: Ingraham NE et al. Crit Care Med. 2020 Nov. doi: 10.1097/CCM.0000000000004524.

COVID-19 patients who survive their hospitalization don’t leave the disease behind upon discharge, as a significant percentage died within 60 days of discharge, with an ICU admission heightening the risk, according to an observational study of 38 Michigan hospitals. What’s more, many of them were burdened with health and emotional challenges ranging from hospital readmission to job loss and financial problems.

“These data confirm that the toll of COVID-19 extends well beyond hospitalization, a finding consistent with long-term sequelae from sepsis and other severe respiratory viral illnesses,” wrote lead author Vineet Chopra, MBBS, of the University of Michigan, Ann Arbor, and colleagues (Ann Intern Med. 2020 Nov 11: doi: 10.7326/M20-5661)

The researchers found that 29.2% of all patients hospitalized for COVID-19 from March 16 to July 1 died. The observational cohort study included 1,648 COVID-19 patients hospitalized at 38 Michigan hospitals participating in a statewide collaborative.

The bulk of those deaths occurred during hospitalization: 24.2% of patients (n = 398). Of the 1,250 patients discharged, 78% (n = 975) went home and 12.6% (n = 158) went to a skilled nursing facility, with the remainder unaccounted for. Within 60 days of discharge, 6.7% (n = 84) of hospitalized survivors had died and 15.2% (n = 189) were readmitted. The researchers gathered 60-day postdischarge data via a telephone survey, contacting 41.8% (n = 488) of discharged patients.

Outcomes were even worse for discharged patients who spent time in the ICU. The death rate among this group was 10.4% (17 of 165) after discharge. That resulted in an overall study death rate of 63.5% (n = 257) for the 405 patients who were in the ICU.

While the study data were in the first wave of the novel coronavirus, the findings have relevance today, said Mary Jo Farmer, MD, PhD, FCCP, directory of pulmonary hypertension services at Baystate Health in Springfield, Mass.

“This is the best information we have to date,” she said. “We have to continue to have an open mind and expect that this information may change as the virus possibly mutates as it spreads, and we should continue doing these types of outcomes studies at 90 days, 120 days, etc.”

The median age of study patients was 62, with a range of 50-72. The three leading comorbidities among discharged patients were hypertension (n = 800, 64%), diabetes (34.9%, n = 436), and cardiovascular disease (24.1%, n = 301).

Poor postdischarge outcomes weren’t limited to mortality and readmission. Almost 19% (n = 92) reported new or worsening cardiopulmonary symptoms such as cough and dyspnea, 13.3% had a persistent loss of taste or smell, and 12% (n = 58) reported more difficulty with daily living tasks.

The after-effects were not only physical. Nearly half of discharged patients (48.7%, n = 238) reported emotional effects and almost 6% (n = 28) sought mental health care. Among the 40% (n = 195) employed before they were hospitalized, 36% (n = 78) couldn’t return to work because of health issues or layoffs. Sixty percent (n = 117) of the pre-employed discharged patients did return to work, but 25% (n = 30) did so with reduced hours or modified job duties because of health problems.

Financial problems were also a burden. More than a third, 36.7% (n = 179), reported some financial impact from their hospitalization. About 10% (n = 47) said they used most or all of their savings, and 7% (n = 35) said they resorted to rationing necessities such as food or medications.

The researchers noted that one in five patients had no primary care follow-up at 2 months post discharge. “Collectively, these findings suggest that better models to support COVID-19 survivors are necessary,” said Dr. Chopra and colleagues.

The postdischarge course for patients involves two humps, said Sachin Gupta, MD, FCCP a pulmonary and critical care specialist at Alameda Health System in Oakland, Calif.: Getting over the hospitalization itself and the recovery phase. “As you look at the median age of the survivors, elderly patients who survive a hospital stay are still going to have a period of recovery, and like any viral illness that leads to someone being hospitalized, when you have an elderly patient with comorbidities, not all of them can make it over that final hump.”

SOURCE: Chopra V et al. Ann Intern Med. 2020 Nov 11. doi: 10.7326/M20-5661.

COVID-19 patients who survive their hospitalization don’t leave the disease behind upon discharge, as a significant percentage died within 60 days of discharge, with an ICU admission heightening the risk, according to an observational study of 38 Michigan hospitals. What’s more, many of them were burdened with health and emotional challenges ranging from hospital readmission to job loss and financial problems.

“These data confirm that the toll of COVID-19 extends well beyond hospitalization, a finding consistent with long-term sequelae from sepsis and other severe respiratory viral illnesses,” wrote lead author Vineet Chopra, MBBS, of the University of Michigan, Ann Arbor, and colleagues (Ann Intern Med. 2020 Nov 11: doi: 10.7326/M20-5661)

The researchers found that 29.2% of all patients hospitalized for COVID-19 from March 16 to July 1 died. The observational cohort study included 1,648 COVID-19 patients hospitalized at 38 Michigan hospitals participating in a statewide collaborative.

The bulk of those deaths occurred during hospitalization: 24.2% of patients (n = 398). Of the 1,250 patients discharged, 78% (n = 975) went home and 12.6% (n = 158) went to a skilled nursing facility, with the remainder unaccounted for. Within 60 days of discharge, 6.7% (n = 84) of hospitalized survivors had died and 15.2% (n = 189) were readmitted. The researchers gathered 60-day postdischarge data via a telephone survey, contacting 41.8% (n = 488) of discharged patients.

Outcomes were even worse for discharged patients who spent time in the ICU. The death rate among this group was 10.4% (17 of 165) after discharge. That resulted in an overall study death rate of 63.5% (n = 257) for the 405 patients who were in the ICU.

While the study data were in the first wave of the novel coronavirus, the findings have relevance today, said Mary Jo Farmer, MD, PhD, FCCP, directory of pulmonary hypertension services at Baystate Health in Springfield, Mass.

“This is the best information we have to date,” she said. “We have to continue to have an open mind and expect that this information may change as the virus possibly mutates as it spreads, and we should continue doing these types of outcomes studies at 90 days, 120 days, etc.”

The median age of study patients was 62, with a range of 50-72. The three leading comorbidities among discharged patients were hypertension (n = 800, 64%), diabetes (34.9%, n = 436), and cardiovascular disease (24.1%, n = 301).

Poor postdischarge outcomes weren’t limited to mortality and readmission. Almost 19% (n = 92) reported new or worsening cardiopulmonary symptoms such as cough and dyspnea, 13.3% had a persistent loss of taste or smell, and 12% (n = 58) reported more difficulty with daily living tasks.

The after-effects were not only physical. Nearly half of discharged patients (48.7%, n = 238) reported emotional effects and almost 6% (n = 28) sought mental health care. Among the 40% (n = 195) employed before they were hospitalized, 36% (n = 78) couldn’t return to work because of health issues or layoffs. Sixty percent (n = 117) of the pre-employed discharged patients did return to work, but 25% (n = 30) did so with reduced hours or modified job duties because of health problems.

Financial problems were also a burden. More than a third, 36.7% (n = 179), reported some financial impact from their hospitalization. About 10% (n = 47) said they used most or all of their savings, and 7% (n = 35) said they resorted to rationing necessities such as food or medications.

The researchers noted that one in five patients had no primary care follow-up at 2 months post discharge. “Collectively, these findings suggest that better models to support COVID-19 survivors are necessary,” said Dr. Chopra and colleagues.

The postdischarge course for patients involves two humps, said Sachin Gupta, MD, FCCP a pulmonary and critical care specialist at Alameda Health System in Oakland, Calif.: Getting over the hospitalization itself and the recovery phase. “As you look at the median age of the survivors, elderly patients who survive a hospital stay are still going to have a period of recovery, and like any viral illness that leads to someone being hospitalized, when you have an elderly patient with comorbidities, not all of them can make it over that final hump.”

SOURCE: Chopra V et al. Ann Intern Med. 2020 Nov 11. doi: 10.7326/M20-5661.

COVID-19 patients who survive their hospitalization don’t leave the disease behind upon discharge, as a significant percentage died within 60 days of discharge, with an ICU admission heightening the risk, according to an observational study of 38 Michigan hospitals. What’s more, many of them were burdened with health and emotional challenges ranging from hospital readmission to job loss and financial problems.

“These data confirm that the toll of COVID-19 extends well beyond hospitalization, a finding consistent with long-term sequelae from sepsis and other severe respiratory viral illnesses,” wrote lead author Vineet Chopra, MBBS, of the University of Michigan, Ann Arbor, and colleagues (Ann Intern Med. 2020 Nov 11: doi: 10.7326/M20-5661)

The researchers found that 29.2% of all patients hospitalized for COVID-19 from March 16 to July 1 died. The observational cohort study included 1,648 COVID-19 patients hospitalized at 38 Michigan hospitals participating in a statewide collaborative.

The bulk of those deaths occurred during hospitalization: 24.2% of patients (n = 398). Of the 1,250 patients discharged, 78% (n = 975) went home and 12.6% (n = 158) went to a skilled nursing facility, with the remainder unaccounted for. Within 60 days of discharge, 6.7% (n = 84) of hospitalized survivors had died and 15.2% (n = 189) were readmitted. The researchers gathered 60-day postdischarge data via a telephone survey, contacting 41.8% (n = 488) of discharged patients.

Outcomes were even worse for discharged patients who spent time in the ICU. The death rate among this group was 10.4% (17 of 165) after discharge. That resulted in an overall study death rate of 63.5% (n = 257) for the 405 patients who were in the ICU.

While the study data were in the first wave of the novel coronavirus, the findings have relevance today, said Mary Jo Farmer, MD, PhD, FCCP, directory of pulmonary hypertension services at Baystate Health in Springfield, Mass.

“This is the best information we have to date,” she said. “We have to continue to have an open mind and expect that this information may change as the virus possibly mutates as it spreads, and we should continue doing these types of outcomes studies at 90 days, 120 days, etc.”

The median age of study patients was 62, with a range of 50-72. The three leading comorbidities among discharged patients were hypertension (n = 800, 64%), diabetes (34.9%, n = 436), and cardiovascular disease (24.1%, n = 301).

Poor postdischarge outcomes weren’t limited to mortality and readmission. Almost 19% (n = 92) reported new or worsening cardiopulmonary symptoms such as cough and dyspnea, 13.3% had a persistent loss of taste or smell, and 12% (n = 58) reported more difficulty with daily living tasks.

The after-effects were not only physical. Nearly half of discharged patients (48.7%, n = 238) reported emotional effects and almost 6% (n = 28) sought mental health care. Among the 40% (n = 195) employed before they were hospitalized, 36% (n = 78) couldn’t return to work because of health issues or layoffs. Sixty percent (n = 117) of the pre-employed discharged patients did return to work, but 25% (n = 30) did so with reduced hours or modified job duties because of health problems.

Financial problems were also a burden. More than a third, 36.7% (n = 179), reported some financial impact from their hospitalization. About 10% (n = 47) said they used most or all of their savings, and 7% (n = 35) said they resorted to rationing necessities such as food or medications.

The researchers noted that one in five patients had no primary care follow-up at 2 months post discharge. “Collectively, these findings suggest that better models to support COVID-19 survivors are necessary,” said Dr. Chopra and colleagues.

The postdischarge course for patients involves two humps, said Sachin Gupta, MD, FCCP a pulmonary and critical care specialist at Alameda Health System in Oakland, Calif.: Getting over the hospitalization itself and the recovery phase. “As you look at the median age of the survivors, elderly patients who survive a hospital stay are still going to have a period of recovery, and like any viral illness that leads to someone being hospitalized, when you have an elderly patient with comorbidities, not all of them can make it over that final hump.”

SOURCE: Chopra V et al. Ann Intern Med. 2020 Nov 11. doi: 10.7326/M20-5661.

Factor XI has emerged as a promising target for new anticoagulants, and several strategies for inhibiting the enzyme to reduce stroke, thromboembolism, and bleeding risk are under investigation, according to Jeffrey I. Weitz, MD.

These strategies could pick up where direct-acting oral anticoagulants leave off, he suggested during a presentation at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

“We all know that the direct oral anticoagulants – the DOACs – are an advance over vitamin K antagonists,” said Dr. Weitz, professor of medicine and biochemistry at McMaster University, Hamilton, Ontario.

Not only are DOACs at least as effective as vitamin K antagonists such as warfarin for stroke prevention in atrial fibrillation or for treatment of venous thromboembolism (VTE), but they also reduce intracranial bleeding and major bleeding risk in those settings, respectively, and they are more convenient to administer because they can be delivered using fixed doses without the need for coagulation monitoring, he added.

Still, new targets are needed, he said, explaining that, although DOACs moved closer to the goal of attenuating thrombosis without increasing the risk of bleeding, annual rates of major bleeding remain at 2%-3% in the atrial fibrillation population, and rates of major and clinically relevant nonmajor bleeding are about 10%.

“The fear of bleeding leads to underuse of anticoagulants for eligible patients with atrial fibrillation and inappropriate use of low-dose [non–vitamin K antagonist oral anticoagulant] regimens, which can leave patients unprotected from thrombotic complications,” he said.
 

Factor XI

That’s where Factor XI (FXI) may come in, Dr. Weitz said.

Current anticoagulants target enzymes, including FXa or thrombin, in the common pathway of coagulation, but the intrinsic pathway at the level of FXI and FXII has attracted attention in recent years.

The intrinsic pathway is activated when blood comes into contact with medical devices like stents, mechanical heart valves, or central venous catheters, but evidence also suggests that it plays a role in clot stabilization and growth, he explained, noting additional evidence of attenuation of thrombosis in mice deficient in FXI or FXII and in animals with FXI or FXII inhibitors.

“There is no bleeding with congenital FXII deficiency, and patients with FXI deficiency rarely have spontaneous bleeding, although they can bleed with surgery or trauma,” he noted. “Therefore, the promise of contact pathway inhibition is that we can attenuate thrombosis with little or no disruption of hemostasis.”

The initiators of the intrinsic pathway are naturally occurring polyphosphates that can activate FXI and FXII, promote platelet activation, and lead to thrombosis. A number of agents are being investigated to target these enzymes – particularly FXI, for which the strongest epidemiological and other evidence of its link with thrombosis exists. He noted that FXI deficiency appears protective against deep-vein thrombosis (DVT) and ischemic stroke, whereas high levels are linked with an increased risk of venous and arterial thrombosis.

Investigative strategies include the use of antisense oligonucleotides to reduce hepatic synthesis of FXI, aptamers to bind FXI and block its activity, antibodies to bind FXI and block its activation or activity, and small molecules to bind reversibly to the active site of FXI and block its activity “much like the DOACs block the activity of FXa or thrombin.”

“We have to remember that the DOACs have taken over from vitamin K antagonists, like warfarin, for many indications, and as they go generic their uptake will increase even further,” Dr. Weitz said. “When we compare the FXI inhibitors with existing anticoagulants, we don’t necessarily want to go up against the DOACs – we’re looking for indications where [DOACs] have yet to be tested or may be unsafe.”

Potential indications include the following:

Prevention of major adverse cardiovascular events in patients with end-stage renal disease with or without atrial fibrillation.

Provision of a safer platform for antiplatelet therapy in patients with acute coronary syndrome.

Secondary stroke prevention.

Prevention or treatment of cancer-associated VTE.

Prevention of thrombosis associated with central venous catheters, left ventricular assist devices, or mechanical heart valves.

Agents in development

Of the FXI inhibitors in development, ISIS-FXI_Rx, an antisense oligonucleotide against FXI, is furthest along. In a study published in Blood, ISIS-FXI_Rx produced a dose-dependent and sustained reduction in FXI levels in healthy volunteers, and in a later randomized study published in The New England Journal of Medicine, it significantly reduced the incidence of DVT in patients undergoing voluntary total knee arthroplasty (30.4% with enoxaparin vs. 4.2% with ISIS-FXI_Rx at a dose of 300 mg). Bleeding rates were 8.3% and 2.6%, respectively.

The findings showed the potential for reducing thrombosis without increasing bleeding by targeting FXI, Dr. Weitz said, adding that ISIS-FXIR_x was also evaluated in a small study of patients with end-stage renal disease undergoing hemodialysis and was shown to produce a dose-dependent reduction in FXI levels and to reduce the incidence of category 3 and 4 clotting in the air trap and dialyzer, compared with placebo, when given in addition to heparin.

This suggests that FXI knockdown can attenuate device-associated clotting to a greater extent than heparin alone, Dr. Weitz said.

The FXIa-directed inhibitory antibody osocimab has also been evaluated in both healthy volunteers and in patients undergoing total knee arthroplasty. In a 2019 study of healthy volunteers, a single IV injection showed a dose-dependent pharmacokinetic profile and produced FXI inhibition for about 1 month, and in the FOXTROT trial published in January in JAMA by Dr. Weitz and colleagues, osocimab was shown to reduce the incidence of symptomatic VTE, asymptomatic DVT, and VTE-related death up to day 10-13 after total knee arthroplasty.

Osocimab at doses ranging from 0.3-1.8 mg/kg given postoperatively or preoperatively were noninferior to enoxaparin (rates of 15.7%-23.7% vs. 26.3%), and osocimab at a preoperative dose of 1.8 mg/kg was superior to both enoxaparin and apixaban (11.5% vs. 26.3% and 14.5%, respectively), he said.

Bleeding rates ranged from 0%-5% with osocimab, compared with 6% with enoxaparin and 2% with apixaban
 

Ongoing studies

Currently ongoing studies of FXI-directed anticoagulation strategies include a study comparing ISIS-FXI_Rx with placebo in 200 patients with end-stage renal disease, a study comparing osocimab with placebo in 600 patients with end-stage renal disease, and a study comparing abelacimab – an antibody that binds to FXI and prevents its activation by either FXIIa or thrombin, with enoxaparin in 700 patients undergoing total knee arthroplasty, Dr. Weitz said.

Additionally, there is “considerable activity” with small molecule inhibitors of FXIa, including a phase 2, placebo-controlled, dose-ranging study looking at the novel JNG-7003/BMS-986177 agent for secondary stroke/transient ischemic attack prevention in 2,500 patients and a phase 2 study comparing it with enoxaparin for postoperative thromboprophylaxis in 1,200 patients undergoing total knee arthroplasty.

Parallel phase 2 studies are also underway to compare the novel BAY-2433334 small molecule inhibitor with placebo for stroke/transient ischemic attack prevention, with apixaban for atrial fibrillation, and for prevention of major adverse cardiovascular events in patients with acute MI.

These ongoing trials will help determine the risk-benefit profile of FXI inhibitors he said.

Session comoderator Anne Rose, PharmD, pharmacy coordinator at the University of Wisconsin, Madison, noted that these types of agents have been discussed “for quite some time” and asked whether they will be available for use in clinical practice in the near future.

Dr. Weitz predicted it will be at least a few years. The studies are just now moving to phase 2b and will still need to be evaluated in phase 3 trials and for appropriate new indications, he said.

Dr. Weitz reported research support from Canadian Institutes of Health research, Heart and Stroke Foundation, and Canadian Fund for Innovation, and he is a consultant and/or scientific advisory board member for Anthos, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Pfizer, Portola, Servier , and Thetherex.

sworcester@mdedge.com

Factor XI has emerged as a promising target for new anticoagulants, and several strategies for inhibiting the enzyme to reduce stroke, thromboembolism, and bleeding risk are under investigation, according to Jeffrey I. Weitz, MD.

These strategies could pick up where direct-acting oral anticoagulants leave off, he suggested during a presentation at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

“We all know that the direct oral anticoagulants – the DOACs – are an advance over vitamin K antagonists,” said Dr. Weitz, professor of medicine and biochemistry at McMaster University, Hamilton, Ontario.

Not only are DOACs at least as effective as vitamin K antagonists such as warfarin for stroke prevention in atrial fibrillation or for treatment of venous thromboembolism (VTE), but they also reduce intracranial bleeding and major bleeding risk in those settings, respectively, and they are more convenient to administer because they can be delivered using fixed doses without the need for coagulation monitoring, he added.

Still, new targets are needed, he said, explaining that, although DOACs moved closer to the goal of attenuating thrombosis without increasing the risk of bleeding, annual rates of major bleeding remain at 2%-3% in the atrial fibrillation population, and rates of major and clinically relevant nonmajor bleeding are about 10%.

“The fear of bleeding leads to underuse of anticoagulants for eligible patients with atrial fibrillation and inappropriate use of low-dose [non–vitamin K antagonist oral anticoagulant] regimens, which can leave patients unprotected from thrombotic complications,” he said.
 

Factor XI

That’s where Factor XI (FXI) may come in, Dr. Weitz said.

Current anticoagulants target enzymes, including FXa or thrombin, in the common pathway of coagulation, but the intrinsic pathway at the level of FXI and FXII has attracted attention in recent years.

The intrinsic pathway is activated when blood comes into contact with medical devices like stents, mechanical heart valves, or central venous catheters, but evidence also suggests that it plays a role in clot stabilization and growth, he explained, noting additional evidence of attenuation of thrombosis in mice deficient in FXI or FXII and in animals with FXI or FXII inhibitors.

“There is no bleeding with congenital FXII deficiency, and patients with FXI deficiency rarely have spontaneous bleeding, although they can bleed with surgery or trauma,” he noted. “Therefore, the promise of contact pathway inhibition is that we can attenuate thrombosis with little or no disruption of hemostasis.”

The initiators of the intrinsic pathway are naturally occurring polyphosphates that can activate FXI and FXII, promote platelet activation, and lead to thrombosis. A number of agents are being investigated to target these enzymes – particularly FXI, for which the strongest epidemiological and other evidence of its link with thrombosis exists. He noted that FXI deficiency appears protective against deep-vein thrombosis (DVT) and ischemic stroke, whereas high levels are linked with an increased risk of venous and arterial thrombosis.

Investigative strategies include the use of antisense oligonucleotides to reduce hepatic synthesis of FXI, aptamers to bind FXI and block its activity, antibodies to bind FXI and block its activation or activity, and small molecules to bind reversibly to the active site of FXI and block its activity “much like the DOACs block the activity of FXa or thrombin.”

“We have to remember that the DOACs have taken over from vitamin K antagonists, like warfarin, for many indications, and as they go generic their uptake will increase even further,” Dr. Weitz said. “When we compare the FXI inhibitors with existing anticoagulants, we don’t necessarily want to go up against the DOACs – we’re looking for indications where [DOACs] have yet to be tested or may be unsafe.”

Potential indications include the following:

Prevention of major adverse cardiovascular events in patients with end-stage renal disease with or without atrial fibrillation.

Provision of a safer platform for antiplatelet therapy in patients with acute coronary syndrome.

Secondary stroke prevention.

Prevention or treatment of cancer-associated VTE.

Prevention of thrombosis associated with central venous catheters, left ventricular assist devices, or mechanical heart valves.

Agents in development

Of the FXI inhibitors in development, ISIS-FXI_Rx, an antisense oligonucleotide against FXI, is furthest along. In a study published in Blood, ISIS-FXI_Rx produced a dose-dependent and sustained reduction in FXI levels in healthy volunteers, and in a later randomized study published in The New England Journal of Medicine, it significantly reduced the incidence of DVT in patients undergoing voluntary total knee arthroplasty (30.4% with enoxaparin vs. 4.2% with ISIS-FXI_Rx at a dose of 300 mg). Bleeding rates were 8.3% and 2.6%, respectively.

The findings showed the potential for reducing thrombosis without increasing bleeding by targeting FXI, Dr. Weitz said, adding that ISIS-FXIR_x was also evaluated in a small study of patients with end-stage renal disease undergoing hemodialysis and was shown to produce a dose-dependent reduction in FXI levels and to reduce the incidence of category 3 and 4 clotting in the air trap and dialyzer, compared with placebo, when given in addition to heparin.

This suggests that FXI knockdown can attenuate device-associated clotting to a greater extent than heparin alone, Dr. Weitz said.

The FXIa-directed inhibitory antibody osocimab has also been evaluated in both healthy volunteers and in patients undergoing total knee arthroplasty. In a 2019 study of healthy volunteers, a single IV injection showed a dose-dependent pharmacokinetic profile and produced FXI inhibition for about 1 month, and in the FOXTROT trial published in January in JAMA by Dr. Weitz and colleagues, osocimab was shown to reduce the incidence of symptomatic VTE, asymptomatic DVT, and VTE-related death up to day 10-13 after total knee arthroplasty.

Osocimab at doses ranging from 0.3-1.8 mg/kg given postoperatively or preoperatively were noninferior to enoxaparin (rates of 15.7%-23.7% vs. 26.3%), and osocimab at a preoperative dose of 1.8 mg/kg was superior to both enoxaparin and apixaban (11.5% vs. 26.3% and 14.5%, respectively), he said.

Bleeding rates ranged from 0%-5% with osocimab, compared with 6% with enoxaparin and 2% with apixaban
 

Ongoing studies

Currently ongoing studies of FXI-directed anticoagulation strategies include a study comparing ISIS-FXI_Rx with placebo in 200 patients with end-stage renal disease, a study comparing osocimab with placebo in 600 patients with end-stage renal disease, and a study comparing abelacimab – an antibody that binds to FXI and prevents its activation by either FXIIa or thrombin, with enoxaparin in 700 patients undergoing total knee arthroplasty, Dr. Weitz said.

Additionally, there is “considerable activity” with small molecule inhibitors of FXIa, including a phase 2, placebo-controlled, dose-ranging study looking at the novel JNG-7003/BMS-986177 agent for secondary stroke/transient ischemic attack prevention in 2,500 patients and a phase 2 study comparing it with enoxaparin for postoperative thromboprophylaxis in 1,200 patients undergoing total knee arthroplasty.

Parallel phase 2 studies are also underway to compare the novel BAY-2433334 small molecule inhibitor with placebo for stroke/transient ischemic attack prevention, with apixaban for atrial fibrillation, and for prevention of major adverse cardiovascular events in patients with acute MI.

These ongoing trials will help determine the risk-benefit profile of FXI inhibitors he said.

Session comoderator Anne Rose, PharmD, pharmacy coordinator at the University of Wisconsin, Madison, noted that these types of agents have been discussed “for quite some time” and asked whether they will be available for use in clinical practice in the near future.

Dr. Weitz predicted it will be at least a few years. The studies are just now moving to phase 2b and will still need to be evaluated in phase 3 trials and for appropriate new indications, he said.

Dr. Weitz reported research support from Canadian Institutes of Health research, Heart and Stroke Foundation, and Canadian Fund for Innovation, and he is a consultant and/or scientific advisory board member for Anthos, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Pfizer, Portola, Servier , and Thetherex.

sworcester@mdedge.com

Factor XI has emerged as a promising target for new anticoagulants, and several strategies for inhibiting the enzyme to reduce stroke, thromboembolism, and bleeding risk are under investigation, according to Jeffrey I. Weitz, MD.

These strategies could pick up where direct-acting oral anticoagulants leave off, he suggested during a presentation at the biennial summit of the Thrombosis & Hemostasis Societies of North America.

“We all know that the direct oral anticoagulants – the DOACs – are an advance over vitamin K antagonists,” said Dr. Weitz, professor of medicine and biochemistry at McMaster University, Hamilton, Ontario.

Not only are DOACs at least as effective as vitamin K antagonists such as warfarin for stroke prevention in atrial fibrillation or for treatment of venous thromboembolism (VTE), but they also reduce intracranial bleeding and major bleeding risk in those settings, respectively, and they are more convenient to administer because they can be delivered using fixed doses without the need for coagulation monitoring, he added.

Still, new targets are needed, he said, explaining that, although DOACs moved closer to the goal of attenuating thrombosis without increasing the risk of bleeding, annual rates of major bleeding remain at 2%-3% in the atrial fibrillation population, and rates of major and clinically relevant nonmajor bleeding are about 10%.

“The fear of bleeding leads to underuse of anticoagulants for eligible patients with atrial fibrillation and inappropriate use of low-dose [non–vitamin K antagonist oral anticoagulant] regimens, which can leave patients unprotected from thrombotic complications,” he said.
 

Factor XI

That’s where Factor XI (FXI) may come in, Dr. Weitz said.

Current anticoagulants target enzymes, including FXa or thrombin, in the common pathway of coagulation, but the intrinsic pathway at the level of FXI and FXII has attracted attention in recent years.

The intrinsic pathway is activated when blood comes into contact with medical devices like stents, mechanical heart valves, or central venous catheters, but evidence also suggests that it plays a role in clot stabilization and growth, he explained, noting additional evidence of attenuation of thrombosis in mice deficient in FXI or FXII and in animals with FXI or FXII inhibitors.

“There is no bleeding with congenital FXII deficiency, and patients with FXI deficiency rarely have spontaneous bleeding, although they can bleed with surgery or trauma,” he noted. “Therefore, the promise of contact pathway inhibition is that we can attenuate thrombosis with little or no disruption of hemostasis.”

The initiators of the intrinsic pathway are naturally occurring polyphosphates that can activate FXI and FXII, promote platelet activation, and lead to thrombosis. A number of agents are being investigated to target these enzymes – particularly FXI, for which the strongest epidemiological and other evidence of its link with thrombosis exists. He noted that FXI deficiency appears protective against deep-vein thrombosis (DVT) and ischemic stroke, whereas high levels are linked with an increased risk of venous and arterial thrombosis.

Investigative strategies include the use of antisense oligonucleotides to reduce hepatic synthesis of FXI, aptamers to bind FXI and block its activity, antibodies to bind FXI and block its activation or activity, and small molecules to bind reversibly to the active site of FXI and block its activity “much like the DOACs block the activity of FXa or thrombin.”

“We have to remember that the DOACs have taken over from vitamin K antagonists, like warfarin, for many indications, and as they go generic their uptake will increase even further,” Dr. Weitz said. “When we compare the FXI inhibitors with existing anticoagulants, we don’t necessarily want to go up against the DOACs – we’re looking for indications where [DOACs] have yet to be tested or may be unsafe.”

Potential indications include the following:

Prevention of major adverse cardiovascular events in patients with end-stage renal disease with or without atrial fibrillation.

Provision of a safer platform for antiplatelet therapy in patients with acute coronary syndrome.

Secondary stroke prevention.

Prevention or treatment of cancer-associated VTE.

Prevention of thrombosis associated with central venous catheters, left ventricular assist devices, or mechanical heart valves.

Agents in development

Of the FXI inhibitors in development, ISIS-FXI_Rx, an antisense oligonucleotide against FXI, is furthest along. In a study published in Blood, ISIS-FXI_Rx produced a dose-dependent and sustained reduction in FXI levels in healthy volunteers, and in a later randomized study published in The New England Journal of Medicine, it significantly reduced the incidence of DVT in patients undergoing voluntary total knee arthroplasty (30.4% with enoxaparin vs. 4.2% with ISIS-FXI_Rx at a dose of 300 mg). Bleeding rates were 8.3% and 2.6%, respectively.

The findings showed the potential for reducing thrombosis without increasing bleeding by targeting FXI, Dr. Weitz said, adding that ISIS-FXIR_x was also evaluated in a small study of patients with end-stage renal disease undergoing hemodialysis and was shown to produce a dose-dependent reduction in FXI levels and to reduce the incidence of category 3 and 4 clotting in the air trap and dialyzer, compared with placebo, when given in addition to heparin.

This suggests that FXI knockdown can attenuate device-associated clotting to a greater extent than heparin alone, Dr. Weitz said.

The FXIa-directed inhibitory antibody osocimab has also been evaluated in both healthy volunteers and in patients undergoing total knee arthroplasty. In a 2019 study of healthy volunteers, a single IV injection showed a dose-dependent pharmacokinetic profile and produced FXI inhibition for about 1 month, and in the FOXTROT trial published in January in JAMA by Dr. Weitz and colleagues, osocimab was shown to reduce the incidence of symptomatic VTE, asymptomatic DVT, and VTE-related death up to day 10-13 after total knee arthroplasty.

Osocimab at doses ranging from 0.3-1.8 mg/kg given postoperatively or preoperatively were noninferior to enoxaparin (rates of 15.7%-23.7% vs. 26.3%), and osocimab at a preoperative dose of 1.8 mg/kg was superior to both enoxaparin and apixaban (11.5% vs. 26.3% and 14.5%, respectively), he said.

Bleeding rates ranged from 0%-5% with osocimab, compared with 6% with enoxaparin and 2% with apixaban
 

Ongoing studies

Currently ongoing studies of FXI-directed anticoagulation strategies include a study comparing ISIS-FXI_Rx with placebo in 200 patients with end-stage renal disease, a study comparing osocimab with placebo in 600 patients with end-stage renal disease, and a study comparing abelacimab – an antibody that binds to FXI and prevents its activation by either FXIIa or thrombin, with enoxaparin in 700 patients undergoing total knee arthroplasty, Dr. Weitz said.

Additionally, there is “considerable activity” with small molecule inhibitors of FXIa, including a phase 2, placebo-controlled, dose-ranging study looking at the novel JNG-7003/BMS-986177 agent for secondary stroke/transient ischemic attack prevention in 2,500 patients and a phase 2 study comparing it with enoxaparin for postoperative thromboprophylaxis in 1,200 patients undergoing total knee arthroplasty.

Parallel phase 2 studies are also underway to compare the novel BAY-2433334 small molecule inhibitor with placebo for stroke/transient ischemic attack prevention, with apixaban for atrial fibrillation, and for prevention of major adverse cardiovascular events in patients with acute MI.

These ongoing trials will help determine the risk-benefit profile of FXI inhibitors he said.

Session comoderator Anne Rose, PharmD, pharmacy coordinator at the University of Wisconsin, Madison, noted that these types of agents have been discussed “for quite some time” and asked whether they will be available for use in clinical practice in the near future.

Dr. Weitz predicted it will be at least a few years. The studies are just now moving to phase 2b and will still need to be evaluated in phase 3 trials and for appropriate new indications, he said.

Dr. Weitz reported research support from Canadian Institutes of Health research, Heart and Stroke Foundation, and Canadian Fund for Innovation, and he is a consultant and/or scientific advisory board member for Anthos, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Ionis Pharmaceuticals, Janssen, Merck, Novartis, Pfizer, Portola, Servier , and Thetherex.

sworcester@mdedge.com

The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).

“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.

“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.

The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.

HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.


 

Relative newcomer

Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.

Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.

A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.

“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.

Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.

In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.

“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
 

Fatalities among older adults

As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.

In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.

Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
 

Supportive care only

“Do we have anything for treatment? The short answer is, No,” Dr. Williams.

Supportive care is currently the only effective approach for patients with severe HMPV infection.

Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.

“It really can’t be recommended, and I don’t recommend it,” he said.
 

Virology may still help

Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.

“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.

“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.

Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.

Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.

The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).

“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.

“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.

The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.

HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.


 

Relative newcomer

Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.

Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.

A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.

“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.

Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.

In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.

“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
 

Fatalities among older adults

As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.

In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.

Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
 

Supportive care only

“Do we have anything for treatment? The short answer is, No,” Dr. Williams.

Supportive care is currently the only effective approach for patients with severe HMPV infection.

Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.

“It really can’t be recommended, and I don’t recommend it,” he said.
 

Virology may still help

Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.

“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.

“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.

Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.

Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.

The all-consuming news about SARS-CoV-2 and COVID-19 has overshadowed other viral pathogens that are the cause of severe or fatal lower respiratory infections (LRI) including human metapneumovirus (HMPV).

“MPV is really a leading cause of LRI not just in children but in adults, with high mortality rates in the frail elderly, long-term care facilities, and cancer patients with pneumonia, “ said John Williams, MD, from the department of pediatric infectious diseases at the University of Pittsburgh Medical Center.

“Right now we have no effective antivirals. There are monoclonal antibodies in development that my group and others have discovered. In fact, some of these treat MPV and RSV [respiratory syncytial virus], so we may have good options,” he said in an online presentation during an annual scientific meeting on infectious diseases.

The virus preys, wolf-like, on the most vulnerable patients, including children and frail elderly adults, as well as other adults with predisposing conditions, he said.

HMPV causes acute respiratory illnesses in approximately 2%-11% of hospitalized adults, 3%-25% of organ transplant recipients or cancer patients, 4%-12% of chronic obstructive pulmonary disease exacerbations, 5%-20% of asthma exacerbations, and it has been identified in multiple outbreaks at long-term care facilities.


 

Relative newcomer

Metapneumovirus was isolated and discovered from children with respiratory tract disease in the early 2000s. Once included in the family of paramyxoviruses (including measles, mumps, Nipah virus, and parainfluenza virus 1-4), HMPV and RSV are now classified as pneumoviruses, based on gene order and other characteristics, Dr. Williams explained.

Various studies have consistently placed the prevalence of HMPV ranging from 5%-14% in young children with LRI, children hospitalized for wheezing, adults with cancer and LRI, adults with asthma admissions, children with upper respiratory infections, and children hospitalized in the United States and Jordan for LRI, as well as children hospitalized in the United States and Peru with acute respiratory infections.

A study tracking respiratory infections in a Rochester, N.Y., cohort from 1999 through 2003 showed that healthy elderly patients had and annual incidence of HMPV infections of 5.9%, compared with 9.1% for high-risk patients, 13.1% for young patients, and 8.5% among hospitalized adult patients.

“These percentages are virtually identical to what has been seen in the same cohort for respiratory syncytial virus, so in this multiyear prospective cohort, metapneumovirus was as common as RSV,” Dr. Williams said.

Although the incidences of both HMPV and RSV were lower among hospitalized adults “clinically, we can’t tell these respiratory viruses apart. If we know it’s circulating we can make a guess, but we really can’t discriminate them,” he added.

In the Rochester cohort the frequency of clinical symptoms – including congestion, sore throat, cough, sputum production, dyspnea, and fever – were similar among patients infected with HMPV, RSV, or influenza A, with the exception of a slightly higher incidence of wheezing (80%) with HMPV, compared with influenza.

“I can tell you as a pediatrician, this is absolutely true in children, that metapneumovirus is indistinguishable from other respiratory viruses in kids,” he said.
 

Fatalities among older adults

As noted before, HMPV can cause severe and fatal illness in adults. For example, during an outbreak in North Dakota in 2016, 3 of 27 hospitalized adults with HMPV (median age, 69 years) died, and 10 required mechanical or noninvasive ventilation.

In a study from Korea comparing outcomes of severe HMPV-associated community-acquired pneumonia (CAP) with those of severe influenza-associated CAP, the investigators found that 30- and 60-day mortality rates were similar between the groups, at 24% of patients with HMPV-associated CAP and 32.1% for influenza-associated CAP, and 32% versus 38.5%, respectively.

Patients at high risk for severe disease or death from HMPV infection include those over 65 years, especially frail elderly, patients with chronic obstructive pulmonary disease, immunocompromised patients, and those with cardiopulmonary diseases such as congestive heart failure.
 

Supportive care only

“Do we have anything for treatment? The short answer is, No,” Dr. Williams.

Supportive care is currently the only effective approach for patients with severe HMPV infection.

Ribavirin, used to treat patients with acute RSV infection, has poor in vitro activity against HMPV and poor oral bioavailability and hemolysis, and there are no randomized controlled trials to support its use in this situation.

“It really can’t be recommended, and I don’t recommend it,” he said.
 

Virology may still help

Mark J. Siedner, MD, an infectious diseases physician at Mass General and associate professor of medicine at Harvard Medical School, both in Boston, who was not involved in the study, said that, despite the inability to clinically distinguish HMPV from RSV or influenza A, there is still clinical value to identifying HMPV infections.

“We spend millions of dollar each year treating people for upper respiratory tract infections, often with antibacterials, sometimes with antivirals, but those have costs to the health care system, and they also have costs in terms of drug resistance,” he said in an interview seeking objective commentary.

“Diagnostic tests that determine the actual source or the cause of these upper respiratory tract infections and encourage both patients and physicians not to be using antibiotics have value,” he said.

Identifying the pathogen can also help clinicians take appropriate infection-control precautions to prevent patient-to-clinician or patient-to-patient transmission of viral infections, he added.

Dr. Williams’ research is supported by the National Institutes of Health, Henry L. Hillman Foundation, and Asher Krop Memorial Fund of Children’s Hospital of Pittsburgh. Dr. Williams and Dr. Siedner reported no relevant conflict of interest disclosures.

In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.

A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.

Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.

Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.

“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.

“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”

Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.

“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”

“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.

“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”

“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.

“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
 

Out-of-hospital cardiac arrest, March 2019 vs. March 2020

Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.

In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.

They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.

There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.

The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).

Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).

The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).

In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).

This drop in survival was greater in communities with moderate to high COVID-19 mortality.

These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.

Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.

Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.

For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”

“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.

“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.

In-hospital cardiac arrest, March Through May 2020

The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.

“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”

To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.

They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).

Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.

There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).

“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”

“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.

Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”

Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
 

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

In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.

A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.

Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.

Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.

“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.

“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”

Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.

“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”

“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.

“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”

“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.

“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
 

Out-of-hospital cardiac arrest, March 2019 vs. March 2020

Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.

In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.

They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.

There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.

The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).

Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).

The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).

In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).

This drop in survival was greater in communities with moderate to high COVID-19 mortality.

These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.

Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.

Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.

For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”

“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.

“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.

In-hospital cardiac arrest, March Through May 2020

The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.

“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”

To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.

They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).

Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.

There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).

“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”

“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.

Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”

Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
 

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

In the early weeks of the COVID-19 pandemic in the United States, rates of sustained return of spontaneous circulation after out-of-hospital cardiac arrest were lower throughout the country, compared with a year earlier, in one study.

A second study of that period showed that patients with COVID-19 had rates that were better than previously reported of surviving in-hospital cardiac arrest.

Paul S. Chan, MD, presented the out-of-hospital cardiac arrest research, and Oscar J. Mitchell, MD, presented the in-hospital cardiac arrest findings in a late-breaking resuscitation science session at the American Heart Association scientific sessions. The former study was also simultaneously published online Nov. 14 in JAMA Cardiology.

Importantly, “the survival rates were not zero in either setting,” said Dr. Chan, commenting on the implications of both studies taken together.

“The survival rates – either return of circulation or survival to discharge – were not futile,” Dr. Chan, from Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, said in an interview.

“And I think that’s an overall important message – that we can’t write off patients who have a cardiac arrest at this point,” he stressed. “They deserve a response. Although the outcomes might not be as good as we had seen in years prior, we are seeing patients making it out of the hospital and surviving.”

Dr. Mitchell, from the University of Pennsylvania in Philadelphia, echoed this message in an interview.

“I think that the key finding here is that survival is possible after patients with COVID-19 suffer an in-hospital cardiac arrest,” Dr. Mitchell said. “We hope that the information from our study will be of use to frontline providers who are treating patients with COVID-19.”

“In coming weeks, there will likely be increased hospital strain and enormous challenges to providing COVID-19 care,” added Benjamin S. Abella, MD, the senior author of the in-hospital study. Dr. Abella is also from the University of Pennsylvania and was cochair of the Resuscitation Science symposium during the AHA meeting.

“It is crucial that hospital leaders prepare now for how they will manage COVID-19 resuscitation efforts,” Dr. Abella said. “Emergency medicine and critical care leaders must be mindful that many COVID-19 patients with arrest could survive to return to their families.”

“It is important to note both studies demonstrated variations in outcome and that those differences were associated with the differential COVID prevalence and mortality,” session comoderator Cindy H. Hsu, MD, PhD, University of Michigan, said in an interview.

“Future studies,” she said, “should address knowledge gaps including associated comorbidities and affected resuscitation process variables during the COVID-19 pandemic.”
 

Out-of-hospital cardiac arrest, March 2019 vs. March 2020

Compared with 2019, in 2020, the reported rates of return of spontaneous circulation after out-of-hospital cardiac arrest fell from 25% to 10.6% in New York and from 13.5% to 5.0% in northern Italy – two areas that were severely affected, Dr. Chan noted.

In this study, the researchers aimed to examine whether out-of-hospital cardiac arrest outcomes would be similar throughout the United States, including areas that were less severely affected, in the first weeks of the pandemic.

They linked data from the Cardiac Arrest Registry to Enhance Survival (CARES), which covers an area with about 152 million U.S. residents, with COVID-19 disease mortality data.

There were 9,863 out-of-hospital arrests from March 16 to April 30, 2020, compared with 9,440 cases during this time in 2019.

The patients in both years had a similar age (mean, 62 years) and sex (62% male), but there were more Black patients in 2020 (28% vs. 23%).

Overall, in communities with low to high rates of death from COVID-19, the rate of return of spontaneous circulation was 18% lower in that early pandemic period than in the same time in the previous year (23% vs. 29.8%; adjusted rate ratio, 0.82).

The rates of return of spontaneous circulation were also lower in communities with a low rate of COVID-19 mortality, but to a lesser extent (11%-15% lower in 2020 vs. 2019).

In the subset of emergency medical agencies with complete data on hospital survival, overall rates of survival to discharge were 17% lower during the studied pandemic period versus the same time a year earlier (6.6% vs. 9.8%; adjusted RR, 0.83).

This drop in survival was greater in communities with moderate to high COVID-19 mortality.

These outcomes were not explained by differences in emergency medical services arrival or treatment times, rates of bystander CPR, or initial out-of-hospital cardiac arrest rhythm.

Dr. Chan was a coauthor of an interim guidance issued April 9, 2020, by the AHA and several other medical societies for ways to protect frontline workers from contracting COVID-19 while they were performing CPR.

Communities that were not heavily affected by COVID-19 could have also been following the recommendations, which might have affected outcomes, he speculated.

For example, “when we pause chest compressions it can potentially worsen survival even if it’s for a short period of time. That might explain the lower rates of return of circulation.”

“That guidance was really meant for heavily affected communities,” Dr. Chan added. “Of course, as we speak, the pandemic is pretty much everywhere in the United States. It’s not just in the northeast; it’s not just in Arizona, Florida, California, Texas like it was in the summer. You are seeing surges in 46 of the 50 states.

“If your community is heavily affected by COVID-19 in terms of deaths at this time, paramedics will need to take caution to also help protect themselves, and the guidance may apply at that point,” he said.

In-hospital cardiac arrest, March Through May 2020

The early studies of in-hospital cardiac arrest in patients with COVID-19 showed “concerningly low rates” of return of spontaneous circulation and survival, said Dr. Mitchell.

“The first was a study from Wuhan, which demonstrated a 2.9% 30-day survival and the second was a small cohort from NYC with 0% survival to hospital discharge,” he said. “This raised concerns that offering CPR to patients who had a cardiac arrest from COVID-19 might only hold a low probability of success.”

To investigate this, the researchers formed a COVID study group comprising two hospitals in New York and nine hospitals in the Northeast and West Coast.

They identified 260 hospitalized adult patients with COVID-19 who had in-hospital cardiac arrest between March 1 and May 31, 2020. The patients had a median age of 69 years, and 72% were male. Most had preexisting comorbidities. Most of the cardiac arrests were in the ICU (64%), and almost all were witnessed (91%).

Return of spontaneous circulation occurred in 22% of the patients, and 12% had survived 30 days later. Of the 260 cardiac arrests, most (204) occurred in the New York hospitals.

There was a huge variation in outcomes. The rate of sustained return of spontaneous circulation was much lower in the two hospitals in New York compared with elsewhere (11% vs. 64%), as was 30-day survival (6% vs. 36%).

“Variation in outcomes from [in-hospital cardiac arrest] has been well described prior to the COVID-19 pandemic,” said Dr. Mitchell, “and is felt to be due to a range of factors, including variation in detection and prevention of cardiac arrest, management of patients during the cardiac arrest, and differences in postarrest care – including targeted temperature management and neuroprognostication.”

“We hypothesize that the strains of the COVID-19 pandemic may have amplified these variations (although we were unable to compare hospital performance before and after the pandemic),” he said.

Nevertheless, “in contrast to [earlier] studies, we have found that survival with a good neurological status is possible after in-hospital cardiac arrest in patients with COVID-19, which is certainly reassuring for those of us on the front line.”

Dr. Chan has received research support from the American Heart Association (which helps fund CARES); the National Heart, Lung, and Blood Institute; and Optum Rx. Dr. Abella has received honoraria from NeuroproteXeon, Becton Dickinson, and Physio-Control, and research grants from Medtronic, PCORI, Physio-Control, Stryker, and TerSera. Dr. Mitchell has disclosed no relevant financial relationships.
 

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