COVID-19 Updates

Low plasma vitamin D levels emerged as an independent risk factor for COVID-19 infection and hospitalization in a large, population-based study.

Participants positive for COVID-19 were 50% more likely to have low vs normal 25(OH)D levels in a multivariate analysis that controlled for other confounders, for example.

The take home message for physicians is to “test patients’ vitamin D levels and keep them optimal for the overall health – as well as for a better immunoresponse to COVID-19,” senior author Milana Frenkel-Morgenstern, PhD, head of the Cancer Genomics and BioComputing of Complex Diseases Lab at Bar-Ilan University in Ramat Gan, Israel, said in an interview.

The study was published online July 23 in The FEBS Journal.

Previous and ongoing studies are evaluating a potential role for vitamin D to prevent or minimize the severity of SARS-CoV-2 infection, building on years of research addressing vitamin D for other viral respiratory infections. The evidence to date regarding COVID-19, primarily observational studies, has yielded mixed results.

Multiple experts weighed in on the controversy in a previous report. Many point out the limitations of observational data, particularly when it comes to ruling out other factors that could affect the severity of COVID-19 infection. In addition, in a video report, JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston, cited an observational study from three South Asian hospitals that found more severe COVID-19 patients had lower vitamin D levels, as well as other “compelling evidence” suggesting an association.

Dr. Frenkel-Morgenstern and colleagues studied data for 7,807 people, of whom 10.1% were COVID-19 positive. They assessed electronic health records for demographics, potential confounders, and outcomes between February 1 and April 30.

Participants positive for COVID-19 tended to be younger and were more likely to be men and live in a lower socioeconomic area, compared with the participants who were negative for COVID-19, in a univariate analysis.

Key findings

A higher proportion of COVID-19–positive patients had low plasma 25(OH)D concentrations, about 90% versus 85% of participants who were negative for COVID-19. The difference was statistically significant (P < .001). Furthermore, the increased likelihood for low vitamin D levels among those positive for COVID-19 held in a multivariate analysis that controlled for demographics and psychiatric and somatic disorders (adjusted odds ratio, 1.50). The difference remained statistically significant (P < .001).

The study also was noteworthy for what it did not find among participants with COVID-19. For example, the prevalence of dementia, cardiovascular disease, chronic lung disorders, and hypertension were significantly higher among the COVID-19 negative participants.

“Severe social contacts restrictions that were imposed on all the population and were even more emphasized in this highly vulnerable population” could explain these findings, the researchers noted.

“We assume that following the Israeli Ministry of Health instructions, patients with chronic medical conditions significantly reduced their social contacts” and thereby reduced their infection risk.

In contrast to previous reports, obesity was not a significant factor associated with increased likelihood for COVID-19 infection or hospitalization in the current study.

The researchers also linked low plasma 25(OH)D level to an increased likelihood of hospitalization for COVID-19 infection (crude OR, 2.09; P < .05).

After controlling for demographics and chronic disorders, the aOR decreased to 1.95 (P = .061) in a multivariate analysis. The only factor that remained statistically significant for hospitalization was age over 50 years (aOR, 2.71; P < .001).

Implications and future plans

The large number of participants and the “real world,” population-based design are strengths of the study. Considering potential confounders is another strength, the researchers noted. The retrospective database design was a limitation.

Going forward, Dr. Frenkel-Morgenstern and colleagues will “try to decipher the potential role of vitamin D in prevention and/or treatment of COVID-19” through three additional studies, she said. Also, they would like to conduct a meta-analysis to combine data from different countries to further explore the potential role of vitamin D in COVID-19.

“A compelling case”

“This is a strong study – large, adjusted for confounders, consistent with the biology and other clinical studies of vitamin D, infections, and COVID-19,” Wayne Jonas, MD, a practicing family physician and executive director of Samueli Integrative Health Programs, said in an interview.

Because the research was retrospective and observational, a causative link between vitamin D levels and COVID-19 risk cannot be interpreted from the findings. “That would need a prospective, randomized study,” said Dr. Jonas, who was not involved with the current study.

However, “the study makes a compelling case for possibly screening vitamin D levels for judging risk of COVID infection and hospitalization,” Dr. Jonas said, “and the compelling need for a large, randomized vitamin D supplement study to see if it can help prevent infection.”

“Given that vitamin D is largely safe, such a study could be done quickly and on healthy people with minimal risk for harm,” he added.
 

More confounders likely?

“I think the study is of interest,” Naveed Sattar, PhD,  professor of metabolic medicine at the University of Glasgow, who also was not affiliated with the research, said in an interview.

“Whilst the authors adjusted for some confounders, there is a strong potential for residual confounding,” said Dr. Sattar, a coauthor of a UK Biobank study that did not find an association between vitamin D stages and COVID-19 infection in multivariate models.

For example, Dr. Sattar said, “Robust adjustment for social class is important since both Vitamin D levels and COVID-19 severity are both strongly associated with social class.” Further, it remains unknown when and what time of year the vitamin D concentrations were measured in the current study.

“In the end, only a robust randomized trial can tell us whether vitamin D supplementation helps lessen COVID-19 severity,” Dr. Sattar added. “I am not hopeful we will find this is the case – but I am glad some such trials are [ongoing].”

Dr. Frenkel-Morgenstern received a COVID-19 Data Sciences Institute grant to support this work. Dr. Frenkel-Morgenstern, Dr. Jonas, and Dr. Sattar have disclosed no relevant financial relationships.
 

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

Low plasma vitamin D levels emerged as an independent risk factor for COVID-19 infection and hospitalization in a large, population-based study.

Participants positive for COVID-19 were 50% more likely to have low vs normal 25(OH)D levels in a multivariate analysis that controlled for other confounders, for example.

The take home message for physicians is to “test patients’ vitamin D levels and keep them optimal for the overall health – as well as for a better immunoresponse to COVID-19,” senior author Milana Frenkel-Morgenstern, PhD, head of the Cancer Genomics and BioComputing of Complex Diseases Lab at Bar-Ilan University in Ramat Gan, Israel, said in an interview.

The study was published online July 23 in The FEBS Journal.

Previous and ongoing studies are evaluating a potential role for vitamin D to prevent or minimize the severity of SARS-CoV-2 infection, building on years of research addressing vitamin D for other viral respiratory infections. The evidence to date regarding COVID-19, primarily observational studies, has yielded mixed results.

Multiple experts weighed in on the controversy in a previous report. Many point out the limitations of observational data, particularly when it comes to ruling out other factors that could affect the severity of COVID-19 infection. In addition, in a video report, JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston, cited an observational study from three South Asian hospitals that found more severe COVID-19 patients had lower vitamin D levels, as well as other “compelling evidence” suggesting an association.

Dr. Frenkel-Morgenstern and colleagues studied data for 7,807 people, of whom 10.1% were COVID-19 positive. They assessed electronic health records for demographics, potential confounders, and outcomes between February 1 and April 30.

Participants positive for COVID-19 tended to be younger and were more likely to be men and live in a lower socioeconomic area, compared with the participants who were negative for COVID-19, in a univariate analysis.

Key findings

A higher proportion of COVID-19–positive patients had low plasma 25(OH)D concentrations, about 90% versus 85% of participants who were negative for COVID-19. The difference was statistically significant (P < .001). Furthermore, the increased likelihood for low vitamin D levels among those positive for COVID-19 held in a multivariate analysis that controlled for demographics and psychiatric and somatic disorders (adjusted odds ratio, 1.50). The difference remained statistically significant (P < .001).

The study also was noteworthy for what it did not find among participants with COVID-19. For example, the prevalence of dementia, cardiovascular disease, chronic lung disorders, and hypertension were significantly higher among the COVID-19 negative participants.

“Severe social contacts restrictions that were imposed on all the population and were even more emphasized in this highly vulnerable population” could explain these findings, the researchers noted.

“We assume that following the Israeli Ministry of Health instructions, patients with chronic medical conditions significantly reduced their social contacts” and thereby reduced their infection risk.

In contrast to previous reports, obesity was not a significant factor associated with increased likelihood for COVID-19 infection or hospitalization in the current study.

The researchers also linked low plasma 25(OH)D level to an increased likelihood of hospitalization for COVID-19 infection (crude OR, 2.09; P < .05).

After controlling for demographics and chronic disorders, the aOR decreased to 1.95 (P = .061) in a multivariate analysis. The only factor that remained statistically significant for hospitalization was age over 50 years (aOR, 2.71; P < .001).

Implications and future plans

The large number of participants and the “real world,” population-based design are strengths of the study. Considering potential confounders is another strength, the researchers noted. The retrospective database design was a limitation.

Going forward, Dr. Frenkel-Morgenstern and colleagues will “try to decipher the potential role of vitamin D in prevention and/or treatment of COVID-19” through three additional studies, she said. Also, they would like to conduct a meta-analysis to combine data from different countries to further explore the potential role of vitamin D in COVID-19.

“A compelling case”

“This is a strong study – large, adjusted for confounders, consistent with the biology and other clinical studies of vitamin D, infections, and COVID-19,” Wayne Jonas, MD, a practicing family physician and executive director of Samueli Integrative Health Programs, said in an interview.

Because the research was retrospective and observational, a causative link between vitamin D levels and COVID-19 risk cannot be interpreted from the findings. “That would need a prospective, randomized study,” said Dr. Jonas, who was not involved with the current study.

However, “the study makes a compelling case for possibly screening vitamin D levels for judging risk of COVID infection and hospitalization,” Dr. Jonas said, “and the compelling need for a large, randomized vitamin D supplement study to see if it can help prevent infection.”

“Given that vitamin D is largely safe, such a study could be done quickly and on healthy people with minimal risk for harm,” he added.
 

More confounders likely?

“I think the study is of interest,” Naveed Sattar, PhD,  professor of metabolic medicine at the University of Glasgow, who also was not affiliated with the research, said in an interview.

“Whilst the authors adjusted for some confounders, there is a strong potential for residual confounding,” said Dr. Sattar, a coauthor of a UK Biobank study that did not find an association between vitamin D stages and COVID-19 infection in multivariate models.

For example, Dr. Sattar said, “Robust adjustment for social class is important since both Vitamin D levels and COVID-19 severity are both strongly associated with social class.” Further, it remains unknown when and what time of year the vitamin D concentrations were measured in the current study.

“In the end, only a robust randomized trial can tell us whether vitamin D supplementation helps lessen COVID-19 severity,” Dr. Sattar added. “I am not hopeful we will find this is the case – but I am glad some such trials are [ongoing].”

Dr. Frenkel-Morgenstern received a COVID-19 Data Sciences Institute grant to support this work. Dr. Frenkel-Morgenstern, Dr. Jonas, and Dr. Sattar have disclosed no relevant financial relationships.
 

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

Low plasma vitamin D levels emerged as an independent risk factor for COVID-19 infection and hospitalization in a large, population-based study.

Participants positive for COVID-19 were 50% more likely to have low vs normal 25(OH)D levels in a multivariate analysis that controlled for other confounders, for example.

The take home message for physicians is to “test patients’ vitamin D levels and keep them optimal for the overall health – as well as for a better immunoresponse to COVID-19,” senior author Milana Frenkel-Morgenstern, PhD, head of the Cancer Genomics and BioComputing of Complex Diseases Lab at Bar-Ilan University in Ramat Gan, Israel, said in an interview.

The study was published online July 23 in The FEBS Journal.

Previous and ongoing studies are evaluating a potential role for vitamin D to prevent or minimize the severity of SARS-CoV-2 infection, building on years of research addressing vitamin D for other viral respiratory infections. The evidence to date regarding COVID-19, primarily observational studies, has yielded mixed results.

Multiple experts weighed in on the controversy in a previous report. Many point out the limitations of observational data, particularly when it comes to ruling out other factors that could affect the severity of COVID-19 infection. In addition, in a video report, JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston, cited an observational study from three South Asian hospitals that found more severe COVID-19 patients had lower vitamin D levels, as well as other “compelling evidence” suggesting an association.

Dr. Frenkel-Morgenstern and colleagues studied data for 7,807 people, of whom 10.1% were COVID-19 positive. They assessed electronic health records for demographics, potential confounders, and outcomes between February 1 and April 30.

Participants positive for COVID-19 tended to be younger and were more likely to be men and live in a lower socioeconomic area, compared with the participants who were negative for COVID-19, in a univariate analysis.

Key findings

A higher proportion of COVID-19–positive patients had low plasma 25(OH)D concentrations, about 90% versus 85% of participants who were negative for COVID-19. The difference was statistically significant (P < .001). Furthermore, the increased likelihood for low vitamin D levels among those positive for COVID-19 held in a multivariate analysis that controlled for demographics and psychiatric and somatic disorders (adjusted odds ratio, 1.50). The difference remained statistically significant (P < .001).

The study also was noteworthy for what it did not find among participants with COVID-19. For example, the prevalence of dementia, cardiovascular disease, chronic lung disorders, and hypertension were significantly higher among the COVID-19 negative participants.

“Severe social contacts restrictions that were imposed on all the population and were even more emphasized in this highly vulnerable population” could explain these findings, the researchers noted.

“We assume that following the Israeli Ministry of Health instructions, patients with chronic medical conditions significantly reduced their social contacts” and thereby reduced their infection risk.

In contrast to previous reports, obesity was not a significant factor associated with increased likelihood for COVID-19 infection or hospitalization in the current study.

The researchers also linked low plasma 25(OH)D level to an increased likelihood of hospitalization for COVID-19 infection (crude OR, 2.09; P < .05).

After controlling for demographics and chronic disorders, the aOR decreased to 1.95 (P = .061) in a multivariate analysis. The only factor that remained statistically significant for hospitalization was age over 50 years (aOR, 2.71; P < .001).

Implications and future plans

The large number of participants and the “real world,” population-based design are strengths of the study. Considering potential confounders is another strength, the researchers noted. The retrospective database design was a limitation.

Going forward, Dr. Frenkel-Morgenstern and colleagues will “try to decipher the potential role of vitamin D in prevention and/or treatment of COVID-19” through three additional studies, she said. Also, they would like to conduct a meta-analysis to combine data from different countries to further explore the potential role of vitamin D in COVID-19.

“A compelling case”

“This is a strong study – large, adjusted for confounders, consistent with the biology and other clinical studies of vitamin D, infections, and COVID-19,” Wayne Jonas, MD, a practicing family physician and executive director of Samueli Integrative Health Programs, said in an interview.

Because the research was retrospective and observational, a causative link between vitamin D levels and COVID-19 risk cannot be interpreted from the findings. “That would need a prospective, randomized study,” said Dr. Jonas, who was not involved with the current study.

However, “the study makes a compelling case for possibly screening vitamin D levels for judging risk of COVID infection and hospitalization,” Dr. Jonas said, “and the compelling need for a large, randomized vitamin D supplement study to see if it can help prevent infection.”

“Given that vitamin D is largely safe, such a study could be done quickly and on healthy people with minimal risk for harm,” he added.
 

More confounders likely?

“I think the study is of interest,” Naveed Sattar, PhD,  professor of metabolic medicine at the University of Glasgow, who also was not affiliated with the research, said in an interview.

“Whilst the authors adjusted for some confounders, there is a strong potential for residual confounding,” said Dr. Sattar, a coauthor of a UK Biobank study that did not find an association between vitamin D stages and COVID-19 infection in multivariate models.

For example, Dr. Sattar said, “Robust adjustment for social class is important since both Vitamin D levels and COVID-19 severity are both strongly associated with social class.” Further, it remains unknown when and what time of year the vitamin D concentrations were measured in the current study.

“In the end, only a robust randomized trial can tell us whether vitamin D supplementation helps lessen COVID-19 severity,” Dr. Sattar added. “I am not hopeful we will find this is the case – but I am glad some such trials are [ongoing].”

Dr. Frenkel-Morgenstern received a COVID-19 Data Sciences Institute grant to support this work. Dr. Frenkel-Morgenstern, Dr. Jonas, and Dr. Sattar have disclosed no relevant financial relationships.
 

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

Sleep difficulties during the COVID-19 crisis may be exacerbated by media overexposure and other factors causing fear and stress, according to findings from a large survey of French individuals.

klebercordeiro/Getty Images

“Physicians usually recommend coping with sleep disorders by exercising, going outside, avoiding screen time, and having a regular schedule – all recommendations difficult to apply during lockdown. Being forced to stay home and the ensuing boredom and loneliness may have led to increased [media exposure], especially among disadvantaged people and overexposure to media COVID-19 content may have contributed to fright and emotional distress,” Damien Leger of the Centre du Sommeil et de la Vigilance, Hôtel Dieu APHP, Université de Paris, and his colleagues wrote in the journal Sleep.

The investigators analyzed data from survey respondents about their sleep problems since the COVID-19 lockdown and other topics such as employment, daily activities, and sleep medications. The survey was part of a large research project, COCONEL, that has been developed to study the French population on a variety of behaviors and comprises 750,000 permanent panelists who respond to surveys. The survey was sent to random sample of panelists with no topic label to avoid selection bias. Of the 25,800 surveys sent, 1,005 responses were recorded.

Respondents were classified as having severe sleep problems if they reported that their daytime activities were affected or if their sleeping medications had increased since the lockdown. While 73% of respondents reported poor sleep in the 8 previous days, 25% reported severe sleep problems, and 54% reported that their sleep problems had worsened during the COVID-19 lockdown.

A media exposure score was created with a Likert scale (strongly agree, agree, disagree, strongly disagree) about media exposures of different types. The investigators also queried respondents about the degree to which they found media coverage of the pandemic provoked a fear response. Overall, 68% of respondents agreed that media images and stories about COVD-19 were frightening.

The researchers found a strong association between severe sleeping problems and a high media exposure score (risk ratio, 1.49; 95% confidence interval, 1.10-2.01; P < .05).

In addition, trepidation and fear from media exposure to COVID-19 news were also associated with severe sleep problems (RR, 1.27; 95% CI, 0.92-1.75; P < .05). “Suffering from sleep problems may have increased media use at night, and thus increased stress and/or psychological distress and reinforced sleeping problems,” the investigators wrote.

Not surprisingly, respondents with financial difficulties due to the pandemic also reported severe sleeping difficulties (RR, 1.99; 95% CI, 1.49-2.65; P < .05).

For individuals who have been treated for sleep problems, the COVID-19 pandemic may ratchet up their sleep challenges. The strongest association with severe sleep problems was found in those respondents who were already taking sleeping medications before the pandemic (RR, 2.72; 95% CI, 2.04-3.61; P < .05).

The COCONEL survey has been funded by the French and National Agency for Research, the Fondation de France, and the National Research Institute for Sustainable Development.

tborden@mdedge.com

SOURCE: Leger D et al. Sleep. 2020, Jul 25. doi: 10.1093/sleep/zsaa125.

Sleep difficulties during the COVID-19 crisis may be exacerbated by media overexposure and other factors causing fear and stress, according to findings from a large survey of French individuals.

klebercordeiro/Getty Images

“Physicians usually recommend coping with sleep disorders by exercising, going outside, avoiding screen time, and having a regular schedule – all recommendations difficult to apply during lockdown. Being forced to stay home and the ensuing boredom and loneliness may have led to increased [media exposure], especially among disadvantaged people and overexposure to media COVID-19 content may have contributed to fright and emotional distress,” Damien Leger of the Centre du Sommeil et de la Vigilance, Hôtel Dieu APHP, Université de Paris, and his colleagues wrote in the journal Sleep.

The investigators analyzed data from survey respondents about their sleep problems since the COVID-19 lockdown and other topics such as employment, daily activities, and sleep medications. The survey was part of a large research project, COCONEL, that has been developed to study the French population on a variety of behaviors and comprises 750,000 permanent panelists who respond to surveys. The survey was sent to random sample of panelists with no topic label to avoid selection bias. Of the 25,800 surveys sent, 1,005 responses were recorded.

Respondents were classified as having severe sleep problems if they reported that their daytime activities were affected or if their sleeping medications had increased since the lockdown. While 73% of respondents reported poor sleep in the 8 previous days, 25% reported severe sleep problems, and 54% reported that their sleep problems had worsened during the COVID-19 lockdown.

A media exposure score was created with a Likert scale (strongly agree, agree, disagree, strongly disagree) about media exposures of different types. The investigators also queried respondents about the degree to which they found media coverage of the pandemic provoked a fear response. Overall, 68% of respondents agreed that media images and stories about COVD-19 were frightening.

The researchers found a strong association between severe sleeping problems and a high media exposure score (risk ratio, 1.49; 95% confidence interval, 1.10-2.01; P < .05).

In addition, trepidation and fear from media exposure to COVID-19 news were also associated with severe sleep problems (RR, 1.27; 95% CI, 0.92-1.75; P < .05). “Suffering from sleep problems may have increased media use at night, and thus increased stress and/or psychological distress and reinforced sleeping problems,” the investigators wrote.

Not surprisingly, respondents with financial difficulties due to the pandemic also reported severe sleeping difficulties (RR, 1.99; 95% CI, 1.49-2.65; P < .05).

For individuals who have been treated for sleep problems, the COVID-19 pandemic may ratchet up their sleep challenges. The strongest association with severe sleep problems was found in those respondents who were already taking sleeping medications before the pandemic (RR, 2.72; 95% CI, 2.04-3.61; P < .05).

The COCONEL survey has been funded by the French and National Agency for Research, the Fondation de France, and the National Research Institute for Sustainable Development.

tborden@mdedge.com

SOURCE: Leger D et al. Sleep. 2020, Jul 25. doi: 10.1093/sleep/zsaa125.

Sleep difficulties during the COVID-19 crisis may be exacerbated by media overexposure and other factors causing fear and stress, according to findings from a large survey of French individuals.

klebercordeiro/Getty Images

“Physicians usually recommend coping with sleep disorders by exercising, going outside, avoiding screen time, and having a regular schedule – all recommendations difficult to apply during lockdown. Being forced to stay home and the ensuing boredom and loneliness may have led to increased [media exposure], especially among disadvantaged people and overexposure to media COVID-19 content may have contributed to fright and emotional distress,” Damien Leger of the Centre du Sommeil et de la Vigilance, Hôtel Dieu APHP, Université de Paris, and his colleagues wrote in the journal Sleep.

The investigators analyzed data from survey respondents about their sleep problems since the COVID-19 lockdown and other topics such as employment, daily activities, and sleep medications. The survey was part of a large research project, COCONEL, that has been developed to study the French population on a variety of behaviors and comprises 750,000 permanent panelists who respond to surveys. The survey was sent to random sample of panelists with no topic label to avoid selection bias. Of the 25,800 surveys sent, 1,005 responses were recorded.

Respondents were classified as having severe sleep problems if they reported that their daytime activities were affected or if their sleeping medications had increased since the lockdown. While 73% of respondents reported poor sleep in the 8 previous days, 25% reported severe sleep problems, and 54% reported that their sleep problems had worsened during the COVID-19 lockdown.

A media exposure score was created with a Likert scale (strongly agree, agree, disagree, strongly disagree) about media exposures of different types. The investigators also queried respondents about the degree to which they found media coverage of the pandemic provoked a fear response. Overall, 68% of respondents agreed that media images and stories about COVD-19 were frightening.

The researchers found a strong association between severe sleeping problems and a high media exposure score (risk ratio, 1.49; 95% confidence interval, 1.10-2.01; P < .05).

In addition, trepidation and fear from media exposure to COVID-19 news were also associated with severe sleep problems (RR, 1.27; 95% CI, 0.92-1.75; P < .05). “Suffering from sleep problems may have increased media use at night, and thus increased stress and/or psychological distress and reinforced sleeping problems,” the investigators wrote.

Not surprisingly, respondents with financial difficulties due to the pandemic also reported severe sleeping difficulties (RR, 1.99; 95% CI, 1.49-2.65; P < .05).

For individuals who have been treated for sleep problems, the COVID-19 pandemic may ratchet up their sleep challenges. The strongest association with severe sleep problems was found in those respondents who were already taking sleeping medications before the pandemic (RR, 2.72; 95% CI, 2.04-3.61; P < .05).

The COCONEL survey has been funded by the French and National Agency for Research, the Fondation de France, and the National Research Institute for Sustainable Development.

tborden@mdedge.com

SOURCE: Leger D et al. Sleep. 2020, Jul 25. doi: 10.1093/sleep/zsaa125.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

Over the last 2 months, more than half of Americans have experienced some sort of adverse effect caused by stress related to the COVID-19 pandemic, according to a survey from the Kaiser Family Foundation (KFF).

More than a third (36%) of the 1,313 respondents said they either had difficulty sleeping, falling asleep, or sleeping too much, KFF said in its latest Health Tracking Poll, conducted July 14-19, 2020. That was followed by poor appetite or overeating, which was mentioned by 32% of those surveyed.

Other adverse effects included frequent headaches or stomachaches (18%), temper-control issues (18%), increased drug or alcohol use (12%), and worsening of chronic conditions such as diabetes or hypertension (12%). Altogether, 52% of Americans have had at least one of these issues in the past 2 months, Liz Hamel and associates at KFF reported.

When asked directly whether worry or stress had has a negative effect on their overall mental health, 53% of the respondents said yes, breaking down to 26% reporting a major impact and 28% reporting a minor impact (figures have been rounded), they said.

“As life with the coronavirus pandemic wears on, Americans increasingly say it is taking a negative toll on their mental health,” the investigators wrote. Earlier polls showed that pandemic-related stress was having an impact on mental health for 39% of respondents in May, compared with 45% in early April and 32% in March.

In the July poll, Black adults were much more likely to report a negative mental health impact (68%) than were Hispanics or Whites, who were both at 51%. Age was also a factor: The youngest group of respondents (ages 18-29 years) had the highest negative-impact rate (62%), and the oldest group (65 years and older) had the lowest (47%), they said.

When it came to reporting the adverse effects of stress or worry, however, the situation was somewhat different. Hispanics had the highest rate of such effects at 63%, while Blacks had a rate of 57% and 47% of Whites reported issues with sleep, eating, temper, and other problems, Ms. Hamel and associates reported.

rfranki@mdedge.com

Over the last 2 months, more than half of Americans have experienced some sort of adverse effect caused by stress related to the COVID-19 pandemic, according to a survey from the Kaiser Family Foundation (KFF).

More than a third (36%) of the 1,313 respondents said they either had difficulty sleeping, falling asleep, or sleeping too much, KFF said in its latest Health Tracking Poll, conducted July 14-19, 2020. That was followed by poor appetite or overeating, which was mentioned by 32% of those surveyed.

Other adverse effects included frequent headaches or stomachaches (18%), temper-control issues (18%), increased drug or alcohol use (12%), and worsening of chronic conditions such as diabetes or hypertension (12%). Altogether, 52% of Americans have had at least one of these issues in the past 2 months, Liz Hamel and associates at KFF reported.

When asked directly whether worry or stress had has a negative effect on their overall mental health, 53% of the respondents said yes, breaking down to 26% reporting a major impact and 28% reporting a minor impact (figures have been rounded), they said.

“As life with the coronavirus pandemic wears on, Americans increasingly say it is taking a negative toll on their mental health,” the investigators wrote. Earlier polls showed that pandemic-related stress was having an impact on mental health for 39% of respondents in May, compared with 45% in early April and 32% in March.

In the July poll, Black adults were much more likely to report a negative mental health impact (68%) than were Hispanics or Whites, who were both at 51%. Age was also a factor: The youngest group of respondents (ages 18-29 years) had the highest negative-impact rate (62%), and the oldest group (65 years and older) had the lowest (47%), they said.

When it came to reporting the adverse effects of stress or worry, however, the situation was somewhat different. Hispanics had the highest rate of such effects at 63%, while Blacks had a rate of 57% and 47% of Whites reported issues with sleep, eating, temper, and other problems, Ms. Hamel and associates reported.

rfranki@mdedge.com

Over the last 2 months, more than half of Americans have experienced some sort of adverse effect caused by stress related to the COVID-19 pandemic, according to a survey from the Kaiser Family Foundation (KFF).

More than a third (36%) of the 1,313 respondents said they either had difficulty sleeping, falling asleep, or sleeping too much, KFF said in its latest Health Tracking Poll, conducted July 14-19, 2020. That was followed by poor appetite or overeating, which was mentioned by 32% of those surveyed.

Other adverse effects included frequent headaches or stomachaches (18%), temper-control issues (18%), increased drug or alcohol use (12%), and worsening of chronic conditions such as diabetes or hypertension (12%). Altogether, 52% of Americans have had at least one of these issues in the past 2 months, Liz Hamel and associates at KFF reported.

When asked directly whether worry or stress had has a negative effect on their overall mental health, 53% of the respondents said yes, breaking down to 26% reporting a major impact and 28% reporting a minor impact (figures have been rounded), they said.

“As life with the coronavirus pandemic wears on, Americans increasingly say it is taking a negative toll on their mental health,” the investigators wrote. Earlier polls showed that pandemic-related stress was having an impact on mental health for 39% of respondents in May, compared with 45% in early April and 32% in March.

In the July poll, Black adults were much more likely to report a negative mental health impact (68%) than were Hispanics or Whites, who were both at 51%. Age was also a factor: The youngest group of respondents (ages 18-29 years) had the highest negative-impact rate (62%), and the oldest group (65 years and older) had the lowest (47%), they said.

When it came to reporting the adverse effects of stress or worry, however, the situation was somewhat different. Hispanics had the highest rate of such effects at 63%, while Blacks had a rate of 57% and 47% of Whites reported issues with sleep, eating, temper, and other problems, Ms. Hamel and associates reported.

rfranki@mdedge.com

From the Multi-County eConsult Initiative, Rancho Cucamonga, CA.

The COVID-19 pandemic has forced many health care professionals and their patients to use telehealth and virtual care to address care needs in new ways.¹ To shed light on care coordination decisions with respect to specialty resource access, we analyzed data collected from the Multi-County eConsult Initiative (MCeI)—the second-largest electronic consultation (eConsult) program in the United States—before and during the COVID-19 pandemic. Our analysis of these data suggests opportunities for improving access to care and reducing unnecessary costs in the health system nationally.

The Inland Empire Health Plan (IEHP) launched MCeI (econsultie.com) in 2018. The initiative is a partnership between IEHP, Arrowhead Regional Medical Center, and Riverside University Health System aimed at improving access to specialty care for the safety-net population across San Bernardino and Riverside counties. IEHP is 1 of the 10 largest Medicaid health plans and the largest not-for-profit Medicare-Medicaid plan in the country, serving more than 1.2 million members.² Data from MCel reveal the impacts of COVID-19 on eConsult use and offer insights into specialty resource availability during and outside of a crisis.

At the time of this analysis, 86 IEHP clinics in rural and urban settings across 38 specialties used the eConsult process to provide and obtain virtual specialty care, as well as timely appointments for in-person specialty care.³ eConsults are facilitated through a HIPAA-secure web-based portal that enables communication and sharing of information between the primary care provider (PCP) and a specialist. eConsult gives PCPs virtual access to specialists to coordinate care for their patients and determine the need for in-person specialty visits. Through the PCP-specialist eConsult dialogue, patients gain virtual access to specialty care. If a PCP-specialist care team determines the patient needs an in-person visit, that specialty referral is automatically authorized by IEHP, without the need for further review. At IEHP, eConsult is the primary method used for obtaining outpatient specialty referrals.

To analyze eConsult utilization before and during the pandemic, we gathered data from the MCeI program for the periods February 20–March 19, 2020, and March 20–April 19, 2020. Measures included eConsult volume and outcomes of eConsults (eConsults closed as referrals for face-to-face specialist visits versus eConsults closed without resulting in referrals for face-to-face specialist visits). Statistical analysis using chi-square tests for independence was performed using IBM SPSS Statistics 25 (IBM, Armonk, NY).

The data show that after California’s stay-at-home order, issued on March 19, 2020,⁴ eConsult volumes initially decreased, reflecting a similar decrease in clinic visits and authorization requests submitted to IEHP. We observed a 4-week average of 1100 eConsults processed before the pandemic, and then a steep drop to a 4-week average of 500 eConsults processed after the stay-at-home order was issued. Despite the overall drop in the volume of eConsults submitted, demand for specialties like hematology and neurology remained high throughout the pandemic.

During the pandemic, certain specialties displayed rising rates of eConsults completed with specialists providing care recommendations to the PCP instead of resulting in a recommendation for a face-to-face (in-person or via telehealth) visit with a specialist (see Figure and Table). The trend of increasing eConsults that concluded without a face-to-face visit suggests newfound clinical consideration of limited medical resources, along with the desire to eliminate unnecessary risks of infection.

eConsults between PCPs and specialist reviewers via the IEHP portal resulted in higher rates of non-face-to-face recommendations. The specialist reviewers were able to provide treatment plans for PCPs to take care of patients without having to refer their patients to a specialist. This increase was significant across most of the specialties live on the MCeI program.

We believe that clinicians’ heightened awareness of the limitations of the US health care system should remain a key consideration and factor in medical decision-making about appropriate referrals after the pandemic has passed. The data demonstrate that the pandemic drove clinicians to make different decisions about referrals and care coordination. Physicians scrutinized individual cases more keenly and were not as quick to recommend a face-to-face visit. This awareness and consideration of specialty access before making a referral provides a valuable lesson. If this approach is applied to health care delivery post-pandemic, eConsults will help reduce unnecessary in-person specialist visits and will free up space and time for patients who genuinely do need in-person specialty care. In this way, eConsult will improve appropriate access to care for everyone and reduce unnecessary costs to the health care system at large.

An examination of eConsult utilization trends across Riverside and San Bernardino counties before and during the COVID-19 pandemic provides useful insights into how to reduce costs and improve access to care. Although the risk of exposure to COVID-19 currently presents a significant obstacle to obtaining in-person specialty care, pre-existing and long-standing barriers, such as long wait times and scarcity of specialists, remain critical issues to receiving care during and after the pandemic. The pandemic has proven eConsult’s value as a tool for effective care coordination. Leveraging provider-to-provider asynchronous communication offers an opportunity to reduce unnecessary utilization of scarce resources during and beyond the pandemic.

Corresponding author: Lisa Aubry, Aubry-L@iehp.org.

Financial disclosures: None.

Keywords: electronic consultation; care coordination; telehealth; telemedicine; virtual care.

From the Multi-County eConsult Initiative, Rancho Cucamonga, CA.

The COVID-19 pandemic has forced many health care professionals and their patients to use telehealth and virtual care to address care needs in new ways.¹ To shed light on care coordination decisions with respect to specialty resource access, we analyzed data collected from the Multi-County eConsult Initiative (MCeI)—the second-largest electronic consultation (eConsult) program in the United States—before and during the COVID-19 pandemic. Our analysis of these data suggests opportunities for improving access to care and reducing unnecessary costs in the health system nationally.

The Inland Empire Health Plan (IEHP) launched MCeI (econsultie.com) in 2018. The initiative is a partnership between IEHP, Arrowhead Regional Medical Center, and Riverside University Health System aimed at improving access to specialty care for the safety-net population across San Bernardino and Riverside counties. IEHP is 1 of the 10 largest Medicaid health plans and the largest not-for-profit Medicare-Medicaid plan in the country, serving more than 1.2 million members.² Data from MCel reveal the impacts of COVID-19 on eConsult use and offer insights into specialty resource availability during and outside of a crisis.

At the time of this analysis, 86 IEHP clinics in rural and urban settings across 38 specialties used the eConsult process to provide and obtain virtual specialty care, as well as timely appointments for in-person specialty care.³ eConsults are facilitated through a HIPAA-secure web-based portal that enables communication and sharing of information between the primary care provider (PCP) and a specialist. eConsult gives PCPs virtual access to specialists to coordinate care for their patients and determine the need for in-person specialty visits. Through the PCP-specialist eConsult dialogue, patients gain virtual access to specialty care. If a PCP-specialist care team determines the patient needs an in-person visit, that specialty referral is automatically authorized by IEHP, without the need for further review. At IEHP, eConsult is the primary method used for obtaining outpatient specialty referrals.

To analyze eConsult utilization before and during the pandemic, we gathered data from the MCeI program for the periods February 20–March 19, 2020, and March 20–April 19, 2020. Measures included eConsult volume and outcomes of eConsults (eConsults closed as referrals for face-to-face specialist visits versus eConsults closed without resulting in referrals for face-to-face specialist visits). Statistical analysis using chi-square tests for independence was performed using IBM SPSS Statistics 25 (IBM, Armonk, NY).

The data show that after California’s stay-at-home order, issued on March 19, 2020,⁴ eConsult volumes initially decreased, reflecting a similar decrease in clinic visits and authorization requests submitted to IEHP. We observed a 4-week average of 1100 eConsults processed before the pandemic, and then a steep drop to a 4-week average of 500 eConsults processed after the stay-at-home order was issued. Despite the overall drop in the volume of eConsults submitted, demand for specialties like hematology and neurology remained high throughout the pandemic.

During the pandemic, certain specialties displayed rising rates of eConsults completed with specialists providing care recommendations to the PCP instead of resulting in a recommendation for a face-to-face (in-person or via telehealth) visit with a specialist (see Figure and Table). The trend of increasing eConsults that concluded without a face-to-face visit suggests newfound clinical consideration of limited medical resources, along with the desire to eliminate unnecessary risks of infection.

eConsults between PCPs and specialist reviewers via the IEHP portal resulted in higher rates of non-face-to-face recommendations. The specialist reviewers were able to provide treatment plans for PCPs to take care of patients without having to refer their patients to a specialist. This increase was significant across most of the specialties live on the MCeI program.

We believe that clinicians’ heightened awareness of the limitations of the US health care system should remain a key consideration and factor in medical decision-making about appropriate referrals after the pandemic has passed. The data demonstrate that the pandemic drove clinicians to make different decisions about referrals and care coordination. Physicians scrutinized individual cases more keenly and were not as quick to recommend a face-to-face visit. This awareness and consideration of specialty access before making a referral provides a valuable lesson. If this approach is applied to health care delivery post-pandemic, eConsults will help reduce unnecessary in-person specialist visits and will free up space and time for patients who genuinely do need in-person specialty care. In this way, eConsult will improve appropriate access to care for everyone and reduce unnecessary costs to the health care system at large.

An examination of eConsult utilization trends across Riverside and San Bernardino counties before and during the COVID-19 pandemic provides useful insights into how to reduce costs and improve access to care. Although the risk of exposure to COVID-19 currently presents a significant obstacle to obtaining in-person specialty care, pre-existing and long-standing barriers, such as long wait times and scarcity of specialists, remain critical issues to receiving care during and after the pandemic. The pandemic has proven eConsult’s value as a tool for effective care coordination. Leveraging provider-to-provider asynchronous communication offers an opportunity to reduce unnecessary utilization of scarce resources during and beyond the pandemic.

Corresponding author: Lisa Aubry, Aubry-L@iehp.org.

Financial disclosures: None.

Keywords: electronic consultation; care coordination; telehealth; telemedicine; virtual care.

From the Multi-County eConsult Initiative, Rancho Cucamonga, CA.

The COVID-19 pandemic has forced many health care professionals and their patients to use telehealth and virtual care to address care needs in new ways.¹ To shed light on care coordination decisions with respect to specialty resource access, we analyzed data collected from the Multi-County eConsult Initiative (MCeI)—the second-largest electronic consultation (eConsult) program in the United States—before and during the COVID-19 pandemic. Our analysis of these data suggests opportunities for improving access to care and reducing unnecessary costs in the health system nationally.

The Inland Empire Health Plan (IEHP) launched MCeI (econsultie.com) in 2018. The initiative is a partnership between IEHP, Arrowhead Regional Medical Center, and Riverside University Health System aimed at improving access to specialty care for the safety-net population across San Bernardino and Riverside counties. IEHP is 1 of the 10 largest Medicaid health plans and the largest not-for-profit Medicare-Medicaid plan in the country, serving more than 1.2 million members.² Data from MCel reveal the impacts of COVID-19 on eConsult use and offer insights into specialty resource availability during and outside of a crisis.

At the time of this analysis, 86 IEHP clinics in rural and urban settings across 38 specialties used the eConsult process to provide and obtain virtual specialty care, as well as timely appointments for in-person specialty care.³ eConsults are facilitated through a HIPAA-secure web-based portal that enables communication and sharing of information between the primary care provider (PCP) and a specialist. eConsult gives PCPs virtual access to specialists to coordinate care for their patients and determine the need for in-person specialty visits. Through the PCP-specialist eConsult dialogue, patients gain virtual access to specialty care. If a PCP-specialist care team determines the patient needs an in-person visit, that specialty referral is automatically authorized by IEHP, without the need for further review. At IEHP, eConsult is the primary method used for obtaining outpatient specialty referrals.

To analyze eConsult utilization before and during the pandemic, we gathered data from the MCeI program for the periods February 20–March 19, 2020, and March 20–April 19, 2020. Measures included eConsult volume and outcomes of eConsults (eConsults closed as referrals for face-to-face specialist visits versus eConsults closed without resulting in referrals for face-to-face specialist visits). Statistical analysis using chi-square tests for independence was performed using IBM SPSS Statistics 25 (IBM, Armonk, NY).

The data show that after California’s stay-at-home order, issued on March 19, 2020,⁴ eConsult volumes initially decreased, reflecting a similar decrease in clinic visits and authorization requests submitted to IEHP. We observed a 4-week average of 1100 eConsults processed before the pandemic, and then a steep drop to a 4-week average of 500 eConsults processed after the stay-at-home order was issued. Despite the overall drop in the volume of eConsults submitted, demand for specialties like hematology and neurology remained high throughout the pandemic.

During the pandemic, certain specialties displayed rising rates of eConsults completed with specialists providing care recommendations to the PCP instead of resulting in a recommendation for a face-to-face (in-person or via telehealth) visit with a specialist (see Figure and Table). The trend of increasing eConsults that concluded without a face-to-face visit suggests newfound clinical consideration of limited medical resources, along with the desire to eliminate unnecessary risks of infection.

eConsults between PCPs and specialist reviewers via the IEHP portal resulted in higher rates of non-face-to-face recommendations. The specialist reviewers were able to provide treatment plans for PCPs to take care of patients without having to refer their patients to a specialist. This increase was significant across most of the specialties live on the MCeI program.

We believe that clinicians’ heightened awareness of the limitations of the US health care system should remain a key consideration and factor in medical decision-making about appropriate referrals after the pandemic has passed. The data demonstrate that the pandemic drove clinicians to make different decisions about referrals and care coordination. Physicians scrutinized individual cases more keenly and were not as quick to recommend a face-to-face visit. This awareness and consideration of specialty access before making a referral provides a valuable lesson. If this approach is applied to health care delivery post-pandemic, eConsults will help reduce unnecessary in-person specialist visits and will free up space and time for patients who genuinely do need in-person specialty care. In this way, eConsult will improve appropriate access to care for everyone and reduce unnecessary costs to the health care system at large.

An examination of eConsult utilization trends across Riverside and San Bernardino counties before and during the COVID-19 pandemic provides useful insights into how to reduce costs and improve access to care. Although the risk of exposure to COVID-19 currently presents a significant obstacle to obtaining in-person specialty care, pre-existing and long-standing barriers, such as long wait times and scarcity of specialists, remain critical issues to receiving care during and after the pandemic. The pandemic has proven eConsult’s value as a tool for effective care coordination. Leveraging provider-to-provider asynchronous communication offers an opportunity to reduce unnecessary utilization of scarce resources during and beyond the pandemic.

Corresponding author: Lisa Aubry, Aubry-L@iehp.org.

Financial disclosures: None.

Keywords: electronic consultation; care coordination; telehealth; telemedicine; virtual care.

One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.

She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.

MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.

A reliable profile of MIS-C is only beginning to emerge from the series of published case series, most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.

In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.¹ The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.

In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. ² Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.

In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.

“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.

Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.

Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.

“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”

Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.

“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.

Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.

None of the speakers had any relevant financial disclosures.

References

1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.

2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.

One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.

She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.

MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.

A reliable profile of MIS-C is only beginning to emerge from the series of published case series, most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.

In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.¹ The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.

In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. ² Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.

In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.

“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.

Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.

Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.

“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”

Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.

“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.

Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.

None of the speakers had any relevant financial disclosures.

References

1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.

2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.

One of the take-away messages from a review of multisystem inflammatory syndrome in children (MIS-C) is that clinicians treating this condition “need to be comfortable with uncertainty,” Melissa Hazen, MD, said at a synthesis of multiple published case series and personal experience summarized at the virtual Pediatric Hospital Medicine meeting.

She emphasized MIS-C patient care “requires flexibility,” and she advised clinicians managing these patients to open the lines of communication with the many specialists who often are required to deal with complications affecting an array of organ systems.

MIS-C might best be understood as the most serious manifestation of an immune-mediated response to COVID-19 infection that ranges from transient mild symptoms to the life-threatening multiple organ involvement that characterizes this newly recognized threat. Although “most children who encounter this pathogen only develop mild disease,” the spectrum of the disease can move in a subset of patients to a “Kawasaki-like illness” without hemodynamic instability and then to MIS-C “with highly elevated systemic inflammatory markers and multiple organ involvement,” explained Dr. Hazen, an attending physician in the rheumatology program at Boston Children’s Hospital.

A reliable profile of MIS-C is only beginning to emerge from the series of published case series, most of which have only recently reached publication, according to Dr. Hazen. In general, the description of the most common symptoms and their course has been relatively consistent.

In 186 cases of MIS-C collected in a study funded by the Centers for Disease Control and Prevention, 148 (80%) were admitted to intensive care, 90 patients (48%) received vasoactive support, 37 (20%) received mechanical ventilation, and 4 (2%) died.¹ The median age was 8 years (range, 3-13 years) in this study. The case definition was fever for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of COVID-19 infection. In this cohort of 186 children, 92% had gastrointestinal, 80% had cardiovascular, 76% had hematologic, and 70% had respiratory system involvement.

In a different series of 95 cases collected in New York State, 79 (80%) were admitted to intensive care, 61 (62%) received vasoactive support, 10 (10%) received mechanical ventilation, 4 (4%) received extracorporeal membrane oxygenation (ECMO), and 2 (2%) died. ² Thirty-one percent patients were aged 0-5 years, 42% were 6-12 years, and 26% were 13-20 years of age. In that series, for which the case definition was elevation of two or more inflammatory markers, virologic evidence of COVID-19 infection, 80% had gastrointestinal system involvement, and 53% had evidence of myocarditis.

In both of these series, as well as others published and unpublished, the peak in MIS-C cases has occurred about 3 to 4 weeks after peak COVID-19 activity, according to Diana Lee, MD, a pediatrician at Icahn School of Medicine at Mount Sinai, New York. This pattern, reported by others, was observed in New York State, where 230 cases of MIS-C were collected from the beginning of May until the end of June, which reflected this 3- to 4-week delay in peak incidence.

“This does seem to be a rare syndrome since this [group of] 230 cases is amongst the entire population of children in New York State. So, yes, we should be keeping this in mind in our differential, but we should not forget all the other reasons that children can have a fever,” she said.

Both Dr. Hazen and Dr. Lee cautioned that MIS-C, despite a general consistency among published studies, remains a moving target in regard to how it is being characterized. In a 2-day period in May, the CDC, the World Health Organization, and New York State all issued descriptions of MIS-C, employing compatible but slightly different terminology and diagnostic criteria. Many questions regarding optimal methods of diagnosis, treatment, and follow-up remain unanswered.

Questions regarding the risk to the cardiovascular system, one of the organs most commonly affected in MIS-C, are among the most urgent. It is not now clear how best to monitor cardiovascular involvement, how to intervene, and how to follow patients in the postinfection period, according to Kevin G. Friedman, MD, a pediatrician at Harvard Medical School, Boston, and an attending physician in the department of cardiology at Boston Children’s Hospital.

“The most frequent complication we have seen is ventricular dysfunction, which occurs in about half of these patients,” he reported. “Usually it is in the mild to moderate range, but occasionally patients have an ejection fraction of less than 40%.”

Coronary abnormalities, typically in the form of dilations or small aneurysms, occur in 10%-20% of children with MIS-C, according to Dr. Friedman. Giant aneurysms have been reported.

“Some of these findings can progress including in both the acute phase and, particularly for the coronary aneurysms, in the subacute phase. We recommend echocardiograms and EKGs at diagnosis and at 1-2 weeks to recheck coronary size or sooner if there are clinical indications,” Dr. Friedman advised.

Protocols like these are constantly under review as more information becomes available. There are as yet no guidelines, and practice differs across institutions, according to the investigators summarizing this information.

None of the speakers had any relevant financial disclosures.

References

1. Feldstein LR et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383:334-46.

2. Dufort EM et al. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347-58.

Laurent Duvernay-Tardif, MD, the only medical doctor on a current NFL roster, has become the first player to opt out of the 2020 NFL season, citing concerns over risk for COVID-19.

Canadian-born Duvernay-Tardif, right guard for the Kansas City Chiefs, announced on Twitter on July 24 what he called “one of the most difficult decisions I have had to make in my life.”

“There is no doubt in my mind the Chiefs’ medical staff have put together a strong plan to minimize the health risks associated with COVID-19, but some risks will remain,” he posted.

“Being at the frontline during this offseason has given me a different perspective on this pandemic and the stress it puts on individuals and our healthcare system. I cannot allow myself to potentially transmit the virus in our communities simply to play the sport that I love. If I am to take risks, I will do it caring for patients.”

According to CNN, Duvernay-Tardif, less than 3 months after helping the Chiefs win the Super Bowl in February, began working at a long-term care facility near Montreal in what he described as a “nursing role.”

Duvernay-Tardif wrote recently in an article for Sports Illustrated that he has not completed his residency and is not yet licensed to practice.

“My first day back in the hospital was April 24,” Duvernay-Tardif wrote. “I felt nervous the night before, but a good nervous, like before a game.”

Duvernay-Tardif has also served on the NFL Players’ Association COVID-19 task force, according to Yahoo News .

A spokesperson for Duvernay-Tardif told Medscape Medical News he was unavailable to comment about the announcement.

Starting His Dual Career

Duvernay-Tardif, 29, was drafted in the sixth round by the Chiefs in 2014.

According to Forbes , he spent 8 years (2010-2018) pursuing his medical degree while still playing college football for McGill University in Montreal. Duvernay-Tardif played offensive tackle for the Redmen and in his senior year (2013) won the Metras Trophy as most outstanding lineman in Canadian college football.

He explained in a previous Medscape interview how he managed his dual career; as a doctor he said he would like to focus on emergency medicine:

“I would say that at around 16-17 years of age, I was pretty convinced that medicine was for me,” he told Medscape.

“I was lucky that I didn’t have to do an undergrad program,” he continued. “In Canada, they have a fast-track program where instead of doing a full undergrad before getting into medical school, you can do a 1-year program where you can do all your physiology and biology classes all together.

“I had the chance to get into that program, and that’s how I was able to manage football and medicine at the same time. There’s no way I could have finished my med school doing part-time med school like I did for the past 4 years.”

ESPN explained the opt-out option: “According to an agreement approved by both the league and the union on [July 24], players considered high risk for COVID-19 can earn $350,000 and an accrued NFL season if they choose to opt out of the 2020 season. Players without risk can earn $150,000 for opting out. Duvernay-Tardif was scheduled to make $2.75 million this season.”

The danger of COVID-19 in professional sports has already been seen in Major League Baseball.

According to USA Today, the Miami Marlins have at least 14 players and staff who have tested positive for COVID-19, and major league baseball Commissioner Rob Manfred must decide whether to further delay the shortened season, cancel it, or allow it to continue.

MLB postponed the Marlins’ home opener July 27 against the Baltimore Orioles as well as the New York Yankees game in Philadelphia against the Phillies.

COVID-19 also shut down professional, college, high school, and recreational sports throughout much of the country beginning in March.

Medicine, Football Intersect

In the previous Medscape interview, Duvernay-Tardif talked about how medicine influenced his football career.

“For me, medicine was really helpful in the sense that I was better able to build a routine and question what works for me and what doesn’t. It gave me the ability to structure my work in order to optimize my time and to make sure that it’s pertinent.

“Another thing is the psychology and the sports psychology. I think there’s a little bit of a stigma around mental health issues in professional sports and everywhere, actually. I think because of medicine, I was more willing to question myself and more willing to use different tools in order to be a better football player.”
 

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

Laurent Duvernay-Tardif, MD, the only medical doctor on a current NFL roster, has become the first player to opt out of the 2020 NFL season, citing concerns over risk for COVID-19.

Canadian-born Duvernay-Tardif, right guard for the Kansas City Chiefs, announced on Twitter on July 24 what he called “one of the most difficult decisions I have had to make in my life.”

“There is no doubt in my mind the Chiefs’ medical staff have put together a strong plan to minimize the health risks associated with COVID-19, but some risks will remain,” he posted.

“Being at the frontline during this offseason has given me a different perspective on this pandemic and the stress it puts on individuals and our healthcare system. I cannot allow myself to potentially transmit the virus in our communities simply to play the sport that I love. If I am to take risks, I will do it caring for patients.”

According to CNN, Duvernay-Tardif, less than 3 months after helping the Chiefs win the Super Bowl in February, began working at a long-term care facility near Montreal in what he described as a “nursing role.”

Duvernay-Tardif wrote recently in an article for Sports Illustrated that he has not completed his residency and is not yet licensed to practice.

“My first day back in the hospital was April 24,” Duvernay-Tardif wrote. “I felt nervous the night before, but a good nervous, like before a game.”

Duvernay-Tardif has also served on the NFL Players’ Association COVID-19 task force, according to Yahoo News .

A spokesperson for Duvernay-Tardif told Medscape Medical News he was unavailable to comment about the announcement.

Starting His Dual Career

Duvernay-Tardif, 29, was drafted in the sixth round by the Chiefs in 2014.

According to Forbes , he spent 8 years (2010-2018) pursuing his medical degree while still playing college football for McGill University in Montreal. Duvernay-Tardif played offensive tackle for the Redmen and in his senior year (2013) won the Metras Trophy as most outstanding lineman in Canadian college football.

He explained in a previous Medscape interview how he managed his dual career; as a doctor he said he would like to focus on emergency medicine:

“I would say that at around 16-17 years of age, I was pretty convinced that medicine was for me,” he told Medscape.

“I was lucky that I didn’t have to do an undergrad program,” he continued. “In Canada, they have a fast-track program where instead of doing a full undergrad before getting into medical school, you can do a 1-year program where you can do all your physiology and biology classes all together.

“I had the chance to get into that program, and that’s how I was able to manage football and medicine at the same time. There’s no way I could have finished my med school doing part-time med school like I did for the past 4 years.”

ESPN explained the opt-out option: “According to an agreement approved by both the league and the union on [July 24], players considered high risk for COVID-19 can earn $350,000 and an accrued NFL season if they choose to opt out of the 2020 season. Players without risk can earn $150,000 for opting out. Duvernay-Tardif was scheduled to make $2.75 million this season.”

The danger of COVID-19 in professional sports has already been seen in Major League Baseball.

According to USA Today, the Miami Marlins have at least 14 players and staff who have tested positive for COVID-19, and major league baseball Commissioner Rob Manfred must decide whether to further delay the shortened season, cancel it, or allow it to continue.

MLB postponed the Marlins’ home opener July 27 against the Baltimore Orioles as well as the New York Yankees game in Philadelphia against the Phillies.

COVID-19 also shut down professional, college, high school, and recreational sports throughout much of the country beginning in March.

Medicine, Football Intersect

In the previous Medscape interview, Duvernay-Tardif talked about how medicine influenced his football career.

“For me, medicine was really helpful in the sense that I was better able to build a routine and question what works for me and what doesn’t. It gave me the ability to structure my work in order to optimize my time and to make sure that it’s pertinent.

“Another thing is the psychology and the sports psychology. I think there’s a little bit of a stigma around mental health issues in professional sports and everywhere, actually. I think because of medicine, I was more willing to question myself and more willing to use different tools in order to be a better football player.”
 

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

Laurent Duvernay-Tardif, MD, the only medical doctor on a current NFL roster, has become the first player to opt out of the 2020 NFL season, citing concerns over risk for COVID-19.

Canadian-born Duvernay-Tardif, right guard for the Kansas City Chiefs, announced on Twitter on July 24 what he called “one of the most difficult decisions I have had to make in my life.”

“There is no doubt in my mind the Chiefs’ medical staff have put together a strong plan to minimize the health risks associated with COVID-19, but some risks will remain,” he posted.

“Being at the frontline during this offseason has given me a different perspective on this pandemic and the stress it puts on individuals and our healthcare system. I cannot allow myself to potentially transmit the virus in our communities simply to play the sport that I love. If I am to take risks, I will do it caring for patients.”

According to CNN, Duvernay-Tardif, less than 3 months after helping the Chiefs win the Super Bowl in February, began working at a long-term care facility near Montreal in what he described as a “nursing role.”

Duvernay-Tardif wrote recently in an article for Sports Illustrated that he has not completed his residency and is not yet licensed to practice.

“My first day back in the hospital was April 24,” Duvernay-Tardif wrote. “I felt nervous the night before, but a good nervous, like before a game.”

Duvernay-Tardif has also served on the NFL Players’ Association COVID-19 task force, according to Yahoo News .

A spokesperson for Duvernay-Tardif told Medscape Medical News he was unavailable to comment about the announcement.

Starting His Dual Career

Duvernay-Tardif, 29, was drafted in the sixth round by the Chiefs in 2014.

According to Forbes , he spent 8 years (2010-2018) pursuing his medical degree while still playing college football for McGill University in Montreal. Duvernay-Tardif played offensive tackle for the Redmen and in his senior year (2013) won the Metras Trophy as most outstanding lineman in Canadian college football.

He explained in a previous Medscape interview how he managed his dual career; as a doctor he said he would like to focus on emergency medicine:

“I would say that at around 16-17 years of age, I was pretty convinced that medicine was for me,” he told Medscape.

“I was lucky that I didn’t have to do an undergrad program,” he continued. “In Canada, they have a fast-track program where instead of doing a full undergrad before getting into medical school, you can do a 1-year program where you can do all your physiology and biology classes all together.

“I had the chance to get into that program, and that’s how I was able to manage football and medicine at the same time. There’s no way I could have finished my med school doing part-time med school like I did for the past 4 years.”

ESPN explained the opt-out option: “According to an agreement approved by both the league and the union on [July 24], players considered high risk for COVID-19 can earn $350,000 and an accrued NFL season if they choose to opt out of the 2020 season. Players without risk can earn $150,000 for opting out. Duvernay-Tardif was scheduled to make $2.75 million this season.”

The danger of COVID-19 in professional sports has already been seen in Major League Baseball.

According to USA Today, the Miami Marlins have at least 14 players and staff who have tested positive for COVID-19, and major league baseball Commissioner Rob Manfred must decide whether to further delay the shortened season, cancel it, or allow it to continue.

MLB postponed the Marlins’ home opener July 27 against the Baltimore Orioles as well as the New York Yankees game in Philadelphia against the Phillies.

COVID-19 also shut down professional, college, high school, and recreational sports throughout much of the country beginning in March.

Medicine, Football Intersect

In the previous Medscape interview, Duvernay-Tardif talked about how medicine influenced his football career.

“For me, medicine was really helpful in the sense that I was better able to build a routine and question what works for me and what doesn’t. It gave me the ability to structure my work in order to optimize my time and to make sure that it’s pertinent.

“Another thing is the psychology and the sports psychology. I think there’s a little bit of a stigma around mental health issues in professional sports and everywhere, actually. I think because of medicine, I was more willing to question myself and more willing to use different tools in order to be a better football player.”
 

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

When the coronavirus pandemic hit New York City in early March, the Hospital for Special Surgery leadership decided that the best way to serve the city was to stop elective orthopedic procedures temporarily and use the facility to take on patients from its sister institution, NewYork–Presbyterian Hospital.

As in other institutions, it was all hands on deck. We have hospitalists that are accustomed to managing postsurgical care and internists familiar with preop surgical clearances. But they needed more help, and soon, other internal medicine subspecialists were asked to volunteer, including rheumatologists and primary care sports medicine doctors.

As a rheumatologist, it had been well over 10 years since I had last done any inpatient work. I was filled with trepidation, but I was also excited to dive in.
 

April 4:

Feeling very unmoored. I am in unfamiliar territory, and it’s terrifying. There are so many things that I no longer know how to do. Thankfully, the hospitalists are gracious, extremely supportive, and helpful.

My N95 doesn’t fit well. It’s never fit — not during residency or fellowship, not in any job I’ve had, and not today. The lady fit-testing me said she was sorry, but the look on her face said, “I’m sorry, but you’re going to die.”
 

April 7:

We don’t know how to treat coronavirus. I’ve sent some patients home, others I’ve sent to the ICU. Thank goodness for treatment algorithms from leadership, but we are sorely lacking good-quality data.

Our infectious disease doctor doesn’t think hydroxychloroquine works at all; I suspect he is right. The guidance right now is to give hydroxychloroquine and azithromycin to everyone who is sick enough to be admitted, but there are methodologic flaws in the early enthusiastic preprints, and so far, I’ve not noticed any demonstrable benefit.

The only thing that seems to be happening is that I am seeing more QT prolongation — not something I previously counseled my rheumatology patients on.
 

April 9:

The patients have been, with a few exceptions, alone in the room. They’re not allowed to have visitors and are required to wear masks all the time. Anyone who enters their rooms is fully covered up so you can barely see them. It’s anonymous and dehumanizing.

We’re instructed to take histories by phone in order to limit the time spent in each room. I buck this instruction; I still take histories in person because human contact seems more important now than ever.

Except maybe I should be smarter about this. One of my patients refuses any treatment, including oxygen support. She firmly believes this is a result of 5G networks — something I later discovered was a common conspiracy theory. She refused to wear a mask despite having a very bad cough. She coughed in my face a lot when we were chatting. My face with my ill-fitting N95 mask. Maybe the fit-testing lady’s eyes weren’t lying and I will die after all.
 

April 15:

On the days when I’m not working as a hospitalist, I am still doing remote visits with my rheumatology patients. It feels good to be doing something familiar and something I’m actually good at. But it is surreal to be faced with the quotidian on one hand and life and death on the other.

I recently saw a fairly new patient, and I still haven’t figured out if she has a rheumatic condition or if her symptoms all stem from an alcohol use disorder. In our previous visits, she could barely acknowledge that her drinking was an issue. On today’s visit, she told me she was 1½ months sober.

I don’t know her very well, but it was the happiest news I’d heard in a long time. I was so beside myself with joy that I cried, which says more about my current emotional state than anything else, really.
 

April 21:

On my panel of patients, I have three women with COVID-19 — all of whom lost their husbands to COVID-19, and none of whom were able to say their goodbyes. I cannot even begin to imagine what it must be like to survive this period of illness, isolation, and fear, only to be met on the other side by grief.

Rheumatology doesn’t lend itself too well to such existential concerns; I am not equipped for this. Perhaps my only advantage as a rheumatologist is that I know how to use IVIG, anakinra, and tocilizumab.

Someone on my panel was started on anakinra, and it turned his case around. Would he have gotten better without it anyway? We’ll never know for sure.
 

April 28:

Patients seem to be requiring prolonged intubation. We have now reached the stage where patients are alive but trached and PEGed. One of my patients had been intubated for close to 3 weeks. She was one of four people in her family who contracted the illness (they had had a dinner party before New York’s state of emergency was declared). We thought she might die once she was extubated, but she is still fighting. Unconscious, unarousable, but breathing on her own.

Will she ever wake up? We don’t know. We put the onus on her family to make decisions about placing a PEG tube in. They can only do so from a distance with imperfect information gleaned from periodic, brief FaceTime interactions — where no interaction happens at all.
 

May 4:

It’s my last day as a “COVID hospitalist.” When I first started, I felt like I was being helpful. Walking home in the middle of the 7 PM cheers for healthcare workers frequently left me teary eyed. As horrible as the situation was, I was proud of myself for volunteering to help and appreciative of a broken city’s gratitude toward all healthcare workers in general. Maybe I bought into the idea that, like many others around me, I am a hero.

I don’t feel like a hero, though. The stuff I saw was easy compared with the stuff that my colleagues in critical care saw. Our hospital accepted the more stable patient transfers from our sister hospitals. Patients who remained in the NewYork–Presbyterian system were sicker, with encephalitis, thrombotic complications, multiorgan failure, and cytokine release syndrome. It’s the doctors who took care of those patients who deserve to be called heroes.

No, I am no hero. But did my volunteering make a difference? It made a difference to me. The overwhelming feeling I am left with isn’t pride; it’s humility. I feel humbled that I could feel so unexpectedly touched by the lives of people that I had no idea I could feel touched by.
 

Postscript:

My patient Esther [name changed to hide her identity] died from COVID-19. She was MY patient — not a patient I met as a COVID hospitalist, but a patient with rheumatoid arthritis whom I cared for for years.

She had scleromalacia and multiple failed scleral grafts, which made her profoundly sad. She fought her anxiety fiercely and always with poise and panache. One way she dealt with her anxiety was that she constantly messaged me via our EHR portal. She ran everything by me and trusted me to be her rock.

The past month has been so busy that I just now noticed it had been a month since I last heard from her. I tried to call her but got her voicemail. It wasn’t until I exchanged messages with her ophthalmologist that I found out she had passed away from complications of COVID-19.

She was taking rituximab and mycophenolate. I wonder if these drugs made her sicker than she would have been otherwise; it fills me with sadness. I wonder if she was alone like my other COVID-19 patients. I wonder if she was afraid. I am sorry that I wasn’t able to say goodbye.

Karmela Kim Chan, MD, is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York City. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for this rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice.

A version of this article originally appeared on Medscape.com. This article is part of a partnership between Medscape and Hospital for Special Surgery.

When the coronavirus pandemic hit New York City in early March, the Hospital for Special Surgery leadership decided that the best way to serve the city was to stop elective orthopedic procedures temporarily and use the facility to take on patients from its sister institution, NewYork–Presbyterian Hospital.

As in other institutions, it was all hands on deck. We have hospitalists that are accustomed to managing postsurgical care and internists familiar with preop surgical clearances. But they needed more help, and soon, other internal medicine subspecialists were asked to volunteer, including rheumatologists and primary care sports medicine doctors.

As a rheumatologist, it had been well over 10 years since I had last done any inpatient work. I was filled with trepidation, but I was also excited to dive in.
 

April 4:

Feeling very unmoored. I am in unfamiliar territory, and it’s terrifying. There are so many things that I no longer know how to do. Thankfully, the hospitalists are gracious, extremely supportive, and helpful.

My N95 doesn’t fit well. It’s never fit — not during residency or fellowship, not in any job I’ve had, and not today. The lady fit-testing me said she was sorry, but the look on her face said, “I’m sorry, but you’re going to die.”
 

April 7:

We don’t know how to treat coronavirus. I’ve sent some patients home, others I’ve sent to the ICU. Thank goodness for treatment algorithms from leadership, but we are sorely lacking good-quality data.

Our infectious disease doctor doesn’t think hydroxychloroquine works at all; I suspect he is right. The guidance right now is to give hydroxychloroquine and azithromycin to everyone who is sick enough to be admitted, but there are methodologic flaws in the early enthusiastic preprints, and so far, I’ve not noticed any demonstrable benefit.

The only thing that seems to be happening is that I am seeing more QT prolongation — not something I previously counseled my rheumatology patients on.
 

April 9:

The patients have been, with a few exceptions, alone in the room. They’re not allowed to have visitors and are required to wear masks all the time. Anyone who enters their rooms is fully covered up so you can barely see them. It’s anonymous and dehumanizing.

We’re instructed to take histories by phone in order to limit the time spent in each room. I buck this instruction; I still take histories in person because human contact seems more important now than ever.

Except maybe I should be smarter about this. One of my patients refuses any treatment, including oxygen support. She firmly believes this is a result of 5G networks — something I later discovered was a common conspiracy theory. She refused to wear a mask despite having a very bad cough. She coughed in my face a lot when we were chatting. My face with my ill-fitting N95 mask. Maybe the fit-testing lady’s eyes weren’t lying and I will die after all.
 

April 15:

On the days when I’m not working as a hospitalist, I am still doing remote visits with my rheumatology patients. It feels good to be doing something familiar and something I’m actually good at. But it is surreal to be faced with the quotidian on one hand and life and death on the other.

I recently saw a fairly new patient, and I still haven’t figured out if she has a rheumatic condition or if her symptoms all stem from an alcohol use disorder. In our previous visits, she could barely acknowledge that her drinking was an issue. On today’s visit, she told me she was 1½ months sober.

I don’t know her very well, but it was the happiest news I’d heard in a long time. I was so beside myself with joy that I cried, which says more about my current emotional state than anything else, really.
 

April 21:

On my panel of patients, I have three women with COVID-19 — all of whom lost their husbands to COVID-19, and none of whom were able to say their goodbyes. I cannot even begin to imagine what it must be like to survive this period of illness, isolation, and fear, only to be met on the other side by grief.

Rheumatology doesn’t lend itself too well to such existential concerns; I am not equipped for this. Perhaps my only advantage as a rheumatologist is that I know how to use IVIG, anakinra, and tocilizumab.

Someone on my panel was started on anakinra, and it turned his case around. Would he have gotten better without it anyway? We’ll never know for sure.
 

April 28:

Patients seem to be requiring prolonged intubation. We have now reached the stage where patients are alive but trached and PEGed. One of my patients had been intubated for close to 3 weeks. She was one of four people in her family who contracted the illness (they had had a dinner party before New York’s state of emergency was declared). We thought she might die once she was extubated, but she is still fighting. Unconscious, unarousable, but breathing on her own.

Will she ever wake up? We don’t know. We put the onus on her family to make decisions about placing a PEG tube in. They can only do so from a distance with imperfect information gleaned from periodic, brief FaceTime interactions — where no interaction happens at all.
 

May 4:

It’s my last day as a “COVID hospitalist.” When I first started, I felt like I was being helpful. Walking home in the middle of the 7 PM cheers for healthcare workers frequently left me teary eyed. As horrible as the situation was, I was proud of myself for volunteering to help and appreciative of a broken city’s gratitude toward all healthcare workers in general. Maybe I bought into the idea that, like many others around me, I am a hero.

I don’t feel like a hero, though. The stuff I saw was easy compared with the stuff that my colleagues in critical care saw. Our hospital accepted the more stable patient transfers from our sister hospitals. Patients who remained in the NewYork–Presbyterian system were sicker, with encephalitis, thrombotic complications, multiorgan failure, and cytokine release syndrome. It’s the doctors who took care of those patients who deserve to be called heroes.

No, I am no hero. But did my volunteering make a difference? It made a difference to me. The overwhelming feeling I am left with isn’t pride; it’s humility. I feel humbled that I could feel so unexpectedly touched by the lives of people that I had no idea I could feel touched by.
 

Postscript:

My patient Esther [name changed to hide her identity] died from COVID-19. She was MY patient — not a patient I met as a COVID hospitalist, but a patient with rheumatoid arthritis whom I cared for for years.

She had scleromalacia and multiple failed scleral grafts, which made her profoundly sad. She fought her anxiety fiercely and always with poise and panache. One way she dealt with her anxiety was that she constantly messaged me via our EHR portal. She ran everything by me and trusted me to be her rock.

The past month has been so busy that I just now noticed it had been a month since I last heard from her. I tried to call her but got her voicemail. It wasn’t until I exchanged messages with her ophthalmologist that I found out she had passed away from complications of COVID-19.

She was taking rituximab and mycophenolate. I wonder if these drugs made her sicker than she would have been otherwise; it fills me with sadness. I wonder if she was alone like my other COVID-19 patients. I wonder if she was afraid. I am sorry that I wasn’t able to say goodbye.

Karmela Kim Chan, MD, is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York City. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for this rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice.

A version of this article originally appeared on Medscape.com. This article is part of a partnership between Medscape and Hospital for Special Surgery.

When the coronavirus pandemic hit New York City in early March, the Hospital for Special Surgery leadership decided that the best way to serve the city was to stop elective orthopedic procedures temporarily and use the facility to take on patients from its sister institution, NewYork–Presbyterian Hospital.

As in other institutions, it was all hands on deck. We have hospitalists that are accustomed to managing postsurgical care and internists familiar with preop surgical clearances. But they needed more help, and soon, other internal medicine subspecialists were asked to volunteer, including rheumatologists and primary care sports medicine doctors.

As a rheumatologist, it had been well over 10 years since I had last done any inpatient work. I was filled with trepidation, but I was also excited to dive in.
 

April 4:

Feeling very unmoored. I am in unfamiliar territory, and it’s terrifying. There are so many things that I no longer know how to do. Thankfully, the hospitalists are gracious, extremely supportive, and helpful.

My N95 doesn’t fit well. It’s never fit — not during residency or fellowship, not in any job I’ve had, and not today. The lady fit-testing me said she was sorry, but the look on her face said, “I’m sorry, but you’re going to die.”
 

April 7:

We don’t know how to treat coronavirus. I’ve sent some patients home, others I’ve sent to the ICU. Thank goodness for treatment algorithms from leadership, but we are sorely lacking good-quality data.

Our infectious disease doctor doesn’t think hydroxychloroquine works at all; I suspect he is right. The guidance right now is to give hydroxychloroquine and azithromycin to everyone who is sick enough to be admitted, but there are methodologic flaws in the early enthusiastic preprints, and so far, I’ve not noticed any demonstrable benefit.

The only thing that seems to be happening is that I am seeing more QT prolongation — not something I previously counseled my rheumatology patients on.
 

April 9:

The patients have been, with a few exceptions, alone in the room. They’re not allowed to have visitors and are required to wear masks all the time. Anyone who enters their rooms is fully covered up so you can barely see them. It’s anonymous and dehumanizing.

We’re instructed to take histories by phone in order to limit the time spent in each room. I buck this instruction; I still take histories in person because human contact seems more important now than ever.

Except maybe I should be smarter about this. One of my patients refuses any treatment, including oxygen support. She firmly believes this is a result of 5G networks — something I later discovered was a common conspiracy theory. She refused to wear a mask despite having a very bad cough. She coughed in my face a lot when we were chatting. My face with my ill-fitting N95 mask. Maybe the fit-testing lady’s eyes weren’t lying and I will die after all.
 

April 15:

On the days when I’m not working as a hospitalist, I am still doing remote visits with my rheumatology patients. It feels good to be doing something familiar and something I’m actually good at. But it is surreal to be faced with the quotidian on one hand and life and death on the other.

I recently saw a fairly new patient, and I still haven’t figured out if she has a rheumatic condition or if her symptoms all stem from an alcohol use disorder. In our previous visits, she could barely acknowledge that her drinking was an issue. On today’s visit, she told me she was 1½ months sober.

I don’t know her very well, but it was the happiest news I’d heard in a long time. I was so beside myself with joy that I cried, which says more about my current emotional state than anything else, really.
 

April 21:

On my panel of patients, I have three women with COVID-19 — all of whom lost their husbands to COVID-19, and none of whom were able to say their goodbyes. I cannot even begin to imagine what it must be like to survive this period of illness, isolation, and fear, only to be met on the other side by grief.

Rheumatology doesn’t lend itself too well to such existential concerns; I am not equipped for this. Perhaps my only advantage as a rheumatologist is that I know how to use IVIG, anakinra, and tocilizumab.

Someone on my panel was started on anakinra, and it turned his case around. Would he have gotten better without it anyway? We’ll never know for sure.
 

April 28:

Patients seem to be requiring prolonged intubation. We have now reached the stage where patients are alive but trached and PEGed. One of my patients had been intubated for close to 3 weeks. She was one of four people in her family who contracted the illness (they had had a dinner party before New York’s state of emergency was declared). We thought she might die once she was extubated, but she is still fighting. Unconscious, unarousable, but breathing on her own.

Will she ever wake up? We don’t know. We put the onus on her family to make decisions about placing a PEG tube in. They can only do so from a distance with imperfect information gleaned from periodic, brief FaceTime interactions — where no interaction happens at all.
 

May 4:

It’s my last day as a “COVID hospitalist.” When I first started, I felt like I was being helpful. Walking home in the middle of the 7 PM cheers for healthcare workers frequently left me teary eyed. As horrible as the situation was, I was proud of myself for volunteering to help and appreciative of a broken city’s gratitude toward all healthcare workers in general. Maybe I bought into the idea that, like many others around me, I am a hero.

I don’t feel like a hero, though. The stuff I saw was easy compared with the stuff that my colleagues in critical care saw. Our hospital accepted the more stable patient transfers from our sister hospitals. Patients who remained in the NewYork–Presbyterian system were sicker, with encephalitis, thrombotic complications, multiorgan failure, and cytokine release syndrome. It’s the doctors who took care of those patients who deserve to be called heroes.

No, I am no hero. But did my volunteering make a difference? It made a difference to me. The overwhelming feeling I am left with isn’t pride; it’s humility. I feel humbled that I could feel so unexpectedly touched by the lives of people that I had no idea I could feel touched by.
 

Postscript:

My patient Esther [name changed to hide her identity] died from COVID-19. She was MY patient — not a patient I met as a COVID hospitalist, but a patient with rheumatoid arthritis whom I cared for for years.

She had scleromalacia and multiple failed scleral grafts, which made her profoundly sad. She fought her anxiety fiercely and always with poise and panache. One way she dealt with her anxiety was that she constantly messaged me via our EHR portal. She ran everything by me and trusted me to be her rock.

The past month has been so busy that I just now noticed it had been a month since I last heard from her. I tried to call her but got her voicemail. It wasn’t until I exchanged messages with her ophthalmologist that I found out she had passed away from complications of COVID-19.

She was taking rituximab and mycophenolate. I wonder if these drugs made her sicker than she would have been otherwise; it fills me with sadness. I wonder if she was alone like my other COVID-19 patients. I wonder if she was afraid. I am sorry that I wasn’t able to say goodbye.

Karmela Kim Chan, MD, is an assistant professor at Weill Cornell Medical College and an attending physician at Hospital for Special Surgery and Memorial Sloan Kettering Cancer Center in New York City. Before moving to New York City, she spent 7 years in private practice in Rhode Island and was a columnist for this rheumatology publication, writing about the challenges of starting life as a full-fledged rheumatologist in a private practice.

A version of this article originally appeared on Medscape.com. This article is part of a partnership between Medscape and Hospital for Special Surgery.

Study Overview

Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.

Design. Double-blinded, randomized, placebo-controlled, multicenter trial.

Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO₂) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.

Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).

Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.

Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.

The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.

Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO₂ ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).

Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).

Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.

Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.

Commentary

Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.¹ Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.^2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.⁴ Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.

The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.

Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,⁴ provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.

The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.⁵ In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.⁶

Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.⁷ Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.

Applications for Clinical Practice

Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.

–Fred Ko, MD, MS

Study Overview

Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.

Design. Double-blinded, randomized, placebo-controlled, multicenter trial.

Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO₂) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.

Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).

Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.

Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.

The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.

Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO₂ ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).

Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).

Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.

Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.

Commentary

Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.¹ Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.^2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.⁴ Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.

The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.

Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,⁴ provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.

The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.⁵ In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.⁶

Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.⁷ Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.

Applications for Clinical Practice

Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.

–Fred Ko, MD, MS

Study Overview

Objective. To assess the clinical efficacy and safety of remdesivir in hospitalized adults with laboratory-confirmed COVID-19 and with evidence of lower respiratory tract involvement.

Design. Double-blinded, randomized, placebo-controlled, multicenter trial.

Setting and participants. Enrollment for the study took place between February 21, 2020, and April 19, 2020, at 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore. Study participants included patients aged ≥ 18 years who were hospitalized and had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as determined by a positive reverse transcription polymerase chain reaction assay on a respiratory specimen. Participants had evidence of lower respiratory tract infection at the time of enrollment; this was defined as radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO₂) ≤ 94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Exclusion criteria for study participation included abnormal liver enzymes (alanine aminotransferase, aspartate aminotransferase) more than 5 times the upper limit of normal range; impaired renal function or need for hemodialysis or hemofiltration; pregnancy or breastfeeding; or anticipated hospital discharge or transfer to another hospital within 72 hours of enrollment.

Intervention. Participants were randomized in a 1:1 ratio to the remdesivir group or the placebo group and were administered either intravenous infusions of remdesivir (200-mg loading dose on day 1, followed by a 100-mg maintenance dose daily on days 2 through 10, or until hospital discharge or death) or placebo for up to 10 days. Blinding was maintained by masking infusions with an opaque bag and tubing. Randomization was stratified by study site and disease severity at enrollment. Supportive care was delivered to all participants according to the standard of care at each trial site hospital. Clinical status, determined using an 8-category ordinal scale and the National Early Warning Score, was assessed daily for each participant while hospitalized (day 1 through day 29).

Blood samples for safety laboratory tests were collected, and oropharyngeal or nasopharyngeal swab testing was performed for viral RNA detection and quantification on days 1, 3, 5, 8, and 11. All serious adverse events (AEs) and grade 3/4 AEs that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions associated with the study drug or placebo administration were recorded.

Main outcome measures. The primary endpoint measure of this study was time to recovery, defined as the first day during the 28 days after enrollment on which a participant satisfied category 1 (ie, not hospitalized, no limitations of activities), 2 (ie, not hospitalized, limitation of activities, home oxygen requirement, or both), or 3 (ie, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; hospitalization was extended for infection-control reason) on the 8-category ordinal scale. Secondary outcomes included all-cause mortality at 14 and 28 days after enrollment and grade 3/4 AEs and serious AEs that occurred during trial participation. Analysis of the primary outcome was performed using a log-rank test of the time to recovery comparing remdesivir with placebo group, stratified by disease severity.

The study’s primary outcome was initially defined as a difference in clinical status as ascertained by the 8-category ordinal scale between groups of participants who were administered remdesivir versus placebo on day 15. Because of new knowledge gained external to the study about a more protracted COVID-19 clinical course than previously recognized, a change in primary outcome to time to recovery was proposed by trial statisticians, who were unaware of treatment assignments (72 participants had been enrolled) or outcome data (no interim data) on March 22, 2020, with subsequent amendment approval on April 2, 2020. On April 27, 2020, the Data and Safety Monitoring Board (DSMB) reviewed the interim study analysis (with data cutoff date of April 22, 2020) and recommended the report and mortality data to be provided to trial team members from the National Institute of Allergy and Infectious Diseases; these findings were subsequently made public.

Main results. A total of 1107 patients were assessed for eligibility, of whom 1063 underwent randomization, with 541 assigned to remdesivir and 522 to placebo. Results were unblinded early at the recommendation of DSMB due to findings from the interim analysis that showed reduced time to recovery in the group that received remdesivir. As of April 28, 2020, a total of 391 participants in the remdesivir group and 340 participants in the placebo group had completed the trial (day 29), recovered, or died. The mean age of participants was 58.9 ± 15.0 years, the majority were men (64.3%) and were White (53.2%), and the most common prespecified coexisting conditions were hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The vast majority of participants (88.7%) had severe COVID-19 disease at enrollment, defined as requiring invasive or noninvasive mechanical ventilation, requiring supplemental oxygen, SpO₂ ≤ 94% on room air, or tachypnea (respiratory rate ≥ 24 breaths per minute).

Based on available data from 1059 participants (538 from the remdesivir group and 521 from the placebo group), those in the remdesivir group had a shorter median recovery time of 11 days (95% confidence interval [CI], 9-12) as compared to 15 days (95% CI, 13-19) in the placebo group, with a rate ratio for recovery of 1.32 (95% CI, 1.12-1.55; P < 0.001). Moreover, the odds of improvement on day 15 in the 8-category ordinal scale score were higher in the remdesivir group, compared to the placebo group (proportional odds model; odds ratio, 1.50; 95% CI, 1.18-1.91; P = 0.001; 844 participants).

Mortality rate by 14 days was numerically lower in the remdesivir group (7.1%) compared to the placebo group (11.9%), but the difference was not statistically significant (Kaplan-Meier, hazard ratio for death, 0.70; 95% CI, 0.47-1.04). Serious AEs were reported in 114 of the 541 (21.1%) participants in the remdesivir group and 141 of the 522 (27.0%) participants in the placebo group. Moreover, grade 3/4 AEs occurred in 156 (28.8%) participants in the remdesivir group and in 172 (33.0%) in the placebo group.

Conclusion. The study found that remdesivir, compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.

Commentary

Since the initial reporting of a cluster of cases of pneumonia in Wuhan, China, on December 31, 2019, SARS-CoV-2 has been identified as the cause of this new disease (COVID-19), and to-date SARS-CoV-2 infection has affected more than 15.2 million people globally, with more than 3.9 million cases in the United States alone.¹ Despite an unprecedented global research effort, as well as public-private research partnerships, both in terms of scale and scope, an effective pharmacologic therapy for COVID-19 has so far eluded the scientific and medical community. Early trials of hydroxychloroquine and lopinavir-ritonavir did not demonstrate a clinical benefit in patients with COVID-19.^2,3 Moreover, the first randomized controlled trial of remdesivir in COVID-19, a nucleoside analogue prodrug and a broad-spectrum antiviral agent previously shown to have inhibitory effects on pathogenic coronaviruses, was an underpowered study, and thus inconclusive.⁴ Thus, given the persistence of the COVID-19 pandemic and a current lack of effective vaccines or curative treatments, the study reported by Beigel and colleagues is timely and provides much needed knowledge in developing potential therapies for COVID-19.

The present report described the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1), which aimed to evaluate the clinical efficacy and safety of intravenous remdesivir, as compared to placebo, in hospitalized adults with laboratory-confirmed COVID-19. The study itself was well-designed and conducted. The successful enrollment of more than 1000 participants randomized in a 1:1 ratio within a 2-month recruitment window, involving 60 international trial sites, shortly after the emergence of a new global pandemic was remarkable. This study provided the first evidence that remdesivir, an antiviral, can shorten time to recovery by approximately 31% compared to placebo in COVID-19 patients with lower respiratory tract involvement.

Interestingly, this beneficial effect of remdesivir on time to recovery was primarily observed in participants within the severe disease stratum (those requiring supplemental oxygen) at baseline (12 days in remdesivir group versus 18 days in placebo group), but not in those with mild-moderate disease at the time of study enrollment (5 days in either remdesivir or placebo group). Moreover, the beneficial effects of remdesivir on reducing time to recovery was not observed in participants who required mechanical ventilation or ECMO at enrollment. Thus, these preliminary results suggest that COVID-19 disease severity and timing, particularly in patients who require supplemental oxygen but prior to disease progression towards requiring mechanical ventilation, may present a window of opportunity to initiate remdesivir treatment in order to improve outcomes. Further analysis utilizing data from the entire cohort, including outcomes data from the full 28-day follow-up period, may better delineate the subgroup of hospitalized COVID-19 patients who may benefit most from remdesivir. Last, safety data from the present study, along with that reported by Wang and colleagues,⁴ provides evidence that intravenous remdesivir administration is likely safe in adults during the treatment period.

The preliminary results from the ACCT-1 provide early evidence that remdesivir shortens time to recovery in adult patients hospitalized for COVID-19 with pulmonary involvement. In light of these results, the US Food and Drug Administration issued an emergency use authorization for remdesivir on May 1, 2020, for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease.⁵ In addition, remdesivir has also recently been approved as a therapy for COVID-19 in Japan, Taiwan, India, Singapore, and the United Arab Emirates, and has received conditional approval for use by the European Commission.⁶

Although these are encouraging developments in the race to identify effective therapeutics for COVID-19, a number of unanswered questions regarding the administration of remdesivir in the treatment of this disease remain. For instance, in an open-label, randomized, multicenter trial of patients with severe COVID-19 not requiring mechanical ventilation, treatment with a 5-day course versus a 10-day course of intravenous remdesivir did not result in a significant difference in efficacy.⁷ Thus, more studies are needed to better determine the shortest effective duration of remdesivir therapy in COVID-19 patients with different disease severity. Also, the mortality rate in COVID-19 patients who were treated with remdesivir remained high in the current study. Therefore, there is ample opportunity to evaluate treatment strategies, including multidrug interventions with remdesivir, to reduce mortality and improve clinical outcomes in patients hospitalized with COVID-19.

Applications for Clinical Practice

Remdesivir shortens time to recovery in adult patients hospitalized with COVID-19 who require supplemental oxygen therapy. While much needs to be learned in order to optimize treatment of COVID-19, preliminary findings from the current study provide an important first step towards these discoveries.

–Fred Ko, MD, MS

More than half of Hispanic adults would be afraid to go to a hospital for a possible heart attack or stroke because they might get infected with SARS-CoV-2, according to a new survey from the American Heart Association.

Compared with Hispanic respondents, 55% of whom said they feared COVID-19, significantly fewer Blacks (45%) and Whites (40%) would be scared to go to the hospital if they thought they were having a heart attack or stroke, the AHA said based on the survey of 2,050 adults, which was conducted May 29 to June 2, 2020, by the Harris Poll.

Hispanics also were significantly more likely to stay home if they thought they were experiencing a heart attack or stroke (41%), rather than risk getting infected at the hospital, than were Blacks (33%), who were significantly more likely than Whites (24%) to stay home, the AHA reported.

White respondents, on the other hand, were the most likely to believe (89%) that a hospital would give them the same quality of care provided to everyone else. Hispanics and Blacks had significantly lower rates, at 78% and 74%, respectively, the AHA noted.

These findings are “yet another challenge for Black and Hispanic communities, who are more likely to have underlying health conditions such as cardiovascular disease and diabetes and dying of COVID-19 at disproportionately high rates,” Rafael Ortiz, MD, American Heart Association volunteer medical expert and chief of neuro-endovascular surgery at Lenox Hill Hospital, New York, said in the AHA statement.

The survey was performed in conjunction with the AHA’s “Don’t Die of Doubt” campaign, which “reminds Americans, especially in Hispanic and Black communities, that the hospital remains the safest place to be if experiencing symptoms of a heart attack or a stroke.”

Among all the survey respondents, 57% said they would feel better if hospitals treated COVID-19 patients in a separate area. A number of other possible precautions ranked lower in helping them feel better:

• Screen all visitors, patients, and staff for COVID-19 symptoms when they enter the hospital: 39%.
• Require all patients, visitors, and staff to wear masks: 30%.
• Put increased cleaning protocols in place to disinfect multiple times per day: 23%.
• “Nothing would make me feel comfortable”: 6%.

Despite all the concerns about the risk of coronavirus infection, however, most Americans (77%) still believe that hospitals are the safest place to be in the event of a medical emergency, and 84% said that hospitals are prepared to safely treat emergencies that are not related to the pandemic, the AHA reported.

“Health care professionals know what to do even when things seem chaotic, and emergency departments have made plans behind the scenes to keep patients and healthcare workers safe even during a pandemic,” Dr. Ortiz pointed out.

rfranki@mdedge.com

More than half of Hispanic adults would be afraid to go to a hospital for a possible heart attack or stroke because they might get infected with SARS-CoV-2, according to a new survey from the American Heart Association.

Compared with Hispanic respondents, 55% of whom said they feared COVID-19, significantly fewer Blacks (45%) and Whites (40%) would be scared to go to the hospital if they thought they were having a heart attack or stroke, the AHA said based on the survey of 2,050 adults, which was conducted May 29 to June 2, 2020, by the Harris Poll.

Hispanics also were significantly more likely to stay home if they thought they were experiencing a heart attack or stroke (41%), rather than risk getting infected at the hospital, than were Blacks (33%), who were significantly more likely than Whites (24%) to stay home, the AHA reported.

White respondents, on the other hand, were the most likely to believe (89%) that a hospital would give them the same quality of care provided to everyone else. Hispanics and Blacks had significantly lower rates, at 78% and 74%, respectively, the AHA noted.

These findings are “yet another challenge for Black and Hispanic communities, who are more likely to have underlying health conditions such as cardiovascular disease and diabetes and dying of COVID-19 at disproportionately high rates,” Rafael Ortiz, MD, American Heart Association volunteer medical expert and chief of neuro-endovascular surgery at Lenox Hill Hospital, New York, said in the AHA statement.

The survey was performed in conjunction with the AHA’s “Don’t Die of Doubt” campaign, which “reminds Americans, especially in Hispanic and Black communities, that the hospital remains the safest place to be if experiencing symptoms of a heart attack or a stroke.”

Among all the survey respondents, 57% said they would feel better if hospitals treated COVID-19 patients in a separate area. A number of other possible precautions ranked lower in helping them feel better:

• Screen all visitors, patients, and staff for COVID-19 symptoms when they enter the hospital: 39%.
• Require all patients, visitors, and staff to wear masks: 30%.
• Put increased cleaning protocols in place to disinfect multiple times per day: 23%.
• “Nothing would make me feel comfortable”: 6%.

Despite all the concerns about the risk of coronavirus infection, however, most Americans (77%) still believe that hospitals are the safest place to be in the event of a medical emergency, and 84% said that hospitals are prepared to safely treat emergencies that are not related to the pandemic, the AHA reported.

“Health care professionals know what to do even when things seem chaotic, and emergency departments have made plans behind the scenes to keep patients and healthcare workers safe even during a pandemic,” Dr. Ortiz pointed out.

rfranki@mdedge.com

More than half of Hispanic adults would be afraid to go to a hospital for a possible heart attack or stroke because they might get infected with SARS-CoV-2, according to a new survey from the American Heart Association.

Compared with Hispanic respondents, 55% of whom said they feared COVID-19, significantly fewer Blacks (45%) and Whites (40%) would be scared to go to the hospital if they thought they were having a heart attack or stroke, the AHA said based on the survey of 2,050 adults, which was conducted May 29 to June 2, 2020, by the Harris Poll.

Hispanics also were significantly more likely to stay home if they thought they were experiencing a heart attack or stroke (41%), rather than risk getting infected at the hospital, than were Blacks (33%), who were significantly more likely than Whites (24%) to stay home, the AHA reported.

White respondents, on the other hand, were the most likely to believe (89%) that a hospital would give them the same quality of care provided to everyone else. Hispanics and Blacks had significantly lower rates, at 78% and 74%, respectively, the AHA noted.

These findings are “yet another challenge for Black and Hispanic communities, who are more likely to have underlying health conditions such as cardiovascular disease and diabetes and dying of COVID-19 at disproportionately high rates,” Rafael Ortiz, MD, American Heart Association volunteer medical expert and chief of neuro-endovascular surgery at Lenox Hill Hospital, New York, said in the AHA statement.

The survey was performed in conjunction with the AHA’s “Don’t Die of Doubt” campaign, which “reminds Americans, especially in Hispanic and Black communities, that the hospital remains the safest place to be if experiencing symptoms of a heart attack or a stroke.”

Among all the survey respondents, 57% said they would feel better if hospitals treated COVID-19 patients in a separate area. A number of other possible precautions ranked lower in helping them feel better:

• Screen all visitors, patients, and staff for COVID-19 symptoms when they enter the hospital: 39%.
• Require all patients, visitors, and staff to wear masks: 30%.
• Put increased cleaning protocols in place to disinfect multiple times per day: 23%.
• “Nothing would make me feel comfortable”: 6%.

Despite all the concerns about the risk of coronavirus infection, however, most Americans (77%) still believe that hospitals are the safest place to be in the event of a medical emergency, and 84% said that hospitals are prepared to safely treat emergencies that are not related to the pandemic, the AHA reported.

“Health care professionals know what to do even when things seem chaotic, and emergency departments have made plans behind the scenes to keep patients and healthcare workers safe even during a pandemic,” Dr. Ortiz pointed out.

rfranki@mdedge.com