Cardiology News

An inexpensive two-drug regimen of sofosbuvir (Sovaldi, Gilead Sciences) plus daclatasvir (Daklinza, Bristol-Myers Squibb) taken for 14 days significantly reduced time to recovery from COVID-19 and improved survival in people hospitalized with severe disease, research from an open-label Iranian study shows.

And the good news is that the treatment combination “already has a well-established safety profile in the treatment of hepatitis C,” said investigator Andrew Hill, PhD, from the University of Liverpool, United Kingdom.

But although the results look promising, they are preliminary, he cautioned. The combination could follow the path of ritonavir plus lopinavir (Kaletra, AbbVie Pharmaceuticals) or hydroxychloroquine (Plaquenil, Sanofi Pharmaceuticals), which showed promise early but did not perform as hoped in large randomized controlled trials.

“We need to remember that conducting research amidst a pandemic with overwhelmed hospitals is a clear challenge, and we cannot be sure of success,” he added.

Three Trials, 176 Patients

Data collected during a four-site trial of the combination treatment in Tehran during an early spike in cases in Iran were presented at the Virtual COVID-19 Conference 2020 by Hannah Wentzel, a masters student in public health at Imperial College London and a member of Hill’s team.

All 66 study participants were diagnosed with moderate to severe COVID-19 and were treated with standard care, which consisted of hydroxychloroquine 200 mg twice daily with or without the combination of lopinavir plus ritonavir 250 mg twice daily.

The 33 patients randomized to the treatment group also received the combination of sofosbuvir plus daclatasvir 460 mg once daily. These patients were slightly younger and more likely to be men than were those in the standard-care group, but the differences were not significant.

All participants were treated for 14 days, and then the researchers assessed fever, respiration rate, and blood oxygen saturation.

More patients in the treatment group than in the standard-care group had recovered at 14 days (88% vs 67%), but the difference was not significant.

However, median time to clinical recovery, which took into account death as a competing risk, was significantly faster in the treatment group than in the standard-care group (6 vs 11 days; P = .041).

The researchers then pooled their Tehran data with those from two other trials of the sofosbuvir plus daclatasvir combination conducted in Iran: one in the city of Sari with 48 patients and one in the city of Abadan with 62 patients.

A meta-analysis showed that clinical recovery in 14 days was 14% better in the treatment group than in the control group in the Sari study, 32% better in the Tehran study, and 82% better in the Abadan study. However, in a sensitivity analysis, because “the trial in Abadan was not properly randomized,” only the improvements in the Sari and Tehran studies were significant, Wentzel reported.

The meta-analysis also showed that patients in the treatment groups were 70% more likely than those in the standard-care groups to survive.

However, the treatment regimens in the standard-care groups of the three studies were all different, reflecting evolving national treatment guidelines in Iran at the time. And SARS-CoV-2 viral loads were not measured in any of the trials, so the effects of the different drugs on the virus itself could not be assessed.

Still, overall, “sofosbuvir and daclatasvir is associated with faster discharge from hospital and improved survival,” Wentzel said.

These findings are hopeful, “provocative, and encouraging,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and he echoed Hill’s call to “get these kinds of studies into randomized controlled trials.”

But he cautioned that more data are needed before the sofosbuvir and daclatasvir combination can be added to the National Institutes of Health COVID-19 Treatment Guidelines, which clinicians who might be under-resourced and overwhelmed with spikes in COVID-19 cases rely on.

Results from three double-blind randomized controlled trials – one each in Iran, Egypt, and South Africa – with an estimated cumulative enrollment of about 2,000 patients, are expected in October, Hill reported.

“Having gone through feeling so desperate to help people and try new things, it’s really important to do these trials,” said Kristen Marks, MD, from Weill Cornell Medicine in New York City.

“You get tempted to just kind of throw anything at people. And I think we really have to have science to guide us,” she told Medscape Medical News.
 

This article first appeared on Medscape.com.

An inexpensive two-drug regimen of sofosbuvir (Sovaldi, Gilead Sciences) plus daclatasvir (Daklinza, Bristol-Myers Squibb) taken for 14 days significantly reduced time to recovery from COVID-19 and improved survival in people hospitalized with severe disease, research from an open-label Iranian study shows.

And the good news is that the treatment combination “already has a well-established safety profile in the treatment of hepatitis C,” said investigator Andrew Hill, PhD, from the University of Liverpool, United Kingdom.

But although the results look promising, they are preliminary, he cautioned. The combination could follow the path of ritonavir plus lopinavir (Kaletra, AbbVie Pharmaceuticals) or hydroxychloroquine (Plaquenil, Sanofi Pharmaceuticals), which showed promise early but did not perform as hoped in large randomized controlled trials.

“We need to remember that conducting research amidst a pandemic with overwhelmed hospitals is a clear challenge, and we cannot be sure of success,” he added.

Three Trials, 176 Patients

Data collected during a four-site trial of the combination treatment in Tehran during an early spike in cases in Iran were presented at the Virtual COVID-19 Conference 2020 by Hannah Wentzel, a masters student in public health at Imperial College London and a member of Hill’s team.

All 66 study participants were diagnosed with moderate to severe COVID-19 and were treated with standard care, which consisted of hydroxychloroquine 200 mg twice daily with or without the combination of lopinavir plus ritonavir 250 mg twice daily.

The 33 patients randomized to the treatment group also received the combination of sofosbuvir plus daclatasvir 460 mg once daily. These patients were slightly younger and more likely to be men than were those in the standard-care group, but the differences were not significant.

All participants were treated for 14 days, and then the researchers assessed fever, respiration rate, and blood oxygen saturation.

More patients in the treatment group than in the standard-care group had recovered at 14 days (88% vs 67%), but the difference was not significant.

However, median time to clinical recovery, which took into account death as a competing risk, was significantly faster in the treatment group than in the standard-care group (6 vs 11 days; P = .041).

The researchers then pooled their Tehran data with those from two other trials of the sofosbuvir plus daclatasvir combination conducted in Iran: one in the city of Sari with 48 patients and one in the city of Abadan with 62 patients.

A meta-analysis showed that clinical recovery in 14 days was 14% better in the treatment group than in the control group in the Sari study, 32% better in the Tehran study, and 82% better in the Abadan study. However, in a sensitivity analysis, because “the trial in Abadan was not properly randomized,” only the improvements in the Sari and Tehran studies were significant, Wentzel reported.

The meta-analysis also showed that patients in the treatment groups were 70% more likely than those in the standard-care groups to survive.

However, the treatment regimens in the standard-care groups of the three studies were all different, reflecting evolving national treatment guidelines in Iran at the time. And SARS-CoV-2 viral loads were not measured in any of the trials, so the effects of the different drugs on the virus itself could not be assessed.

Still, overall, “sofosbuvir and daclatasvir is associated with faster discharge from hospital and improved survival,” Wentzel said.

These findings are hopeful, “provocative, and encouraging,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and he echoed Hill’s call to “get these kinds of studies into randomized controlled trials.”

But he cautioned that more data are needed before the sofosbuvir and daclatasvir combination can be added to the National Institutes of Health COVID-19 Treatment Guidelines, which clinicians who might be under-resourced and overwhelmed with spikes in COVID-19 cases rely on.

Results from three double-blind randomized controlled trials – one each in Iran, Egypt, and South Africa – with an estimated cumulative enrollment of about 2,000 patients, are expected in October, Hill reported.

“Having gone through feeling so desperate to help people and try new things, it’s really important to do these trials,” said Kristen Marks, MD, from Weill Cornell Medicine in New York City.

“You get tempted to just kind of throw anything at people. And I think we really have to have science to guide us,” she told Medscape Medical News.
 

This article first appeared on Medscape.com.

An inexpensive two-drug regimen of sofosbuvir (Sovaldi, Gilead Sciences) plus daclatasvir (Daklinza, Bristol-Myers Squibb) taken for 14 days significantly reduced time to recovery from COVID-19 and improved survival in people hospitalized with severe disease, research from an open-label Iranian study shows.

And the good news is that the treatment combination “already has a well-established safety profile in the treatment of hepatitis C,” said investigator Andrew Hill, PhD, from the University of Liverpool, United Kingdom.

But although the results look promising, they are preliminary, he cautioned. The combination could follow the path of ritonavir plus lopinavir (Kaletra, AbbVie Pharmaceuticals) or hydroxychloroquine (Plaquenil, Sanofi Pharmaceuticals), which showed promise early but did not perform as hoped in large randomized controlled trials.

“We need to remember that conducting research amidst a pandemic with overwhelmed hospitals is a clear challenge, and we cannot be sure of success,” he added.

Three Trials, 176 Patients

Data collected during a four-site trial of the combination treatment in Tehran during an early spike in cases in Iran were presented at the Virtual COVID-19 Conference 2020 by Hannah Wentzel, a masters student in public health at Imperial College London and a member of Hill’s team.

All 66 study participants were diagnosed with moderate to severe COVID-19 and were treated with standard care, which consisted of hydroxychloroquine 200 mg twice daily with or without the combination of lopinavir plus ritonavir 250 mg twice daily.

The 33 patients randomized to the treatment group also received the combination of sofosbuvir plus daclatasvir 460 mg once daily. These patients were slightly younger and more likely to be men than were those in the standard-care group, but the differences were not significant.

All participants were treated for 14 days, and then the researchers assessed fever, respiration rate, and blood oxygen saturation.

More patients in the treatment group than in the standard-care group had recovered at 14 days (88% vs 67%), but the difference was not significant.

However, median time to clinical recovery, which took into account death as a competing risk, was significantly faster in the treatment group than in the standard-care group (6 vs 11 days; P = .041).

The researchers then pooled their Tehran data with those from two other trials of the sofosbuvir plus daclatasvir combination conducted in Iran: one in the city of Sari with 48 patients and one in the city of Abadan with 62 patients.

A meta-analysis showed that clinical recovery in 14 days was 14% better in the treatment group than in the control group in the Sari study, 32% better in the Tehran study, and 82% better in the Abadan study. However, in a sensitivity analysis, because “the trial in Abadan was not properly randomized,” only the improvements in the Sari and Tehran studies were significant, Wentzel reported.

The meta-analysis also showed that patients in the treatment groups were 70% more likely than those in the standard-care groups to survive.

However, the treatment regimens in the standard-care groups of the three studies were all different, reflecting evolving national treatment guidelines in Iran at the time. And SARS-CoV-2 viral loads were not measured in any of the trials, so the effects of the different drugs on the virus itself could not be assessed.

Still, overall, “sofosbuvir and daclatasvir is associated with faster discharge from hospital and improved survival,” Wentzel said.

These findings are hopeful, “provocative, and encouraging,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and he echoed Hill’s call to “get these kinds of studies into randomized controlled trials.”

But he cautioned that more data are needed before the sofosbuvir and daclatasvir combination can be added to the National Institutes of Health COVID-19 Treatment Guidelines, which clinicians who might be under-resourced and overwhelmed with spikes in COVID-19 cases rely on.

Results from three double-blind randomized controlled trials – one each in Iran, Egypt, and South Africa – with an estimated cumulative enrollment of about 2,000 patients, are expected in October, Hill reported.

“Having gone through feeling so desperate to help people and try new things, it’s really important to do these trials,” said Kristen Marks, MD, from Weill Cornell Medicine in New York City.

“You get tempted to just kind of throw anything at people. And I think we really have to have science to guide us,” she told Medscape Medical News.
 

This article first appeared on Medscape.com.

Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.

The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.

They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.

The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”

It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”

The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.

Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

What role for vitamin D in COVID-19?

Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.

During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.

However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.

“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.

Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”

Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.

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

Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.

The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.

They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.

The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”

It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”

The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.

Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

What role for vitamin D in COVID-19?

Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.

During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.

However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.

“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.

Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”

Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.

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

Six medical societies from across the globe are emphasizing the importance of individuals obtaining the daily recommended dose of vitamin D, especially given the impact of the COVID-19 pandemic on outdoor time.

The statement, “Joint Guidance on Vitamin D in the Era of COVID-19,” is supported by the American Society for Bone and Mineral Research, the Endocrine Society, and the American Association of Clinical Endocrinologists, among others.

They felt the need to clarify the recommendations for clinicians. Central to the guidance is the recommendation to directly expose the skin to sunlight for 15-30 minutes per day, while taking care to avoid sunburn.

The statement noted that “vitamin D is very safe when taken at reasonable dosages and is important for musculoskeletal health. Levels are likely to decline as individuals reduce outside activity (sun exposure) during the pandemic.”

It added that “most older and younger adults can safely take 400-1000 IU daily to keep vitamin D levels within the optimal range as recommended by [the US] Institute of Medicine guidelines.”

The statement also noted that the scientific evidence clearly supports the benefits that vitamin D (in combination with calcium intake) plays in building a strong skeleton and preventing bone loss.

Other societies supporting the statement are the European Calcified Tissue Society, the National Osteoporosis Foundation, and the International Osteoporosis Foundation.

What role for vitamin D in COVID-19?

Over recent months, the role of vitamin D in relation to prevention of COVID-19 has been the subject of intense debate. Now, these societies have joined forces and endorsed evidence-based guidance to clarify the issue around obtaining the daily recommended dosage of vitamin D.

During the pandemic, orders to stay at home meant individuals were likely to spend less time outdoors and have less opportunity to draw their vitamin D directly from sunlight, which is its main source, other than a limited number of foods or as a dietary supplement, the societies explained.

However, they acknowledged that the role of vitamin D in COVID-19 remains unclear.

“The current data do not provide any evidence that vitamin D supplementation will help prevent or treat COVID-19 infection; however, our guidance does not preclude further study of the potential effects of vitamin D on COVID-19,” the joint statement said.

Research to date suggests that vitamin D may play a role in enhancing the immune response, and given prior work demonstrating a role for the activated form of vitamin D – 1,25(OH)2D – in immune responses, “further research into vitamin D supplementation in COVID-19 disease is warranted,” it added. “Trials to date have been observational and there have been no randomized, controlled trials from which firm conclusions about causal relationships can be drawn. Observational studies suggest associations between low vitamin D concentrations and higher rates of COVID-19 infection.”

Medscape Medical News previously reported on the existing observational data regarding vitamin D in COVID-19. A recent rapid evidence review by the National Institute for Health and Care Excellence failed to find any evidence that vitamin D supplementation reduces the risk or severity of COVID-19.

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

Nearly half of hospitalized COVID-19 patients without a prior diabetes diagnosis have hyperglycemia, and the latter is an independent predictor of mortality at 28 days, new research indicates.

The findings, from a retrospective analysis of 605 patients with COVID-19 seen at two hospitals in Wuhan, China, were published online July 10 in Diabetologia by Sufei Wang, of the department of respiratory and critical care medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and colleagues.

Several previous studies have demonstrated a link between hyperglycemia and worse outcomes in COVID-19, and at least one diabetes diagnosis, but this is the first to focus specifically on that group of patients.

Wang and colleagues found that a fasting blood glucose of 7.0 mmol/L (126 mg/dL) or greater on admission – present in 45.6% of those without a prior diabetes diagnosis – was an independent predictor of 28-day mortality.

Although A1c data weren’t analyzed, the population is believed to include both individuals with preexisting but undiagnosed diabetes and those without diabetes who have acute stress hyperglycemia.

“Glycemic testing and control should be recommended for all COVID-19 patients even if they do not have preexisting diabetes, as most COVID-19 patients are prone to glucose metabolic disorders,” they emphasized.

“Addressing elevated fasting blood glucose at an early stage can help clinicians better manage the condition and lower the mortality risk of COVID-19 patients,” Wang and colleagues noted.
 

Hyperglycemia predicts COVID-19 death, complications

The study involved consecutive patients with COVID-19 and definitive 28-day outcome and fasting blood glucose measurement on admission to two Wuhan-area hospitals between Jan. 24 to Feb. 10, 2020. A total of 605 patients did not have a previous diabetes diagnosis. They were a median age of 59 years and 53.2% were men.

Just over half, 54.4%, had a fasting blood glucose below 6.1 mmol/L (110.0 mg/dL). The rest had dysglycemia: 16.5% had a fasting blood glucose of 6.1-6.9 mmol/L (110-125 mg/dL), considered the prediabetes range, and 29.1% had a fasting blood glucose of 7 mmol/L (126 mg/dL) or above, the cutoff for diabetes.

“These results indicate that our study included both undiagnosed diabetic patients and nondiabetic patients with hyperglycemia caused by an acute blood glucose disorder,” the authors noted.

Over 28 days of hospitalization, 18.8% (114) of the patients died and 39.2% developed one or more in-hospital complications. 

The authors used the CRB-65 score, which assigns 1 point for each of four indicators – confusion, respiratory rate >30 breaths/min, systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤60 mm Hg, and age ≥65 years – to assess pneumonia severity.

Just over half, 55.2%, had a CRB-65 score of 0, 43.1% had a score of 1-2, and 1.7% had a score of 3-4.

In multivariable analysis, significant independent predictors of 28-day mortality were age (hazard ratio, 1.02), male sex (HR, 1.75), CRB-65 score 1-2 (HR, 2.68), CRB-65 score 3-4 (HR, 5.25), and fasting blood glucose ≥7.0 mmol/L (HR, 2.30).

Compared with patients with normal glucose (<6.1 mmol/L), 28-day mortality was twice as high (HR, 2.06) for those with a fasting blood glucose of 6.1-6.9 mmol/L and more than threefold higher for ≥7.0 mmol/L (HR, 3.54).

Pneumonia severity also predicted 28-day mortality, with hazard ratios of 4.35 and 13.80 for patients with CRB-65 scores of 1-2 and 3-4, respectively, compared with 0.

Inhospital complications, including acute respiratory distress syndrome or acute cardiac, kidney, or liver injury or cerebrovascular accident, occurred in 14.2%, 7.9%, and 17.0% of those in the lowest to highest fasting blood glucose groups.

Complications were more than twice as common in patients with a fasting blood glucose of 6.1-6.9 mmol/L (HR, 2.61) and four times more common (HR, 3.99) among those with a fasting blood glucose ≥7.0 mmol/L, compared with those with normoglycemia.

The study was supported by the National Natural Science Foundation of China and Major Projects of the National Science and Technology. The authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Nearly half of hospitalized COVID-19 patients without a prior diabetes diagnosis have hyperglycemia, and the latter is an independent predictor of mortality at 28 days, new research indicates.

The findings, from a retrospective analysis of 605 patients with COVID-19 seen at two hospitals in Wuhan, China, were published online July 10 in Diabetologia by Sufei Wang, of the department of respiratory and critical care medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and colleagues.

Several previous studies have demonstrated a link between hyperglycemia and worse outcomes in COVID-19, and at least one diabetes diagnosis, but this is the first to focus specifically on that group of patients.

Wang and colleagues found that a fasting blood glucose of 7.0 mmol/L (126 mg/dL) or greater on admission – present in 45.6% of those without a prior diabetes diagnosis – was an independent predictor of 28-day mortality.

Although A1c data weren’t analyzed, the population is believed to include both individuals with preexisting but undiagnosed diabetes and those without diabetes who have acute stress hyperglycemia.

“Glycemic testing and control should be recommended for all COVID-19 patients even if they do not have preexisting diabetes, as most COVID-19 patients are prone to glucose metabolic disorders,” they emphasized.

“Addressing elevated fasting blood glucose at an early stage can help clinicians better manage the condition and lower the mortality risk of COVID-19 patients,” Wang and colleagues noted.
 

Hyperglycemia predicts COVID-19 death, complications

The study involved consecutive patients with COVID-19 and definitive 28-day outcome and fasting blood glucose measurement on admission to two Wuhan-area hospitals between Jan. 24 to Feb. 10, 2020. A total of 605 patients did not have a previous diabetes diagnosis. They were a median age of 59 years and 53.2% were men.

Just over half, 54.4%, had a fasting blood glucose below 6.1 mmol/L (110.0 mg/dL). The rest had dysglycemia: 16.5% had a fasting blood glucose of 6.1-6.9 mmol/L (110-125 mg/dL), considered the prediabetes range, and 29.1% had a fasting blood glucose of 7 mmol/L (126 mg/dL) or above, the cutoff for diabetes.

“These results indicate that our study included both undiagnosed diabetic patients and nondiabetic patients with hyperglycemia caused by an acute blood glucose disorder,” the authors noted.

Over 28 days of hospitalization, 18.8% (114) of the patients died and 39.2% developed one or more in-hospital complications. 

The authors used the CRB-65 score, which assigns 1 point for each of four indicators – confusion, respiratory rate >30 breaths/min, systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤60 mm Hg, and age ≥65 years – to assess pneumonia severity.

Just over half, 55.2%, had a CRB-65 score of 0, 43.1% had a score of 1-2, and 1.7% had a score of 3-4.

In multivariable analysis, significant independent predictors of 28-day mortality were age (hazard ratio, 1.02), male sex (HR, 1.75), CRB-65 score 1-2 (HR, 2.68), CRB-65 score 3-4 (HR, 5.25), and fasting blood glucose ≥7.0 mmol/L (HR, 2.30).

Compared with patients with normal glucose (<6.1 mmol/L), 28-day mortality was twice as high (HR, 2.06) for those with a fasting blood glucose of 6.1-6.9 mmol/L and more than threefold higher for ≥7.0 mmol/L (HR, 3.54).

Pneumonia severity also predicted 28-day mortality, with hazard ratios of 4.35 and 13.80 for patients with CRB-65 scores of 1-2 and 3-4, respectively, compared with 0.

Inhospital complications, including acute respiratory distress syndrome or acute cardiac, kidney, or liver injury or cerebrovascular accident, occurred in 14.2%, 7.9%, and 17.0% of those in the lowest to highest fasting blood glucose groups.

Complications were more than twice as common in patients with a fasting blood glucose of 6.1-6.9 mmol/L (HR, 2.61) and four times more common (HR, 3.99) among those with a fasting blood glucose ≥7.0 mmol/L, compared with those with normoglycemia.

The study was supported by the National Natural Science Foundation of China and Major Projects of the National Science and Technology. The authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Nearly half of hospitalized COVID-19 patients without a prior diabetes diagnosis have hyperglycemia, and the latter is an independent predictor of mortality at 28 days, new research indicates.

The findings, from a retrospective analysis of 605 patients with COVID-19 seen at two hospitals in Wuhan, China, were published online July 10 in Diabetologia by Sufei Wang, of the department of respiratory and critical care medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and colleagues.

Several previous studies have demonstrated a link between hyperglycemia and worse outcomes in COVID-19, and at least one diabetes diagnosis, but this is the first to focus specifically on that group of patients.

Wang and colleagues found that a fasting blood glucose of 7.0 mmol/L (126 mg/dL) or greater on admission – present in 45.6% of those without a prior diabetes diagnosis – was an independent predictor of 28-day mortality.

Although A1c data weren’t analyzed, the population is believed to include both individuals with preexisting but undiagnosed diabetes and those without diabetes who have acute stress hyperglycemia.

“Glycemic testing and control should be recommended for all COVID-19 patients even if they do not have preexisting diabetes, as most COVID-19 patients are prone to glucose metabolic disorders,” they emphasized.

“Addressing elevated fasting blood glucose at an early stage can help clinicians better manage the condition and lower the mortality risk of COVID-19 patients,” Wang and colleagues noted.
 

Hyperglycemia predicts COVID-19 death, complications

The study involved consecutive patients with COVID-19 and definitive 28-day outcome and fasting blood glucose measurement on admission to two Wuhan-area hospitals between Jan. 24 to Feb. 10, 2020. A total of 605 patients did not have a previous diabetes diagnosis. They were a median age of 59 years and 53.2% were men.

Just over half, 54.4%, had a fasting blood glucose below 6.1 mmol/L (110.0 mg/dL). The rest had dysglycemia: 16.5% had a fasting blood glucose of 6.1-6.9 mmol/L (110-125 mg/dL), considered the prediabetes range, and 29.1% had a fasting blood glucose of 7 mmol/L (126 mg/dL) or above, the cutoff for diabetes.

“These results indicate that our study included both undiagnosed diabetic patients and nondiabetic patients with hyperglycemia caused by an acute blood glucose disorder,” the authors noted.

Over 28 days of hospitalization, 18.8% (114) of the patients died and 39.2% developed one or more in-hospital complications. 

The authors used the CRB-65 score, which assigns 1 point for each of four indicators – confusion, respiratory rate >30 breaths/min, systolic blood pressure ≤90 mm Hg or diastolic blood pressure ≤60 mm Hg, and age ≥65 years – to assess pneumonia severity.

Just over half, 55.2%, had a CRB-65 score of 0, 43.1% had a score of 1-2, and 1.7% had a score of 3-4.

In multivariable analysis, significant independent predictors of 28-day mortality were age (hazard ratio, 1.02), male sex (HR, 1.75), CRB-65 score 1-2 (HR, 2.68), CRB-65 score 3-4 (HR, 5.25), and fasting blood glucose ≥7.0 mmol/L (HR, 2.30).

Compared with patients with normal glucose (<6.1 mmol/L), 28-day mortality was twice as high (HR, 2.06) for those with a fasting blood glucose of 6.1-6.9 mmol/L and more than threefold higher for ≥7.0 mmol/L (HR, 3.54).

Pneumonia severity also predicted 28-day mortality, with hazard ratios of 4.35 and 13.80 for patients with CRB-65 scores of 1-2 and 3-4, respectively, compared with 0.

Inhospital complications, including acute respiratory distress syndrome or acute cardiac, kidney, or liver injury or cerebrovascular accident, occurred in 14.2%, 7.9%, and 17.0% of those in the lowest to highest fasting blood glucose groups.

Complications were more than twice as common in patients with a fasting blood glucose of 6.1-6.9 mmol/L (HR, 2.61) and four times more common (HR, 3.99) among those with a fasting blood glucose ≥7.0 mmol/L, compared with those with normoglycemia.

The study was supported by the National Natural Science Foundation of China and Major Projects of the National Science and Technology. The authors have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Two studies published this week in BMJ provide support for eating more fruits, vegetables, and whole grain foods to lower the risk of developing diabetes.

Lisovskaya/iStock/Getty Images Plus

In a pooled analysis of three large prospective American cohorts, people with the highest versus lowest total consumption of whole grain foods had a significantly lower risk of type 2 diabetes.

“These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes,” wrote the authors led by Yang Hu, a doctoral student at Harvard School of Public Health, Boston.

Similarly, in a large European case-cohort study, people with higher values for plasma vitamin C and carotenoids (fruit and vegetable intake) had a lower incidence of type 2 diabetes.

“This study suggests that even a modest increase in fruit and vegetable intake could help to prevent type 2 diabetes ... regardless of whether the increase is among people with initially low or high intake,” wrote Ju-Sheng Zheng, PhD, University of Cambridge (England), and colleagues.
 

Individual whole grain foods

Previous studies have shown that high consumption of whole grains is associated with a lower risk of developing chronic diseases, including type 2 diabetes, cardiovascular disease, obesity, and some types of cancer, Mr. Hu and colleagues wrote.

Although research has shown that whole grain breakfast cereal and brown rice are linked with a lower risk of type 2 diabetes, the effect of other commonly consumed whole grain foods – which contain different amounts of dietary fiber, antioxidants, magnesium, and phytochemicals – has not been established.

Mr. Hu and colleagues analyzed pooled data from 158,259 U.S. women who participated in the Nurses’ Health Study (1984-2014) or the Nurses’ Health Study II (1991-2017) and 36,525 U.S. men who took part in the Health Professionals Follow-Up Study (1986-2016), who were free of diabetes, cardiovascular disease, and cancer.

Participants’ baseline consumption of seven types of whole grain foods – whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, wheat germ, and popcorn – was based on self-replies to food frequency questionnaires.

During an average 24-year follow-up, 18,629 participants developed type 2 diabetes.

After adjusting for body mass index, lifestyle, and dietary risk factors, participants in the highest quintile of total whole grain consumption had a 29% lower risk of incident type 2 diabetes than those in the lowest quintile.

The most commonly consumed whole grain foods were whole grain cold breakfast cereal, dark bread, and popcorn.

Compared with eating less than one serving a month of whole grain cold breakfast cereal or dark bread, eating one or more servings a day was associated with a 19% and 21% lower risk of developing diabetes, respectively.

For popcorn, a J-shaped association was found for intake, where the risk of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day, which led to about an 8% increased risk of developing diabetes – likely related to fat and sugar added to the popcorn, the researchers wrote.

For the less frequently consumed whole grain foods, compared with eating less than one serving a month of oatmeal, brown rice, added bran, or wheat germ, participants who ate two or more servings a week had a 21%, 12%, 15%, and 12% lower risk of developing type 2 diabetes, respectively.

Lean or overweight individuals had a greater decreased risk of diabetes with increased consumption of whole grain foods; however, because individuals with obesity have a higher risk of diabetes, even a small decrease in risk is still meaningful.

Limitations include the study was observational and may have had unknown confounders, and the results may not be generalizable to other populations, the authors note.
 

‘Five a day’ fruits and vegetables

Only one previous small published study from the United Kingdom has examined how blood levels of vitamin C and carotenoids are associated with incident type 2 diabetes, Dr. Zheng and colleagues wrote.

They investigated the relationship in 9,754 adults who developed new-onset type 2 diabetes and a comparison group of 13,662 adults who remained diabetes free during an average 9.7-year follow-up, from 340,234 participants in the European Prospective Investigation Into Cancer and Nutrition–InterAct study.

Participants were from Denmark, France, Germany, Italy, the Netherlands, Spain, Sweden, and the United Kingdom, and incident type 2 diabetes occurred between 1991 and 2007.

The researchers used high-performance liquid chromatography–ultraviolet methods to determine participants’ plasma levels of vitamin C and six carotenoids (alphta-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), which they used to calculate a composite biomarker score.

The recommendation to eat at least five fruits and vegetables a day corresponds to eating ≥400 g/day, according to Dr. Zheng and colleagues. The self-reported median fruit and vegetable intake in the current study was 274, 357, 396, 452, and 508 g/day from lowest to highest quintile.

After multivariable adjustment, higher levels of plasma vitamin C and carotenoids were associated with an 18% and 25% lower risk of incident type 2 diabetes per standard deviation, respectively.

Compared with patients whose vitamin C and carotenoid composite biomarker scores were in the lowest 20%, those with scores in the top 20% had half the risk of incident diabetes. Increasing fruit and vegetable consumption by 66 g/day was associated with a 25% lower risk of developing diabetes.

“These findings provide strong evidence from objectively measured biomarkers for the recommendation that fruit and vegetable intake should be increased to prevent type 2 diabetes,” according to the researchers.

However, consumption of fruits and vegetables remains far below guideline recommendations, they observed. “Although five portions a day of fruit and vegetables have been recommended for decades, in 2014-2015, 69% of U.K. adults ate fewer than this number, and this proportion is even higher in European adults (86%).”

Dr. Zheng and colleagues acknowledged that study limitations include those that are inherent with observational studies.

Although they could not distinguish between juice, fortified products, or whole foods, the analyses “were adjusted for vitamin supplement use, and suggest that as biomarkers of fruit and vegetable intake these findings endorse the consumption of fruit and vegetables, not that of supplements,” they maintained.

The study by Mr. Hu and colleagues was funded by the National Institutes of Health. The InterAct project was funded by the EU FP6 program. Biomarker measurements for vitamin C and carotenoids were funded by the InterAct project, EPIC-CVD project, MRC Cambridge Initiative, European Commission Framework Program 7, European Research Council, and National Institute for Health Research. Dr. Zheng has reported receiving funding from Westlake University and the EU Horizon 2020 program.

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

Two studies published this week in BMJ provide support for eating more fruits, vegetables, and whole grain foods to lower the risk of developing diabetes.

Lisovskaya/iStock/Getty Images Plus

In a pooled analysis of three large prospective American cohorts, people with the highest versus lowest total consumption of whole grain foods had a significantly lower risk of type 2 diabetes.

“These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes,” wrote the authors led by Yang Hu, a doctoral student at Harvard School of Public Health, Boston.

Similarly, in a large European case-cohort study, people with higher values for plasma vitamin C and carotenoids (fruit and vegetable intake) had a lower incidence of type 2 diabetes.

“This study suggests that even a modest increase in fruit and vegetable intake could help to prevent type 2 diabetes ... regardless of whether the increase is among people with initially low or high intake,” wrote Ju-Sheng Zheng, PhD, University of Cambridge (England), and colleagues.
 

Individual whole grain foods

Previous studies have shown that high consumption of whole grains is associated with a lower risk of developing chronic diseases, including type 2 diabetes, cardiovascular disease, obesity, and some types of cancer, Mr. Hu and colleagues wrote.

Although research has shown that whole grain breakfast cereal and brown rice are linked with a lower risk of type 2 diabetes, the effect of other commonly consumed whole grain foods – which contain different amounts of dietary fiber, antioxidants, magnesium, and phytochemicals – has not been established.

Mr. Hu and colleagues analyzed pooled data from 158,259 U.S. women who participated in the Nurses’ Health Study (1984-2014) or the Nurses’ Health Study II (1991-2017) and 36,525 U.S. men who took part in the Health Professionals Follow-Up Study (1986-2016), who were free of diabetes, cardiovascular disease, and cancer.

Participants’ baseline consumption of seven types of whole grain foods – whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, wheat germ, and popcorn – was based on self-replies to food frequency questionnaires.

During an average 24-year follow-up, 18,629 participants developed type 2 diabetes.

After adjusting for body mass index, lifestyle, and dietary risk factors, participants in the highest quintile of total whole grain consumption had a 29% lower risk of incident type 2 diabetes than those in the lowest quintile.

The most commonly consumed whole grain foods were whole grain cold breakfast cereal, dark bread, and popcorn.

Compared with eating less than one serving a month of whole grain cold breakfast cereal or dark bread, eating one or more servings a day was associated with a 19% and 21% lower risk of developing diabetes, respectively.

For popcorn, a J-shaped association was found for intake, where the risk of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day, which led to about an 8% increased risk of developing diabetes – likely related to fat and sugar added to the popcorn, the researchers wrote.

For the less frequently consumed whole grain foods, compared with eating less than one serving a month of oatmeal, brown rice, added bran, or wheat germ, participants who ate two or more servings a week had a 21%, 12%, 15%, and 12% lower risk of developing type 2 diabetes, respectively.

Lean or overweight individuals had a greater decreased risk of diabetes with increased consumption of whole grain foods; however, because individuals with obesity have a higher risk of diabetes, even a small decrease in risk is still meaningful.

Limitations include the study was observational and may have had unknown confounders, and the results may not be generalizable to other populations, the authors note.
 

‘Five a day’ fruits and vegetables

Only one previous small published study from the United Kingdom has examined how blood levels of vitamin C and carotenoids are associated with incident type 2 diabetes, Dr. Zheng and colleagues wrote.

They investigated the relationship in 9,754 adults who developed new-onset type 2 diabetes and a comparison group of 13,662 adults who remained diabetes free during an average 9.7-year follow-up, from 340,234 participants in the European Prospective Investigation Into Cancer and Nutrition–InterAct study.

Participants were from Denmark, France, Germany, Italy, the Netherlands, Spain, Sweden, and the United Kingdom, and incident type 2 diabetes occurred between 1991 and 2007.

The researchers used high-performance liquid chromatography–ultraviolet methods to determine participants’ plasma levels of vitamin C and six carotenoids (alphta-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), which they used to calculate a composite biomarker score.

The recommendation to eat at least five fruits and vegetables a day corresponds to eating ≥400 g/day, according to Dr. Zheng and colleagues. The self-reported median fruit and vegetable intake in the current study was 274, 357, 396, 452, and 508 g/day from lowest to highest quintile.

After multivariable adjustment, higher levels of plasma vitamin C and carotenoids were associated with an 18% and 25% lower risk of incident type 2 diabetes per standard deviation, respectively.

Compared with patients whose vitamin C and carotenoid composite biomarker scores were in the lowest 20%, those with scores in the top 20% had half the risk of incident diabetes. Increasing fruit and vegetable consumption by 66 g/day was associated with a 25% lower risk of developing diabetes.

“These findings provide strong evidence from objectively measured biomarkers for the recommendation that fruit and vegetable intake should be increased to prevent type 2 diabetes,” according to the researchers.

However, consumption of fruits and vegetables remains far below guideline recommendations, they observed. “Although five portions a day of fruit and vegetables have been recommended for decades, in 2014-2015, 69% of U.K. adults ate fewer than this number, and this proportion is even higher in European adults (86%).”

Dr. Zheng and colleagues acknowledged that study limitations include those that are inherent with observational studies.

Although they could not distinguish between juice, fortified products, or whole foods, the analyses “were adjusted for vitamin supplement use, and suggest that as biomarkers of fruit and vegetable intake these findings endorse the consumption of fruit and vegetables, not that of supplements,” they maintained.

The study by Mr. Hu and colleagues was funded by the National Institutes of Health. The InterAct project was funded by the EU FP6 program. Biomarker measurements for vitamin C and carotenoids were funded by the InterAct project, EPIC-CVD project, MRC Cambridge Initiative, European Commission Framework Program 7, European Research Council, and National Institute for Health Research. Dr. Zheng has reported receiving funding from Westlake University and the EU Horizon 2020 program.

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

Two studies published this week in BMJ provide support for eating more fruits, vegetables, and whole grain foods to lower the risk of developing diabetes.

Lisovskaya/iStock/Getty Images Plus

In a pooled analysis of three large prospective American cohorts, people with the highest versus lowest total consumption of whole grain foods had a significantly lower risk of type 2 diabetes.

“These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes,” wrote the authors led by Yang Hu, a doctoral student at Harvard School of Public Health, Boston.

Similarly, in a large European case-cohort study, people with higher values for plasma vitamin C and carotenoids (fruit and vegetable intake) had a lower incidence of type 2 diabetes.

“This study suggests that even a modest increase in fruit and vegetable intake could help to prevent type 2 diabetes ... regardless of whether the increase is among people with initially low or high intake,” wrote Ju-Sheng Zheng, PhD, University of Cambridge (England), and colleagues.
 

Individual whole grain foods

Previous studies have shown that high consumption of whole grains is associated with a lower risk of developing chronic diseases, including type 2 diabetes, cardiovascular disease, obesity, and some types of cancer, Mr. Hu and colleagues wrote.

Although research has shown that whole grain breakfast cereal and brown rice are linked with a lower risk of type 2 diabetes, the effect of other commonly consumed whole grain foods – which contain different amounts of dietary fiber, antioxidants, magnesium, and phytochemicals – has not been established.

Mr. Hu and colleagues analyzed pooled data from 158,259 U.S. women who participated in the Nurses’ Health Study (1984-2014) or the Nurses’ Health Study II (1991-2017) and 36,525 U.S. men who took part in the Health Professionals Follow-Up Study (1986-2016), who were free of diabetes, cardiovascular disease, and cancer.

Participants’ baseline consumption of seven types of whole grain foods – whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, wheat germ, and popcorn – was based on self-replies to food frequency questionnaires.

During an average 24-year follow-up, 18,629 participants developed type 2 diabetes.

After adjusting for body mass index, lifestyle, and dietary risk factors, participants in the highest quintile of total whole grain consumption had a 29% lower risk of incident type 2 diabetes than those in the lowest quintile.

The most commonly consumed whole grain foods were whole grain cold breakfast cereal, dark bread, and popcorn.

Compared with eating less than one serving a month of whole grain cold breakfast cereal or dark bread, eating one or more servings a day was associated with a 19% and 21% lower risk of developing diabetes, respectively.

For popcorn, a J-shaped association was found for intake, where the risk of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day, which led to about an 8% increased risk of developing diabetes – likely related to fat and sugar added to the popcorn, the researchers wrote.

For the less frequently consumed whole grain foods, compared with eating less than one serving a month of oatmeal, brown rice, added bran, or wheat germ, participants who ate two or more servings a week had a 21%, 12%, 15%, and 12% lower risk of developing type 2 diabetes, respectively.

Lean or overweight individuals had a greater decreased risk of diabetes with increased consumption of whole grain foods; however, because individuals with obesity have a higher risk of diabetes, even a small decrease in risk is still meaningful.

Limitations include the study was observational and may have had unknown confounders, and the results may not be generalizable to other populations, the authors note.
 

‘Five a day’ fruits and vegetables

Only one previous small published study from the United Kingdom has examined how blood levels of vitamin C and carotenoids are associated with incident type 2 diabetes, Dr. Zheng and colleagues wrote.

They investigated the relationship in 9,754 adults who developed new-onset type 2 diabetes and a comparison group of 13,662 adults who remained diabetes free during an average 9.7-year follow-up, from 340,234 participants in the European Prospective Investigation Into Cancer and Nutrition–InterAct study.

Participants were from Denmark, France, Germany, Italy, the Netherlands, Spain, Sweden, and the United Kingdom, and incident type 2 diabetes occurred between 1991 and 2007.

The researchers used high-performance liquid chromatography–ultraviolet methods to determine participants’ plasma levels of vitamin C and six carotenoids (alphta-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), which they used to calculate a composite biomarker score.

The recommendation to eat at least five fruits and vegetables a day corresponds to eating ≥400 g/day, according to Dr. Zheng and colleagues. The self-reported median fruit and vegetable intake in the current study was 274, 357, 396, 452, and 508 g/day from lowest to highest quintile.

After multivariable adjustment, higher levels of plasma vitamin C and carotenoids were associated with an 18% and 25% lower risk of incident type 2 diabetes per standard deviation, respectively.

Compared with patients whose vitamin C and carotenoid composite biomarker scores were in the lowest 20%, those with scores in the top 20% had half the risk of incident diabetes. Increasing fruit and vegetable consumption by 66 g/day was associated with a 25% lower risk of developing diabetes.

“These findings provide strong evidence from objectively measured biomarkers for the recommendation that fruit and vegetable intake should be increased to prevent type 2 diabetes,” according to the researchers.

However, consumption of fruits and vegetables remains far below guideline recommendations, they observed. “Although five portions a day of fruit and vegetables have been recommended for decades, in 2014-2015, 69% of U.K. adults ate fewer than this number, and this proportion is even higher in European adults (86%).”

Dr. Zheng and colleagues acknowledged that study limitations include those that are inherent with observational studies.

Although they could not distinguish between juice, fortified products, or whole foods, the analyses “were adjusted for vitamin supplement use, and suggest that as biomarkers of fruit and vegetable intake these findings endorse the consumption of fruit and vegetables, not that of supplements,” they maintained.

The study by Mr. Hu and colleagues was funded by the National Institutes of Health. The InterAct project was funded by the EU FP6 program. Biomarker measurements for vitamin C and carotenoids were funded by the InterAct project, EPIC-CVD project, MRC Cambridge Initiative, European Commission Framework Program 7, European Research Council, and National Institute for Health Research. Dr. Zheng has reported receiving funding from Westlake University and the EU Horizon 2020 program.

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

What do you do now?

Your waiting room is filled with mask-wearing individuals, except for one person. Your staff offers a mask to this person, citing your office policy of requiring masks for all persons in order to prevent asymptomatic COVID-19 spread, and the patient refuses to put it on.

What can you/should you/must you do? Are you required to see a patient who refuses to wear a mask? If you ask the patient to leave without being seen, can you be accused of patient abandonment? If you allow the patient to stay, could you be liable for negligence for exposing others to a deadly illness?

The rules on mask-wearing, while initially downright confusing, have inexorably come to a rough consensus. By governors’ orders, masks are now mandatory in most states, though when and where they are required varies. For example, effective July 7, the governor of Washington has ordered that a business not allow a customer to enter without a face covering.

So far, there are no cases or court decisions to guide us about whether it is negligence to allow an unmasked patient to commingle in a medical practice. Nor do we have case law to help us determine whether patient abandonment would apply if a patient is sent home without being seen.

We can apply the legal principles and cases from other situations to this one, however, to tell us what constitutes negligence or patient abandonment. The practical questions, legally, are who might sue and on what basis?

Who might sue?

Someone who is injured in a public place may sue the owner for negligence if the owner knew or should have known of a danger and didn’t do anything about it. For example, individuals have sued grocery stores successfully after they slipped on a banana peel and fell. If, say, the banana peel was black, that indicates that it had been there for a while, and judges have found that the store management should have known about it and removed it.

Compare the banana peel scenario with the scenario where most news outlets and health departments are telling people, every day, to wear masks while in indoor public spaces, yet owners of a medical practice or facility allow individuals who are not wearing masks to sit in their waiting room. If an individual who was also in the waiting room with the unmasked individual develops COVID-19 2 days later, the ill individual may sue the medical practice for negligence for not removing the unmasked individual.

What about the individual’s responsibility to move away from the person not wearing a mask? That is the aspect of this scenario that attorneys and experts could argue about, for days, in a court case. But to go back to the banana peel case, one could argue that a customer in a grocery store should be looking out for banana peels on the floor and avoid them, yet courts have assigned liability to grocery stores when customers slip and fall.

Let’s review the four elements of negligence which a plaintiff would need to prove:

• Duty: Obligation of one person to another
• Breach: Improper act or omission, in the context of proper behavior to avoid imposing undue risks of harm to other persons and their property
• Damage
• Causation: That the act or omission caused the harm

Those who run medical offices and facilities have a duty to provide reasonably safe public spaces. Unmasked individuals are a risk to others nearby, so the “breach” element is satisfied if a practice fails to impose safety measures. Causation could be proven, or at least inferred, if contact tracing of an individual with COVID-19 showed that the only contact likely to have exposed the ill individual to the virus was an unmasked individual in a medical practice’s waiting room, especially if the unmasked individual was COVID-19 positive before, during, or shortly after the visit to the practice.

What about patient abandonment?

“Patient abandonment” is the legal term for terminating the physician-patient relationship in such a manner that the patient is denied necessary medical care. It is a form of negligence.

Refusing to see a patient unless the patient wears a mask is not denying care, in this attorney’s view, but rather establishing reasonable conditions for getting care. The patient simply needs to put on a mask.

What about the patient who refuses to wear a mask for medical reasons? There are exceptions in most of the governors’ orders for individuals with medical conditions that preclude covering nose and mouth with a mask. A medical office is the perfect place to test an individual’s ability or inability to breathe well while wearing a mask. “Put the mask on and we’ll see how you do” is a reasonable response. Monitor the patient visually and apply a pulse oximeter with mask off and mask on.

One physician recently wrote about measuring her own oxygen levels while wearing four different masks for 5 minutes each, with no change in breathing.

Editor’s note: Read more about mask exemptions in a Medscape interview with pulmonologist Albert Rizzo, MD, chief medical officer of the American Lung Association.

What are some practical tips?

Assuming that a patient is not in acute distress, options in this scenario include:

• Send the patient home and offer a return visit if masked or when the pandemic is over.
• Offer a telehealth visit, with the patient at home.

What if the unmasked person is not a patient but the companion of a patient? What if the individual refusing to wear a mask is an employee? In neither of these two hypotheticals is there a basis for legal action against a practice whose policy requires that everyone wear masks on the premises.

A companion who arrives without a mask should leave the office. An employee who refuses to mask up could be sent home. If the employee has a disability covered by the Americans with Disabilities Act, then the practice may need to make reasonable accommodations so that the employee works in a room alone if unable to work from home.

Those who manage medical practices should check the websites of the state health department and medical societies at least weekly, to see whether the agencies have issued guidance. For example, the Texas Medical Association has issued limited guidance.

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

What do you do now?

Your waiting room is filled with mask-wearing individuals, except for one person. Your staff offers a mask to this person, citing your office policy of requiring masks for all persons in order to prevent asymptomatic COVID-19 spread, and the patient refuses to put it on.

What can you/should you/must you do? Are you required to see a patient who refuses to wear a mask? If you ask the patient to leave without being seen, can you be accused of patient abandonment? If you allow the patient to stay, could you be liable for negligence for exposing others to a deadly illness?

The rules on mask-wearing, while initially downright confusing, have inexorably come to a rough consensus. By governors’ orders, masks are now mandatory in most states, though when and where they are required varies. For example, effective July 7, the governor of Washington has ordered that a business not allow a customer to enter without a face covering.

So far, there are no cases or court decisions to guide us about whether it is negligence to allow an unmasked patient to commingle in a medical practice. Nor do we have case law to help us determine whether patient abandonment would apply if a patient is sent home without being seen.

We can apply the legal principles and cases from other situations to this one, however, to tell us what constitutes negligence or patient abandonment. The practical questions, legally, are who might sue and on what basis?

Who might sue?

Someone who is injured in a public place may sue the owner for negligence if the owner knew or should have known of a danger and didn’t do anything about it. For example, individuals have sued grocery stores successfully after they slipped on a banana peel and fell. If, say, the banana peel was black, that indicates that it had been there for a while, and judges have found that the store management should have known about it and removed it.

Compare the banana peel scenario with the scenario where most news outlets and health departments are telling people, every day, to wear masks while in indoor public spaces, yet owners of a medical practice or facility allow individuals who are not wearing masks to sit in their waiting room. If an individual who was also in the waiting room with the unmasked individual develops COVID-19 2 days later, the ill individual may sue the medical practice for negligence for not removing the unmasked individual.

What about the individual’s responsibility to move away from the person not wearing a mask? That is the aspect of this scenario that attorneys and experts could argue about, for days, in a court case. But to go back to the banana peel case, one could argue that a customer in a grocery store should be looking out for banana peels on the floor and avoid them, yet courts have assigned liability to grocery stores when customers slip and fall.

Let’s review the four elements of negligence which a plaintiff would need to prove:

• Duty: Obligation of one person to another
• Breach: Improper act or omission, in the context of proper behavior to avoid imposing undue risks of harm to other persons and their property
• Damage
• Causation: That the act or omission caused the harm

Those who run medical offices and facilities have a duty to provide reasonably safe public spaces. Unmasked individuals are a risk to others nearby, so the “breach” element is satisfied if a practice fails to impose safety measures. Causation could be proven, or at least inferred, if contact tracing of an individual with COVID-19 showed that the only contact likely to have exposed the ill individual to the virus was an unmasked individual in a medical practice’s waiting room, especially if the unmasked individual was COVID-19 positive before, during, or shortly after the visit to the practice.

What about patient abandonment?

“Patient abandonment” is the legal term for terminating the physician-patient relationship in such a manner that the patient is denied necessary medical care. It is a form of negligence.

Refusing to see a patient unless the patient wears a mask is not denying care, in this attorney’s view, but rather establishing reasonable conditions for getting care. The patient simply needs to put on a mask.

What about the patient who refuses to wear a mask for medical reasons? There are exceptions in most of the governors’ orders for individuals with medical conditions that preclude covering nose and mouth with a mask. A medical office is the perfect place to test an individual’s ability or inability to breathe well while wearing a mask. “Put the mask on and we’ll see how you do” is a reasonable response. Monitor the patient visually and apply a pulse oximeter with mask off and mask on.

One physician recently wrote about measuring her own oxygen levels while wearing four different masks for 5 minutes each, with no change in breathing.

Editor’s note: Read more about mask exemptions in a Medscape interview with pulmonologist Albert Rizzo, MD, chief medical officer of the American Lung Association.

What are some practical tips?

Assuming that a patient is not in acute distress, options in this scenario include:

• Send the patient home and offer a return visit if masked or when the pandemic is over.
• Offer a telehealth visit, with the patient at home.

What if the unmasked person is not a patient but the companion of a patient? What if the individual refusing to wear a mask is an employee? In neither of these two hypotheticals is there a basis for legal action against a practice whose policy requires that everyone wear masks on the premises.

A companion who arrives without a mask should leave the office. An employee who refuses to mask up could be sent home. If the employee has a disability covered by the Americans with Disabilities Act, then the practice may need to make reasonable accommodations so that the employee works in a room alone if unable to work from home.

Those who manage medical practices should check the websites of the state health department and medical societies at least weekly, to see whether the agencies have issued guidance. For example, the Texas Medical Association has issued limited guidance.

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

What do you do now?

Your waiting room is filled with mask-wearing individuals, except for one person. Your staff offers a mask to this person, citing your office policy of requiring masks for all persons in order to prevent asymptomatic COVID-19 spread, and the patient refuses to put it on.

What can you/should you/must you do? Are you required to see a patient who refuses to wear a mask? If you ask the patient to leave without being seen, can you be accused of patient abandonment? If you allow the patient to stay, could you be liable for negligence for exposing others to a deadly illness?

The rules on mask-wearing, while initially downright confusing, have inexorably come to a rough consensus. By governors’ orders, masks are now mandatory in most states, though when and where they are required varies. For example, effective July 7, the governor of Washington has ordered that a business not allow a customer to enter without a face covering.

So far, there are no cases or court decisions to guide us about whether it is negligence to allow an unmasked patient to commingle in a medical practice. Nor do we have case law to help us determine whether patient abandonment would apply if a patient is sent home without being seen.

We can apply the legal principles and cases from other situations to this one, however, to tell us what constitutes negligence or patient abandonment. The practical questions, legally, are who might sue and on what basis?

Who might sue?

Someone who is injured in a public place may sue the owner for negligence if the owner knew or should have known of a danger and didn’t do anything about it. For example, individuals have sued grocery stores successfully after they slipped on a banana peel and fell. If, say, the banana peel was black, that indicates that it had been there for a while, and judges have found that the store management should have known about it and removed it.

Compare the banana peel scenario with the scenario where most news outlets and health departments are telling people, every day, to wear masks while in indoor public spaces, yet owners of a medical practice or facility allow individuals who are not wearing masks to sit in their waiting room. If an individual who was also in the waiting room with the unmasked individual develops COVID-19 2 days later, the ill individual may sue the medical practice for negligence for not removing the unmasked individual.

What about the individual’s responsibility to move away from the person not wearing a mask? That is the aspect of this scenario that attorneys and experts could argue about, for days, in a court case. But to go back to the banana peel case, one could argue that a customer in a grocery store should be looking out for banana peels on the floor and avoid them, yet courts have assigned liability to grocery stores when customers slip and fall.

Let’s review the four elements of negligence which a plaintiff would need to prove:

• Duty: Obligation of one person to another
• Breach: Improper act or omission, in the context of proper behavior to avoid imposing undue risks of harm to other persons and their property
• Damage
• Causation: That the act or omission caused the harm

Those who run medical offices and facilities have a duty to provide reasonably safe public spaces. Unmasked individuals are a risk to others nearby, so the “breach” element is satisfied if a practice fails to impose safety measures. Causation could be proven, or at least inferred, if contact tracing of an individual with COVID-19 showed that the only contact likely to have exposed the ill individual to the virus was an unmasked individual in a medical practice’s waiting room, especially if the unmasked individual was COVID-19 positive before, during, or shortly after the visit to the practice.

What about patient abandonment?

“Patient abandonment” is the legal term for terminating the physician-patient relationship in such a manner that the patient is denied necessary medical care. It is a form of negligence.

Refusing to see a patient unless the patient wears a mask is not denying care, in this attorney’s view, but rather establishing reasonable conditions for getting care. The patient simply needs to put on a mask.

What about the patient who refuses to wear a mask for medical reasons? There are exceptions in most of the governors’ orders for individuals with medical conditions that preclude covering nose and mouth with a mask. A medical office is the perfect place to test an individual’s ability or inability to breathe well while wearing a mask. “Put the mask on and we’ll see how you do” is a reasonable response. Monitor the patient visually and apply a pulse oximeter with mask off and mask on.

One physician recently wrote about measuring her own oxygen levels while wearing four different masks for 5 minutes each, with no change in breathing.

Editor’s note: Read more about mask exemptions in a Medscape interview with pulmonologist Albert Rizzo, MD, chief medical officer of the American Lung Association.

What are some practical tips?

Assuming that a patient is not in acute distress, options in this scenario include:

• Send the patient home and offer a return visit if masked or when the pandemic is over.
• Offer a telehealth visit, with the patient at home.

What if the unmasked person is not a patient but the companion of a patient? What if the individual refusing to wear a mask is an employee? In neither of these two hypotheticals is there a basis for legal action against a practice whose policy requires that everyone wear masks on the premises.

A companion who arrives without a mask should leave the office. An employee who refuses to mask up could be sent home. If the employee has a disability covered by the Americans with Disabilities Act, then the practice may need to make reasonable accommodations so that the employee works in a room alone if unable to work from home.

Those who manage medical practices should check the websites of the state health department and medical societies at least weekly, to see whether the agencies have issued guidance. For example, the Texas Medical Association has issued limited guidance.

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

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children who were overweight or obese at ages 2-3 years and at 6-7 years were significantly more likely than were healthy-weight children to show cardiometabolic risk factors at 11-12 years in a population-based study of more than 5,000 children.

SolStock/iStock

Previous studies of the impact of childhood body mass index on cardiovascular disease have used a single BMI measurement, wrote Kate Lycett, PhD, of Deakin University, Victoria, Australia, and colleagues. “This overlooks the considerable physiologic changes in BMI throughout childhood as part of typical growth.”

In a study published in Pediatrics, the researchers examined overweight and obesity at five time points in a cohort of 5,107 infants by measuring BMI every 2 years between the ages of 2-3 years and 10-11 years.

Overall, children with consistently high BMI trajectories from age 3 years had the highest risk of metabolic syndrome. At age 6-7 years, overweight and obese children had, respectively, higher metabolic syndrome risk scores by 0.23 and 0.76 mean standard deviation (SD) units, compared with healthy-weight children; these associations approximately doubled by age 11-12 years.

In addition, obese children had higher pulse wave velocity (PWV) from age 6-7 years (0.64-0.73 standard deviation units) and slightly higher carotid artery intima-media thickness (cIMT) at all measured ages, compared with healthy-weight children (0.20-0.30 SD units).

The findings were limited by several factors, including the inability to evaluate the effects of BMI on actual cardiovascular disease because of the young age of the study population, the researchers noted.

However, the “results are in keeping with previous studies but provide additional important insights that suggest BMI from as early as 2 to 3 years of age is predictive of preclinical cardiometabolic phenotypes by ages 11 to 12 years,” Dr. Lycett and associates said. The results have implications for public health by highlighting the subclinical effects of obesity in childhood and the importance of early intervention, they concluded.

“This important and comprehensive study has two important implications: first, high BMI by age 2 to 3 tends to stay high, and second, normal BMI occasionally increases to high BMI, but the reverse is rarely true,” Sarah Armstrong, MD, Jennifer S. Li, MD, and Asheley C. Skinner, PhD, wrote in an accompanying editorial (Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2020-1353).

The finding that children who were obese at age 3 years showed significant markers of silent atherosclerotic disease by age 11 years was “striking,” noted the editorialists, who are affiliated with Duke University, Durham, N.C.

“An important caveat is that although the relationships were significant, the amount of variance attributable directly to child BMI was small,” which highlights the complex relationship between obesity and health, they noted.

“Early-onset obesity is unlikely to change and, if it persists, will lead to detectable precursors of atherosclerosis by the time a child enters middle school,” and parents and primary care providers have an opportunity to “flatten the curve” by addressing BMI increases early in life to delay or prevent obesity, the editorialists concluded.

The study was supported by Australia’s National Health and Medical Research Council, The Royal Children’s Hospital Foundation, Murdoch Children’s Research Institute, The University of Melbourne, National Heart Foundation of Australia, Financial Markets Foundation for Children, and Victorian Deaf Education Institute. A number of the researchers were supported by grants from these and other universities and organizations. The researchers had no relevant financial disclosures. The editorialists had no financial conflicts to disclose.

SOURCE: Lycett K et al. Pediatrics. 2020 Jul 6. doi: 10.1542/peds.2019-3666.

Children appear less likely than adults to be the first cases of COVID-19 within a household, based on data from families of 39 children younger than 16 years.

Courtesy NIAID

“Unlike with other viral respiratory infections, children do not seem to be a major vector of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, with most pediatric cases described inside familial clusters and no documentation of child-to-child or child-to-adult transmission,” said Klara M. Posfay-Barbe, MD, of the University of Geneva, Switzerland, and colleagues.

In a study published in Pediatrics, the researchers analyzed data from all COVID-19 patients younger than 16 years who were identified between March 10, 2020, and April 10, 2020, through a hospital surveillance network. Parents and household contacts were called for contact tracing.

In 31 of 39 (79%) households, at least one adult family member had a suspected or confirmed SARS-CoV-2 infection before onset of symptoms in the child. These findings support data from previous studies suggesting that children mainly become infected from adult family members rather than transmitting the virus to them, the researchers said

In only 3 of 39 (8%) households was the study child the first to develop symptoms. “Surprisingly, in 33% of households, symptomatic HHCs [household contacts] tested negative despite belonging to a familial cluster with confirmed SARS-CoV-2 cases, suggesting an underreporting of cases,” Dr. Posfay-Barbe and associates noted.

The findings were limited by several factors including potential underreporting of cases because those with mild or atypical presentations may not have sought medical care, and the inability to confirm child-to-adult transmission. The results were strengthened by the extensive contact tracing and very few individuals lost to follow-up, they said; however, more diagnostic screening and contact tracing are needed to improve understanding of household transmission of SARS-CoV-2, they concluded.

Resolving the issue of how much children contribute to transmission of SARS-CoV-2 is essential to making informed decisions about public health, including how to structure schools and child-care facility reopening, Benjamin Lee, MD, and William V. Raszka Jr., MD, both of the University of Vermont, Burlington, said in an accompanying editorial (Pediatrics. 2020 Jul 10. doi: 10.1542/peds/2020-004879).

The data in the current study support other studies of transmission among household contacts in China suggesting that, in most cases of childhood infections, “the child was not the source of infection and that children most frequently acquire COVID-19 from adults, rather than transmitting it to them,” they wrote.

In addition, the limited data on transmission of SARS-CoV-2 by children outside of the household show few cases of secondary infection from children identified with SARS-CoV-2 in school settings in studies from France and Australia, Dr. Lee and Dr. Raszka noted.

“On the basis of these data, SARS-CoV2 transmission in schools may be less important in community transmission than initially feared,” the editorialists wrote. “This would be another manner by which SARS-CoV2 differs drastically from influenza, for which school-based transmission is well recognized as a significant driver of epidemic disease and forms the basis for most evidence regarding school closures as public health strategy.”

“Therefore, serious consideration should be paid toward strategies that allow schools to remain open, even during periods of COVID-19 spread,” the editorialists concluded. “In doing so, we could minimize the potentially profound adverse social, developmental, and health costs that our children will continue to suffer until an effective treatment or vaccine can be developed and distributed or, failing that, until we reach herd immunity,” Dr. Lee and Dr. Raszka emphasized.

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

SOURCE: Posfay-Barbe KM et al. Pediatrics. 2020 Jul 10. doi: 10.1542/peds.2020-1576.

Children appear less likely than adults to be the first cases of COVID-19 within a household, based on data from families of 39 children younger than 16 years.

Courtesy NIAID

“Unlike with other viral respiratory infections, children do not seem to be a major vector of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, with most pediatric cases described inside familial clusters and no documentation of child-to-child or child-to-adult transmission,” said Klara M. Posfay-Barbe, MD, of the University of Geneva, Switzerland, and colleagues.

In a study published in Pediatrics, the researchers analyzed data from all COVID-19 patients younger than 16 years who were identified between March 10, 2020, and April 10, 2020, through a hospital surveillance network. Parents and household contacts were called for contact tracing.

In 31 of 39 (79%) households, at least one adult family member had a suspected or confirmed SARS-CoV-2 infection before onset of symptoms in the child. These findings support data from previous studies suggesting that children mainly become infected from adult family members rather than transmitting the virus to them, the researchers said

In only 3 of 39 (8%) households was the study child the first to develop symptoms. “Surprisingly, in 33% of households, symptomatic HHCs [household contacts] tested negative despite belonging to a familial cluster with confirmed SARS-CoV-2 cases, suggesting an underreporting of cases,” Dr. Posfay-Barbe and associates noted.

The findings were limited by several factors including potential underreporting of cases because those with mild or atypical presentations may not have sought medical care, and the inability to confirm child-to-adult transmission. The results were strengthened by the extensive contact tracing and very few individuals lost to follow-up, they said; however, more diagnostic screening and contact tracing are needed to improve understanding of household transmission of SARS-CoV-2, they concluded.

Resolving the issue of how much children contribute to transmission of SARS-CoV-2 is essential to making informed decisions about public health, including how to structure schools and child-care facility reopening, Benjamin Lee, MD, and William V. Raszka Jr., MD, both of the University of Vermont, Burlington, said in an accompanying editorial (Pediatrics. 2020 Jul 10. doi: 10.1542/peds/2020-004879).

The data in the current study support other studies of transmission among household contacts in China suggesting that, in most cases of childhood infections, “the child was not the source of infection and that children most frequently acquire COVID-19 from adults, rather than transmitting it to them,” they wrote.

In addition, the limited data on transmission of SARS-CoV-2 by children outside of the household show few cases of secondary infection from children identified with SARS-CoV-2 in school settings in studies from France and Australia, Dr. Lee and Dr. Raszka noted.

“On the basis of these data, SARS-CoV2 transmission in schools may be less important in community transmission than initially feared,” the editorialists wrote. “This would be another manner by which SARS-CoV2 differs drastically from influenza, for which school-based transmission is well recognized as a significant driver of epidemic disease and forms the basis for most evidence regarding school closures as public health strategy.”

“Therefore, serious consideration should be paid toward strategies that allow schools to remain open, even during periods of COVID-19 spread,” the editorialists concluded. “In doing so, we could minimize the potentially profound adverse social, developmental, and health costs that our children will continue to suffer until an effective treatment or vaccine can be developed and distributed or, failing that, until we reach herd immunity,” Dr. Lee and Dr. Raszka emphasized.

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

SOURCE: Posfay-Barbe KM et al. Pediatrics. 2020 Jul 10. doi: 10.1542/peds.2020-1576.

Children appear less likely than adults to be the first cases of COVID-19 within a household, based on data from families of 39 children younger than 16 years.

Courtesy NIAID

“Unlike with other viral respiratory infections, children do not seem to be a major vector of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, with most pediatric cases described inside familial clusters and no documentation of child-to-child or child-to-adult transmission,” said Klara M. Posfay-Barbe, MD, of the University of Geneva, Switzerland, and colleagues.

In a study published in Pediatrics, the researchers analyzed data from all COVID-19 patients younger than 16 years who were identified between March 10, 2020, and April 10, 2020, through a hospital surveillance network. Parents and household contacts were called for contact tracing.

In 31 of 39 (79%) households, at least one adult family member had a suspected or confirmed SARS-CoV-2 infection before onset of symptoms in the child. These findings support data from previous studies suggesting that children mainly become infected from adult family members rather than transmitting the virus to them, the researchers said

In only 3 of 39 (8%) households was the study child the first to develop symptoms. “Surprisingly, in 33% of households, symptomatic HHCs [household contacts] tested negative despite belonging to a familial cluster with confirmed SARS-CoV-2 cases, suggesting an underreporting of cases,” Dr. Posfay-Barbe and associates noted.

The findings were limited by several factors including potential underreporting of cases because those with mild or atypical presentations may not have sought medical care, and the inability to confirm child-to-adult transmission. The results were strengthened by the extensive contact tracing and very few individuals lost to follow-up, they said; however, more diagnostic screening and contact tracing are needed to improve understanding of household transmission of SARS-CoV-2, they concluded.

Resolving the issue of how much children contribute to transmission of SARS-CoV-2 is essential to making informed decisions about public health, including how to structure schools and child-care facility reopening, Benjamin Lee, MD, and William V. Raszka Jr., MD, both of the University of Vermont, Burlington, said in an accompanying editorial (Pediatrics. 2020 Jul 10. doi: 10.1542/peds/2020-004879).

The data in the current study support other studies of transmission among household contacts in China suggesting that, in most cases of childhood infections, “the child was not the source of infection and that children most frequently acquire COVID-19 from adults, rather than transmitting it to them,” they wrote.

In addition, the limited data on transmission of SARS-CoV-2 by children outside of the household show few cases of secondary infection from children identified with SARS-CoV-2 in school settings in studies from France and Australia, Dr. Lee and Dr. Raszka noted.

“On the basis of these data, SARS-CoV2 transmission in schools may be less important in community transmission than initially feared,” the editorialists wrote. “This would be another manner by which SARS-CoV2 differs drastically from influenza, for which school-based transmission is well recognized as a significant driver of epidemic disease and forms the basis for most evidence regarding school closures as public health strategy.”

“Therefore, serious consideration should be paid toward strategies that allow schools to remain open, even during periods of COVID-19 spread,” the editorialists concluded. “In doing so, we could minimize the potentially profound adverse social, developmental, and health costs that our children will continue to suffer until an effective treatment or vaccine can be developed and distributed or, failing that, until we reach herd immunity,” Dr. Lee and Dr. Raszka emphasized.

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

SOURCE: Posfay-Barbe KM et al. Pediatrics. 2020 Jul 10. doi: 10.1542/peds.2020-1576.

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

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

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

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

Patients in the Veterans Health Administration (VHA) system 75 years or older, free of cardiovascular (CV) disease and prescribed statins for the first time, had a one-fourth lower risk for death and a 20% lower risk for CV death over an average 7 years than that of comparable patients not prescribed the drugs in an observational study.

The findings, based on more than 320,000 predominantly white male patients, initially without atherosclerotic cardiovascular disease (ASCVD), underscore the notion that “age on its own shouldn’t be a criterion not to use these drugs,” Ariela R. Orkaby, MD, MPH, lead author on the study, published in the July 7 issue of JAMA, said in an interview.

The very elderly are frequently undertreated, particularly in primary prevention, as many physicians consider it unnecessary for them to initiate or continue preventive measures, said Dr. Orkaby, of VA Boston Healthcare System and Harvard Medical School, Boston.

“From available data, we don’t really expect statins to start providing benefit in primary prevention until they’ve been taken for about 2 to 5 years. So for people who have very limited life expectancy, it may not be a great idea to add to their pill burden or increase the possibility that they might decline functionally,” Dr. Orkaby said.

“But what we saw in this study is that there is benefit to prescribing statins even in elderly patients, even within 2 years” of follow-up.

Despite being among the most studied drugs in the world, statins are understudied in older people. Fewer than 2% of the 186,854 participants in 28 statin trials were aged 75 years or older, wrote Dr. Orkaby and associates.

Most of what is known about initiating statin therapy in the 75-and-older age group comes from underpowered subgroup analyses and a few observational studies, Steven J. Nicholls, MBBS, PhD, Monash University, Melbourne, and Adam J. Nelson, MBBS, PhD, Duke Clinical Research Institute, Durham, N.C., wrote in an accompanying editorial. As a result, the evidence is conflicting, with some reports suggesting marked benefit and others possible harm.

The current findings, they wrote, “provide additional support for treatment guidelines that have increasingly advocated for more widespread use of statin therapy for ASCVD prevention in older individuals.”

Of the 326,981 people in the analysis, 57,178 (17.5%) were new statin users or initiated a statin during the study period, usually simvastatin. Their mean age was about 81 years, and 97.3% of the patients were men, 90% were white, and 72% were former smokers.

Using propensity scoring, the authors compared statin users with the other remaining patients who had the same likelihood of being prescribed a statin based on clinical characteristics but did not receive a prescription for a statin.

Michael W. Rich, MD, Washington University, St. Louis, who was not involved in the study but has previously worked with Dr. Orkaby, praised the analysis.

“It’s one of the best studies I’ve seen addressing this particular issue. It’s a large sample size, the analysis was very well done, and I think that it comes to a pretty unequivocal conclusion that, at least in this population, those individuals who were started on statins for the first time, and having no known prior ASCVD, clearly had a lower all-cause mortality and cardiovascular mortality, as well as a lower risk of composite cardiovascular events,” he said in an interview.

But the data have limitations, he added. The findings are still observational and could be confounded by unknown variables, and the select population – mostly white, male veterans – is known to be at somewhat higher risk for events than the general population.

Perhaps even more impressive than the risk reductions seen at a mean 6.8 years of follow-up, Dr. Rich said, are the sensitivity analyses at 2, 4, and 6 years that showed the benefit manifesting early.

The researchers saw a 32% reduction in all-cause mortality risk (P < .05) at 2 years, 21% at 4 years, and 13% at 6 years (P < .05 for all). Risk reductions for CV death followed a similar pattern, they wrote.

Dr. Rich said that the trial, although not a “slam dunk,” has persuaded him to shift from being very conservative about prescribing statins to elderly patients to being much more willing to consider it.

“This doesn’t mean that I will be running to routinely prescribe my 90-plus patients a statin, nor should we should be starting statins in everyone over 75, not even in all male former smokers over 75 – the type of people in this study – but I do think that it provides a stronger basis for talking to these patients about the possibility of starting a statin.”

There are two ongoing trials that may provide greater clarity, the authors observed. The STAREE trial has enrolled adults 70 years and older in Australia and includes serial evaluation of cognitive scores. Also, PREVENTABLE will examine the role of statins for prevention of dementia and disability-free survival in adults 75 years and older.

However, neither trial may fully resolve the question of primary prevention statin use in the elderly, they wrote. “While these trials are necessary to broaden the evidence base for older adults, it is unlikely that any trial will enroll large numbers of individuals at very advanced ages, black individuals, and those with dementia, as were included in this study.”

Dr. Orkaby had no disclosures; potential conflicts for the other authors are in the report. Dr. Rich reported having no conflicts of interest. Dr. Nicholls disclosed receiving research support from AstraZeneca, Amgen, Anthera, Eli Lilly, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and receiving consulting fees or honoraria from AstraZeneca, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr. Nelson had no disclosures.

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

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

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

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

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

Although the adverse effects of systemic glucocorticoids (GCs) are well known, their association with hypertension in rheumatoid arthritis (RA) has been unclear. Now, a large population-based study shows that the drugs are linked to a 17% overall increased risk for incident hypertension among patients with RA.

Further, when the researchers stratified participants by dose category, they found that doses higher than 7.5 mg were significantly associated with hypertension. Cumulative dosage was not tied to any clear pattern of risk.

The authors, led by Ruth E. Costello, a researcher at the Centre for Epidemiology Versus Arthritis in the Centre for Musculoskeletal Research at the University of Manchester (England) concluded that patients who are taking these drugs for the treatment of RA should be monitored for high blood pressure, which is an important but modifiable cardiovascular risk factor, and treated appropriately.

The results of Ms. Costello and colleagues’ study were published June 27 in Rheumatology.

“While fractures associated with these steroid drugs are well studied, hypertension is a side effect that seems to have been less well studied, and yet it is an important cardiovascular risk factor that can be managed,” Ms. Costello said in an interview.

To better understand the possible association, Ms. Costello and colleagues identified 17,760 patients who were newly diagnosed with RA between 1992 and 2019 and were included in the Clinical Practice Research Datalink, which represents about 7% of the U.K. population. None of the patients had hypertension at initial RA diagnosis. Slightly more than two-thirds were women (68.1%), and the mean age was 56.3 years.

Of those patients, 7,421 (41.8%) were prescribed GCs during postdiagnosis follow-up. Most patients (73%) were followed for at least 2 years.

Patients who used GCs were slightly older than never-users (mean age, 57.7 vs. 55.3 years), were predominantly women, had a history of smoking, and had more comorbidities.

The overall incidence rate (IR) of hypertension was 64.1 per 1,000 person-years (95% confidence interval, 62.5-65.7). There were 6,243 cases of incident hypertension over 97,547 person-years of follow-up.

Among those exposed to GCs, 1,321 patients developed hypertension, for an IR of 87.6 per 1,000 person-years. Among unexposed participants, the IR for hypertension was 59.7 per 1,000 person-years. In Cox proportional hazards modeling, GC use was associated with a 17% increased risk for hypertension (hazard ratio, 1.17; 95% CI, 1.10-1.24).

The researchers noted that 40% of GC users with hypertension were not prescribed an antihypertensive agent at any point during the study. “Whilst some may have been offered lifestyle advice, left untreated this has important implications in terms of addressing modifiable risk factors in an RA population already at increased risk of CV disease,” they wrote.

They noted that cardiovascular disease is a major driver of the elevated mortality risk seen among adults with RA compared with the general population and that recent treatment recommendations address management of cardiovascular risks in these patients.

“There are several routes by which GCs may promote cardiovascular disease, including hypertension, metabolic changes, diabetes, and weight gain. We don’t currently know the extent to which each of these individual mechanisms may be increasing cardiovascular disease,” said Ms. Costello.

“Glucocorticoids increase fluid retention and promote obesity and hypertension,” said Rajat S. Bhatt, MD, a rheumatologist at Prime Rheumatology and Memorial Hermann Katy Hospital in Richmond, Texas, who sees hypertension in GC users in his clinical practice. “So patients need to be monitored for these risk factors,” he said in an interview.

Although hypertension may be a significant factor in the increase in cardiovascular disease in the RA population, Dr. Bhatt said the major driver is likely the intrinsic inflammatory state caused by the disease itself. As to why the GC-hypertension connection has flown under the radar in RA, he added, “That specific link has been difficult to tease out since RA patients are often on multiple medications.”

In regard to the role of dosage, Dr. Bhatt said that hypertension risk increases with higher GC doses, as the U.K. study indicates, and usually subsides when patients stop using GCs.

“Whether the observed dose association is causal or influenced by the underlying disease severity, our results suggest we should be vigilant in patients on all doses of GC, especially higher doses,” Ms. Costello added.

In regard to using drugs that are less cardiotoxic than GCs, Dr. Bhatt said that there are clinical scenarios in which GC therapy is the best choice, so just switching to nonsteroidal drugs is no panacea. “All RA drugs have adverse side effects, and anyway, the goal of rheumatology treatment is always to get patients off corticosteroids as soon as possible,” he said.

Ms. Costello and colleagues noted that their results are consonant with earlier research, including a single-center, cross-sectional study in which less than 6 months’ use of prednisolone at a median dose of 7.5 mg was associated with hypertension. In a German registry study, among patients who received doses of less than 7.5 mg for less than 6 months, there were higher rates of self-reported elevations in blood pressure.

The findings are at odds, however, with a recent matched-cohort study, which also used data from the Clinical Practice Research Datalink. That study found no association between GC use and hypertension.

GCs have come under increasing scrutiny in regard to several diseases. A study published July 7 found that even short-term courses of a few days’ duration entail risks for serious adverse events.

Ms. Costello’s group says that an estimate of GC-related incident hypertension in RA should allow more informed treatment decisions and that their findings highlight the ongoing need to monitor for and address this risk.

The study was supported by the Centre for Epidemiology Versus Arthritis and by the National Institute for Health Research Manchester Biomedical Research Centre. Coauthor William G. Dixon, PhD, has received consultancy fees from Google and Bayer unrelated to this study. Dr. Bhatt has disclosed no relevant financial relationships.

SOURCE: Costello RE et al. Rheumatology. 2020 June 27. doi: 10.1093/rheumatology/keaa209.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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

The COVID-19 literature has been peppered with reports about myocarditis accompanying the disease. If true, this could, in part, explain some of the observed cardiac injury and arrhythmias in seriously ill patients, but also have implications for prognosis.

But endomyocardial biopsies and autopsies, the gold-standard confirmation tests, have been few and far between. That has led some cardiologists to question the true rate of myocarditis with SARS-CoV-2, or even if there is definitive proof the virus causes myocarditis.

Predictors of death in COVID-19 are older age, cardiovascular comorbidities, and elevated troponin or NT-proBNP – none of which actually fit well with the epidemiology of myocarditis due to other causes, Alida L.P. Caforio, MD, of Padua (Italy) University said in an interview. Myocarditis is traditionally a disease of the young, and most cases are immune-mediated and do not release troponin.

Moreover, myocarditis is a diagnosis of exclusion. For it to be made with any certainty requires proof, by biopsy or autopsy, of inflammatory infiltrates within the myocardium with myocyte necrosis not typical of myocardial infarction, said Dr. Caforio, who chaired the European Society of Cardiology’s writing committee for its 2013 position statement on myocardial and pericardial diseases.

“We have one biopsy-proven case, and in this case there were no viruses in the myocardium, including COVID-19,” she said. “There’s no proof that we have COVID-19 causing myocarditis because it has not been found in the cardiomyocytes.”
 

Emerging evidence

The virus-negative case from Lombardy, Italy, followed an early case series suggesting fulminant myocarditis was involved in 7% of COVID-related deaths in Wuhan, China.

Other case reports include cardiac magnetic resonance (CMR) findings typical of acute myocarditis in a man with no lung involvement or fever but a massive troponin spike, and myocarditis presenting as reverse takotsubo syndrome in a woman undergoing CMR and endomyocardial biopsy.

A CMR analysis in May said acute myocarditis, by 2018 Lake Louise Criteria, was present in eight of 10 patients with “myocarditis-like syndrome,” and a study just out June 30 said the coronavirus can infect heart cells in a lab dish.

Among the few autopsy series, a preprint on 12 patients with COVID-19 in the Seattle area showed coronavirus in the heart tissue of 1 patient.

“It was a low level, so there’s the possibility that it could be viremia, but the fact we do see actual cardiomyocyte injury associated with inflammation, that’s a myocarditis pattern. So it could be related to the SARS-CoV-2 virus,” said Desiree Marshall, MD, director of autopsy and after-death services, University of Washington Medical Center, Seattle.

The “waters are a little bit muddy,” however, because the patient had a coinfection clinically with influenza and methicillin-susceptible Staphylococcus aureus, which raises the specter that influenza could also have contributed, she said.

Data pending publication from two additional patients show no coronavirus in the heart. Acute respiratory distress syndrome pathology was common in all patients, but there was no evidence of vascular inflammation, such as endotheliitis, Dr. Marshall said.

SARS-CoV-2 cell entry depends on the angiotensin-converting enzyme 2 (ACE2) receptor, which is widely expressed in the heart and on endothelial cells and is linked to inflammatory activation. Autopsy data from three COVID-19 patients showed endothelial cell infection in the heart and diffuse endothelial inflammation, but no sign of lymphocytic myocarditis.
 

Defining myocarditis

“There are some experts who believe we’re likely still dealing with myocarditis but with atypical features, while others suggest there is no myocarditis by strict classic criteria,” said Peter Liu, MD, chief scientific officer/vice president of research, University of Ottawa Heart Institute.

“I don’t think either extreme is accurate,” he said. “The truth is likely somewhere in between, with evidence of both cardiac injury and inflammation. But nothing in COVID-19, as we know today, is classic; it’s a new disease, so we need to be more open minded as new data emerge.”

Part of the divide may indeed stem from the way myocarditis is defined. “Based on traditional Dallas criteria, classic myocarditis requires evidence of myocyte necrosis, which we have, but also inflammatory cell infiltrate, which we don’t consistently have,” he said. “But on the other hand, there is evidence of inflammation-induced cardiac damage, often aggregated around blood vessels.”

The situation is evolving in recent days, and new data under review demonstrated inflammatory infiltrates, which fits the traditional myocarditis criteria, Dr. Liu noted. Yet the viral etiology for the inflammation is still elusive in definitive proof.

In traditional myocarditis, there is an abundance of lymphocytes and foci of inflammation in the myocardium, but COVID-19 is very unusual, in that these lymphocytes are not as exuberant, he said. Lymphopenia or low lymphocyte counts occur in up to 80% of patients. Also, older patients, who initially made up the bulk of the severe COVID-19 cases, are less T-lymphocyte responsive.

“So the lower your lymphocyte count, the worse your outcome is going to be and the more likely you’re going to get cytokine storm,” Dr. Liu said. “And that may be the reason the suspected myocarditis in COVID-19 is atypical because the lymphocytes, in fact, are being suppressed and there is instead more vasculitis.”

Recent data from myocardial gene expression analysis showed that the viral receptor ACE2 is present in the myocardium, and can be upregulated in conditions such as heart failure, he said. However, the highest ACE2 expression is found in pericytes around blood vessels, not myocytes. “This may explain the preferential vascular involvement often observed.”
 

Cardiac damage in the young

Evidence started evolving in early April that young COVID-19 patients without lung disease, generally in their 20s and 30s, can have very high troponin peaks and a form of cardiac damage that does not appear to be related to sepsis, systemic shock, or cytokine storm.

“That’s the group that I do think has some myocarditis, but it’s different. It’s not lymphocytic myocarditis, like enteroviral myocarditis,” Leslie T. Cooper Jr., MD, a myocarditis expert at Mayo Clinic, Jacksonville, Florida, said in an interview.

“The data to date suggest that most SARS cardiac injury is related to stress or high circulating cytokine levels. However, myocarditis probably does affect some patients, he added. “The few published cases suggest a role for macrophages or endothelial cells, which could affect cardiac myocyte function. This type of injury could cause the ST-segment elevation MI-like patterns we have seen in young people with normal epicardial coronary arteries.”

Dr. Cooper, who coauthored a report on the management of COVID-19 cardiovascular syndrome, pointed out that it’s been hard for researchers to isolate genome from autopsy samples because of RNA degradation prior to autopsy and the use of formalin fixation for tissues prior to RNA extraction.

“Most labs are not doing next-generation sequencing, and even with that, RNA protection and fresh tissue may be required to detect viral genome,” he said.
 

No proven therapy

Although up to 50% of acute myocarditis cases undergo spontaneous healing, recognition and multidisciplinary management of clinically suspected myocarditis is important. The optimal treatment remains unclear.

An early case report suggested use of methylprednisolone and intravenous immunoglobulin helped spare the life of a 37-year-old with clinically suspected fulminant myocarditis with cardiogenic shock.

In a related commentary, Dr. Caforio and colleagues pointed out that the World Health Organization considers the use of IV corticosteroids controversial, even in pneumonia due to COVID-19, because it may reduce viral clearance and increase sepsis risk. Intravenous immunoglobulin is also questionable because there is no IgG response to COVID-19 in the plasma donors’ pool.

“Immunosuppression should be reserved for only virus-negative non-COVID myocarditis,” Dr. Caforio said in an interview. “There is no appropriate treatment nowadays for clinically suspected COVID-19 myocarditis. There is no proven therapy for COVID-19, even less for COVID-19 myocarditis.”

Although definitive publication of the RECOVERY trial is still pending, the benefits of dexamethasone – a steroid that works predominantly through its anti-inflammatory effects – appear to be in the sickest patients, such as those requiring ICU admission or respiratory support.

“Many of the same patients would have systemic inflammation and would have also shown elevated cardiac biomarkers,” Dr. Liu observed. “Therefore, it is conceivable that a subset who had cardiac inflammation also benefited from the treatment. Further data, possibly through subgroup analysis and eventually meta-analysis, may help us to understand if dexamethasone also benefited patients with dominant cardiac injury.”

Dr. Caforio, Dr. Marshall, Dr. Liu, and Dr. Cooper reported having no relevant conflicts of interest.

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