Clinical Endocrinology News

The Endocrine Society will now hold its annual meeting online in June.

ENDO 2020, originally scheduled for March 27-31 in San Francisco, was canceled March 9 because of the COVID-19 pandemic. Virtual press briefings were held on March 30 and 31.

Now, ENDO Online 2020, scheduled for June 8-22, will include both on-demand and live programming. Registration will be complimentary for health care providers who treat endocrine conditions and researchers in the field.

“The Endocrine Society will host its largest-ever online meeting in June to ensure endocrine researchers and clinicians continue to have access to the latest scientific information, despite the COVID-19 pandemic,” the society said in an announcement.

Content will include on-demand clinical sessions, continuing medical education sessions, programming for early career endocrinologists, and a digital exhibit hall.

The exact content mix is still being worked out, Endocrine Society spokeswoman Jenni Gingery told Medscape Medical News.

Society President E. Dale Abel, MD, PhD, said: “We recognize that many of the members of our field have been mobilized and are actively responding to the COVID-19 pandemic, and we also acknowledge that many have had to close their offices and labs.”

However, Abel, of the University of Iowa, Carver College of Medicine, Iowa City, noted, “We have received feedback that many endocrine investigators, clinicians, and trainees have indicated their desire to continue to advance their clinical knowledge and to be exposed to emerging science. We are proud to support them by virtually delivering the content they need during this challenging period.”

About 9,500 attendees were expected to attend ENDO 2020 in San Francisco.

This is only the third annual meeting cancellation in the Society’s 104-year history. The other two were both during World War II.

This article first appeared on Medscape.com.

The Endocrine Society will now hold its annual meeting online in June.

ENDO 2020, originally scheduled for March 27-31 in San Francisco, was canceled March 9 because of the COVID-19 pandemic. Virtual press briefings were held on March 30 and 31.

Now, ENDO Online 2020, scheduled for June 8-22, will include both on-demand and live programming. Registration will be complimentary for health care providers who treat endocrine conditions and researchers in the field.

“The Endocrine Society will host its largest-ever online meeting in June to ensure endocrine researchers and clinicians continue to have access to the latest scientific information, despite the COVID-19 pandemic,” the society said in an announcement.

Content will include on-demand clinical sessions, continuing medical education sessions, programming for early career endocrinologists, and a digital exhibit hall.

The exact content mix is still being worked out, Endocrine Society spokeswoman Jenni Gingery told Medscape Medical News.

Society President E. Dale Abel, MD, PhD, said: “We recognize that many of the members of our field have been mobilized and are actively responding to the COVID-19 pandemic, and we also acknowledge that many have had to close their offices and labs.”

However, Abel, of the University of Iowa, Carver College of Medicine, Iowa City, noted, “We have received feedback that many endocrine investigators, clinicians, and trainees have indicated their desire to continue to advance their clinical knowledge and to be exposed to emerging science. We are proud to support them by virtually delivering the content they need during this challenging period.”

About 9,500 attendees were expected to attend ENDO 2020 in San Francisco.

This is only the third annual meeting cancellation in the Society’s 104-year history. The other two were both during World War II.

This article first appeared on Medscape.com.

The Endocrine Society will now hold its annual meeting online in June.

ENDO 2020, originally scheduled for March 27-31 in San Francisco, was canceled March 9 because of the COVID-19 pandemic. Virtual press briefings were held on March 30 and 31.

Now, ENDO Online 2020, scheduled for June 8-22, will include both on-demand and live programming. Registration will be complimentary for health care providers who treat endocrine conditions and researchers in the field.

“The Endocrine Society will host its largest-ever online meeting in June to ensure endocrine researchers and clinicians continue to have access to the latest scientific information, despite the COVID-19 pandemic,” the society said in an announcement.

Content will include on-demand clinical sessions, continuing medical education sessions, programming for early career endocrinologists, and a digital exhibit hall.

The exact content mix is still being worked out, Endocrine Society spokeswoman Jenni Gingery told Medscape Medical News.

Society President E. Dale Abel, MD, PhD, said: “We recognize that many of the members of our field have been mobilized and are actively responding to the COVID-19 pandemic, and we also acknowledge that many have had to close their offices and labs.”

However, Abel, of the University of Iowa, Carver College of Medicine, Iowa City, noted, “We have received feedback that many endocrine investigators, clinicians, and trainees have indicated their desire to continue to advance their clinical knowledge and to be exposed to emerging science. We are proud to support them by virtually delivering the content they need during this challenging period.”

About 9,500 attendees were expected to attend ENDO 2020 in San Francisco.

This is only the third annual meeting cancellation in the Society’s 104-year history. The other two were both during World War II.

This article first appeared on Medscape.com.

PHOENIX, ARIZ. – Diabetes patients in China who were enrolled in a team-based care intervention with clinical decision support systems significantly reduced their hemoglobin A_1c, systolic blood pressure, and LDL cholesterol over 18 months, compared with those who received team-based care alone.

Doug Brunk/MDedge News

The finding comes from the Diabetes Complication Control in Community Clinics (D4C), a cluster randomized trial conducted in 38 community health centers in Xiamen, China.

“Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries where populations are large and growing and health care resources are limited,” Jiang He, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

According to Dr. He, chair and professor of epidemiology at Tulane School of Public Health and Tropical Medicine, New Orleans, the prevalence of diabetes has increased rapidly in recent decades in China, from 2.5% in 1994 to 11.6% in 2010. “It was estimated that 114 million Chinese adults had diabetes in 2010,” he said. “Hyperglycemia, high blood pressure, and elevated LDL cholesterol are major risk factors for cardiovascular disease and premature death. The majority of patients with diabetes have multiple uncontrolled CVD risk factors due to suboptimal care. Diabetes and its complications further strain an already overburdened and overwhelmed health care system, especially tertiary care facilities, in China. On the other hand, community health centers are underutilized.”

In D4C, Dr. He and colleagues set out to evaluate changes in CVD risk factors among patients with diabetes after implementing a team-based care model at community health centers in Xiamen, China. They compared the effectiveness of team-based care with clinical decision support systems versus team-based care alone on CVD risk factor control among patients with diabetes at these community health centers.

The study population consisted of 10,942 patients aged 50 years and older with uncontrolled diabetes and at least one of the following three additional CVD risk factors: systolic BP of at least 140 mm Hg and/or diastolic BP of at least 90 mm Hg; LDL cholesterol of at least 100 mg/dL, or clinical atherosclerotic cardiovascular disease (ASCVD). At the intervention clinics, team-based care was delivered by a team of primary care physicians, nurses, and diabetes specialists. The researchers trained the primary care physicians and nurses, and a clinical decision support system was integrated with guideline-based treatment algorithms for controlling glycemia, blood pressure, and lipids.

At the enhanced care control clinics, team-based care was delivered by a team of primary care physicians, nurses, and diabetes specialists. The city health commission trained the primary care physicians and nurses. The intervention lasted for 18 months in both groups.

Dr. He, the D4C study chair, reported findings from 10,942 patients: 5,394 in the intervention group and 5,548 in the enhanced care group. The mean baseline age was similar between the intervention group and the enhanced care group (a mean of 63 years), as was body mass index (a mean of 24.9 kg/m²), hemoglobin A_1c (a mean of 8.8 vs. 8.7%, respectively), LDL cholesterol (121.2 vs. 121.1 mg/dL), systolic blood pressure (136.6 vs. 136.9 mm Hg), and diastolic blood pressure (79.7 vs. 79.8 mm Hg).

The researchers found patients in both groups experienced significant reductions in HbA_1c, LDL cholesterol, and BP over the 18-month follow-up, but those in the intervention group fared better in all measures. Specifically, the mean change in HbA_1c from baseline was –.85% in the intervention group, compared with –.66% in the enhanced care group, while the change in LDL was –19 mg/dL, compared with –12.8 mg/dL, respectively; the change in systolic blood pressure was –8.9 mm Hg vs. –7.7 mm Hg, and the change in 10-year ASCVD risk was .57% vs. .28% (P < .0001 for all associations).

The researchers also observed that the proportions of controlled HbA_1c, LDL, and blood pressure at 18 months were higher in the intervention group, compared with the enhanced care group. Specifically, 38% of patients in the intervention group achieved glycemic control, compared with 35% of those in the enhanced care group (P =. 0006), while 48% vs. 39%, respectively, achieved control of LDL cholesterol (P < .0001), and 78% vs. 75% achieved control of blood pressure (P = .0009). In addition, 15% vs. 12% achieved control of all three risk factors at 18 months (P < .0001).

“Implementing team-based care with a clinical decision support system is an effective and sustainable strategy for diabetes control in primary care settings,” Dr. He said at the meeting, which was sponsored by the American Heart Association. “This implementation strategy could be scaled up within primary care settings in China and other low- to middle-income countries to improve CVD risk factor control in patients with diabetes.”

In an interview, session moderator Joshua J. Joseph, MD, of Ohio State University, Columbus, pointed out that since only 12%-15% of study participants achieved control of all three CVD risk factors, “that leaves a great opportunity for [figuring out] how to we get the other 88% or 85% of patients to target levels. That’s going to be important as we think about cardiovascular disease prevention in type 2 diabetes. The more we can use team-based care along with clinical decision support tools, the more we will continue to improve the lives of patients.”

The study was supported by the Xiamen City Health Commission. Dr. He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: He J et al. EPI/LIFESTYLE 2020, session 7A, abstract 17.

PHOENIX, ARIZ. – Diabetes patients in China who were enrolled in a team-based care intervention with clinical decision support systems significantly reduced their hemoglobin A_1c, systolic blood pressure, and LDL cholesterol over 18 months, compared with those who received team-based care alone.

Doug Brunk/MDedge News

The finding comes from the Diabetes Complication Control in Community Clinics (D4C), a cluster randomized trial conducted in 38 community health centers in Xiamen, China.

“Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries where populations are large and growing and health care resources are limited,” Jiang He, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

According to Dr. He, chair and professor of epidemiology at Tulane School of Public Health and Tropical Medicine, New Orleans, the prevalence of diabetes has increased rapidly in recent decades in China, from 2.5% in 1994 to 11.6% in 2010. “It was estimated that 114 million Chinese adults had diabetes in 2010,” he said. “Hyperglycemia, high blood pressure, and elevated LDL cholesterol are major risk factors for cardiovascular disease and premature death. The majority of patients with diabetes have multiple uncontrolled CVD risk factors due to suboptimal care. Diabetes and its complications further strain an already overburdened and overwhelmed health care system, especially tertiary care facilities, in China. On the other hand, community health centers are underutilized.”

In D4C, Dr. He and colleagues set out to evaluate changes in CVD risk factors among patients with diabetes after implementing a team-based care model at community health centers in Xiamen, China. They compared the effectiveness of team-based care with clinical decision support systems versus team-based care alone on CVD risk factor control among patients with diabetes at these community health centers.

The study population consisted of 10,942 patients aged 50 years and older with uncontrolled diabetes and at least one of the following three additional CVD risk factors: systolic BP of at least 140 mm Hg and/or diastolic BP of at least 90 mm Hg; LDL cholesterol of at least 100 mg/dL, or clinical atherosclerotic cardiovascular disease (ASCVD). At the intervention clinics, team-based care was delivered by a team of primary care physicians, nurses, and diabetes specialists. The researchers trained the primary care physicians and nurses, and a clinical decision support system was integrated with guideline-based treatment algorithms for controlling glycemia, blood pressure, and lipids.

At the enhanced care control clinics, team-based care was delivered by a team of primary care physicians, nurses, and diabetes specialists. The city health commission trained the primary care physicians and nurses. The intervention lasted for 18 months in both groups.

Dr. He, the D4C study chair, reported findings from 10,942 patients: 5,394 in the intervention group and 5,548 in the enhanced care group. The mean baseline age was similar between the intervention group and the enhanced care group (a mean of 63 years), as was body mass index (a mean of 24.9 kg/m²), hemoglobin A_1c (a mean of 8.8 vs. 8.7%, respectively), LDL cholesterol (121.2 vs. 121.1 mg/dL), systolic blood pressure (136.6 vs. 136.9 mm Hg), and diastolic blood pressure (79.7 vs. 79.8 mm Hg).

The researchers found patients in both groups experienced significant reductions in HbA_1c, LDL cholesterol, and BP over the 18-month follow-up, but those in the intervention group fared better in all measures. Specifically, the mean change in HbA_1c from baseline was –.85% in the intervention group, compared with –.66% in the enhanced care group, while the change in LDL was –19 mg/dL, compared with –12.8 mg/dL, respectively; the change in systolic blood pressure was –8.9 mm Hg vs. –7.7 mm Hg, and the change in 10-year ASCVD risk was .57% vs. .28% (P < .0001 for all associations).

The researchers also observed that the proportions of controlled HbA_1c, LDL, and blood pressure at 18 months were higher in the intervention group, compared with the enhanced care group. Specifically, 38% of patients in the intervention group achieved glycemic control, compared with 35% of those in the enhanced care group (P =. 0006), while 48% vs. 39%, respectively, achieved control of LDL cholesterol (P < .0001), and 78% vs. 75% achieved control of blood pressure (P = .0009). In addition, 15% vs. 12% achieved control of all three risk factors at 18 months (P < .0001).

“Implementing team-based care with a clinical decision support system is an effective and sustainable strategy for diabetes control in primary care settings,” Dr. He said at the meeting, which was sponsored by the American Heart Association. “This implementation strategy could be scaled up within primary care settings in China and other low- to middle-income countries to improve CVD risk factor control in patients with diabetes.”

In an interview, session moderator Joshua J. Joseph, MD, of Ohio State University, Columbus, pointed out that since only 12%-15% of study participants achieved control of all three CVD risk factors, “that leaves a great opportunity for [figuring out] how to we get the other 88% or 85% of patients to target levels. That’s going to be important as we think about cardiovascular disease prevention in type 2 diabetes. The more we can use team-based care along with clinical decision support tools, the more we will continue to improve the lives of patients.”

The study was supported by the Xiamen City Health Commission. Dr. He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: He J et al. EPI/LIFESTYLE 2020, session 7A, abstract 17.

PHOENIX, ARIZ. – Diabetes patients in China who were enrolled in a team-based care intervention with clinical decision support systems significantly reduced their hemoglobin A_1c, systolic blood pressure, and LDL cholesterol over 18 months, compared with those who received team-based care alone.

Doug Brunk/MDedge News

The finding comes from the Diabetes Complication Control in Community Clinics (D4C), a cluster randomized trial conducted in 38 community health centers in Xiamen, China.

“Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries where populations are large and growing and health care resources are limited,” Jiang He, MD, PhD, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting.

According to Dr. He, chair and professor of epidemiology at Tulane School of Public Health and Tropical Medicine, New Orleans, the prevalence of diabetes has increased rapidly in recent decades in China, from 2.5% in 1994 to 11.6% in 2010. “It was estimated that 114 million Chinese adults had diabetes in 2010,” he said. “Hyperglycemia, high blood pressure, and elevated LDL cholesterol are major risk factors for cardiovascular disease and premature death. The majority of patients with diabetes have multiple uncontrolled CVD risk factors due to suboptimal care. Diabetes and its complications further strain an already overburdened and overwhelmed health care system, especially tertiary care facilities, in China. On the other hand, community health centers are underutilized.”

In D4C, Dr. He and colleagues set out to evaluate changes in CVD risk factors among patients with diabetes after implementing a team-based care model at community health centers in Xiamen, China. They compared the effectiveness of team-based care with clinical decision support systems versus team-based care alone on CVD risk factor control among patients with diabetes at these community health centers.

The study population consisted of 10,942 patients aged 50 years and older with uncontrolled diabetes and at least one of the following three additional CVD risk factors: systolic BP of at least 140 mm Hg and/or diastolic BP of at least 90 mm Hg; LDL cholesterol of at least 100 mg/dL, or clinical atherosclerotic cardiovascular disease (ASCVD). At the intervention clinics, team-based care was delivered by a team of primary care physicians, nurses, and diabetes specialists. The researchers trained the primary care physicians and nurses, and a clinical decision support system was integrated with guideline-based treatment algorithms for controlling glycemia, blood pressure, and lipids.

At the enhanced care control clinics, team-based care was delivered by a team of primary care physicians, nurses, and diabetes specialists. The city health commission trained the primary care physicians and nurses. The intervention lasted for 18 months in both groups.

Dr. He, the D4C study chair, reported findings from 10,942 patients: 5,394 in the intervention group and 5,548 in the enhanced care group. The mean baseline age was similar between the intervention group and the enhanced care group (a mean of 63 years), as was body mass index (a mean of 24.9 kg/m²), hemoglobin A_1c (a mean of 8.8 vs. 8.7%, respectively), LDL cholesterol (121.2 vs. 121.1 mg/dL), systolic blood pressure (136.6 vs. 136.9 mm Hg), and diastolic blood pressure (79.7 vs. 79.8 mm Hg).

The researchers found patients in both groups experienced significant reductions in HbA_1c, LDL cholesterol, and BP over the 18-month follow-up, but those in the intervention group fared better in all measures. Specifically, the mean change in HbA_1c from baseline was –.85% in the intervention group, compared with –.66% in the enhanced care group, while the change in LDL was –19 mg/dL, compared with –12.8 mg/dL, respectively; the change in systolic blood pressure was –8.9 mm Hg vs. –7.7 mm Hg, and the change in 10-year ASCVD risk was .57% vs. .28% (P < .0001 for all associations).

The researchers also observed that the proportions of controlled HbA_1c, LDL, and blood pressure at 18 months were higher in the intervention group, compared with the enhanced care group. Specifically, 38% of patients in the intervention group achieved glycemic control, compared with 35% of those in the enhanced care group (P =. 0006), while 48% vs. 39%, respectively, achieved control of LDL cholesterol (P < .0001), and 78% vs. 75% achieved control of blood pressure (P = .0009). In addition, 15% vs. 12% achieved control of all three risk factors at 18 months (P < .0001).

“Implementing team-based care with a clinical decision support system is an effective and sustainable strategy for diabetes control in primary care settings,” Dr. He said at the meeting, which was sponsored by the American Heart Association. “This implementation strategy could be scaled up within primary care settings in China and other low- to middle-income countries to improve CVD risk factor control in patients with diabetes.”

In an interview, session moderator Joshua J. Joseph, MD, of Ohio State University, Columbus, pointed out that since only 12%-15% of study participants achieved control of all three CVD risk factors, “that leaves a great opportunity for [figuring out] how to we get the other 88% or 85% of patients to target levels. That’s going to be important as we think about cardiovascular disease prevention in type 2 diabetes. The more we can use team-based care along with clinical decision support tools, the more we will continue to improve the lives of patients.”

The study was supported by the Xiamen City Health Commission. Dr. He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: He J et al. EPI/LIFESTYLE 2020, session 7A, abstract 17.

Greater prevalence of underlying health conditions such as diabetes and chronic lung disease was seen among nearly 7,200 Americans hospitalized with coronavirus disease 2019 (COVID-19), according to the Centers for Disease Control and Prevention.

Of the 122,653 laboratory-confirmed COVID-19 cases reported to the CDC as of March 28, the COVID-19 Response Team had access to data on the presence or absence of underlying health conditions and other recognized risk factors for severe outcomes from respiratory infections for 7,162 (5.8%) patients.

“Among these patients, higher percentages of patients with underlying conditions were admitted to the hospital and to an ICU than patients without reported underlying conditions. These results are consistent with findings from China and Italy,” Katherine Fleming-Dutra, MD, and associates said in the MMWR.

Individuals with underlying health conditions/risk factors made up 37.6% of all COVID-19 patients in the study but represented a majority of ICU (78%) and non-ICU (71%) hospital admissions. In contrast, 73% of COVID-19 patients who were not hospitalized had no underlying conditions, Dr. Fleming-Dutra and the CDC COVID-19 Response Team reported.

With a prevalence of 10.9%, diabetes mellitus was the most common condition reported among all COVID-19 patients, followed by chronic lung disease (9.2%) and cardiovascular disease (9.0%), the investigators said.

Another look at the data shows that 40.5% of those with underlying conditions were hospitalized, compared with 9.0% of the 4,470 COVID-19 patients without any risk factors.

“Strategies to protect all persons and especially those with underlying health conditions, including social distancing and handwashing, should be implemented by all communities and all persons to help slow the spread of COVID-19,” the response team wrote.

rfranki@mdedge.com

SOURCE: Fleming-Dutra K et al. MMWR. 2020 Mar 31;69 (early release):1-5.

Greater prevalence of underlying health conditions such as diabetes and chronic lung disease was seen among nearly 7,200 Americans hospitalized with coronavirus disease 2019 (COVID-19), according to the Centers for Disease Control and Prevention.

Of the 122,653 laboratory-confirmed COVID-19 cases reported to the CDC as of March 28, the COVID-19 Response Team had access to data on the presence or absence of underlying health conditions and other recognized risk factors for severe outcomes from respiratory infections for 7,162 (5.8%) patients.

“Among these patients, higher percentages of patients with underlying conditions were admitted to the hospital and to an ICU than patients without reported underlying conditions. These results are consistent with findings from China and Italy,” Katherine Fleming-Dutra, MD, and associates said in the MMWR.

Individuals with underlying health conditions/risk factors made up 37.6% of all COVID-19 patients in the study but represented a majority of ICU (78%) and non-ICU (71%) hospital admissions. In contrast, 73% of COVID-19 patients who were not hospitalized had no underlying conditions, Dr. Fleming-Dutra and the CDC COVID-19 Response Team reported.

With a prevalence of 10.9%, diabetes mellitus was the most common condition reported among all COVID-19 patients, followed by chronic lung disease (9.2%) and cardiovascular disease (9.0%), the investigators said.

Another look at the data shows that 40.5% of those with underlying conditions were hospitalized, compared with 9.0% of the 4,470 COVID-19 patients without any risk factors.

“Strategies to protect all persons and especially those with underlying health conditions, including social distancing and handwashing, should be implemented by all communities and all persons to help slow the spread of COVID-19,” the response team wrote.

rfranki@mdedge.com

SOURCE: Fleming-Dutra K et al. MMWR. 2020 Mar 31;69 (early release):1-5.

Greater prevalence of underlying health conditions such as diabetes and chronic lung disease was seen among nearly 7,200 Americans hospitalized with coronavirus disease 2019 (COVID-19), according to the Centers for Disease Control and Prevention.

Of the 122,653 laboratory-confirmed COVID-19 cases reported to the CDC as of March 28, the COVID-19 Response Team had access to data on the presence or absence of underlying health conditions and other recognized risk factors for severe outcomes from respiratory infections for 7,162 (5.8%) patients.

“Among these patients, higher percentages of patients with underlying conditions were admitted to the hospital and to an ICU than patients without reported underlying conditions. These results are consistent with findings from China and Italy,” Katherine Fleming-Dutra, MD, and associates said in the MMWR.

Individuals with underlying health conditions/risk factors made up 37.6% of all COVID-19 patients in the study but represented a majority of ICU (78%) and non-ICU (71%) hospital admissions. In contrast, 73% of COVID-19 patients who were not hospitalized had no underlying conditions, Dr. Fleming-Dutra and the CDC COVID-19 Response Team reported.

With a prevalence of 10.9%, diabetes mellitus was the most common condition reported among all COVID-19 patients, followed by chronic lung disease (9.2%) and cardiovascular disease (9.0%), the investigators said.

Another look at the data shows that 40.5% of those with underlying conditions were hospitalized, compared with 9.0% of the 4,470 COVID-19 patients without any risk factors.

“Strategies to protect all persons and especially those with underlying health conditions, including social distancing and handwashing, should be implemented by all communities and all persons to help slow the spread of COVID-19,” the response team wrote.

rfranki@mdedge.com

SOURCE: Fleming-Dutra K et al. MMWR. 2020 Mar 31;69 (early release):1-5.

The immune responses of specific antibodies were maintained in more than 90% of recovered SARS-CoV patients for 2 years, raising the likelihood that the similarly behaving SARS-CoV-2 might provoke the same response, according to an online communication published in the Journal of Microbiology, Immunology and Infection.

Courtesy NIAID-RML

The authors cited a cohort study of convalescent SARS-CoV patients (56 cases, from the Beijing hospital of the Armed Forces Police, China) that showed that specific IgG antibodies and neutralizing antibodies were highly correlated, peaking at month 4 after the onset of disease and decreasing gradually thereafter.

This and other studies suggest that the immune responses of specific antibodies were maintained in more than 90% of recovered SARS-CoV patients for 2 years, according to the authors.

However, of particular concern is the fact that only 11.8% of patients acquire specific SARS-CoV Abs in the early period after recovery at day 7, not reaching 100% until day 90, which highlights the importance of the detection of antibody titers for convalescent COVID-19 patients, according to the authors. “Otherwise, these patients with low titers of antibodies may not be efficient for the clearance of SARS-CoV-2.”

The authors also cited a recent study that showed how neutralizing antibody from a convalescent SARS patient could block the SARS-CoV-2 from entering into target cells in vitro, and suggested that previous experimental SARS-CoV vaccines and neutralizing antibodies could provide novel preventive and therapeutic options for COVID-19.

“These experiences from SARS-CoV are expected to have some implications for the treatment, management and surveillance of SARS-CoV-2 patients,” the authors concluded.

mlesney@mdedge.com

SOURCE: Lin Q et al. J Microbiol Immunol Infect. 2020 Mar 25. https://doi.org/10.1016/j.jmii.2020.03.015.

The immune responses of specific antibodies were maintained in more than 90% of recovered SARS-CoV patients for 2 years, raising the likelihood that the similarly behaving SARS-CoV-2 might provoke the same response, according to an online communication published in the Journal of Microbiology, Immunology and Infection.

Courtesy NIAID-RML

The authors cited a cohort study of convalescent SARS-CoV patients (56 cases, from the Beijing hospital of the Armed Forces Police, China) that showed that specific IgG antibodies and neutralizing antibodies were highly correlated, peaking at month 4 after the onset of disease and decreasing gradually thereafter.

This and other studies suggest that the immune responses of specific antibodies were maintained in more than 90% of recovered SARS-CoV patients for 2 years, according to the authors.

However, of particular concern is the fact that only 11.8% of patients acquire specific SARS-CoV Abs in the early period after recovery at day 7, not reaching 100% until day 90, which highlights the importance of the detection of antibody titers for convalescent COVID-19 patients, according to the authors. “Otherwise, these patients with low titers of antibodies may not be efficient for the clearance of SARS-CoV-2.”

The authors also cited a recent study that showed how neutralizing antibody from a convalescent SARS patient could block the SARS-CoV-2 from entering into target cells in vitro, and suggested that previous experimental SARS-CoV vaccines and neutralizing antibodies could provide novel preventive and therapeutic options for COVID-19.

“These experiences from SARS-CoV are expected to have some implications for the treatment, management and surveillance of SARS-CoV-2 patients,” the authors concluded.

mlesney@mdedge.com

SOURCE: Lin Q et al. J Microbiol Immunol Infect. 2020 Mar 25. https://doi.org/10.1016/j.jmii.2020.03.015.

The immune responses of specific antibodies were maintained in more than 90% of recovered SARS-CoV patients for 2 years, raising the likelihood that the similarly behaving SARS-CoV-2 might provoke the same response, according to an online communication published in the Journal of Microbiology, Immunology and Infection.

Courtesy NIAID-RML

The authors cited a cohort study of convalescent SARS-CoV patients (56 cases, from the Beijing hospital of the Armed Forces Police, China) that showed that specific IgG antibodies and neutralizing antibodies were highly correlated, peaking at month 4 after the onset of disease and decreasing gradually thereafter.

This and other studies suggest that the immune responses of specific antibodies were maintained in more than 90% of recovered SARS-CoV patients for 2 years, according to the authors.

However, of particular concern is the fact that only 11.8% of patients acquire specific SARS-CoV Abs in the early period after recovery at day 7, not reaching 100% until day 90, which highlights the importance of the detection of antibody titers for convalescent COVID-19 patients, according to the authors. “Otherwise, these patients with low titers of antibodies may not be efficient for the clearance of SARS-CoV-2.”

The authors also cited a recent study that showed how neutralizing antibody from a convalescent SARS patient could block the SARS-CoV-2 from entering into target cells in vitro, and suggested that previous experimental SARS-CoV vaccines and neutralizing antibodies could provide novel preventive and therapeutic options for COVID-19.

“These experiences from SARS-CoV are expected to have some implications for the treatment, management and surveillance of SARS-CoV-2 patients,” the authors concluded.

mlesney@mdedge.com

SOURCE: Lin Q et al. J Microbiol Immunol Infect. 2020 Mar 25. https://doi.org/10.1016/j.jmii.2020.03.015.

Prescribing liraglutide plus lifestyle therapy for adolescents with obesity resulted in greater weight loss and greater reduction in body mass index, compared with those prescribed lifestyle therapy alone, according to findings from a new study published in The New England Journal of Medicine.

Liraglutide with lifestyle therapy also “compared favorably in terms of [body mass index] reduction,” compared with other pediatric weight-management programs in the United States and with use of orlistat, wrote Aaron S. Kelly, PhD, of the University of Minnesota, Minneapolis, and colleagues. The study abstract was presented during a virtual news conference held by The Endocrine Society. It had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

The study included adolescents aged 12-17 years, who had obesity (BMI, ≥30 kg/m²) and had responded poorly to recommendations involving lifestyle therapy only, as judged by the site investigator and documented in the participant’s medical records. The adolescents participated at one of five sites in Belgium, Mexico, Russia, Sweden, and the United States.

In the randomized, controlled, double-blind trial, 125 participants received 3 mg liraglutide, and 126 received placebo for 56 weeks, during which both groups received lifestyle therapy, “defined as counseling about healthy nutrition and physical activity for weight loss,” the authors wrote.

After 12-weeks of run-in, the treatment period lasted 56 weeks, with a follow-up 26 weeks after treatment ended. The liraglutide group retained 80.8% of its participants, and the placebo group, 79.4%.

At week 56, there were no significant differences between the groups in blood pressure, fasting lipids, fasting plasma glucose, or hemoglobin A_1c, the authors noted.

However, in the liraglutide group, 43.3% of participants lost at least 5% of their BMI, compared with 18.7% in the control group. Similarly, 26.1% of those in the liraglutide group had a BMI reduction of at least 10%, compared with 8.1% in the control group.

Participants in the liraglutide group also saw a greater reduction in BMI, compared with those in the placebo group (estimated difference, 4.64 percentage points), and those taking liraglutide lost 9.9 pounds (4.5 kg) more than those receiving placebo – a relative reduction of 5%. The authors noted that a weight loss of 3%-5% “significantly improves some health-related outcomes in adults.”

In addition, the liraglutide group had a BMI standard-deviation score that was 0.22 lower than that in the placebo group (P = .002), but after the participants discontinued with the trial, “a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (0.15),” the authors reported.

“Although evidence in children is limited, a change in BMI standard-deviation score of at least 0.20 has been suggested to be clinically meaningful,” they wrote. “Some studies indicate that even temporary weight loss may have long-term benefits, but the extent to which this applies in adolescents and the extent to which long-term adherence to pharmacotherapy can be expected are unknown.”

The researchers added that the reduction in standard-deviation score seen in this study, of 0.22, was a bigger reduction than that seen in lifestyle therapy trials from the U.S. Preventive Services Task Force and from an overview of six Cochrane reviews. Their trial also, however, had a fairly high adherence rate, over 80%.

No notable differences in cardiometabolic markers or in quality of life showed up between the liraglutide and placebo groups. The heterogeneous treatment response in this and past studies suggests the need for future trials to “characterize predictors of treatment response to identify patients who would benefit the most from treatment,” the authors wrote.

About twice as many participants taking liraglutide experienced gastrointestinal adverse events compared with those receiving placebo (64.8% vs. 36.5%, respectively). Those symptoms, a known side effect of this drug type, included nausea, vomiting, and diarrhea and occurred primarily during escalation of the drug dose before then dropping in frequency. Still, the authors note that the high rate of gastrointestinal effects “suggests that this treatment may not be suitable for all patients.”

None of the adolescents receiving the placebo stopped treatment, but 10.4% of those taking liraglutide discontinued. One participant in the liraglutide group died by suicide, but the death was determined to be unrelated to the therapy.

Although the 0.22 reduction in the BMI standard-deviation score was for the intent-to-treat population, the authors calculated that the difference would have been 0.26 “if all participants had adhered to the treatment throughout the trial.”

Novo Nordisk funded the research. Several of the authors reported that they are employees of the company.

The abstract will also be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will ost ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

Source: Kelly AS et al. NEJM. 2020 Mar 31. doi: 10.1056/NEJMoa1916038.

Prescribing liraglutide plus lifestyle therapy for adolescents with obesity resulted in greater weight loss and greater reduction in body mass index, compared with those prescribed lifestyle therapy alone, according to findings from a new study published in The New England Journal of Medicine.

Liraglutide with lifestyle therapy also “compared favorably in terms of [body mass index] reduction,” compared with other pediatric weight-management programs in the United States and with use of orlistat, wrote Aaron S. Kelly, PhD, of the University of Minnesota, Minneapolis, and colleagues. The study abstract was presented during a virtual news conference held by The Endocrine Society. It had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

The study included adolescents aged 12-17 years, who had obesity (BMI, ≥30 kg/m²) and had responded poorly to recommendations involving lifestyle therapy only, as judged by the site investigator and documented in the participant’s medical records. The adolescents participated at one of five sites in Belgium, Mexico, Russia, Sweden, and the United States.

In the randomized, controlled, double-blind trial, 125 participants received 3 mg liraglutide, and 126 received placebo for 56 weeks, during which both groups received lifestyle therapy, “defined as counseling about healthy nutrition and physical activity for weight loss,” the authors wrote.

After 12-weeks of run-in, the treatment period lasted 56 weeks, with a follow-up 26 weeks after treatment ended. The liraglutide group retained 80.8% of its participants, and the placebo group, 79.4%.

At week 56, there were no significant differences between the groups in blood pressure, fasting lipids, fasting plasma glucose, or hemoglobin A_1c, the authors noted.

However, in the liraglutide group, 43.3% of participants lost at least 5% of their BMI, compared with 18.7% in the control group. Similarly, 26.1% of those in the liraglutide group had a BMI reduction of at least 10%, compared with 8.1% in the control group.

Participants in the liraglutide group also saw a greater reduction in BMI, compared with those in the placebo group (estimated difference, 4.64 percentage points), and those taking liraglutide lost 9.9 pounds (4.5 kg) more than those receiving placebo – a relative reduction of 5%. The authors noted that a weight loss of 3%-5% “significantly improves some health-related outcomes in adults.”

In addition, the liraglutide group had a BMI standard-deviation score that was 0.22 lower than that in the placebo group (P = .002), but after the participants discontinued with the trial, “a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (0.15),” the authors reported.

“Although evidence in children is limited, a change in BMI standard-deviation score of at least 0.20 has been suggested to be clinically meaningful,” they wrote. “Some studies indicate that even temporary weight loss may have long-term benefits, but the extent to which this applies in adolescents and the extent to which long-term adherence to pharmacotherapy can be expected are unknown.”

The researchers added that the reduction in standard-deviation score seen in this study, of 0.22, was a bigger reduction than that seen in lifestyle therapy trials from the U.S. Preventive Services Task Force and from an overview of six Cochrane reviews. Their trial also, however, had a fairly high adherence rate, over 80%.

No notable differences in cardiometabolic markers or in quality of life showed up between the liraglutide and placebo groups. The heterogeneous treatment response in this and past studies suggests the need for future trials to “characterize predictors of treatment response to identify patients who would benefit the most from treatment,” the authors wrote.

About twice as many participants taking liraglutide experienced gastrointestinal adverse events compared with those receiving placebo (64.8% vs. 36.5%, respectively). Those symptoms, a known side effect of this drug type, included nausea, vomiting, and diarrhea and occurred primarily during escalation of the drug dose before then dropping in frequency. Still, the authors note that the high rate of gastrointestinal effects “suggests that this treatment may not be suitable for all patients.”

None of the adolescents receiving the placebo stopped treatment, but 10.4% of those taking liraglutide discontinued. One participant in the liraglutide group died by suicide, but the death was determined to be unrelated to the therapy.

Although the 0.22 reduction in the BMI standard-deviation score was for the intent-to-treat population, the authors calculated that the difference would have been 0.26 “if all participants had adhered to the treatment throughout the trial.”

Novo Nordisk funded the research. Several of the authors reported that they are employees of the company.

The abstract will also be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will ost ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

Source: Kelly AS et al. NEJM. 2020 Mar 31. doi: 10.1056/NEJMoa1916038.

Prescribing liraglutide plus lifestyle therapy for adolescents with obesity resulted in greater weight loss and greater reduction in body mass index, compared with those prescribed lifestyle therapy alone, according to findings from a new study published in The New England Journal of Medicine.

Liraglutide with lifestyle therapy also “compared favorably in terms of [body mass index] reduction,” compared with other pediatric weight-management programs in the United States and with use of orlistat, wrote Aaron S. Kelly, PhD, of the University of Minnesota, Minneapolis, and colleagues. The study abstract was presented during a virtual news conference held by The Endocrine Society. It had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

The study included adolescents aged 12-17 years, who had obesity (BMI, ≥30 kg/m²) and had responded poorly to recommendations involving lifestyle therapy only, as judged by the site investigator and documented in the participant’s medical records. The adolescents participated at one of five sites in Belgium, Mexico, Russia, Sweden, and the United States.

In the randomized, controlled, double-blind trial, 125 participants received 3 mg liraglutide, and 126 received placebo for 56 weeks, during which both groups received lifestyle therapy, “defined as counseling about healthy nutrition and physical activity for weight loss,” the authors wrote.

After 12-weeks of run-in, the treatment period lasted 56 weeks, with a follow-up 26 weeks after treatment ended. The liraglutide group retained 80.8% of its participants, and the placebo group, 79.4%.

At week 56, there were no significant differences between the groups in blood pressure, fasting lipids, fasting plasma glucose, or hemoglobin A_1c, the authors noted.

However, in the liraglutide group, 43.3% of participants lost at least 5% of their BMI, compared with 18.7% in the control group. Similarly, 26.1% of those in the liraglutide group had a BMI reduction of at least 10%, compared with 8.1% in the control group.

Participants in the liraglutide group also saw a greater reduction in BMI, compared with those in the placebo group (estimated difference, 4.64 percentage points), and those taking liraglutide lost 9.9 pounds (4.5 kg) more than those receiving placebo – a relative reduction of 5%. The authors noted that a weight loss of 3%-5% “significantly improves some health-related outcomes in adults.”

In addition, the liraglutide group had a BMI standard-deviation score that was 0.22 lower than that in the placebo group (P = .002), but after the participants discontinued with the trial, “a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (0.15),” the authors reported.

“Although evidence in children is limited, a change in BMI standard-deviation score of at least 0.20 has been suggested to be clinically meaningful,” they wrote. “Some studies indicate that even temporary weight loss may have long-term benefits, but the extent to which this applies in adolescents and the extent to which long-term adherence to pharmacotherapy can be expected are unknown.”

The researchers added that the reduction in standard-deviation score seen in this study, of 0.22, was a bigger reduction than that seen in lifestyle therapy trials from the U.S. Preventive Services Task Force and from an overview of six Cochrane reviews. Their trial also, however, had a fairly high adherence rate, over 80%.

No notable differences in cardiometabolic markers or in quality of life showed up between the liraglutide and placebo groups. The heterogeneous treatment response in this and past studies suggests the need for future trials to “characterize predictors of treatment response to identify patients who would benefit the most from treatment,” the authors wrote.

About twice as many participants taking liraglutide experienced gastrointestinal adverse events compared with those receiving placebo (64.8% vs. 36.5%, respectively). Those symptoms, a known side effect of this drug type, included nausea, vomiting, and diarrhea and occurred primarily during escalation of the drug dose before then dropping in frequency. Still, the authors note that the high rate of gastrointestinal effects “suggests that this treatment may not be suitable for all patients.”

None of the adolescents receiving the placebo stopped treatment, but 10.4% of those taking liraglutide discontinued. One participant in the liraglutide group died by suicide, but the death was determined to be unrelated to the therapy.

Although the 0.22 reduction in the BMI standard-deviation score was for the intent-to-treat population, the authors calculated that the difference would have been 0.26 “if all participants had adhered to the treatment throughout the trial.”

Novo Nordisk funded the research. Several of the authors reported that they are employees of the company.

The abstract will also be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will ost ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.

Source: Kelly AS et al. NEJM. 2020 Mar 31. doi: 10.1056/NEJMoa1916038.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A controversial study led by Didier Raoult, MD, PhD, on the combination of hydroxychloroquine and azithromycin in patients with COVID-19 was published March 20. The latest results from the same Marseille team, which involve 80 patients, were reported on March 27.

The investigators report a significant reduction in the viral load (83% patients had negative results on quantitative polymerase chain reaction testing at day 7, and 93% had negative results on day 8). There was a “clinical improvement compared to the natural progression.” One death occurred, and three patients were transferred to intensive care units.

If the data seem encouraging, the lack of a control arm in the study leaves clinicians perplexed, however.

Benjamin Davido, MD, an infectious disease specialist at Raymond-Poincaré Hospital in Garches, Paris, spoke in an interview about the implications of these new results.
 

What do you think about the new results presented by Prof. Raoult’s team? Do they confirm the effectiveness of hydroxychloroquine?

These results are complementary [to the original results] but don’t offer any new information or new statistical evidence. They are absolutely superimposable and say overall that, between 5 and 7 days [of treatment], very few patients shed the virus. But that is not the question that everyone is asking.

Even if we don’t necessarily have to conduct a randomized study, we should at least compare the treatment, either against another therapy – which could be hydroxychloroquine monotherapy, or just standard of care. It needed an authentic control arm.

To recruit 80 patients so quickly, the researchers probably took people with essentially ambulatory forms of the disease (there was a call for screening in the south of France) – therefore, by definition, less severe cases.

But to describe such a population of patients as going home and saying, “There were very few hospitalizations and it is going well,” does not in any way prove that the treatment reduces hospitalizations.
 

The argument for not having a control arm in this study was that it would be unethical. What do you think?

I agree with this argument when it comes to patients presenting with risk factors or who are starting to develop pneumonia.

But I don’t think this is the case at the beginning of the illness. Of course, you don’t want to wait to have severe disease or for the patient to be in intensive care to start treatment. In these cases, it is indeed very difficult to find a control arm.
 

In the ongoing Discovery trial, which involves more than 3,000 patients in Europe, including 800 in France, the patients have severe disease, and there are five treatment arms. Moreover, hydroxychloroquine is given without azithromycin. What do you think of this?

I think it’s a mistake. It will not answer the question of the effectiveness of hydroxychloroquine in COVID-19, especially as they’re not studying azithromycin in a situation where the compound seems necessary for the effectiveness of the treatment.

In addition, Discovery reinforces the notion of studying Kaletra [lopinavir/ritonavir, AbbVie] again, while Chinese researchers have shown that it does not work, the argument being that Kaletra was given too late (N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282). Therefore, if we make the same mistakes from a methodological point of view, we will end up with negative results.
 

What should have been done in the Marseille study?

The question is: Are there more or fewer hospitalizations when we treat a homogeneous population straight away?

The answer could be very clear, as a control already exists! They are the patients that flow into our hospitals every day – ironically, these 80 patients [in the latest results, presented March 27] could be among the 80% who had a form similar to nasopharyngitis and resolved.

In this illness, we know that there are 80% spontaneous recoveries and 20% so-called severe forms. Therefore, with 80 patients, we are very underpowered. The cohort is too small for a disease in which 80% of the evolution is benign.

It would take 1,000 patients, and then, even without a control arm, we would have an answer.

On March 26, Didier Raoult’s team also announced having already treated 700 patients with hydroxychloroquine, with only one death. Therefore, if this cohort increases significantly in Marseille and we see that, on the map, there are fewer issues with patient flow and saturation in Marseille and that there are fewer patients in intensive care, you will have to wonder about the effect of hydroxychloroquine.

We will find out very quickly. If it really works, and they treat all the patients presenting at Timone Hospital, we will soon have the answer. It will be a real-life study.
 

What are the other studies on hydroxychloroquine that could give us answers?

There was a Chinese study that did not show a difference in effectiveness between hydroxychloroquine and placebo, but that was, again, conducted in only around 20 patients (J Zhejiang Univ (Med Sci). 2020. doi: 10.3785/j.issn.1008-9292.2020.03.03). This cohort is too small and tells us nothing; it cannot show anything. We must wait for the results of larger trials being conducted in China.

It surprises me that, today, we still do not have Italian data on the use of chloroquine-type drugs ... perhaps because they have a care pathway that means there is no outpatient treatment and that they arrive already with severe disease. The Italian recommendations nevertheless indicate the use of hydroxychloroquine.

I also wonder about the lack of studies of cohorts where, in retrospect, we could have followed people previously treated with hydroxychloroquine for chronic diseases (e.g., rheumatoid arthritis, lupus, etc.). Or we could identify all those patients on the health insurance system who had prescriptions.

That is how we discovered the AIDS epidemic in San Francisco: There was an increase in the number of prescriptions for trimethoprim/sulfamethoxazole (Bactrim) that corresponded to a population subtype (homosexual), and we realized that it was for a disease that resembled pneumocystosis. We discovered that via the drug!

If hydroxychloroquine is effective, it is enough to look at people who took it before the epidemic and see how they fared. And there, we do not need a control arm. This could give us some direction. The March 26 decree of the new Véran Law states that community pharmacies can dispense to patients with a previous prescription, so we can find these individuals.
 

Do you think that the lack of, or difficulty in setting up, studies on hydroxychloroquine in France is linked to decisions that are more political than scientific?

Perhaps the contaminated blood scandal still casts a shadow in France, and there is a great deal of anxiety over the fact that we are already in a crisis, and we do not want a second one. I can understand that.

However, just a week ago, access to this drug (and others with market approval that have been on the market for several years) was blocked in hospital central pharmacies, while we are the medical specialists with the authorization! It was unacceptable.

It was sorted out 48 hours ago: hydroxychloroquine is now available in the hospital, and to my knowledge, we no longer have a problem obtaining it.

It took time to alleviate doubts over the major health risks with this drug. [Officials] seemed almost like amateurs in their hesitation; I think they lacked foresight. We have forgotten that the treatment advocated by Prof. Didier Raoult is not chloroquine but rather hydroxychloroquine, and we know that the adverse effects are less [with hydroxychloroquine] than with chloroquine.
 

You yourself have treated patients with chloroquine, despite the risk for toxicity highlighted by some.

Initially, when we first started treating patients, we thought of chloroquine because we did not have data on hydroxychloroquine, only Chinese data with chloroquine. We therefore prescribed chloroquine several days before prescribing hydroxychloroquine.

The question of the toxicity of chloroquine was not unjustified, but I think we took far too much time to decide on the toxicity of hydroxychloroquine. Is [the latter] political? I don’t know. It was widely publicized, which amazes me for a drug that is already available.

On the other hand, everyone was talking at the same time about the toxicity of NSAIDs. ... One has the impression it was to create a diversion. I think there were double standards at play and a scapegoat was needed to gain some time and ask questions.

What is sure is that it is probably not for financial reasons, as hydroxychloroquine costs nothing. That’s to say there were probably pharmaceutical issues at stake for possible competitors of hydroxychloroquine; I do not want to get into this debate, and it doesn’t matter, as long as we have an answer.

Today, the only thing we have advanced on is the “safety” of hydroxychloroquine, the low risk to the general population. ... On the other hand, we have still not made any progress on the evidence of efficacy, compared with other treatments.

Personally, I really believe in hydroxychloroquine. It would nevertheless be a shame to think we had found the fountain of youth and realize, in 4 weeks, that we have the same number of deaths. That is the problem. I hope that we will soon have solid data so we do not waste time focusing solely on hydroxychloroquine.
 

What are the other avenues of research that grab your attention?

The Discovery trial will probably give an answer on remdesivir [GS-5734, Gilead], which is a direct antiviral and could be interesting. But there are other studies being conducted currently in China.

There is also favipiravir [T-705, Avigan, Toyama Chemical], which is an anti-influenza drug used in Japan, which could explain, in part, the control of the epidemic in that country. There are effects in vitro on coronavirus. But it is not at all studied in France at the moment. Therefore, we should not focus exclusively on hydroxychloroquine; we must keep a close eye on other molecules, in particular the “old” drugs, like this antiviral.

The study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency, under the Investissements d’avenir program, Région Provence Alpes Côte d’Azur, and European funding FEDER PRIMI. The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

In a physician WhatsApp group, a doctor posted he had fever of 101 °F and muscle ache, gently confessing that it felt like his typical “man flu” which heals with rest and scotch. Nevertheless, he worried that he had coronavirus. When the reverse transcription polymerase chain reaction (RT-PCR) for the virus on his nasal swab came back negative, he jubilantly announced his relief.

Like Twitter, in WhatsApp emotions quickly outstrip facts. After he received a flurry of cheerful emojis, I ruined the party, advising that, despite the negative test, he assume he’s infected and quarantine for 2 weeks, with a bottle of scotch.

It’s conventional wisdom that the secret sauce to fighting the pandemic is testing for the virus. To gauge the breadth of the response against the pandemic we must know who and how many are infected. The depth of the response will be different if 25% of the population is infected than 1%. Testing is the third way, rejecting the false choice between death and economic depression. Without testing, strategy is faith based.

Our reliance on testing has clinical precedence – scarcely any decision in medicine is made without laboratory tests or imaging. Testing is as ingrained in medicine as the GPS is in driving. We use it even when we know our way home. But tests impose a question – what’ll you do differently if the test is negative?

That depends on the test’s performance and the consequences of being wrong. Though coronavirus damages the lungs with reckless abandon, it’s oddly a shy virus. In many patients, it takes 3-4 swabs to get a positive RT-PCR. The Chinese ophthalmologist, Li Wenliang, who originally sounded the alarm about coronavirus, had several negative tests. He died from the infection.

In one Chinese study, the sensitivity of RT-PCR – that’s the proportion of the infected who test positive – was around 70%. To put this in perspective, of 1,000 people infected with coronavirus, 700 will test positive but 300 will test negative.

Is this good enough?

Three hundred “false-negative” people may believe they’re not contagious because they got a clean chit and could infect others. False negatives could undo the hard work of containment.

Surely, better an imperfect test than no test. Isn’t flying with partially accurate weather information safer than no information? Here, aviation analogies aren’t helpful. Better to think of a forest fire.

Imagine only 80% of a burning forest is doused because it’s mistakenly believed that 20% of the forest isn’t burning because we can’t see it burning. It must be extinguished before it relights the whole forest, but to douse it you must know it’s burning – a Catch-22. That “20% of the forest” is a false negative – it’s burning but you think it’s not burning.

Because coronavirus isn’t planning to leave in a hurry and long-term lockdown has grave economic consequences, testing may enable precision quarantining of people, communities, and cities. Rather than applying a one-size-fits-all lockdown on the whole nation, testing could tell us who can work and who should stay home. Why should Austin, if it has a low prevalence of infection, shut shop just because of New York City’s high prevalence?

Testing enables us to think globally but act locally. But it’s the asymptomatic people who drive the epidemic. To emphasize – asymptomatics are yet to have symptoms such as cough and fever. They’re feeling well and don’t know they’ve been colonized by the virus. Theoretically, if we test en masse we can find asymptomatics. If only those who test positive are quarantined, the rest can have some breathing space. Will this approach work?

RT-PCR’s sensitivity, which is low in early illness, is even lower in asymptomatics, likely because of lower viral load, which means even more false negatives. The virus’s average incubation time of 5 days is enough time for false negative asymptomatics – remember they resemble the uninfected – to visit Disney World and infect another four.

Whether false negatives behave like tinder or a controllable fire will determine the testing strategy’s success. The net contagiousness of false negatives depends how many there are, which depends on how many are infected. To know how many are infected we need to test. Or, to know whether to believe a negative test in any person we must test widely – another Catch-22.

Maybe we need a bigger test.

Chest CT is an alternative. It’s rapid – takes less than an hour whereas RT-PCR can take over a day to report. In one study CT had a sensitivity of 97% in symptomatic patients and was often positive before RT-PCR. But there are caveats.

The real sensitivity of CT is likely much lower than 97% because the study has biases which inflate performance. CT, like RT-PCR, has a low sensitivity in early illness and even lower sensitivity in asymptomatic carriers for the same reason – lower viral load. Furthermore, CT has to be disinfected to prevent spread, which limits its access for other patients.

Coronavirus’s signature on CT – white patches in lungs, known as ground glass opacities – doesn’t have the uniqueness of the Mark of Zorro, and looks like lung injury from other rogue actors, which means we can mistake other serious conditions for coronavirus. Imagine hyenas in wolf’s clothing.

No test is perfect. We still use imaging despite its imperfections. But, let’s ask: What would you do differently if the test is negative and you have mild symptoms of cough and fever? Should you not self-isolate? What if you’re falsely negative and still contagious? If the advice dispensed whether the test is positive or negative is the same – i.e. quarantine for 2 weeks – what’s the test’s value?

Perhaps people will more likely comply with voluntary quarantine if they know they’re infected. Information can nudge behavior. But the logical corollary is that to comply with social distancing you need to be tested. People flocking to CT scans to affirm they’re not infected could infect those hitherto uninfected. A pandemic is no time to test nudge theories.

Does that mean testing has no value? Testing is valuable in managing populations. To individuals, the results must be framed wisely, such as by advising those who test positive to quarantine because “you’re infected” and those who test negative to keep social distancing because “you could still be infected.”

Even when policy goals are uniform, messaging can be oppositional. “Get yourself tested now” contradicts “you must hunker down now.” When messages contradict, one must choose which message to amplify.

The calculus of testing can change with new tests such as antibodies. The value of testing depends also on what isolation entails. A couple of weeks watching Netflix on your couch isn’t a big ask. If quarantine means being detained in an isolation center fenced by barbed wires, the cost of frivolous quarantining is higher and testing becomes more valuable.

I knew the doctor with the negative RT-PCR well. He’s heroically nonchalant about his wellbeing, an endearing quality that’s a liability in a contagion. In no time he’d be back in the hospital; or helping his elderly parents with grocery. Not all false negatives are equal. False-negative doctors could infect not just their patients but their colleagues, leaving fewer firefighters to fight fires.

It is better to mistake the man flu for coronavirus than coronavirus for the man flu. All he has to do is hunker down, which is what we should all be doing as much as we can.

Dr. Jha is a contributing editor to The Health Care Blog, where this article first appeared. He can be reached @RogueRad.

This article appeared on Medscape.com.

SAN DIEGO – On the days family physician Nick Yphantides, MD, announces updates on the COVID-19 epidemic to San Diego County residents, he can’t help but think about his late father.

In June of 2009, 75-year-old George Yphantides, a Steinway-trained piano technician who lived in Escondido, Calif., became the third person in the United States to die from complications of the pandemic H1N1 swine flu – just days before a vaccine became available.

“I loved my dad,” Dr. Yphantides, who has been San Diego County’s Chief Medical Officer since the year of his father’s death, said in an interview. “So, when you take a step back and take into consideration my sense of purpose in serving the 3.3 million residents of San Diego County, my passion based on my personal Christian faith, and my activation in terms of what happened to my dad, I have such a storm of internal sense of urgency right now.”

San Diego County and public health officials got experience with COVID-19 in advance of the country’s widely documented cases of community-based transmission. Around 9 pm on Jan. 31, 2020 – the Friday of Super Bowl weekend – Dr. Yphantides answered a phone call from Eric C. McDonald, MD, the county’s medical director of epidemiology. Dr. McDonald informed him that in a few days, a plane full of American citizens traveling from Wuhan, China, would be landing at Marine Corp Air Station Miramar in San Diego for a 2-week quarantine and that the task of providing medical support to any affected individuals fell on county officials.

“I will never forget that phone call,” he said. “We did have two positive cases. What we experienced with those evacuees was amazing surge preparation, and without exaggeration, I have worked 18-20 hours a day since that day.”

Fast forward to March 31, 2020, the county’s confirmed COVID-19 caseload had grown to 734, up 131 from the day before. As of the final day of March, nine people have died, with an age range between 25 and 87 years. Of confirmed cases, 61% are between the ages of 20 and 49, 43% are female, 19% have required hospitalization, 7% have required admission to intensive care, and the mortality rate has been 1.2%. Data currently show optimal proactive hospital capacity.

In the opinion of Dr. Yphantides, the 734 COVID-19 cases represent a tip of the iceberg. “How big is that iceberg? I can’t tell you yet,” he said.

Courtesy Tim McClain

Instead of being fearful or apprehensive about this uncertainty, Dr. Yphantides said he is “energized.”

"I see this as the Super Bowl of public health,” he exclaimed.

At least some of Dr. Yphantides’ vigor seems to be fueled by his pride in his team of professionals who have been helping him respond to the surge of COVID-19 cases.

As the county’s CMO, Dr. Yphantides serves as the liaison for the entire Emergency Medical System, the entire local health care delivery system, the entire physician and medical society network, the payor system, and the proportion of the area population using Medi-Cal.

Dr. Yphantides, who attended medical school at the University of California, San Diego, said that, compared with other regions of the country, San Diego County has made “tremendous progress” in overcoming many chronic lifestyle illnesses. For example, cardiovascular disease is no longer the number one cause of death in the county; it’s bookended by cancer and Alzheimer’s disease.

“In the context of the COVID-19 response, [the county’s health care team established] an entire incident command system in our emergency operations center. Our emergency operations center is activated to the top level,” he said.

Dr. Yphantides shares public communication efforts with Dr. McDonald and Wilma J. Wooten, MD, the county’s public health officer. The San Diego County CMO also engages with policymakers, including the board of supervisors, local mayors, state legislators, and national legislators.

“Because of the relational trust capital that I have in this community, I get pulled into unexpected rooms of discussion,” he said. This included meeting with top executives from the San Diego Padres in early March, putting them on notice that the 2020 Major League Baseball season would likely be postponed. (This was officially announced on March 16.)

“We have made some decisions that have devastated some people economically. Talk about flipping the switch. We are living and making history every day. It is unbelievable,” he said.

“San Diego is a more aged population compared to many other parts of the country. ... [Part] of the reason why I’m so frantically doing everything I can to prepare, to batten down the hatches, and to optimize our health care delivery system is because we have a population that collectively is more at risk [for more serious complications from COVID-19]. A lot of what drives me is advocacy,” Dr. Yphantides noted.
 

A colleague’s perspective

Kristi L. Koenig, MD, medical director of emergency medical services for the County of San Diego, characterized Dr. Yphantides’ management style as collaborative. “Under his leadership, we have the perspective of ‘just focus on patient care, get it done, be creative, work together as a team,’ ” said Dr. Koenig, who coedited the textbook, “Koenig and Schultz’s Disaster Medicine: Comprehensive Principles and Practices” (Cambridge University Press, 2016). “He’s decisive and he’s responsive. You don’t have to wait a long time to get a decision, which is very important right now because this is so fast moving.”

Dr. Koenig, who has worked with Dr. Yphantides for 3 years, said that she routinely feeds him information that might help the team navigate its response to COVID-19. “For example, if I see an idea for how to get more [personal protective equipment] and feed it to him, he might have a contact somewhere in a factory that could make the PPE,” she said. “We work together by my reminding him to keep it within the incident command system structure, so that we can coordinate all the resources and not duplicate efforts.”

He uses his personal connections in a way to implement ideas that are beneficial to the overall goal of decreasing morbidity and mortality,” Dr. Koenig added.
 

Predictions for San Diego County

Dr. Yphantides said he considers San Diego to still be in the calm before the storm and that he is working hard to “board up his community.” The county CMO is also trying to prepare the health care delivery system to optimize its capacity, of doing interventions with hopes of lowering the curve and enhancing the capacity, he said.

When the storm hits, “it’s going be brutal, because we’re going to lose life,” Dr. Yphantides said.

“I am praying that maybe by some of our efforts, instead of a Category 5 storm, it’ll be a Category 3 storm,” he remarked.
 

The future of health care

Dr. Yphantides views the COVID-19 pandemic as “an absolute game-changer” in terms of what the future of health care delivery will look like in the United States. “Whether the right word is the ‘Amazonification’ of health care, or the ‘Uberization’ of health care, I don’t know, but the essence of how we deliver care is radically being transformed literally before our eyes,” he said. “I would encourage my colleagues to embrace that” and take care of their people by doing whatever it takes under this unprecedented paradigm.

Meanwhile, Dr. Yphantides braces for a potential surge of COVID-19 cases in San Diego County in the coming weeks. He honors the memory of his dad, and he expresses thanks for his mom, who cares for his two teenaged daughters while he helps steward the region’s response to the pandemic.

“Without my mom I could not function in the way that I’m currently functioning,” he said. “So, when you add all of those factors up, and wrap it with a bowtie of sincere love and passion for my community, there’s a fire that’s burning inside of me right now.”
 

dbrunk@mdedge.com

SAN DIEGO – On the days family physician Nick Yphantides, MD, announces updates on the COVID-19 epidemic to San Diego County residents, he can’t help but think about his late father.

In June of 2009, 75-year-old George Yphantides, a Steinway-trained piano technician who lived in Escondido, Calif., became the third person in the United States to die from complications of the pandemic H1N1 swine flu – just days before a vaccine became available.

“I loved my dad,” Dr. Yphantides, who has been San Diego County’s Chief Medical Officer since the year of his father’s death, said in an interview. “So, when you take a step back and take into consideration my sense of purpose in serving the 3.3 million residents of San Diego County, my passion based on my personal Christian faith, and my activation in terms of what happened to my dad, I have such a storm of internal sense of urgency right now.”

San Diego County and public health officials got experience with COVID-19 in advance of the country’s widely documented cases of community-based transmission. Around 9 pm on Jan. 31, 2020 – the Friday of Super Bowl weekend – Dr. Yphantides answered a phone call from Eric C. McDonald, MD, the county’s medical director of epidemiology. Dr. McDonald informed him that in a few days, a plane full of American citizens traveling from Wuhan, China, would be landing at Marine Corp Air Station Miramar in San Diego for a 2-week quarantine and that the task of providing medical support to any affected individuals fell on county officials.

“I will never forget that phone call,” he said. “We did have two positive cases. What we experienced with those evacuees was amazing surge preparation, and without exaggeration, I have worked 18-20 hours a day since that day.”

Fast forward to March 31, 2020, the county’s confirmed COVID-19 caseload had grown to 734, up 131 from the day before. As of the final day of March, nine people have died, with an age range between 25 and 87 years. Of confirmed cases, 61% are between the ages of 20 and 49, 43% are female, 19% have required hospitalization, 7% have required admission to intensive care, and the mortality rate has been 1.2%. Data currently show optimal proactive hospital capacity.

In the opinion of Dr. Yphantides, the 734 COVID-19 cases represent a tip of the iceberg. “How big is that iceberg? I can’t tell you yet,” he said.

Courtesy Tim McClain

Instead of being fearful or apprehensive about this uncertainty, Dr. Yphantides said he is “energized.”

"I see this as the Super Bowl of public health,” he exclaimed.

At least some of Dr. Yphantides’ vigor seems to be fueled by his pride in his team of professionals who have been helping him respond to the surge of COVID-19 cases.

As the county’s CMO, Dr. Yphantides serves as the liaison for the entire Emergency Medical System, the entire local health care delivery system, the entire physician and medical society network, the payor system, and the proportion of the area population using Medi-Cal.

Dr. Yphantides, who attended medical school at the University of California, San Diego, said that, compared with other regions of the country, San Diego County has made “tremendous progress” in overcoming many chronic lifestyle illnesses. For example, cardiovascular disease is no longer the number one cause of death in the county; it’s bookended by cancer and Alzheimer’s disease.

“In the context of the COVID-19 response, [the county’s health care team established] an entire incident command system in our emergency operations center. Our emergency operations center is activated to the top level,” he said.

Dr. Yphantides shares public communication efforts with Dr. McDonald and Wilma J. Wooten, MD, the county’s public health officer. The San Diego County CMO also engages with policymakers, including the board of supervisors, local mayors, state legislators, and national legislators.

“Because of the relational trust capital that I have in this community, I get pulled into unexpected rooms of discussion,” he said. This included meeting with top executives from the San Diego Padres in early March, putting them on notice that the 2020 Major League Baseball season would likely be postponed. (This was officially announced on March 16.)

“We have made some decisions that have devastated some people economically. Talk about flipping the switch. We are living and making history every day. It is unbelievable,” he said.

“San Diego is a more aged population compared to many other parts of the country. ... [Part] of the reason why I’m so frantically doing everything I can to prepare, to batten down the hatches, and to optimize our health care delivery system is because we have a population that collectively is more at risk [for more serious complications from COVID-19]. A lot of what drives me is advocacy,” Dr. Yphantides noted.
 

A colleague’s perspective

Kristi L. Koenig, MD, medical director of emergency medical services for the County of San Diego, characterized Dr. Yphantides’ management style as collaborative. “Under his leadership, we have the perspective of ‘just focus on patient care, get it done, be creative, work together as a team,’ ” said Dr. Koenig, who coedited the textbook, “Koenig and Schultz’s Disaster Medicine: Comprehensive Principles and Practices” (Cambridge University Press, 2016). “He’s decisive and he’s responsive. You don’t have to wait a long time to get a decision, which is very important right now because this is so fast moving.”

Dr. Koenig, who has worked with Dr. Yphantides for 3 years, said that she routinely feeds him information that might help the team navigate its response to COVID-19. “For example, if I see an idea for how to get more [personal protective equipment] and feed it to him, he might have a contact somewhere in a factory that could make the PPE,” she said. “We work together by my reminding him to keep it within the incident command system structure, so that we can coordinate all the resources and not duplicate efforts.”

He uses his personal connections in a way to implement ideas that are beneficial to the overall goal of decreasing morbidity and mortality,” Dr. Koenig added.
 

Predictions for San Diego County

Dr. Yphantides said he considers San Diego to still be in the calm before the storm and that he is working hard to “board up his community.” The county CMO is also trying to prepare the health care delivery system to optimize its capacity, of doing interventions with hopes of lowering the curve and enhancing the capacity, he said.

When the storm hits, “it’s going be brutal, because we’re going to lose life,” Dr. Yphantides said.

“I am praying that maybe by some of our efforts, instead of a Category 5 storm, it’ll be a Category 3 storm,” he remarked.
 

The future of health care

Dr. Yphantides views the COVID-19 pandemic as “an absolute game-changer” in terms of what the future of health care delivery will look like in the United States. “Whether the right word is the ‘Amazonification’ of health care, or the ‘Uberization’ of health care, I don’t know, but the essence of how we deliver care is radically being transformed literally before our eyes,” he said. “I would encourage my colleagues to embrace that” and take care of their people by doing whatever it takes under this unprecedented paradigm.

Meanwhile, Dr. Yphantides braces for a potential surge of COVID-19 cases in San Diego County in the coming weeks. He honors the memory of his dad, and he expresses thanks for his mom, who cares for his two teenaged daughters while he helps steward the region’s response to the pandemic.

“Without my mom I could not function in the way that I’m currently functioning,” he said. “So, when you add all of those factors up, and wrap it with a bowtie of sincere love and passion for my community, there’s a fire that’s burning inside of me right now.”
 

dbrunk@mdedge.com

SAN DIEGO – On the days family physician Nick Yphantides, MD, announces updates on the COVID-19 epidemic to San Diego County residents, he can’t help but think about his late father.

In June of 2009, 75-year-old George Yphantides, a Steinway-trained piano technician who lived in Escondido, Calif., became the third person in the United States to die from complications of the pandemic H1N1 swine flu – just days before a vaccine became available.

“I loved my dad,” Dr. Yphantides, who has been San Diego County’s Chief Medical Officer since the year of his father’s death, said in an interview. “So, when you take a step back and take into consideration my sense of purpose in serving the 3.3 million residents of San Diego County, my passion based on my personal Christian faith, and my activation in terms of what happened to my dad, I have such a storm of internal sense of urgency right now.”

San Diego County and public health officials got experience with COVID-19 in advance of the country’s widely documented cases of community-based transmission. Around 9 pm on Jan. 31, 2020 – the Friday of Super Bowl weekend – Dr. Yphantides answered a phone call from Eric C. McDonald, MD, the county’s medical director of epidemiology. Dr. McDonald informed him that in a few days, a plane full of American citizens traveling from Wuhan, China, would be landing at Marine Corp Air Station Miramar in San Diego for a 2-week quarantine and that the task of providing medical support to any affected individuals fell on county officials.

“I will never forget that phone call,” he said. “We did have two positive cases. What we experienced with those evacuees was amazing surge preparation, and without exaggeration, I have worked 18-20 hours a day since that day.”

Fast forward to March 31, 2020, the county’s confirmed COVID-19 caseload had grown to 734, up 131 from the day before. As of the final day of March, nine people have died, with an age range between 25 and 87 years. Of confirmed cases, 61% are between the ages of 20 and 49, 43% are female, 19% have required hospitalization, 7% have required admission to intensive care, and the mortality rate has been 1.2%. Data currently show optimal proactive hospital capacity.

In the opinion of Dr. Yphantides, the 734 COVID-19 cases represent a tip of the iceberg. “How big is that iceberg? I can’t tell you yet,” he said.

Courtesy Tim McClain

Instead of being fearful or apprehensive about this uncertainty, Dr. Yphantides said he is “energized.”

"I see this as the Super Bowl of public health,” he exclaimed.

At least some of Dr. Yphantides’ vigor seems to be fueled by his pride in his team of professionals who have been helping him respond to the surge of COVID-19 cases.

As the county’s CMO, Dr. Yphantides serves as the liaison for the entire Emergency Medical System, the entire local health care delivery system, the entire physician and medical society network, the payor system, and the proportion of the area population using Medi-Cal.

Dr. Yphantides, who attended medical school at the University of California, San Diego, said that, compared with other regions of the country, San Diego County has made “tremendous progress” in overcoming many chronic lifestyle illnesses. For example, cardiovascular disease is no longer the number one cause of death in the county; it’s bookended by cancer and Alzheimer’s disease.

“In the context of the COVID-19 response, [the county’s health care team established] an entire incident command system in our emergency operations center. Our emergency operations center is activated to the top level,” he said.

Dr. Yphantides shares public communication efforts with Dr. McDonald and Wilma J. Wooten, MD, the county’s public health officer. The San Diego County CMO also engages with policymakers, including the board of supervisors, local mayors, state legislators, and national legislators.

“Because of the relational trust capital that I have in this community, I get pulled into unexpected rooms of discussion,” he said. This included meeting with top executives from the San Diego Padres in early March, putting them on notice that the 2020 Major League Baseball season would likely be postponed. (This was officially announced on March 16.)

“We have made some decisions that have devastated some people economically. Talk about flipping the switch. We are living and making history every day. It is unbelievable,” he said.

“San Diego is a more aged population compared to many other parts of the country. ... [Part] of the reason why I’m so frantically doing everything I can to prepare, to batten down the hatches, and to optimize our health care delivery system is because we have a population that collectively is more at risk [for more serious complications from COVID-19]. A lot of what drives me is advocacy,” Dr. Yphantides noted.
 

A colleague’s perspective

Kristi L. Koenig, MD, medical director of emergency medical services for the County of San Diego, characterized Dr. Yphantides’ management style as collaborative. “Under his leadership, we have the perspective of ‘just focus on patient care, get it done, be creative, work together as a team,’ ” said Dr. Koenig, who coedited the textbook, “Koenig and Schultz’s Disaster Medicine: Comprehensive Principles and Practices” (Cambridge University Press, 2016). “He’s decisive and he’s responsive. You don’t have to wait a long time to get a decision, which is very important right now because this is so fast moving.”

Dr. Koenig, who has worked with Dr. Yphantides for 3 years, said that she routinely feeds him information that might help the team navigate its response to COVID-19. “For example, if I see an idea for how to get more [personal protective equipment] and feed it to him, he might have a contact somewhere in a factory that could make the PPE,” she said. “We work together by my reminding him to keep it within the incident command system structure, so that we can coordinate all the resources and not duplicate efforts.”

He uses his personal connections in a way to implement ideas that are beneficial to the overall goal of decreasing morbidity and mortality,” Dr. Koenig added.
 

Predictions for San Diego County

Dr. Yphantides said he considers San Diego to still be in the calm before the storm and that he is working hard to “board up his community.” The county CMO is also trying to prepare the health care delivery system to optimize its capacity, of doing interventions with hopes of lowering the curve and enhancing the capacity, he said.

When the storm hits, “it’s going be brutal, because we’re going to lose life,” Dr. Yphantides said.

“I am praying that maybe by some of our efforts, instead of a Category 5 storm, it’ll be a Category 3 storm,” he remarked.
 

The future of health care

Dr. Yphantides views the COVID-19 pandemic as “an absolute game-changer” in terms of what the future of health care delivery will look like in the United States. “Whether the right word is the ‘Amazonification’ of health care, or the ‘Uberization’ of health care, I don’t know, but the essence of how we deliver care is radically being transformed literally before our eyes,” he said. “I would encourage my colleagues to embrace that” and take care of their people by doing whatever it takes under this unprecedented paradigm.

Meanwhile, Dr. Yphantides braces for a potential surge of COVID-19 cases in San Diego County in the coming weeks. He honors the memory of his dad, and he expresses thanks for his mom, who cares for his two teenaged daughters while he helps steward the region’s response to the pandemic.

“Without my mom I could not function in the way that I’m currently functioning,” he said. “So, when you add all of those factors up, and wrap it with a bowtie of sincere love and passion for my community, there’s a fire that’s burning inside of me right now.”
 

dbrunk@mdedge.com

Exposure during pregnancy to a specific per- and polyfluoroalkyl substance (PFAS), combined with a low cholesterol level, is linked to a heightened risk of abdominal and whole-body obesity in granddaughters, according to a new analysis of the Child Health and Development Studies, which have been ongoing since the 1960s.

Researchers directly measured levels of N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA) in blood samples from the grandmothers, which had been taken shortly after delivery, and then analyzed measures of obesity and other metabolic factors in their daughters at ages 30 years and 50 years, and their granddaughters at age 20.

PFASs are synthetic compounds commonly used as oil and water repellents; coatings for cookware, carpets, and textiles; and as firefighting foams. The compounds do not break down in the environment or the human body and accumulate over time. They are known to disrupt the endocrine system.

EtFOSAA is a metabolite of a raw material used in the manufacturing of packaging and paper products, and itself gets converted to perfluorooctane sulfonic acid (PFOS), which is extremely stable in the environment and within organisms, leading to bioaccumulation that has the potential to span generations, Barbara A. Cohn, PhD, director of child health and development studies at the Public Health Institute in Berkeley, Calif., said during a virtual press conference held by The Endocrine Society. The study was slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Abdominal obesity was defined as a waist circumference of more than 34.6 inches (88 cm), and whole-body obesity was defined as a body mass index of more than 30 kg/m². Findings from a previous study drawn from the same cohort showed that exposure to EtFOSAA, combined with high maternal cholesterol levels, was linked to increased risk of breast cancer in daughters.

“I want to emphasize that we don’t understand the mechanism, but we do know that this finding [from the current study], if it is confirmed, has implications for the current epidemic of obesity. Exposure to these compounds is very widespread, [having] started in the 1940s and 50s, and is consistent with the timing of the obesity epidemic,” said Dr. Cohn, during the virtual press conference.

Robert Sargis, MD, professor of endocrinology, diabetes, and metabolism at the University of Illinois at Chicago, said the mechanistic connection could be complex. “It’s a combination of the possibility that the chemicals themselves are passed down either through breast milk or across the placenta, or that the biological impact is somehow coded epigenetically, and then that epigenetic code is somehow passed on to subsequent generations,” he said in an interview. He was not associated with the research.

Dr. Cohn said her team is investigating both of those possibilities through analysis of the existing blood samples. “There are implications for PFAS clean-up if [these findings are] confirmed, and there’s an opportunity for setting up precautions for pregnant women on how they can try to avoid this contamination to [offset] a rekindling of this generational effect 60 years down the road,” Dr. Cohn added.

Daughters of the original participants (now grandmothers) were measured at an average age of 50, and the granddaughters, at an average of 20 (219 dyads, 657 women in total). Daughters also reported their weight at age 30, which was close to the mean age at which they had given birth. This allowed the researchers to control for obesity present during gestation of the granddaughters.

The researchers analyzed EtFOSAA, PFOS, and cholesterol levels from archived blood samples taken from grandmothers within 3 days of delivery. There was an association between EtFOSAA and self-reported obesity at age 30 in daughters, as well as measured abdominal, whole-body obesity, and blood pressure at age 20 in granddaughters, and all were modified by low cholesterol levels (25% interquartile) in grandmothers (P < .05).

In granddaughters, the combined risk of abdominal and whole-body obesity was 2.3-fold higher in those whose grandmothers were in the top 25% of EtFOSAA exposure, compared with those whose grandmothers were in the lowest 25% (95% confidence interval, 1.1-4.8). Those associations remained after adjustments for race, being overweight in early pregnancy (BMI, >25 kg/m²), and serum PFOS levels.

Although the weight of daughters did not affect the association between the granddaughters’ risk for obesity risk and EtFOSAA levels in grandmothers, it did predict high metabolic risk in granddaughters. That suggests that the burden may be building over generations. “Independently, their mothers themselves are heavier and fatter, and that heaviness of the mother is also a source of increasing body size for the granddaughter. We have a multiplying, very ugly situation that may be helping us to understand this really quick rise of obesity,” said Dr. Cohn.

She also emphasized that PFAS may not be the only culprit in fueling obesity. “Most of us believe that there is sufficient data in the animal studies and, now, growing data in human studies, to suggest that these obesogens exist and are contributing to the health problems that are going to be following the obesity epidemic in young people now.”

Dr. Cohn noted that the study is limited by its lack of a control group.

The California Breast Research Foundation, the National Institutes of Health, and the State of California funded the study. Dr. Cohn and Dr. Sargis reported no relevant financial disclosures.

The study abstract will be published in the Journal of the Endocrine Society. In addition to a series of news conferences held on March 30-31, the society will host ENDO Online 2020 during June 8-22 with programming for clinicians and researchers.
 

SOURCE: Cohn B et al. ENDO 2020, Abstract LB132.

Exposure during pregnancy to a specific per- and polyfluoroalkyl substance (PFAS), combined with a low cholesterol level, is linked to a heightened risk of abdominal and whole-body obesity in granddaughters, according to a new analysis of the Child Health and Development Studies, which have been ongoing since the 1960s.

Researchers directly measured levels of N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA) in blood samples from the grandmothers, which had been taken shortly after delivery, and then analyzed measures of obesity and other metabolic factors in their daughters at ages 30 years and 50 years, and their granddaughters at age 20.

PFASs are synthetic compounds commonly used as oil and water repellents; coatings for cookware, carpets, and textiles; and as firefighting foams. The compounds do not break down in the environment or the human body and accumulate over time. They are known to disrupt the endocrine system.

EtFOSAA is a metabolite of a raw material used in the manufacturing of packaging and paper products, and itself gets converted to perfluorooctane sulfonic acid (PFOS), which is extremely stable in the environment and within organisms, leading to bioaccumulation that has the potential to span generations, Barbara A. Cohn, PhD, director of child health and development studies at the Public Health Institute in Berkeley, Calif., said during a virtual press conference held by The Endocrine Society. The study was slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Abdominal obesity was defined as a waist circumference of more than 34.6 inches (88 cm), and whole-body obesity was defined as a body mass index of more than 30 kg/m². Findings from a previous study drawn from the same cohort showed that exposure to EtFOSAA, combined with high maternal cholesterol levels, was linked to increased risk of breast cancer in daughters.

“I want to emphasize that we don’t understand the mechanism, but we do know that this finding [from the current study], if it is confirmed, has implications for the current epidemic of obesity. Exposure to these compounds is very widespread, [having] started in the 1940s and 50s, and is consistent with the timing of the obesity epidemic,” said Dr. Cohn, during the virtual press conference.

Robert Sargis, MD, professor of endocrinology, diabetes, and metabolism at the University of Illinois at Chicago, said the mechanistic connection could be complex. “It’s a combination of the possibility that the chemicals themselves are passed down either through breast milk or across the placenta, or that the biological impact is somehow coded epigenetically, and then that epigenetic code is somehow passed on to subsequent generations,” he said in an interview. He was not associated with the research.

Dr. Cohn said her team is investigating both of those possibilities through analysis of the existing blood samples. “There are implications for PFAS clean-up if [these findings are] confirmed, and there’s an opportunity for setting up precautions for pregnant women on how they can try to avoid this contamination to [offset] a rekindling of this generational effect 60 years down the road,” Dr. Cohn added.

Daughters of the original participants (now grandmothers) were measured at an average age of 50, and the granddaughters, at an average of 20 (219 dyads, 657 women in total). Daughters also reported their weight at age 30, which was close to the mean age at which they had given birth. This allowed the researchers to control for obesity present during gestation of the granddaughters.

The researchers analyzed EtFOSAA, PFOS, and cholesterol levels from archived blood samples taken from grandmothers within 3 days of delivery. There was an association between EtFOSAA and self-reported obesity at age 30 in daughters, as well as measured abdominal, whole-body obesity, and blood pressure at age 20 in granddaughters, and all were modified by low cholesterol levels (25% interquartile) in grandmothers (P < .05).

In granddaughters, the combined risk of abdominal and whole-body obesity was 2.3-fold higher in those whose grandmothers were in the top 25% of EtFOSAA exposure, compared with those whose grandmothers were in the lowest 25% (95% confidence interval, 1.1-4.8). Those associations remained after adjustments for race, being overweight in early pregnancy (BMI, >25 kg/m²), and serum PFOS levels.

Although the weight of daughters did not affect the association between the granddaughters’ risk for obesity risk and EtFOSAA levels in grandmothers, it did predict high metabolic risk in granddaughters. That suggests that the burden may be building over generations. “Independently, their mothers themselves are heavier and fatter, and that heaviness of the mother is also a source of increasing body size for the granddaughter. We have a multiplying, very ugly situation that may be helping us to understand this really quick rise of obesity,” said Dr. Cohn.

She also emphasized that PFAS may not be the only culprit in fueling obesity. “Most of us believe that there is sufficient data in the animal studies and, now, growing data in human studies, to suggest that these obesogens exist and are contributing to the health problems that are going to be following the obesity epidemic in young people now.”

Dr. Cohn noted that the study is limited by its lack of a control group.

The California Breast Research Foundation, the National Institutes of Health, and the State of California funded the study. Dr. Cohn and Dr. Sargis reported no relevant financial disclosures.

The study abstract will be published in the Journal of the Endocrine Society. In addition to a series of news conferences held on March 30-31, the society will host ENDO Online 2020 during June 8-22 with programming for clinicians and researchers.
 

SOURCE: Cohn B et al. ENDO 2020, Abstract LB132.

Exposure during pregnancy to a specific per- and polyfluoroalkyl substance (PFAS), combined with a low cholesterol level, is linked to a heightened risk of abdominal and whole-body obesity in granddaughters, according to a new analysis of the Child Health and Development Studies, which have been ongoing since the 1960s.

Researchers directly measured levels of N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA) in blood samples from the grandmothers, which had been taken shortly after delivery, and then analyzed measures of obesity and other metabolic factors in their daughters at ages 30 years and 50 years, and their granddaughters at age 20.

PFASs are synthetic compounds commonly used as oil and water repellents; coatings for cookware, carpets, and textiles; and as firefighting foams. The compounds do not break down in the environment or the human body and accumulate over time. They are known to disrupt the endocrine system.

EtFOSAA is a metabolite of a raw material used in the manufacturing of packaging and paper products, and itself gets converted to perfluorooctane sulfonic acid (PFOS), which is extremely stable in the environment and within organisms, leading to bioaccumulation that has the potential to span generations, Barbara A. Cohn, PhD, director of child health and development studies at the Public Health Institute in Berkeley, Calif., said during a virtual press conference held by The Endocrine Society. The study was slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.

Abdominal obesity was defined as a waist circumference of more than 34.6 inches (88 cm), and whole-body obesity was defined as a body mass index of more than 30 kg/m². Findings from a previous study drawn from the same cohort showed that exposure to EtFOSAA, combined with high maternal cholesterol levels, was linked to increased risk of breast cancer in daughters.

“I want to emphasize that we don’t understand the mechanism, but we do know that this finding [from the current study], if it is confirmed, has implications for the current epidemic of obesity. Exposure to these compounds is very widespread, [having] started in the 1940s and 50s, and is consistent with the timing of the obesity epidemic,” said Dr. Cohn, during the virtual press conference.

Robert Sargis, MD, professor of endocrinology, diabetes, and metabolism at the University of Illinois at Chicago, said the mechanistic connection could be complex. “It’s a combination of the possibility that the chemicals themselves are passed down either through breast milk or across the placenta, or that the biological impact is somehow coded epigenetically, and then that epigenetic code is somehow passed on to subsequent generations,” he said in an interview. He was not associated with the research.

Dr. Cohn said her team is investigating both of those possibilities through analysis of the existing blood samples. “There are implications for PFAS clean-up if [these findings are] confirmed, and there’s an opportunity for setting up precautions for pregnant women on how they can try to avoid this contamination to [offset] a rekindling of this generational effect 60 years down the road,” Dr. Cohn added.

Daughters of the original participants (now grandmothers) were measured at an average age of 50, and the granddaughters, at an average of 20 (219 dyads, 657 women in total). Daughters also reported their weight at age 30, which was close to the mean age at which they had given birth. This allowed the researchers to control for obesity present during gestation of the granddaughters.

The researchers analyzed EtFOSAA, PFOS, and cholesterol levels from archived blood samples taken from grandmothers within 3 days of delivery. There was an association between EtFOSAA and self-reported obesity at age 30 in daughters, as well as measured abdominal, whole-body obesity, and blood pressure at age 20 in granddaughters, and all were modified by low cholesterol levels (25% interquartile) in grandmothers (P < .05).

In granddaughters, the combined risk of abdominal and whole-body obesity was 2.3-fold higher in those whose grandmothers were in the top 25% of EtFOSAA exposure, compared with those whose grandmothers were in the lowest 25% (95% confidence interval, 1.1-4.8). Those associations remained after adjustments for race, being overweight in early pregnancy (BMI, >25 kg/m²), and serum PFOS levels.

Although the weight of daughters did not affect the association between the granddaughters’ risk for obesity risk and EtFOSAA levels in grandmothers, it did predict high metabolic risk in granddaughters. That suggests that the burden may be building over generations. “Independently, their mothers themselves are heavier and fatter, and that heaviness of the mother is also a source of increasing body size for the granddaughter. We have a multiplying, very ugly situation that may be helping us to understand this really quick rise of obesity,” said Dr. Cohn.

She also emphasized that PFAS may not be the only culprit in fueling obesity. “Most of us believe that there is sufficient data in the animal studies and, now, growing data in human studies, to suggest that these obesogens exist and are contributing to the health problems that are going to be following the obesity epidemic in young people now.”

Dr. Cohn noted that the study is limited by its lack of a control group.

The California Breast Research Foundation, the National Institutes of Health, and the State of California funded the study. Dr. Cohn and Dr. Sargis reported no relevant financial disclosures.

The study abstract will be published in the Journal of the Endocrine Society. In addition to a series of news conferences held on March 30-31, the society will host ENDO Online 2020 during June 8-22 with programming for clinicians and researchers.
 

SOURCE: Cohn B et al. ENDO 2020, Abstract LB132.

The risk for death from COVID-19 is 1.38% overall, according to a new study. However, the fatality rate rises with age, from well below 1% among children aged 9 years or younger to nearly 8% for seniors aged 80 years or older, the latest statistics show.

“These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death,” Robert Verity, PhD, of University College London, and colleagues, wrote in a study published online in the Lancet Infectious Diseases.

Among those infected with SARS-CoV-2, the virus that causes COVID-19, the risk for hospitalization also increases with age. Specifically, 11.8% of people in their 60s require admission, as do 16.6% of people in their 70s and 18.4% for those in their 80s or older.

The case fatality estimates are based on data regarding individual patients who died from COVID-19 in Hubei, China, through Feb. 8, as well as those who died in Hong Kong, Macau, and 37 countries outside China through Feb. 25.

“It is clear from the data that have emerged from China that case fatality ratio increases substantially with age. Our results suggest a very low fatality ratio in those under the age of 20 years. As there are very few cases in this age group, it remains unclear whether this reflects a low risk of death or a difference in susceptibility, although early results indicate young people are not at lower risk of infection than adults,” Dr. Verity and colleagues wrote.

The authors emphasized that serologic testing of adolescents and children will be vital to understanding how individuals younger than 20 years may be driving viral transmission.

In an accompanying editorial Shigui Ruan, PhD, of the department of mathematics at the University of Miami in Coral Gables, Fla., wrote that early detection, diagnosis, isolation, and treatment, as practiced in China, may help to prevent more deaths

“Even though the fatality rate is low for younger people, it is very clear that any suggestion of COVID-19 being just like influenza is false: Even for those aged 20-29 years, once infected with SARS-CoV-2, the mortality rate is 33 times higher than that from seasonal influenza,” he noted.

Dr. Ruan, who uses applied mathematics to model disease transmission, noted that otherwise healthy people stand a good chance – approximately 95% – of surviving COVID-19, but the odds of survival for people with comorbidities will be “considerably decreased.”

Time to death or discharge

Dr. Verity and colleagues first used data on deaths of 24 patients in mainland China and on 165 persons who recovered from infection outside of China to estimate the time between onset of symptoms and either death or discharge from the hospital. They estimated that the mean duration from symptom onset to death is 17.8 days, and the mean duration to discharge is 24.7 days.

They then estimated age-stratified case fatality ratios among all clinically diagnosed and laboratory-confirmed cases in mainland China to the end of the study period (70,117 cases).

The estimated crude case fatality ratio, adjusted for censoring, was 3.67%. With further adjustment for demographic characteristics and under-ascertainment, the authors’ best estimate of a case fatality ratio in China is 1.38%.

The following figure shows adjusted fatality infection rates by age group.

Hospitalizations rise with age

The investigators also estimated the proportion of infected patients who require hospitalization. Their estimation was based on data from a subset of cases reported in mainland China. The hospitalization estimates range from zero among the youngest patients to 18% among the oldest.

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

The risk for death from COVID-19 is 1.38% overall, according to a new study. However, the fatality rate rises with age, from well below 1% among children aged 9 years or younger to nearly 8% for seniors aged 80 years or older, the latest statistics show.

“These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death,” Robert Verity, PhD, of University College London, and colleagues, wrote in a study published online in the Lancet Infectious Diseases.

Among those infected with SARS-CoV-2, the virus that causes COVID-19, the risk for hospitalization also increases with age. Specifically, 11.8% of people in their 60s require admission, as do 16.6% of people in their 70s and 18.4% for those in their 80s or older.

The case fatality estimates are based on data regarding individual patients who died from COVID-19 in Hubei, China, through Feb. 8, as well as those who died in Hong Kong, Macau, and 37 countries outside China through Feb. 25.

“It is clear from the data that have emerged from China that case fatality ratio increases substantially with age. Our results suggest a very low fatality ratio in those under the age of 20 years. As there are very few cases in this age group, it remains unclear whether this reflects a low risk of death or a difference in susceptibility, although early results indicate young people are not at lower risk of infection than adults,” Dr. Verity and colleagues wrote.

The authors emphasized that serologic testing of adolescents and children will be vital to understanding how individuals younger than 20 years may be driving viral transmission.

In an accompanying editorial Shigui Ruan, PhD, of the department of mathematics at the University of Miami in Coral Gables, Fla., wrote that early detection, diagnosis, isolation, and treatment, as practiced in China, may help to prevent more deaths

“Even though the fatality rate is low for younger people, it is very clear that any suggestion of COVID-19 being just like influenza is false: Even for those aged 20-29 years, once infected with SARS-CoV-2, the mortality rate is 33 times higher than that from seasonal influenza,” he noted.

Dr. Ruan, who uses applied mathematics to model disease transmission, noted that otherwise healthy people stand a good chance – approximately 95% – of surviving COVID-19, but the odds of survival for people with comorbidities will be “considerably decreased.”

Time to death or discharge

Dr. Verity and colleagues first used data on deaths of 24 patients in mainland China and on 165 persons who recovered from infection outside of China to estimate the time between onset of symptoms and either death or discharge from the hospital. They estimated that the mean duration from symptom onset to death is 17.8 days, and the mean duration to discharge is 24.7 days.

They then estimated age-stratified case fatality ratios among all clinically diagnosed and laboratory-confirmed cases in mainland China to the end of the study period (70,117 cases).

The estimated crude case fatality ratio, adjusted for censoring, was 3.67%. With further adjustment for demographic characteristics and under-ascertainment, the authors’ best estimate of a case fatality ratio in China is 1.38%.

The following figure shows adjusted fatality infection rates by age group.

Hospitalizations rise with age

The investigators also estimated the proportion of infected patients who require hospitalization. Their estimation was based on data from a subset of cases reported in mainland China. The hospitalization estimates range from zero among the youngest patients to 18% among the oldest.

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

The risk for death from COVID-19 is 1.38% overall, according to a new study. However, the fatality rate rises with age, from well below 1% among children aged 9 years or younger to nearly 8% for seniors aged 80 years or older, the latest statistics show.

“These early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and show a strong age gradient in risk of death,” Robert Verity, PhD, of University College London, and colleagues, wrote in a study published online in the Lancet Infectious Diseases.

Among those infected with SARS-CoV-2, the virus that causes COVID-19, the risk for hospitalization also increases with age. Specifically, 11.8% of people in their 60s require admission, as do 16.6% of people in their 70s and 18.4% for those in their 80s or older.

The case fatality estimates are based on data regarding individual patients who died from COVID-19 in Hubei, China, through Feb. 8, as well as those who died in Hong Kong, Macau, and 37 countries outside China through Feb. 25.

“It is clear from the data that have emerged from China that case fatality ratio increases substantially with age. Our results suggest a very low fatality ratio in those under the age of 20 years. As there are very few cases in this age group, it remains unclear whether this reflects a low risk of death or a difference in susceptibility, although early results indicate young people are not at lower risk of infection than adults,” Dr. Verity and colleagues wrote.

The authors emphasized that serologic testing of adolescents and children will be vital to understanding how individuals younger than 20 years may be driving viral transmission.

In an accompanying editorial Shigui Ruan, PhD, of the department of mathematics at the University of Miami in Coral Gables, Fla., wrote that early detection, diagnosis, isolation, and treatment, as practiced in China, may help to prevent more deaths

“Even though the fatality rate is low for younger people, it is very clear that any suggestion of COVID-19 being just like influenza is false: Even for those aged 20-29 years, once infected with SARS-CoV-2, the mortality rate is 33 times higher than that from seasonal influenza,” he noted.

Dr. Ruan, who uses applied mathematics to model disease transmission, noted that otherwise healthy people stand a good chance – approximately 95% – of surviving COVID-19, but the odds of survival for people with comorbidities will be “considerably decreased.”

Time to death or discharge

Dr. Verity and colleagues first used data on deaths of 24 patients in mainland China and on 165 persons who recovered from infection outside of China to estimate the time between onset of symptoms and either death or discharge from the hospital. They estimated that the mean duration from symptom onset to death is 17.8 days, and the mean duration to discharge is 24.7 days.

They then estimated age-stratified case fatality ratios among all clinically diagnosed and laboratory-confirmed cases in mainland China to the end of the study period (70,117 cases).

The estimated crude case fatality ratio, adjusted for censoring, was 3.67%. With further adjustment for demographic characteristics and under-ascertainment, the authors’ best estimate of a case fatality ratio in China is 1.38%.

The following figure shows adjusted fatality infection rates by age group.

Hospitalizations rise with age

The investigators also estimated the proportion of infected patients who require hospitalization. Their estimation was based on data from a subset of cases reported in mainland China. The hospitalization estimates range from zero among the youngest patients to 18% among the oldest.

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