Covid ICYMI

Having COVID-19 during pregnancy is linked to a significantly increased risk for gestational hypertension and preeclampsia compared with not having COVID-19 while pregnant, according to findings from a retrospective study presented Jan. 28 at the Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

“This was not entirely surprising given that inflammation has been implicated in the pathogenesis of both hypertensive disorders of pregnancy and COVID-19 infection and thus may serve to exacerbate each other,” Nigel Madden, MD, a resident physician in the ob.gyn. department at Columbia University, New York. , told this news organization after she presented the results.

Hypertensive disorders of pregnancy occur in 10%-15% of all pregnancies and are the leading cause of maternal and perinatal morbidity and mortality worldwide, Dr. Madden told attendees of the meeting. Although it’s not clear what causes hypertensive diseases in pregnancy generally, “it is possible that the acute inflammatory state of the COVID infection may incite or exacerbate hypertensive disease of pregnancy,” Dr. Madden said.

The researchers conducted a retrospective chart review of 1,715 patients who had a singleton pregnancy and who underwent routine nasal polymerase chain reaction testing at admission to one institution’s labor and delivery department between March and June 2020. The researchers excluded patients who had a history of chronic hypertension.

Overall, 10% of the patients tested positive for COVID-19 (n = 167), and 90% tested negative (n = 1,548). There were several differences at baseline between the groups. Those who tested positive tended to be younger, with an average age of 28, compared with an average age of 31 years for the group that tested negative. The group that tested negative also had a higher proportion of mothers aged 35 and older (P < .01). There were also significant differences in the racial makeup of the groups. Half of those in the COVID-positive group reported “other” for their race. The biggest baseline disparity between the groups was with regard to insurance type: 73% of those who tested positive for COVID-19 used Medicaid; only 36% of patients in the COVID-negative group used Medicaid. Those with private insurance were more likely to test negative (43%) than positive (25%) (P < .01).

The researchers defined gestational hypertension as having a systolic blood pressure greater than or equal to 140 mm Hg or a diastolic blood pressure greater than or equal to 90 mm Hg on two occasions at least 4 hours apart. A preeclampsia diagnosis required elevated blood pressure (using the same definition as for hypertension) as well as proteinuria, characterized by a protein/creatine ratio greater than or equal to 0.3 mg/dL or greater than or equal to 300 mg of protein on a 24-hour urine collection. Preeclampsia with severe features required prespecified laboratory abnormalities, pulmonary edema, or symptoms of headache, vision changes, chest pain, shortness of breath, or right upper quadrant pain.

More than twice as many patients with COVID had a hypertensive disorder of pregnancy (18%) as those who tested negative (8%). The patients who were COVID positive were significantly more likely than those who tested negative to have gestational hypertension and preeclampsia without severe features. Rates of preeclampsia with severe features were not significantly different between the groups.

The severity of hypertensive disease did not differ between the groups. Limitations of the study included its retrospective design, the small number of COVID-positive patients, and the fact that it was conducted at a single institution in New York. However, the study population was diverse, and it was conducted during the height of infections at the epicenter of the COVID-19 pandemic.

“This was a study of great clinical significance,” said Kim Boggess, MD, of the University of North Carolina at Chapel Hill, while moderating the session. “I would argue that you guys in New York are the best poised to answer some of the questions that need to be answered as it relates to the effect of coronavirus infection in pregnancy.”

Dr. Boggess asked whether the study examined associations related to the severity of COVID-19. Only 10 of the patients were symptomatic, Dr. Madden said, and only one of those patients developed preeclampsia with severe features.

Michelle Y. Owens, MD, professor and chief of maternal fetal medicine at the University of Mississippi Medical Center, Jackson, who also moderated the session, said in an interview that the findings call for physicians to remain vigilant about evaluating patients who test positive for COVID-19 for hypertensive disease and disorders.

“Additionally, these women should be educated about hypertensive disorders and the common symptoms to facilitate early diagnosis and treatment when indicated,” Dr. Owens said. “I believe this is of particular interest in those women who are not severely affected by COVID, as these changes may occur while they are undergoing quarantine or being monitored remotely. This amplifies the need for remote assessment or home monitoring of maternal blood pressures.”

Dr. Madden, Dr. Boggess, and Dr. Owens have disclosed no relevant financial relationships.

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

Having COVID-19 during pregnancy is linked to a significantly increased risk for gestational hypertension and preeclampsia compared with not having COVID-19 while pregnant, according to findings from a retrospective study presented Jan. 28 at the Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

“This was not entirely surprising given that inflammation has been implicated in the pathogenesis of both hypertensive disorders of pregnancy and COVID-19 infection and thus may serve to exacerbate each other,” Nigel Madden, MD, a resident physician in the ob.gyn. department at Columbia University, New York. , told this news organization after she presented the results.

Hypertensive disorders of pregnancy occur in 10%-15% of all pregnancies and are the leading cause of maternal and perinatal morbidity and mortality worldwide, Dr. Madden told attendees of the meeting. Although it’s not clear what causes hypertensive diseases in pregnancy generally, “it is possible that the acute inflammatory state of the COVID infection may incite or exacerbate hypertensive disease of pregnancy,” Dr. Madden said.

The researchers conducted a retrospective chart review of 1,715 patients who had a singleton pregnancy and who underwent routine nasal polymerase chain reaction testing at admission to one institution’s labor and delivery department between March and June 2020. The researchers excluded patients who had a history of chronic hypertension.

Overall, 10% of the patients tested positive for COVID-19 (n = 167), and 90% tested negative (n = 1,548). There were several differences at baseline between the groups. Those who tested positive tended to be younger, with an average age of 28, compared with an average age of 31 years for the group that tested negative. The group that tested negative also had a higher proportion of mothers aged 35 and older (P < .01). There were also significant differences in the racial makeup of the groups. Half of those in the COVID-positive group reported “other” for their race. The biggest baseline disparity between the groups was with regard to insurance type: 73% of those who tested positive for COVID-19 used Medicaid; only 36% of patients in the COVID-negative group used Medicaid. Those with private insurance were more likely to test negative (43%) than positive (25%) (P < .01).

The researchers defined gestational hypertension as having a systolic blood pressure greater than or equal to 140 mm Hg or a diastolic blood pressure greater than or equal to 90 mm Hg on two occasions at least 4 hours apart. A preeclampsia diagnosis required elevated blood pressure (using the same definition as for hypertension) as well as proteinuria, characterized by a protein/creatine ratio greater than or equal to 0.3 mg/dL or greater than or equal to 300 mg of protein on a 24-hour urine collection. Preeclampsia with severe features required prespecified laboratory abnormalities, pulmonary edema, or symptoms of headache, vision changes, chest pain, shortness of breath, or right upper quadrant pain.

More than twice as many patients with COVID had a hypertensive disorder of pregnancy (18%) as those who tested negative (8%). The patients who were COVID positive were significantly more likely than those who tested negative to have gestational hypertension and preeclampsia without severe features. Rates of preeclampsia with severe features were not significantly different between the groups.

The severity of hypertensive disease did not differ between the groups. Limitations of the study included its retrospective design, the small number of COVID-positive patients, and the fact that it was conducted at a single institution in New York. However, the study population was diverse, and it was conducted during the height of infections at the epicenter of the COVID-19 pandemic.

“This was a study of great clinical significance,” said Kim Boggess, MD, of the University of North Carolina at Chapel Hill, while moderating the session. “I would argue that you guys in New York are the best poised to answer some of the questions that need to be answered as it relates to the effect of coronavirus infection in pregnancy.”

Dr. Boggess asked whether the study examined associations related to the severity of COVID-19. Only 10 of the patients were symptomatic, Dr. Madden said, and only one of those patients developed preeclampsia with severe features.

Michelle Y. Owens, MD, professor and chief of maternal fetal medicine at the University of Mississippi Medical Center, Jackson, who also moderated the session, said in an interview that the findings call for physicians to remain vigilant about evaluating patients who test positive for COVID-19 for hypertensive disease and disorders.

“Additionally, these women should be educated about hypertensive disorders and the common symptoms to facilitate early diagnosis and treatment when indicated,” Dr. Owens said. “I believe this is of particular interest in those women who are not severely affected by COVID, as these changes may occur while they are undergoing quarantine or being monitored remotely. This amplifies the need for remote assessment or home monitoring of maternal blood pressures.”

Dr. Madden, Dr. Boggess, and Dr. Owens have disclosed no relevant financial relationships.

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

Having COVID-19 during pregnancy is linked to a significantly increased risk for gestational hypertension and preeclampsia compared with not having COVID-19 while pregnant, according to findings from a retrospective study presented Jan. 28 at the Society for Maternal-Fetal Medicine 2021 Annual Pregnancy Meeting.

“This was not entirely surprising given that inflammation has been implicated in the pathogenesis of both hypertensive disorders of pregnancy and COVID-19 infection and thus may serve to exacerbate each other,” Nigel Madden, MD, a resident physician in the ob.gyn. department at Columbia University, New York. , told this news organization after she presented the results.

Hypertensive disorders of pregnancy occur in 10%-15% of all pregnancies and are the leading cause of maternal and perinatal morbidity and mortality worldwide, Dr. Madden told attendees of the meeting. Although it’s not clear what causes hypertensive diseases in pregnancy generally, “it is possible that the acute inflammatory state of the COVID infection may incite or exacerbate hypertensive disease of pregnancy,” Dr. Madden said.

The researchers conducted a retrospective chart review of 1,715 patients who had a singleton pregnancy and who underwent routine nasal polymerase chain reaction testing at admission to one institution’s labor and delivery department between March and June 2020. The researchers excluded patients who had a history of chronic hypertension.

Overall, 10% of the patients tested positive for COVID-19 (n = 167), and 90% tested negative (n = 1,548). There were several differences at baseline between the groups. Those who tested positive tended to be younger, with an average age of 28, compared with an average age of 31 years for the group that tested negative. The group that tested negative also had a higher proportion of mothers aged 35 and older (P < .01). There were also significant differences in the racial makeup of the groups. Half of those in the COVID-positive group reported “other” for their race. The biggest baseline disparity between the groups was with regard to insurance type: 73% of those who tested positive for COVID-19 used Medicaid; only 36% of patients in the COVID-negative group used Medicaid. Those with private insurance were more likely to test negative (43%) than positive (25%) (P < .01).

The researchers defined gestational hypertension as having a systolic blood pressure greater than or equal to 140 mm Hg or a diastolic blood pressure greater than or equal to 90 mm Hg on two occasions at least 4 hours apart. A preeclampsia diagnosis required elevated blood pressure (using the same definition as for hypertension) as well as proteinuria, characterized by a protein/creatine ratio greater than or equal to 0.3 mg/dL or greater than or equal to 300 mg of protein on a 24-hour urine collection. Preeclampsia with severe features required prespecified laboratory abnormalities, pulmonary edema, or symptoms of headache, vision changes, chest pain, shortness of breath, or right upper quadrant pain.

More than twice as many patients with COVID had a hypertensive disorder of pregnancy (18%) as those who tested negative (8%). The patients who were COVID positive were significantly more likely than those who tested negative to have gestational hypertension and preeclampsia without severe features. Rates of preeclampsia with severe features were not significantly different between the groups.

The severity of hypertensive disease did not differ between the groups. Limitations of the study included its retrospective design, the small number of COVID-positive patients, and the fact that it was conducted at a single institution in New York. However, the study population was diverse, and it was conducted during the height of infections at the epicenter of the COVID-19 pandemic.

“This was a study of great clinical significance,” said Kim Boggess, MD, of the University of North Carolina at Chapel Hill, while moderating the session. “I would argue that you guys in New York are the best poised to answer some of the questions that need to be answered as it relates to the effect of coronavirus infection in pregnancy.”

Dr. Boggess asked whether the study examined associations related to the severity of COVID-19. Only 10 of the patients were symptomatic, Dr. Madden said, and only one of those patients developed preeclampsia with severe features.

Michelle Y. Owens, MD, professor and chief of maternal fetal medicine at the University of Mississippi Medical Center, Jackson, who also moderated the session, said in an interview that the findings call for physicians to remain vigilant about evaluating patients who test positive for COVID-19 for hypertensive disease and disorders.

“Additionally, these women should be educated about hypertensive disorders and the common symptoms to facilitate early diagnosis and treatment when indicated,” Dr. Owens said. “I believe this is of particular interest in those women who are not severely affected by COVID, as these changes may occur while they are undergoing quarantine or being monitored remotely. This amplifies the need for remote assessment or home monitoring of maternal blood pressures.”

Dr. Madden, Dr. Boggess, and Dr. Owens have disclosed no relevant financial relationships.

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

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

Autopsies on patients who died from COVID-19 are providing important clues on how to treat the disease. In an analysis of 40 hearts from COVID-19 patients who died early in the pandemic, myocyte necrosis was seen in 14 hearts, or 35%.

In the majority of these hearts, pathologists found both small areas of focal necrosis and cardiac thrombi, most of which were microthrombi in myocardial capillaries, arterioles, and small muscular cells.

In an interview, senior author Aloke V. Finn, MD, CVPath Institute, Gaithersburg, Md., stressed the importance of understanding what they saw, but also what they didn’t see.

“What we saw in the majority of patients with myocardial injury were these small areas of infarct and microthrombi in small vessels. What we didn’t see was any evidence of myocarditis and or huge infarcts in, like, the LAD artery,” he said.

“What we’re seeing here is not clinically detectable. ... There is no test that will tell you there are microthrombi and no imaging tests that will show these focal areas of necrosis, but that doesn’t mean it’s not there,” he added.

The finding of myocyte necrosis in about one-third of samples is consistent with another study that showed that 30%-40% of patients hospitalized with COVID-19 have elevated troponins, noted Dr. Finn. The investigators were unable to obtain troponin levels on their patients, which could limit the clinical translation of myocardial necrosis detected at autopsy.

Dr. Finn and colleagues, including first author Dario Pellegrini, MD, from Ospedale Papa Giovanni XXIII in Bergamo, Italy, published their findings online in Circulation on Jan. 22, 2020.

The report is a follow-up to another just published by Dr. Finn’s group in the Journal of the American College of Cardiology, which showed that myocarditis is a very rare finding in COVID-19 autopsies.

Only three of 14 individuals (21.4%) with evidence of myocyte necrosis showed evidence of acute MI, which Dr. Finn and colleagues define as an area of necrosis at least 1 cm² in size. The remaining 11 (78.6%) had only discrete areas of myocyte necrosis (>20 necrotic myocytes with an area of ≥0.05 mm², but <1 cm²).

“This makes sense when we saw what type of thrombus there was in these cases; it wasn’t thrombus in major epicardial vessels but microthombi in small vessels,” said Dr. Finn.

In those with necrosis, cardiac thrombi were present in 11 of 14 (78.6%) cases, with 2 of 14 (14.2%) having epicardial coronary artery thrombi and 0 of 14 (64.3%) having microthrombi in myocardial capillaries, arterioles, and small muscular arteries.

Further supporting the role of COVID-19–related hypercoagulability as the cause of myocardial injury in many patients, the investigators noted that the incidence of severe coronary artery disease (defined as >75% cross sectional narrowing) did not differ significantly between those with and without necrosis.
 

COVID-19 vs. non–COVID-19 thrombi

Going one step further, Dr. Finn’s team compared cardiac microthrombi from their COVID-19–positive autopsy cases with intramyocardial thromboemboli from COVID-19 cases. They also compared the samples with aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19–infected patients presenting with ST-segment elevation MI (STEMI).

The autopsy-obtained microthrombi had significantly more fibrin and terminal complement C5b-9 immunostaining than intramyocardial thromboemboli from COVID-19–negative subjects and than aspirated thrombi from either COVID-positive or COVID-negative STEMI patients.

“Basically, what we’re seeing in these thrombi is evidence of an immune-mediated reaction,” said Dr. Finn, explaining that complement C5b-9 is an innate immune system protein that circulates in the blood in response to any kind of activation of the immune system. “It is nonspecific but can also lead to coagulation problems,” he said.
 

Anticoagulation, yes, but dose unclear

These findings clearly support the use of anticoagulation in hospitalized COVID patients, said Jeffrey Weitz, MD, director of the Thrombosis & Atherosclerosis Research Institute, McMaster University, Hamilton, Ont. But the details of how much anticoagulation, what kind, and for whom are still a moving target.

“I think what we can say at this point is that these autopsy findings fit with previous studies that have shown microthrombi in the lungs and thrombi in the legs and gut, and support the notion that these patients should receive prophylactic doses of anticoagulants if they’re sick enough to be hospitalized,” said Dr. Weitz.

“But it’s not as simple as to say that this study shows clots form in the heart of COVID patients and therefore more anticoagulation is going to be better than less anticoagulation,” he said in an interview.

Recent top-line findings from three linked clinical trials – REMAP-CAP, ACTIV-4, and ATTACC – show that full-dose anticoagulation was beneficial in moderately ill patients hospitalized for COVID-19 and reduced the need for mechanical ventilation.

Moderately ill patients are those not in intensive care and who did not require organ support, such as mechanical ventilation, at the time of enrollment.

However, the same group reported findings in December that showed that routine use of full-dose anticoagulation when started in the ICU in critically ill patients was not beneficial and possibly harmful.

Dr. Weitz was only a little bit surprised by this finding of potential harm in the sickest patients. “I figured everybody should get prophylaxis but I wasn’t sure that everybody should get intensified anticoagulant. But my assumption was that if anybody is going to benefit from it, it would be the ICU patients.”

It was notable, said Dr. Weitz, that levels of D-dimer, a fibrin degradation product, were not associated with outcomes. “So, it doesn’t seem to be that patients with evidence of more clotting are more likely to benefit, which might indicate that it’s not the anticoagulant effect of the heparin that’s helping, but maybe the anti-inflammatory effect. At this point, we just don’t know.”

All three studies have paused enrollment of the critically ill subgroup, but are continuing to enroll patients with moderate illness and expect to publish results in the coming months, according to previous coverage from this news organization.

The study was funded by CVPath, a nonprofit institute that receives funding from a number of different industry entities. Dr. Finn and Dr. Weitz reported no relevant conflicts of interest.

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

The Blitz was a Nazi bombing campaign targeting London. It was designed to break the spirit of the British. Knowing London would be the centerpiece of the campaign, the British rather hastily established several psychiatric hospitals for the expected panic in the streets. However, despite 9 months of bombing, 43,000 civilians killed and 139,000 more wounded, the predicted chaos in the streets did not manifest. Civilians continued to work, industry continued to churn, and eventually, Hitler’s eye turned east toward Russia.

H. F. Davis/Wikimedia Commons/Public Domain

The surprising lack of pandemonium in London inspired Dr. John T. MacCurdy, who chronicled his findings in a book The Structure of Morale, more recently popularized in Malcolm Gladwell’s David and Goliath. A brief summary of Dr. MacCurdy’s theory divides the targeted Londoners into the following categories:

• Direct hit
• Near miss
• Remote miss

The direct hit group was defined as those killed by the bombing. However, As Dr. MacCurdy stated, “The morale of the community depends on the reaction of the survivors…Put this way, the fact is obvious, corpses do not run about spreading panic.”

A near miss were those for whom wounds were inflicted or loved ones were killed. This group felt the real repercussions of the bombing. However, with 139,000 wounded out of a city of 8 million people, they were a small minority.

The majority of Londoners, then, fit into the third group – the remote miss. These people faced a serious fear, but survived, often totally unscathed. The process of facing that fear without having panicked or having been harmed, then, led to “a feeling of excitement with a flavour of invulnerability.”

Therefore, rather than a city of millions running in fear in the streets, requiring military presence to control the chaos, London became a city of people who felt themselves, perhaps, invincible.

A similar threat passed through the world in the first several months of the COVID-19 pandemic. Hospitals were expected to be overrun, and ethics committees convened to discuss allocation of scarce ventilators. However, due, at least in part, to the impressive efforts of the populace of the United States, the majority of civilians did not feel the burden of this frightening disease. Certainly, in a few places, hospitals were overwhelmed, and resources were unavailable due to sheer numbers. These places saw those who suffered direct hits with the highest frequency. However, a disease with an infection fatality ratio recently estimated at 0.5-1%, with a relatively high rate of asymptomatic disease, led to a large majority of people who experienced the first wave of COVID-19 in the United States as a remote miss. COVID-19’s flattened first peak gave much of the population a sense of relief, and, perhaps, a “flavour of invulnerability.”

An anonymous, but concerned, household contact wrote The New York Times and illustrated perfectly the invulnerable feelings of a remote miss:

“I’m doing my best to avoid social contact, along with two other members of my household. We have sufficient supplies for a month. Despite that, one member insists on going out for trivial reasons, such as not liking the kind of apples we have. He’s 92. I’ve tried explaining and cajoling, using graphs and anecdotes to make the danger to all of us seem ‘real.’ It doesn’t take. His risk of death is many times greater than mine, and he’s poking holes in a lifeboat we all have to rely on. What is the correct path?”

American culture expects certainty from science. Therein lies the problem with a new disease no medical provider or researcher had seen prior to November 2019. Action was required in the effort to slow the spread with little to no data as a guide. Therefore, messages that seemed contradictory reached the public. “A mask less than N-95 grade will not protect you,” evolved to, “everyone should wear a homemade cloth mask.” As the pandemic evolved and data was gathered, new recommendations were presented. Unfortunately, such well-meaning and necessary changes led to confusion, mistrust, and conspiracy theories.

Medicine’s response

The science of COVID-19 carries phenomenal uncertainties, but the psychology of those who have suffered direct hits or near misses are the daily bedside challenge of all physicians, but particularly of hospitalists. We live at the front lines of disease – as one colleague put it to me, “we are the watchers on the wall.” Though we do not yet have our hoped-for, evidence-based treatment for this virus, we are familiar with acute illness. We know the rapid change of health to disease, and we know the chronically ill who suffer exacerbations of such illness. Supporting patients and their loved ones through those times is our daily practice.

On the other hand, those who have experienced only remote misses remain vulnerable in this pandemic, despite their feelings of invincibility. Those that feel invincible may be the least interested in our advice. This, too, is no strange position for a physician. We have tools to reach patients who do not reach out to us. Traditional media outlets have been saturated with headlines and talking points about this disease. Physicians who have taken to social media have been met with appreciation in some situations, but ignored, doubted, or shunned in others. In May 2020, NBC News reported an ED doctor’s attempt to dispel some COVID myths on social media. Unfortunately, his remarks were summarily dismissed. Through the frustration, we persevere.

Out of the many responsible authorities who help battle misinformation, the World Health Organization’s mythbusting website (www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters) directly confronts many incorrect circulating ideas. My personal favorite at the time of this writing is: “Being able to hold your breath for 10 seconds or more without coughing or feeling discomfort DOES NOT mean you are free from COVID-19.”

For the policy and communication side of medicine in the midst of this pandemic, I will not claim to have a silver bullet. There are many intelligent, policy-minded people who are working on that very problem. However, as individual practitioners and as individual citizens, I can see two powerful tools that may help us move forward.

1) Confidence and humility: We live in a world of uncertainty, and we struggle against that every day. This pandemic has put our uncertainty clearly on display. However, we may also be confident in providing the best currently known care, even while holding the humility that what we know will likely change. Before COVID-19, we have all seen patients who received multiple different answers from multiple different providers. When I am willing to admit my uncertainty, I have witnessed patients’ skepticism transform into assuming an active role in their care.

For those who have suffered a direct hit or a near miss, honest conversations are vital to build a trusting physician-patient relationship. For the remote miss group, speaking candidly about our uncertainty displays our authenticity and helps combat conspiracy-type theories of ulterior motives. This becomes all the more crucial when new technologies are being deployed – for instance, a September 2020 CBS News survey showed only 21% of Americans planned to get a COVID-19 vaccine “as soon as possible.”

2) Insight into our driving emotions: While the near miss patients are likely ready to continue prevention measures, the remote miss group is often more difficult. When we do have the opportunity to discuss actions to impede the virus’ spread with the remote miss group, understanding their potentially unrecognized motivations helps with that conversation. I have shared the story of the London Blitz and the remote miss and seen people connect the dots with their own emotions. Effective counseling – expecting the feelings of invulnerability amongst the remote miss group – can support endurance with prevention measures amongst that group and help flatten the curve.

Communicating our strengths, transparently discussing our weaknesses, and better understanding underlying emotions for ourselves and our patients may help save lives. As physicians, that is our daily practice, unchanged even as medicine takes center stage in our national conversation.

Dr. Walthall completed his internal medicine residency at the Medical University of South Carolina in Charleston, SC. After residency, he joined the faculty at MUSC in the Division of Hospital Medicine. He is also interested in systems-based care and has taken on the role of physician advisor. This essay appeared first on The Hospital Leader, the official blog of SHM.

The Blitz was a Nazi bombing campaign targeting London. It was designed to break the spirit of the British. Knowing London would be the centerpiece of the campaign, the British rather hastily established several psychiatric hospitals for the expected panic in the streets. However, despite 9 months of bombing, 43,000 civilians killed and 139,000 more wounded, the predicted chaos in the streets did not manifest. Civilians continued to work, industry continued to churn, and eventually, Hitler’s eye turned east toward Russia.

H. F. Davis/Wikimedia Commons/Public Domain

The surprising lack of pandemonium in London inspired Dr. John T. MacCurdy, who chronicled his findings in a book The Structure of Morale, more recently popularized in Malcolm Gladwell’s David and Goliath. A brief summary of Dr. MacCurdy’s theory divides the targeted Londoners into the following categories:

• Direct hit
• Near miss
• Remote miss

The direct hit group was defined as those killed by the bombing. However, As Dr. MacCurdy stated, “The morale of the community depends on the reaction of the survivors…Put this way, the fact is obvious, corpses do not run about spreading panic.”

A near miss were those for whom wounds were inflicted or loved ones were killed. This group felt the real repercussions of the bombing. However, with 139,000 wounded out of a city of 8 million people, they were a small minority.

The majority of Londoners, then, fit into the third group – the remote miss. These people faced a serious fear, but survived, often totally unscathed. The process of facing that fear without having panicked or having been harmed, then, led to “a feeling of excitement with a flavour of invulnerability.”

Therefore, rather than a city of millions running in fear in the streets, requiring military presence to control the chaos, London became a city of people who felt themselves, perhaps, invincible.

A similar threat passed through the world in the first several months of the COVID-19 pandemic. Hospitals were expected to be overrun, and ethics committees convened to discuss allocation of scarce ventilators. However, due, at least in part, to the impressive efforts of the populace of the United States, the majority of civilians did not feel the burden of this frightening disease. Certainly, in a few places, hospitals were overwhelmed, and resources were unavailable due to sheer numbers. These places saw those who suffered direct hits with the highest frequency. However, a disease with an infection fatality ratio recently estimated at 0.5-1%, with a relatively high rate of asymptomatic disease, led to a large majority of people who experienced the first wave of COVID-19 in the United States as a remote miss. COVID-19’s flattened first peak gave much of the population a sense of relief, and, perhaps, a “flavour of invulnerability.”

An anonymous, but concerned, household contact wrote The New York Times and illustrated perfectly the invulnerable feelings of a remote miss:

“I’m doing my best to avoid social contact, along with two other members of my household. We have sufficient supplies for a month. Despite that, one member insists on going out for trivial reasons, such as not liking the kind of apples we have. He’s 92. I’ve tried explaining and cajoling, using graphs and anecdotes to make the danger to all of us seem ‘real.’ It doesn’t take. His risk of death is many times greater than mine, and he’s poking holes in a lifeboat we all have to rely on. What is the correct path?”

American culture expects certainty from science. Therein lies the problem with a new disease no medical provider or researcher had seen prior to November 2019. Action was required in the effort to slow the spread with little to no data as a guide. Therefore, messages that seemed contradictory reached the public. “A mask less than N-95 grade will not protect you,” evolved to, “everyone should wear a homemade cloth mask.” As the pandemic evolved and data was gathered, new recommendations were presented. Unfortunately, such well-meaning and necessary changes led to confusion, mistrust, and conspiracy theories.

Medicine’s response

The science of COVID-19 carries phenomenal uncertainties, but the psychology of those who have suffered direct hits or near misses are the daily bedside challenge of all physicians, but particularly of hospitalists. We live at the front lines of disease – as one colleague put it to me, “we are the watchers on the wall.” Though we do not yet have our hoped-for, evidence-based treatment for this virus, we are familiar with acute illness. We know the rapid change of health to disease, and we know the chronically ill who suffer exacerbations of such illness. Supporting patients and their loved ones through those times is our daily practice.

On the other hand, those who have experienced only remote misses remain vulnerable in this pandemic, despite their feelings of invincibility. Those that feel invincible may be the least interested in our advice. This, too, is no strange position for a physician. We have tools to reach patients who do not reach out to us. Traditional media outlets have been saturated with headlines and talking points about this disease. Physicians who have taken to social media have been met with appreciation in some situations, but ignored, doubted, or shunned in others. In May 2020, NBC News reported an ED doctor’s attempt to dispel some COVID myths on social media. Unfortunately, his remarks were summarily dismissed. Through the frustration, we persevere.

Out of the many responsible authorities who help battle misinformation, the World Health Organization’s mythbusting website (www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters) directly confronts many incorrect circulating ideas. My personal favorite at the time of this writing is: “Being able to hold your breath for 10 seconds or more without coughing or feeling discomfort DOES NOT mean you are free from COVID-19.”

For the policy and communication side of medicine in the midst of this pandemic, I will not claim to have a silver bullet. There are many intelligent, policy-minded people who are working on that very problem. However, as individual practitioners and as individual citizens, I can see two powerful tools that may help us move forward.

1) Confidence and humility: We live in a world of uncertainty, and we struggle against that every day. This pandemic has put our uncertainty clearly on display. However, we may also be confident in providing the best currently known care, even while holding the humility that what we know will likely change. Before COVID-19, we have all seen patients who received multiple different answers from multiple different providers. When I am willing to admit my uncertainty, I have witnessed patients’ skepticism transform into assuming an active role in their care.

For those who have suffered a direct hit or a near miss, honest conversations are vital to build a trusting physician-patient relationship. For the remote miss group, speaking candidly about our uncertainty displays our authenticity and helps combat conspiracy-type theories of ulterior motives. This becomes all the more crucial when new technologies are being deployed – for instance, a September 2020 CBS News survey showed only 21% of Americans planned to get a COVID-19 vaccine “as soon as possible.”

2) Insight into our driving emotions: While the near miss patients are likely ready to continue prevention measures, the remote miss group is often more difficult. When we do have the opportunity to discuss actions to impede the virus’ spread with the remote miss group, understanding their potentially unrecognized motivations helps with that conversation. I have shared the story of the London Blitz and the remote miss and seen people connect the dots with their own emotions. Effective counseling – expecting the feelings of invulnerability amongst the remote miss group – can support endurance with prevention measures amongst that group and help flatten the curve.

Communicating our strengths, transparently discussing our weaknesses, and better understanding underlying emotions for ourselves and our patients may help save lives. As physicians, that is our daily practice, unchanged even as medicine takes center stage in our national conversation.

Dr. Walthall completed his internal medicine residency at the Medical University of South Carolina in Charleston, SC. After residency, he joined the faculty at MUSC in the Division of Hospital Medicine. He is also interested in systems-based care and has taken on the role of physician advisor. This essay appeared first on The Hospital Leader, the official blog of SHM.

The Blitz was a Nazi bombing campaign targeting London. It was designed to break the spirit of the British. Knowing London would be the centerpiece of the campaign, the British rather hastily established several psychiatric hospitals for the expected panic in the streets. However, despite 9 months of bombing, 43,000 civilians killed and 139,000 more wounded, the predicted chaos in the streets did not manifest. Civilians continued to work, industry continued to churn, and eventually, Hitler’s eye turned east toward Russia.

H. F. Davis/Wikimedia Commons/Public Domain

The surprising lack of pandemonium in London inspired Dr. John T. MacCurdy, who chronicled his findings in a book The Structure of Morale, more recently popularized in Malcolm Gladwell’s David and Goliath. A brief summary of Dr. MacCurdy’s theory divides the targeted Londoners into the following categories:

• Direct hit
• Near miss
• Remote miss

The direct hit group was defined as those killed by the bombing. However, As Dr. MacCurdy stated, “The morale of the community depends on the reaction of the survivors…Put this way, the fact is obvious, corpses do not run about spreading panic.”

A near miss were those for whom wounds were inflicted or loved ones were killed. This group felt the real repercussions of the bombing. However, with 139,000 wounded out of a city of 8 million people, they were a small minority.

The majority of Londoners, then, fit into the third group – the remote miss. These people faced a serious fear, but survived, often totally unscathed. The process of facing that fear without having panicked or having been harmed, then, led to “a feeling of excitement with a flavour of invulnerability.”

Therefore, rather than a city of millions running in fear in the streets, requiring military presence to control the chaos, London became a city of people who felt themselves, perhaps, invincible.

A similar threat passed through the world in the first several months of the COVID-19 pandemic. Hospitals were expected to be overrun, and ethics committees convened to discuss allocation of scarce ventilators. However, due, at least in part, to the impressive efforts of the populace of the United States, the majority of civilians did not feel the burden of this frightening disease. Certainly, in a few places, hospitals were overwhelmed, and resources were unavailable due to sheer numbers. These places saw those who suffered direct hits with the highest frequency. However, a disease with an infection fatality ratio recently estimated at 0.5-1%, with a relatively high rate of asymptomatic disease, led to a large majority of people who experienced the first wave of COVID-19 in the United States as a remote miss. COVID-19’s flattened first peak gave much of the population a sense of relief, and, perhaps, a “flavour of invulnerability.”

An anonymous, but concerned, household contact wrote The New York Times and illustrated perfectly the invulnerable feelings of a remote miss:

“I’m doing my best to avoid social contact, along with two other members of my household. We have sufficient supplies for a month. Despite that, one member insists on going out for trivial reasons, such as not liking the kind of apples we have. He’s 92. I’ve tried explaining and cajoling, using graphs and anecdotes to make the danger to all of us seem ‘real.’ It doesn’t take. His risk of death is many times greater than mine, and he’s poking holes in a lifeboat we all have to rely on. What is the correct path?”

American culture expects certainty from science. Therein lies the problem with a new disease no medical provider or researcher had seen prior to November 2019. Action was required in the effort to slow the spread with little to no data as a guide. Therefore, messages that seemed contradictory reached the public. “A mask less than N-95 grade will not protect you,” evolved to, “everyone should wear a homemade cloth mask.” As the pandemic evolved and data was gathered, new recommendations were presented. Unfortunately, such well-meaning and necessary changes led to confusion, mistrust, and conspiracy theories.

Medicine’s response

The science of COVID-19 carries phenomenal uncertainties, but the psychology of those who have suffered direct hits or near misses are the daily bedside challenge of all physicians, but particularly of hospitalists. We live at the front lines of disease – as one colleague put it to me, “we are the watchers on the wall.” Though we do not yet have our hoped-for, evidence-based treatment for this virus, we are familiar with acute illness. We know the rapid change of health to disease, and we know the chronically ill who suffer exacerbations of such illness. Supporting patients and their loved ones through those times is our daily practice.

On the other hand, those who have experienced only remote misses remain vulnerable in this pandemic, despite their feelings of invincibility. Those that feel invincible may be the least interested in our advice. This, too, is no strange position for a physician. We have tools to reach patients who do not reach out to us. Traditional media outlets have been saturated with headlines and talking points about this disease. Physicians who have taken to social media have been met with appreciation in some situations, but ignored, doubted, or shunned in others. In May 2020, NBC News reported an ED doctor’s attempt to dispel some COVID myths on social media. Unfortunately, his remarks were summarily dismissed. Through the frustration, we persevere.

Out of the many responsible authorities who help battle misinformation, the World Health Organization’s mythbusting website (www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters) directly confronts many incorrect circulating ideas. My personal favorite at the time of this writing is: “Being able to hold your breath for 10 seconds or more without coughing or feeling discomfort DOES NOT mean you are free from COVID-19.”

For the policy and communication side of medicine in the midst of this pandemic, I will not claim to have a silver bullet. There are many intelligent, policy-minded people who are working on that very problem. However, as individual practitioners and as individual citizens, I can see two powerful tools that may help us move forward.

1) Confidence and humility: We live in a world of uncertainty, and we struggle against that every day. This pandemic has put our uncertainty clearly on display. However, we may also be confident in providing the best currently known care, even while holding the humility that what we know will likely change. Before COVID-19, we have all seen patients who received multiple different answers from multiple different providers. When I am willing to admit my uncertainty, I have witnessed patients’ skepticism transform into assuming an active role in their care.

For those who have suffered a direct hit or a near miss, honest conversations are vital to build a trusting physician-patient relationship. For the remote miss group, speaking candidly about our uncertainty displays our authenticity and helps combat conspiracy-type theories of ulterior motives. This becomes all the more crucial when new technologies are being deployed – for instance, a September 2020 CBS News survey showed only 21% of Americans planned to get a COVID-19 vaccine “as soon as possible.”

2) Insight into our driving emotions: While the near miss patients are likely ready to continue prevention measures, the remote miss group is often more difficult. When we do have the opportunity to discuss actions to impede the virus’ spread with the remote miss group, understanding their potentially unrecognized motivations helps with that conversation. I have shared the story of the London Blitz and the remote miss and seen people connect the dots with their own emotions. Effective counseling – expecting the feelings of invulnerability amongst the remote miss group – can support endurance with prevention measures amongst that group and help flatten the curve.

Communicating our strengths, transparently discussing our weaknesses, and better understanding underlying emotions for ourselves and our patients may help save lives. As physicians, that is our daily practice, unchanged even as medicine takes center stage in our national conversation.

Dr. Walthall completed his internal medicine residency at the Medical University of South Carolina in Charleston, SC. After residency, he joined the faculty at MUSC in the Division of Hospital Medicine. He is also interested in systems-based care and has taken on the role of physician advisor. This essay appeared first on The Hospital Leader, the official blog of SHM.

The National Institutes of Health has launched a database to track COVID-19–related neurologic symptoms, complications, and outcomes as well as the effects of the virus on preexisting neurologic conditions.

“We know COVID-19 can disrupt multiple body systems, but the effects of the virus and the body’s response to COVID-19 infection on the brain, spinal cord, nerves, and muscle can be particularly devastating and contribute to persistence of disability even after the virus is cleared,” said Barbara Karp, MD, program director at the National Institute of Neurological Disorders and Stroke.

“There is an urgent need to understand COVID-19–related neurological problems, which not uncommonly include headaches, fatigue, cognitive difficulties, stroke, pain, and sleep disorders as well as some very rare complications of serious infections,” said Dr. Karp.

The COVID-19 NeuroDatabank/BioBank (NeuroCOVID) is funded by the NINDS. It was created and will be maintained by researchers at NYU Langone Health in New York.

The project is led by Andrea Troxel, ScD, professor of population health, and Eva Petkova, PhD, professor of population health and child and adolescent psychiatry, both at New York University.

“We’ve built a pretty comprehensive database that will accept deidentified patient information about new neurological issues that coincide with their COVID disease or worsening of preexisting neurological problems,” said Dr. Troxel. “In addition, we have a bio repository that will accept almost any kind of biological sample, such as blood, plasma, cerebrospinal fluid, and tissue,” she said.

“Neuroimages are very difficult to store because the files are so enormous, but we’ve had some questions about that, and we’re looking into whether we can accommodate neuroimages,” Dr. Troxel noted.

Dr. Troxel said a “blast of information and invitations” has gone out in an effort to acquire data and biospecimens. “We’ve been really pleased with the amount of interest already, interest not only from large academic medical centers, as you might expect, but also from some smaller stand-alone clinics and even some individuals who have either experienced some of these neurological problems of COVID or know those who have and are really eager to try to provide information,” she added.

Researchers interested in using data and biosamples from the database may submit requests to the NeuroCOVID Steering Committee. More information is available online on the NeuroCOVID website.

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

The National Institutes of Health has launched a database to track COVID-19–related neurologic symptoms, complications, and outcomes as well as the effects of the virus on preexisting neurologic conditions.

“We know COVID-19 can disrupt multiple body systems, but the effects of the virus and the body’s response to COVID-19 infection on the brain, spinal cord, nerves, and muscle can be particularly devastating and contribute to persistence of disability even after the virus is cleared,” said Barbara Karp, MD, program director at the National Institute of Neurological Disorders and Stroke.

“There is an urgent need to understand COVID-19–related neurological problems, which not uncommonly include headaches, fatigue, cognitive difficulties, stroke, pain, and sleep disorders as well as some very rare complications of serious infections,” said Dr. Karp.

The COVID-19 NeuroDatabank/BioBank (NeuroCOVID) is funded by the NINDS. It was created and will be maintained by researchers at NYU Langone Health in New York.

The project is led by Andrea Troxel, ScD, professor of population health, and Eva Petkova, PhD, professor of population health and child and adolescent psychiatry, both at New York University.

“We’ve built a pretty comprehensive database that will accept deidentified patient information about new neurological issues that coincide with their COVID disease or worsening of preexisting neurological problems,” said Dr. Troxel. “In addition, we have a bio repository that will accept almost any kind of biological sample, such as blood, plasma, cerebrospinal fluid, and tissue,” she said.

“Neuroimages are very difficult to store because the files are so enormous, but we’ve had some questions about that, and we’re looking into whether we can accommodate neuroimages,” Dr. Troxel noted.

Dr. Troxel said a “blast of information and invitations” has gone out in an effort to acquire data and biospecimens. “We’ve been really pleased with the amount of interest already, interest not only from large academic medical centers, as you might expect, but also from some smaller stand-alone clinics and even some individuals who have either experienced some of these neurological problems of COVID or know those who have and are really eager to try to provide information,” she added.

Researchers interested in using data and biosamples from the database may submit requests to the NeuroCOVID Steering Committee. More information is available online on the NeuroCOVID website.

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

The National Institutes of Health has launched a database to track COVID-19–related neurologic symptoms, complications, and outcomes as well as the effects of the virus on preexisting neurologic conditions.

“We know COVID-19 can disrupt multiple body systems, but the effects of the virus and the body’s response to COVID-19 infection on the brain, spinal cord, nerves, and muscle can be particularly devastating and contribute to persistence of disability even after the virus is cleared,” said Barbara Karp, MD, program director at the National Institute of Neurological Disorders and Stroke.

“There is an urgent need to understand COVID-19–related neurological problems, which not uncommonly include headaches, fatigue, cognitive difficulties, stroke, pain, and sleep disorders as well as some very rare complications of serious infections,” said Dr. Karp.

The COVID-19 NeuroDatabank/BioBank (NeuroCOVID) is funded by the NINDS. It was created and will be maintained by researchers at NYU Langone Health in New York.

The project is led by Andrea Troxel, ScD, professor of population health, and Eva Petkova, PhD, professor of population health and child and adolescent psychiatry, both at New York University.

“We’ve built a pretty comprehensive database that will accept deidentified patient information about new neurological issues that coincide with their COVID disease or worsening of preexisting neurological problems,” said Dr. Troxel. “In addition, we have a bio repository that will accept almost any kind of biological sample, such as blood, plasma, cerebrospinal fluid, and tissue,” she said.

“Neuroimages are very difficult to store because the files are so enormous, but we’ve had some questions about that, and we’re looking into whether we can accommodate neuroimages,” Dr. Troxel noted.

Dr. Troxel said a “blast of information and invitations” has gone out in an effort to acquire data and biospecimens. “We’ve been really pleased with the amount of interest already, interest not only from large academic medical centers, as you might expect, but also from some smaller stand-alone clinics and even some individuals who have either experienced some of these neurological problems of COVID or know those who have and are really eager to try to provide information,” she added.

Researchers interested in using data and biosamples from the database may submit requests to the NeuroCOVID Steering Committee. More information is available online on the NeuroCOVID website.

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

Researchers from the National Institute of Neurological Disorders and Stroke studying the brains of patients who died from COVID-19, “consistently” found microvascular damage—but no signs of COVID-19 infection. Of the 19 patients in the study, 14 had chronic illnesses, including diabetes mellitus and hypertension, and 11 had ben found dead or had died unexpectedly. Of the 16 with available medical histories, one had delirium and the others had respiratory or unknown symptoms. Two had pulmonary embolism.

                Patients with COVID-19 often have neurological problems, such as headaches, delirium, and dizziness. Some have strokes. Several studies have shown that COVID-19 can cause inflammation and blood vessel damage, but the precise mode of action is still unclear. In this study, the researchers used a magnetic resonance imaging (MRI) scanner 4 to 10 times more sensitive than most MRI scanners to examine samples of the olfactory bulbs and brainstems from the samples.

                In 9 patients, the MRI scan showed punctate hyperintensities (bright spots representing areas of microvascular injury and fibrinogen leakage) that often indicate inflammation. In 10 brains, they found punctate hypointensities (dark spots) that corresponded to congested blood vessels, with surrounding areas of fibrinogen leakage and relatively intact vasculature. Areas of linear hypointensities (dark spots) were interpreted as microhemorrhages.

                Using the scans as a guide, the researchers examined the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaked blood proteins into the brain. This, the researchers say, seemed to trigger an immune reaction. The spots were surrounded by T cells from the blood and the brain’s own immune cells. In contrast, the dark spots contained clotted and leaky blood vessels but no immune response.

                Moreover, although they used several methods for detecting genetic material or proteins from SAS-CoV-2, they found none. It’s possible, the researchers say, that the virus was cleared by the time of death or that viral copy numbers were undetectable by their assays.

                We were completely surprised,” said Avindra Nath, MD, NINDS clinical director. “Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases.”

                In future, Nath says, they plan to study how COVID-19 harms the blood vessels and whether that produces some of the short- and long-term symptoms seen. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”

Researchers from the National Institute of Neurological Disorders and Stroke studying the brains of patients who died from COVID-19, “consistently” found microvascular damage—but no signs of COVID-19 infection. Of the 19 patients in the study, 14 had chronic illnesses, including diabetes mellitus and hypertension, and 11 had ben found dead or had died unexpectedly. Of the 16 with available medical histories, one had delirium and the others had respiratory or unknown symptoms. Two had pulmonary embolism.

                Patients with COVID-19 often have neurological problems, such as headaches, delirium, and dizziness. Some have strokes. Several studies have shown that COVID-19 can cause inflammation and blood vessel damage, but the precise mode of action is still unclear. In this study, the researchers used a magnetic resonance imaging (MRI) scanner 4 to 10 times more sensitive than most MRI scanners to examine samples of the olfactory bulbs and brainstems from the samples.

                In 9 patients, the MRI scan showed punctate hyperintensities (bright spots representing areas of microvascular injury and fibrinogen leakage) that often indicate inflammation. In 10 brains, they found punctate hypointensities (dark spots) that corresponded to congested blood vessels, with surrounding areas of fibrinogen leakage and relatively intact vasculature. Areas of linear hypointensities (dark spots) were interpreted as microhemorrhages.

                Using the scans as a guide, the researchers examined the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaked blood proteins into the brain. This, the researchers say, seemed to trigger an immune reaction. The spots were surrounded by T cells from the blood and the brain’s own immune cells. In contrast, the dark spots contained clotted and leaky blood vessels but no immune response.

                Moreover, although they used several methods for detecting genetic material or proteins from SAS-CoV-2, they found none. It’s possible, the researchers say, that the virus was cleared by the time of death or that viral copy numbers were undetectable by their assays.

                We were completely surprised,” said Avindra Nath, MD, NINDS clinical director. “Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases.”

                In future, Nath says, they plan to study how COVID-19 harms the blood vessels and whether that produces some of the short- and long-term symptoms seen. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”

Researchers from the National Institute of Neurological Disorders and Stroke studying the brains of patients who died from COVID-19, “consistently” found microvascular damage—but no signs of COVID-19 infection. Of the 19 patients in the study, 14 had chronic illnesses, including diabetes mellitus and hypertension, and 11 had ben found dead or had died unexpectedly. Of the 16 with available medical histories, one had delirium and the others had respiratory or unknown symptoms. Two had pulmonary embolism.

                Patients with COVID-19 often have neurological problems, such as headaches, delirium, and dizziness. Some have strokes. Several studies have shown that COVID-19 can cause inflammation and blood vessel damage, but the precise mode of action is still unclear. In this study, the researchers used a magnetic resonance imaging (MRI) scanner 4 to 10 times more sensitive than most MRI scanners to examine samples of the olfactory bulbs and brainstems from the samples.

                In 9 patients, the MRI scan showed punctate hyperintensities (bright spots representing areas of microvascular injury and fibrinogen leakage) that often indicate inflammation. In 10 brains, they found punctate hypointensities (dark spots) that corresponded to congested blood vessels, with surrounding areas of fibrinogen leakage and relatively intact vasculature. Areas of linear hypointensities (dark spots) were interpreted as microhemorrhages.

                Using the scans as a guide, the researchers examined the spots more closely under a microscope. They found that the bright spots contained blood vessels that were thinner than normal and sometimes leaked blood proteins into the brain. This, the researchers say, seemed to trigger an immune reaction. The spots were surrounded by T cells from the blood and the brain’s own immune cells. In contrast, the dark spots contained clotted and leaky blood vessels but no immune response.

                Moreover, although they used several methods for detecting genetic material or proteins from SAS-CoV-2, they found none. It’s possible, the researchers say, that the virus was cleared by the time of death or that viral copy numbers were undetectable by their assays.

                We were completely surprised,” said Avindra Nath, MD, NINDS clinical director. “Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases.”

                In future, Nath says, they plan to study how COVID-19 harms the blood vessels and whether that produces some of the short- and long-term symptoms seen. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”

Coinfection with COVID-19 and influenza was reported early in the pandemic. Although both infections on their own can cause severe complications and death, coinfection can double the odds of death when compared with COVID infection alone. Moreover, those odds can be raised by chronic medical conditions and environmental or occupational factors, such as congregate living settings, say physicians who report on the first 2 confirmed cases of COVID-19 and influenza coinfection among US Department of Defense personnel within the US Central Command area of responsibility.

                In the first case, a 56-year-old contractor presented to a Role I clinic with anorexia, fever, chills, and headache, which had begun 3 days before. His initial vital signs were “unremarkable,” and he did not have symptoms of respiratory distress. An antigen test was positive for influenza type A. A COVID-19 test also was positive. He was placed on isolation and treated with oseltamivir, amlodipine, hydrochlorothiazide, and losartan. His condition did not warrant hospitalization. Of 3 close contacts, 1 tested positive and was isolated. Two remained asymptomatic during the 14-day quarantine. Ten days after onset, the patient returned to duty.

                The second patient, a 34-year-old officer in the Army, was initially identified as a close contact of a confirmed COVID-19 case and placed in quarantine. He was asymptomatic but tested positive and was placed in isolation with precautions. As with the first patient, his vital signs were unremarkable. He continued to be asymptomatic, although he reported myalgias 2 days later. Since those are a classic sign of seasonal influenzas, he was tested and proved positive for type B influenza. He, too, was started on oseltamivir. By the end of the first week, he experienced loss of taste and smell, cough, and shortness of breath, but his vital signs remained normal. His symptoms improved through supportive care. All 6 of his close contacts remained asymptomatic. Ten days after his symptoms began, he also returned to duty.

                Influenza-associated deaths among the US military have been relatively few, the authors say, most likely because of the good preexisting health status of the US military, prompt detection with rapid influenza diagnostic tests, several effective antiviral therapeutics, and a “robust, compulsory vaccination program.” Nonetheless, neither patient had received the 2020-2021 influenza vaccine, which underscores the importance of this intervention, the authors say.

                Because both infections present with a wide variety of clinical manifestations and overlapping symptoms, providers should stay alert to the possibility of coinfection, especially among personnel who are higher risk. For instance, as a linguist who interacted daily with host nation partners, the civilian contractor had a high occupational exposure.

                While the authors only discuss 2 cases, a Medical Surveillance Monthly Report editorial comment says their report “nevertheless supports the importance of implementing force health protection (FHP) measures to prevent, detect, and respond to the spread of both of these health threats.” It’s particularly important, the comment notes, in the current context of a drawdown in forces in many deployed locations, as further losses of personnel to illness may degrade the execution of critical missions.

Coinfection with COVID-19 and influenza was reported early in the pandemic. Although both infections on their own can cause severe complications and death, coinfection can double the odds of death when compared with COVID infection alone. Moreover, those odds can be raised by chronic medical conditions and environmental or occupational factors, such as congregate living settings, say physicians who report on the first 2 confirmed cases of COVID-19 and influenza coinfection among US Department of Defense personnel within the US Central Command area of responsibility.

                In the first case, a 56-year-old contractor presented to a Role I clinic with anorexia, fever, chills, and headache, which had begun 3 days before. His initial vital signs were “unremarkable,” and he did not have symptoms of respiratory distress. An antigen test was positive for influenza type A. A COVID-19 test also was positive. He was placed on isolation and treated with oseltamivir, amlodipine, hydrochlorothiazide, and losartan. His condition did not warrant hospitalization. Of 3 close contacts, 1 tested positive and was isolated. Two remained asymptomatic during the 14-day quarantine. Ten days after onset, the patient returned to duty.

                The second patient, a 34-year-old officer in the Army, was initially identified as a close contact of a confirmed COVID-19 case and placed in quarantine. He was asymptomatic but tested positive and was placed in isolation with precautions. As with the first patient, his vital signs were unremarkable. He continued to be asymptomatic, although he reported myalgias 2 days later. Since those are a classic sign of seasonal influenzas, he was tested and proved positive for type B influenza. He, too, was started on oseltamivir. By the end of the first week, he experienced loss of taste and smell, cough, and shortness of breath, but his vital signs remained normal. His symptoms improved through supportive care. All 6 of his close contacts remained asymptomatic. Ten days after his symptoms began, he also returned to duty.

                Influenza-associated deaths among the US military have been relatively few, the authors say, most likely because of the good preexisting health status of the US military, prompt detection with rapid influenza diagnostic tests, several effective antiviral therapeutics, and a “robust, compulsory vaccination program.” Nonetheless, neither patient had received the 2020-2021 influenza vaccine, which underscores the importance of this intervention, the authors say.

                Because both infections present with a wide variety of clinical manifestations and overlapping symptoms, providers should stay alert to the possibility of coinfection, especially among personnel who are higher risk. For instance, as a linguist who interacted daily with host nation partners, the civilian contractor had a high occupational exposure.

                While the authors only discuss 2 cases, a Medical Surveillance Monthly Report editorial comment says their report “nevertheless supports the importance of implementing force health protection (FHP) measures to prevent, detect, and respond to the spread of both of these health threats.” It’s particularly important, the comment notes, in the current context of a drawdown in forces in many deployed locations, as further losses of personnel to illness may degrade the execution of critical missions.

Coinfection with COVID-19 and influenza was reported early in the pandemic. Although both infections on their own can cause severe complications and death, coinfection can double the odds of death when compared with COVID infection alone. Moreover, those odds can be raised by chronic medical conditions and environmental or occupational factors, such as congregate living settings, say physicians who report on the first 2 confirmed cases of COVID-19 and influenza coinfection among US Department of Defense personnel within the US Central Command area of responsibility.

                In the first case, a 56-year-old contractor presented to a Role I clinic with anorexia, fever, chills, and headache, which had begun 3 days before. His initial vital signs were “unremarkable,” and he did not have symptoms of respiratory distress. An antigen test was positive for influenza type A. A COVID-19 test also was positive. He was placed on isolation and treated with oseltamivir, amlodipine, hydrochlorothiazide, and losartan. His condition did not warrant hospitalization. Of 3 close contacts, 1 tested positive and was isolated. Two remained asymptomatic during the 14-day quarantine. Ten days after onset, the patient returned to duty.

                The second patient, a 34-year-old officer in the Army, was initially identified as a close contact of a confirmed COVID-19 case and placed in quarantine. He was asymptomatic but tested positive and was placed in isolation with precautions. As with the first patient, his vital signs were unremarkable. He continued to be asymptomatic, although he reported myalgias 2 days later. Since those are a classic sign of seasonal influenzas, he was tested and proved positive for type B influenza. He, too, was started on oseltamivir. By the end of the first week, he experienced loss of taste and smell, cough, and shortness of breath, but his vital signs remained normal. His symptoms improved through supportive care. All 6 of his close contacts remained asymptomatic. Ten days after his symptoms began, he also returned to duty.

                Influenza-associated deaths among the US military have been relatively few, the authors say, most likely because of the good preexisting health status of the US military, prompt detection with rapid influenza diagnostic tests, several effective antiviral therapeutics, and a “robust, compulsory vaccination program.” Nonetheless, neither patient had received the 2020-2021 influenza vaccine, which underscores the importance of this intervention, the authors say.

                Because both infections present with a wide variety of clinical manifestations and overlapping symptoms, providers should stay alert to the possibility of coinfection, especially among personnel who are higher risk. For instance, as a linguist who interacted daily with host nation partners, the civilian contractor had a high occupational exposure.

                While the authors only discuss 2 cases, a Medical Surveillance Monthly Report editorial comment says their report “nevertheless supports the importance of implementing force health protection (FHP) measures to prevent, detect, and respond to the spread of both of these health threats.” It’s particularly important, the comment notes, in the current context of a drawdown in forces in many deployed locations, as further losses of personnel to illness may degrade the execution of critical missions.

Schizophrenia spectrum disorder is associated with a significantly increased risk of dying from COVID-19, new research shows.

After adjusting for demographic and medical risk factors, the investigators found that patients who had been diagnosed with schizophrenia were two to three times more likely to die of COVID-19 if they contracted the disease.

“This means that people with schizophrenia should be prioritized for vaccination, and efforts should be taken to reduce risk of infection [social distancing, masks, etc.], particularly in people with schizophrenia who live in congregate living situations [hospitals and group residences],” Donald Goff, MD, department of psychiatry, New York University Langone Medical Center, said in an interview.

The study was published online Jan. 27 in JAMA Psychiatry.

The study included 7,348 adults with laboratory-confirmed SARS-CoV-2 infection from the NYU Langone Health System; 75 (1.0%) had a history of schizophrenia spectrum disorder, 564 (7.7%) had a history of a mood disorder, and 360 (4.9%) had a history of an anxiety disorder.

Overall, 864 patients (11.8%) died or were discharged to hospice within 45 days of a positive SARS-CoV-2 test.

In the fully adjusted model, a premorbid diagnosis of schizophrenia spectrum disorder, but not mood or anxiety disorder, was significantly associated with an increased risk of dying from COVID-19 within 45 days.

‘Alarming finding’

In an interview, Luming Li, MD, Yale New Haven (Conn.) Psychiatric Hospital, noted that, although the number patients with schizophrenia spectrum disorders in the sample is “fairly low,” she was not surprised by the increased risk for death from COVID-19.

“Schizophrenia falls into the serious mental illness category, and these patients are more often predisposed to homelessness, comorbid medical and substance use, living in congregate settings, lower socioeconomic status, etc,” Dr. Li noted.

Dr. Li’s advice for clinicians who treat patients who have schizophrenia during the COVID-19 pandemic is to minimize their risk in various care settings through the use of personal protective equipment and other infection prevention techniques.

“If a patient does contract COVID-19, make sure patient’s care is escalated appropriately, given the higher risk for mortality in patients with schizophrenia spectrum disorders,” she said.

Tom Pollak, PhD, MRCPsych, King’s College London, said that it has been known for some time that patients with serious mental illness have poorer physical health outcomes. More recently, it has been shown that those who have been diagnosed with psychiatric disorders appear to be at greater risk for poor COVID-19 outcomes.

“This study is the first to specifically highlight schizophrenia spectrum disorders as being particularly at risk. This is an alarming finding. These patients are already amongst the most vulnerable members of society and are probably underserved by most health care systems worldwide,” Dr. Pollak said in a statement.

“Although these findings need urgent replication in larger samples, there are clear reasons for policymakers to take notice now, including giving immediate consideration for prioritization of patients with serious mental illness in nationwide COVID-19 vaccination programs,” he added.

Matthew Hotopf, PhD, FRCPsych, FMedSci, also with King’s College London, said that the New York group has identified people with severe mental disorders as “a high-risk group, and this has immediate public health implications regarding vaccination – that’s the important message of the paper.

“Schizophrenia and other severe psychiatric disorders are risk factors for mortality in the general population before COVID. This is a group with a 10- to 20-year reduction in life expectancy – more than for many diseases we associated with early death,” said Dr. Hotopf.

“The reasons for this are multifactorial, including social deprivation, lifestyle factors (people with schizophrenia smoke more and have high rates of obesity), harms associated with some medications used to treat psychosis, and differential access to health care,” he noted.

“In COVID, we know that deprivation is associated with a much higher mortality, so we would therefore expect that people with severe mental illness will be particularly disadvantaged,” he said.

The study had no specific funding. Dr. Goff has received research support and travel reimbursement from Avanir Pharmaceuticals and Takeda. Dr. Nemani, Dr. Li, Dr. Pollak, and Dr. Hotopf disclosed no relevant financial relationships.

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

Schizophrenia spectrum disorder is associated with a significantly increased risk of dying from COVID-19, new research shows.

After adjusting for demographic and medical risk factors, the investigators found that patients who had been diagnosed with schizophrenia were two to three times more likely to die of COVID-19 if they contracted the disease.

“This means that people with schizophrenia should be prioritized for vaccination, and efforts should be taken to reduce risk of infection [social distancing, masks, etc.], particularly in people with schizophrenia who live in congregate living situations [hospitals and group residences],” Donald Goff, MD, department of psychiatry, New York University Langone Medical Center, said in an interview.

The study was published online Jan. 27 in JAMA Psychiatry.

The study included 7,348 adults with laboratory-confirmed SARS-CoV-2 infection from the NYU Langone Health System; 75 (1.0%) had a history of schizophrenia spectrum disorder, 564 (7.7%) had a history of a mood disorder, and 360 (4.9%) had a history of an anxiety disorder.

Overall, 864 patients (11.8%) died or were discharged to hospice within 45 days of a positive SARS-CoV-2 test.

In the fully adjusted model, a premorbid diagnosis of schizophrenia spectrum disorder, but not mood or anxiety disorder, was significantly associated with an increased risk of dying from COVID-19 within 45 days.

‘Alarming finding’

In an interview, Luming Li, MD, Yale New Haven (Conn.) Psychiatric Hospital, noted that, although the number patients with schizophrenia spectrum disorders in the sample is “fairly low,” she was not surprised by the increased risk for death from COVID-19.

“Schizophrenia falls into the serious mental illness category, and these patients are more often predisposed to homelessness, comorbid medical and substance use, living in congregate settings, lower socioeconomic status, etc,” Dr. Li noted.

Dr. Li’s advice for clinicians who treat patients who have schizophrenia during the COVID-19 pandemic is to minimize their risk in various care settings through the use of personal protective equipment and other infection prevention techniques.

“If a patient does contract COVID-19, make sure patient’s care is escalated appropriately, given the higher risk for mortality in patients with schizophrenia spectrum disorders,” she said.

Tom Pollak, PhD, MRCPsych, King’s College London, said that it has been known for some time that patients with serious mental illness have poorer physical health outcomes. More recently, it has been shown that those who have been diagnosed with psychiatric disorders appear to be at greater risk for poor COVID-19 outcomes.

“This study is the first to specifically highlight schizophrenia spectrum disorders as being particularly at risk. This is an alarming finding. These patients are already amongst the most vulnerable members of society and are probably underserved by most health care systems worldwide,” Dr. Pollak said in a statement.

“Although these findings need urgent replication in larger samples, there are clear reasons for policymakers to take notice now, including giving immediate consideration for prioritization of patients with serious mental illness in nationwide COVID-19 vaccination programs,” he added.

Matthew Hotopf, PhD, FRCPsych, FMedSci, also with King’s College London, said that the New York group has identified people with severe mental disorders as “a high-risk group, and this has immediate public health implications regarding vaccination – that’s the important message of the paper.

“Schizophrenia and other severe psychiatric disorders are risk factors for mortality in the general population before COVID. This is a group with a 10- to 20-year reduction in life expectancy – more than for many diseases we associated with early death,” said Dr. Hotopf.

“The reasons for this are multifactorial, including social deprivation, lifestyle factors (people with schizophrenia smoke more and have high rates of obesity), harms associated with some medications used to treat psychosis, and differential access to health care,” he noted.

“In COVID, we know that deprivation is associated with a much higher mortality, so we would therefore expect that people with severe mental illness will be particularly disadvantaged,” he said.

The study had no specific funding. Dr. Goff has received research support and travel reimbursement from Avanir Pharmaceuticals and Takeda. Dr. Nemani, Dr. Li, Dr. Pollak, and Dr. Hotopf disclosed no relevant financial relationships.

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

Schizophrenia spectrum disorder is associated with a significantly increased risk of dying from COVID-19, new research shows.

After adjusting for demographic and medical risk factors, the investigators found that patients who had been diagnosed with schizophrenia were two to three times more likely to die of COVID-19 if they contracted the disease.

“This means that people with schizophrenia should be prioritized for vaccination, and efforts should be taken to reduce risk of infection [social distancing, masks, etc.], particularly in people with schizophrenia who live in congregate living situations [hospitals and group residences],” Donald Goff, MD, department of psychiatry, New York University Langone Medical Center, said in an interview.

The study was published online Jan. 27 in JAMA Psychiatry.

The study included 7,348 adults with laboratory-confirmed SARS-CoV-2 infection from the NYU Langone Health System; 75 (1.0%) had a history of schizophrenia spectrum disorder, 564 (7.7%) had a history of a mood disorder, and 360 (4.9%) had a history of an anxiety disorder.

Overall, 864 patients (11.8%) died or were discharged to hospice within 45 days of a positive SARS-CoV-2 test.

In the fully adjusted model, a premorbid diagnosis of schizophrenia spectrum disorder, but not mood or anxiety disorder, was significantly associated with an increased risk of dying from COVID-19 within 45 days.

‘Alarming finding’

In an interview, Luming Li, MD, Yale New Haven (Conn.) Psychiatric Hospital, noted that, although the number patients with schizophrenia spectrum disorders in the sample is “fairly low,” she was not surprised by the increased risk for death from COVID-19.

“Schizophrenia falls into the serious mental illness category, and these patients are more often predisposed to homelessness, comorbid medical and substance use, living in congregate settings, lower socioeconomic status, etc,” Dr. Li noted.

Dr. Li’s advice for clinicians who treat patients who have schizophrenia during the COVID-19 pandemic is to minimize their risk in various care settings through the use of personal protective equipment and other infection prevention techniques.

“If a patient does contract COVID-19, make sure patient’s care is escalated appropriately, given the higher risk for mortality in patients with schizophrenia spectrum disorders,” she said.

Tom Pollak, PhD, MRCPsych, King’s College London, said that it has been known for some time that patients with serious mental illness have poorer physical health outcomes. More recently, it has been shown that those who have been diagnosed with psychiatric disorders appear to be at greater risk for poor COVID-19 outcomes.

“This study is the first to specifically highlight schizophrenia spectrum disorders as being particularly at risk. This is an alarming finding. These patients are already amongst the most vulnerable members of society and are probably underserved by most health care systems worldwide,” Dr. Pollak said in a statement.

“Although these findings need urgent replication in larger samples, there are clear reasons for policymakers to take notice now, including giving immediate consideration for prioritization of patients with serious mental illness in nationwide COVID-19 vaccination programs,” he added.

Matthew Hotopf, PhD, FRCPsych, FMedSci, also with King’s College London, said that the New York group has identified people with severe mental disorders as “a high-risk group, and this has immediate public health implications regarding vaccination – that’s the important message of the paper.

“Schizophrenia and other severe psychiatric disorders are risk factors for mortality in the general population before COVID. This is a group with a 10- to 20-year reduction in life expectancy – more than for many diseases we associated with early death,” said Dr. Hotopf.

“The reasons for this are multifactorial, including social deprivation, lifestyle factors (people with schizophrenia smoke more and have high rates of obesity), harms associated with some medications used to treat psychosis, and differential access to health care,” he noted.

“In COVID, we know that deprivation is associated with a much higher mortality, so we would therefore expect that people with severe mental illness will be particularly disadvantaged,” he said.

The study had no specific funding. Dr. Goff has received research support and travel reimbursement from Avanir Pharmaceuticals and Takeda. Dr. Nemani, Dr. Li, Dr. Pollak, and Dr. Hotopf disclosed no relevant financial relationships.

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

The Janssen/Johnson & Johnson single-dose adenovirus vaccine provides 85% efficacy globally against severe COVID-19 illness, according to the highly anticipated interim phase 3 results announced this morning.

The efficacy against severe disease provided by the Janssen/J&J vaccine held true regardless of age, race/ethnicity, absence or presence of comorbidities, and geography. The 44,000-participant ENSEMBLE study was conducted in the United States, South America, and South Africa.

“The team is very diligently monitoring all the variants that come up, and there are literally thousands of these. We are acting in anticipation of a variant being a potential problem. The South African variant we too acted on right away. So we too are preparing that antigen for testing.

“With data today, we do see that not a single South African, after 28 days post vaccination, ended up needing to go to the hospital, no South African died who was vaccinated.

“We do see that 85%-plus protection in South African against severe disease. That is one of the most exciting results in the dataset today,” said Mathai Mammen, MD, PhD, global head of Janssen Research & Development.

The overall efficacy was 66% globally, 72% in the United States, 66% in Latin America, and 57% in South Africa against moderate to severe SARS-CoV-2 28 days post vaccination, officials from the National Institutes of Health and Janssen reported during a media briefing.

But the J&J vaccine has potential advantages over the existing two-dose Pfizer/BioNTech and Moderna mRNA vaccines because it’s single dose and has less stringent storage requirements – only regular refrigeration is needed versus a need to freeze the two-dose Pfizer/BioNTech and Moderna COVID-19 vaccines. The J&J vaccine can be refrigerated for up to 3 months at 36°-46° F (2°-8° C).

But the difference between these just-released efficacy figures and the 94%-95% efficacy provided by the existing Pfizer/BioNTech and Moderna mRNA vaccines generated many questions during the briefing.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the focus should not just be on the overall numbers. “The most important thing from a public health standpoint domestically is to keep people out of the hospital and prevent them from getting severe illness,” he said. “Many in the general public might look at a number and want to know if they get symptomatic disease or not.”

“More important than preventing someone from getting some aches and a sore throat is to prevent people – particularly people who have underlying conditions and the elderly, the ones most susceptible to a severe outcome – [from getting] severe disease,” Dr. Fauci added. Prevention of severe outcomes in a high percentage of individuals “will alleviate so much of the stress, human suffering, and death.”

Dr. Fauci acknowledged that many people will naturally focus on the distinction between 72% efficacy and 94%-95% efficacy. “This could be a messaging challenge [but] you have to make sure people understand the implications.”

It is more complex, he added, than just asking people: “If you go to the door on the left, you get 94% or 95%. If you go to the door to the right, you get 72%. What door do you want to go to?”

Instead, the messaging should be that “this and the other vaccines we have are actually preventing severe disease to a very substantial degree.”
 

Company defends numbers

Janssen defended their efficacy findings, pointing out that it is not a fair comparison.

“The vaccine programs that went a couple of months ago, they ran their studies during different times, when the pandemic was less complex. There were not these variants, and there was not the same level of incidence, which puts pressure on vaccine efficacy,” said Mathai Mammen, MD, PhD, global head of research and development for Janssen.

“So the numbers cannot really be compared, and that does pose a messaging challenge,” he said. “But the reality is, if one was to run the same studies [for the Pfizer and Moderna vaccines] today you would likely see different results.”

Asked if the efficacy figures could affect vaccine hesitancy, National Institutes of Health Director Francis Collins, MD, PhD, said at the announcement that most reluctance among people to get vaccinated against SARS-CoV-2 stems from concerns about safety. “The safety record is extremely good for this vaccine, as it is for the others that have received emergency use authorization.”

Janssen/J&J plans to submit for emergency use authorization from the U.S. Food and Drug Administration next week, at which point the company plans to release more information on side effects, deaths, and patient subpopulation efficacy, and more from the ENSEMBLE trial.

Janssen is aiming to provide 1 billion doses by the end of this year.

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

The Janssen/Johnson & Johnson single-dose adenovirus vaccine provides 85% efficacy globally against severe COVID-19 illness, according to the highly anticipated interim phase 3 results announced this morning.

The efficacy against severe disease provided by the Janssen/J&J vaccine held true regardless of age, race/ethnicity, absence or presence of comorbidities, and geography. The 44,000-participant ENSEMBLE study was conducted in the United States, South America, and South Africa.

“The team is very diligently monitoring all the variants that come up, and there are literally thousands of these. We are acting in anticipation of a variant being a potential problem. The South African variant we too acted on right away. So we too are preparing that antigen for testing.

“With data today, we do see that not a single South African, after 28 days post vaccination, ended up needing to go to the hospital, no South African died who was vaccinated.

“We do see that 85%-plus protection in South African against severe disease. That is one of the most exciting results in the dataset today,” said Mathai Mammen, MD, PhD, global head of Janssen Research & Development.

The overall efficacy was 66% globally, 72% in the United States, 66% in Latin America, and 57% in South Africa against moderate to severe SARS-CoV-2 28 days post vaccination, officials from the National Institutes of Health and Janssen reported during a media briefing.

But the J&J vaccine has potential advantages over the existing two-dose Pfizer/BioNTech and Moderna mRNA vaccines because it’s single dose and has less stringent storage requirements – only regular refrigeration is needed versus a need to freeze the two-dose Pfizer/BioNTech and Moderna COVID-19 vaccines. The J&J vaccine can be refrigerated for up to 3 months at 36°-46° F (2°-8° C).

But the difference between these just-released efficacy figures and the 94%-95% efficacy provided by the existing Pfizer/BioNTech and Moderna mRNA vaccines generated many questions during the briefing.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the focus should not just be on the overall numbers. “The most important thing from a public health standpoint domestically is to keep people out of the hospital and prevent them from getting severe illness,” he said. “Many in the general public might look at a number and want to know if they get symptomatic disease or not.”

“More important than preventing someone from getting some aches and a sore throat is to prevent people – particularly people who have underlying conditions and the elderly, the ones most susceptible to a severe outcome – [from getting] severe disease,” Dr. Fauci added. Prevention of severe outcomes in a high percentage of individuals “will alleviate so much of the stress, human suffering, and death.”

Dr. Fauci acknowledged that many people will naturally focus on the distinction between 72% efficacy and 94%-95% efficacy. “This could be a messaging challenge [but] you have to make sure people understand the implications.”

It is more complex, he added, than just asking people: “If you go to the door on the left, you get 94% or 95%. If you go to the door to the right, you get 72%. What door do you want to go to?”

Instead, the messaging should be that “this and the other vaccines we have are actually preventing severe disease to a very substantial degree.”
 

Company defends numbers

Janssen defended their efficacy findings, pointing out that it is not a fair comparison.

“The vaccine programs that went a couple of months ago, they ran their studies during different times, when the pandemic was less complex. There were not these variants, and there was not the same level of incidence, which puts pressure on vaccine efficacy,” said Mathai Mammen, MD, PhD, global head of research and development for Janssen.

“So the numbers cannot really be compared, and that does pose a messaging challenge,” he said. “But the reality is, if one was to run the same studies [for the Pfizer and Moderna vaccines] today you would likely see different results.”

Asked if the efficacy figures could affect vaccine hesitancy, National Institutes of Health Director Francis Collins, MD, PhD, said at the announcement that most reluctance among people to get vaccinated against SARS-CoV-2 stems from concerns about safety. “The safety record is extremely good for this vaccine, as it is for the others that have received emergency use authorization.”

Janssen/J&J plans to submit for emergency use authorization from the U.S. Food and Drug Administration next week, at which point the company plans to release more information on side effects, deaths, and patient subpopulation efficacy, and more from the ENSEMBLE trial.

Janssen is aiming to provide 1 billion doses by the end of this year.

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

The Janssen/Johnson & Johnson single-dose adenovirus vaccine provides 85% efficacy globally against severe COVID-19 illness, according to the highly anticipated interim phase 3 results announced this morning.

The efficacy against severe disease provided by the Janssen/J&J vaccine held true regardless of age, race/ethnicity, absence or presence of comorbidities, and geography. The 44,000-participant ENSEMBLE study was conducted in the United States, South America, and South Africa.

“The team is very diligently monitoring all the variants that come up, and there are literally thousands of these. We are acting in anticipation of a variant being a potential problem. The South African variant we too acted on right away. So we too are preparing that antigen for testing.

“With data today, we do see that not a single South African, after 28 days post vaccination, ended up needing to go to the hospital, no South African died who was vaccinated.

“We do see that 85%-plus protection in South African against severe disease. That is one of the most exciting results in the dataset today,” said Mathai Mammen, MD, PhD, global head of Janssen Research & Development.

The overall efficacy was 66% globally, 72% in the United States, 66% in Latin America, and 57% in South Africa against moderate to severe SARS-CoV-2 28 days post vaccination, officials from the National Institutes of Health and Janssen reported during a media briefing.

But the J&J vaccine has potential advantages over the existing two-dose Pfizer/BioNTech and Moderna mRNA vaccines because it’s single dose and has less stringent storage requirements – only regular refrigeration is needed versus a need to freeze the two-dose Pfizer/BioNTech and Moderna COVID-19 vaccines. The J&J vaccine can be refrigerated for up to 3 months at 36°-46° F (2°-8° C).

But the difference between these just-released efficacy figures and the 94%-95% efficacy provided by the existing Pfizer/BioNTech and Moderna mRNA vaccines generated many questions during the briefing.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said the focus should not just be on the overall numbers. “The most important thing from a public health standpoint domestically is to keep people out of the hospital and prevent them from getting severe illness,” he said. “Many in the general public might look at a number and want to know if they get symptomatic disease or not.”

“More important than preventing someone from getting some aches and a sore throat is to prevent people – particularly people who have underlying conditions and the elderly, the ones most susceptible to a severe outcome – [from getting] severe disease,” Dr. Fauci added. Prevention of severe outcomes in a high percentage of individuals “will alleviate so much of the stress, human suffering, and death.”

Dr. Fauci acknowledged that many people will naturally focus on the distinction between 72% efficacy and 94%-95% efficacy. “This could be a messaging challenge [but] you have to make sure people understand the implications.”

It is more complex, he added, than just asking people: “If you go to the door on the left, you get 94% or 95%. If you go to the door to the right, you get 72%. What door do you want to go to?”

Instead, the messaging should be that “this and the other vaccines we have are actually preventing severe disease to a very substantial degree.”
 

Company defends numbers

Janssen defended their efficacy findings, pointing out that it is not a fair comparison.

“The vaccine programs that went a couple of months ago, they ran their studies during different times, when the pandemic was less complex. There were not these variants, and there was not the same level of incidence, which puts pressure on vaccine efficacy,” said Mathai Mammen, MD, PhD, global head of research and development for Janssen.

“So the numbers cannot really be compared, and that does pose a messaging challenge,” he said. “But the reality is, if one was to run the same studies [for the Pfizer and Moderna vaccines] today you would likely see different results.”

Asked if the efficacy figures could affect vaccine hesitancy, National Institutes of Health Director Francis Collins, MD, PhD, said at the announcement that most reluctance among people to get vaccinated against SARS-CoV-2 stems from concerns about safety. “The safety record is extremely good for this vaccine, as it is for the others that have received emergency use authorization.”

Janssen/J&J plans to submit for emergency use authorization from the U.S. Food and Drug Administration next week, at which point the company plans to release more information on side effects, deaths, and patient subpopulation efficacy, and more from the ENSEMBLE trial.

Janssen is aiming to provide 1 billion doses by the end of this year.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

The United States is facing a “Category 5” storm as coronavirus variants begin to spread across the country, one of the nation’s top infectious disease experts said Sunday.

“We are going to see something like we have not seen yet in this country,” Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said on NBC’s Meet the Press.

The United States has reported 467 cases of the coronavirus variant first identified in the United Kingdom, across 32 states, according to the CDC variant tracker. The United States has also reported three cases of the variant first identified in South Africa in South Carolina and Maryland. One case of the variant first identified in Brazil has been found in Minnesota.

Although overall COVID-19 cases and hospitalizations have declined during the past few weeks, another storm is brewing on the horizon with the variants, Dr. Osterholm told host Chuck Todd. The U.K. variant will likely cause a surge in COVID-19 cases during the next 6-14 weeks, he said. “You and I are sitting on this beach where it’s 70 degrees, perfectly blue skies, gentle breeze. But I see that hurricane 5, Category 5 or higher, 450 miles offshore. And telling people to evacuate on that nice blue sky day is going to be hard. But I can also tell you that hurricane is coming.”

Dr. Osterholm urged federal and state officials to vaccinate as many people as possible to reduce the oncoming storm. The United States has distributed 49.9 million doses and administered 31.1 million doses, according to the latest CDC data updated Sunday, including 25.2 million first doses and 5.6 million second doses.

Doling out more doses to older Americans, rather than holding onto the second dose of the two-shot regimen, is an urgent decision, Dr. Osterholm said.

“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce serious illnesses and deaths that are going to occur over the weeks ahead,” he said.

The U.K. variant will likely become the dominant coronavirus strain in the United States in coming weeks, Dr. Osterholm said, adding that COVID-19 vaccines should be able to protect against it. In the meantime, however, he’s worried that the variant will cause more infections and deaths until more people get vaccinated.

“What we have to do now is also anticipate this and understand that we’re going to have change quickly,” he said. “As fast as we’re opening restaurants, we’re likely going to be closing them in the near term.”

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

The United States is facing a “Category 5” storm as coronavirus variants begin to spread across the country, one of the nation’s top infectious disease experts said Sunday.

“We are going to see something like we have not seen yet in this country,” Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said on NBC’s Meet the Press.

The United States has reported 467 cases of the coronavirus variant first identified in the United Kingdom, across 32 states, according to the CDC variant tracker. The United States has also reported three cases of the variant first identified in South Africa in South Carolina and Maryland. One case of the variant first identified in Brazil has been found in Minnesota.

Although overall COVID-19 cases and hospitalizations have declined during the past few weeks, another storm is brewing on the horizon with the variants, Dr. Osterholm told host Chuck Todd. The U.K. variant will likely cause a surge in COVID-19 cases during the next 6-14 weeks, he said. “You and I are sitting on this beach where it’s 70 degrees, perfectly blue skies, gentle breeze. But I see that hurricane 5, Category 5 or higher, 450 miles offshore. And telling people to evacuate on that nice blue sky day is going to be hard. But I can also tell you that hurricane is coming.”

Dr. Osterholm urged federal and state officials to vaccinate as many people as possible to reduce the oncoming storm. The United States has distributed 49.9 million doses and administered 31.1 million doses, according to the latest CDC data updated Sunday, including 25.2 million first doses and 5.6 million second doses.

Doling out more doses to older Americans, rather than holding onto the second dose of the two-shot regimen, is an urgent decision, Dr. Osterholm said.

“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce serious illnesses and deaths that are going to occur over the weeks ahead,” he said.

The U.K. variant will likely become the dominant coronavirus strain in the United States in coming weeks, Dr. Osterholm said, adding that COVID-19 vaccines should be able to protect against it. In the meantime, however, he’s worried that the variant will cause more infections and deaths until more people get vaccinated.

“What we have to do now is also anticipate this and understand that we’re going to have change quickly,” he said. “As fast as we’re opening restaurants, we’re likely going to be closing them in the near term.”

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

The United States is facing a “Category 5” storm as coronavirus variants begin to spread across the country, one of the nation’s top infectious disease experts said Sunday.

“We are going to see something like we have not seen yet in this country,” Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, Minneapolis, said on NBC’s Meet the Press.

The United States has reported 467 cases of the coronavirus variant first identified in the United Kingdom, across 32 states, according to the CDC variant tracker. The United States has also reported three cases of the variant first identified in South Africa in South Carolina and Maryland. One case of the variant first identified in Brazil has been found in Minnesota.

Although overall COVID-19 cases and hospitalizations have declined during the past few weeks, another storm is brewing on the horizon with the variants, Dr. Osterholm told host Chuck Todd. The U.K. variant will likely cause a surge in COVID-19 cases during the next 6-14 weeks, he said. “You and I are sitting on this beach where it’s 70 degrees, perfectly blue skies, gentle breeze. But I see that hurricane 5, Category 5 or higher, 450 miles offshore. And telling people to evacuate on that nice blue sky day is going to be hard. But I can also tell you that hurricane is coming.”

Dr. Osterholm urged federal and state officials to vaccinate as many people as possible to reduce the oncoming storm. The United States has distributed 49.9 million doses and administered 31.1 million doses, according to the latest CDC data updated Sunday, including 25.2 million first doses and 5.6 million second doses.

Doling out more doses to older Americans, rather than holding onto the second dose of the two-shot regimen, is an urgent decision, Dr. Osterholm said.

“I think right now, in advance of this surge, we need to get as many one doses in as many people over 65 as we possibly can to reduce serious illnesses and deaths that are going to occur over the weeks ahead,” he said.

The U.K. variant will likely become the dominant coronavirus strain in the United States in coming weeks, Dr. Osterholm said, adding that COVID-19 vaccines should be able to protect against it. In the meantime, however, he’s worried that the variant will cause more infections and deaths until more people get vaccinated.

“What we have to do now is also anticipate this and understand that we’re going to have change quickly,” he said. “As fast as we’re opening restaurants, we’re likely going to be closing them in the near term.”

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