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azzed
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bullturds
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cocaine
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cocainees
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crackwhore
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cum
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cumsluted
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cunthunterer
cunthunteres
cunthuntering
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cunthunters
cunting
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cuntlicked
cuntlicker
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dagos
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damn
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damneder
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dickbag
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dickbags
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dickdippered
dickdipperer
dickdipperes
dickdippering
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dicker
dickes
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dickfaceed
dickfaceer
dickfacees
dickfaceing
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dickflippered
dickflipperer
dickflipperes
dickflippering
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dickheaded
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dickheadser
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dingleed
dingleer
dinglees
dingleing
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dipship
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dipshipes
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dizzyed
dizzyer
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dizzying
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dizzys
doggiestyleed
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dopeyer
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drunker
drunkes
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dumass
dumassed
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dumasses
dumassing
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dumasss
dumbass
dumbassed
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dumbassing
dumbassly
dumbasss
dummy
dummyed
dummyer
dummyes
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dyke
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dykeer
dykees
dykeing
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erotic
eroticed
eroticer
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erotics
extacy
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extacying
extacyly
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extasy
extasyed
extasyer
extasyes
extasying
extasyly
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facked
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faged
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fagged
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faggoted
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fagoted
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faiged
faiger
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faigts
fannybandit
fannybandited
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fannybandits
farted
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fartknockered
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fartly
farts
felch
felched
felcher
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fellateer
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fellateing
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fellatio
fellatioed
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feltched
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floozy
floozyed
floozyer
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foad
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freexes
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friggaer
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fuckined
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fuckinged
fuckinger
fuckinges
fuckinging
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fuckings
fuckining
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Seek safe strategies to diagnose gestational diabetes during pandemic
Clinicians and pregnant women are less likely to prescribe and undergo the oral glucose tolerance test (OGTT) to diagnose gestational diabetes in the context of the COVID-19 pandemic, according to a review by H. David McIntyre, MD, of the University of Queensland, Brisbane, Australia, and Robert G. Moses, MD, of Wollongong (Australia) Hospital.
National and international discussions of whether a one- or two-step test for gestational diabetes mellitus (GDM) is optimal, and which women should be tested are ongoing, but the potential for exposure risks to COVID-19 are impacting the test process, they wrote in a commentary published in Diabetes Care.
“Any national or local guidelines should be developed with the primary aim of being protective for pregnant women and workable in the current health crisis,” they wrote.
Key concerns expressed by women and health care providers include the need for travel to be tested, the possible need for two visits, and the several hours spent in a potentially high-risk specimen collection center.
“Further, a GDM diagnosis generally involves additional health service visits for diabetes education, glucose monitoring review, and fetal ultrasonography, all of which carry exposure risks during a pandemic,” Dr. McIntyre and Dr. Moses noted.
Professional societies in the United Kingdom, Canada, and Australia have issued guidance to clinicians for modifying GDM diagnoses criteria during the pandemic that aim to reduce the need for the oral glucose tolerance test both during and after pregnancy.
Pandemic guidelines for all three of these countries support the identification of GDM using early pregnancy hemoglobin A1c (HbA1c) of at least 41 mmol/mol (5.9%).
Then, professionals in the United Kingdom recommend testing based on risk factors and diagnosing GDM based on any of these criteria: HbA1c of at least 39 mmol/mol (5.7%), fasting venous plasma glucose of at least 5.6 mmol/L (preferred), or random VPG of at least 9.0 mmol/L.
The revised testing pathway for Canada accepts an HbA1c of at least 39 mmol/mol (5.7%) and/or random VPG of at least 11.1 mmol/L.
“The revised Australian pathway does not include HbA1c but recommends a fasting VPG with progression to OGTT only if this result is 4.7-5.0 mmol/L,” Dr. McIntyre and Dr. Moses explained.
Overall, the revised guidelines for GDM testing will likely miss some women and only identify those with higher levels of hyperglycemia, the authors wrote. In addition, “the evidence base for these revised pathways is limited and that each alternative strategy should be evaluated over the course of the current pandemic.”
Validation of new testing strategies are needed, and the pandemic may provide and opportunity to adopt an alternative to the OGTT. The World Health Organization has not issued revised guidance for other methods of testing, but fasting VPG alone may be the simplest and most cost effective, at least for the short term, they noted.
“In this ‘new COVID world,’ GDM should not be ignored but pragmatically merits a lower priority than the avoidance of exposure to the COVID-19 virus,” although no single alternative strategy applies in all countries and situations, the authors concluded. Pragmatic measures and documentation of outcomes at the local level will offer the “least worst” solution while the pandemic continues.
The authors had no relevant financial disclosures.
SOURCE: McIntyre HD, Moses RG. Diabetes Care. 2020 May. doi: 10.2337/dci20-0026.
A major concern against the backdrop of COVID-19 is ensuring long-term health while urgent care is – understandably so – being prioritized over preventive care. We can already see the impact that the decrease in primary care has had: Rates of childhood vaccination appear to have dropped; the cancellation or indefinite delay of elective medical procedures has meant a reduction in preventive cancer screenings, such as colonoscopies and mammograms; and concerns about COVID-19 may be keeping those experiencing cardiac events from seeking emergency care.
However, an outcropping of the coronavirus pandemic is an ingenuity to adapt to our new “normal.” Medical licenses have been recognized across state lines to allow much-needed professionals to practice in the hardest-hit areas. Doctors retrofitted a sleep apnea machine to be used as a makeshift ventilator. Those in the wearable device market now have a greater onus to deliver on quality, utility, security, and accuracy.
Obstetricians have had to dramatically change delivery of ante-, intra- and postpartum care. The recent commentary by Dr. McIntyre and Dr. Moses focuses on one particular area of concern: screening, diagnosis, and management of gestational diabetes mellitus (GDM).
Screening and diagnosis are mainstays to reduce the adverse maternal and neonatal outcomes of diabetes in pregnancy. Although there is no universally accepted approach to evaluating GDM, all current methods utilize an oral glucose tolerance test (OGTT), which requires significant time spent in a clinical office setting, thus increasing risk for COVID-19 exposure.
Several countries have adopted modified GDM criteria within the last months. At the time of this writing, the United States has not. Although not testing women for GDM, which is what Dr. McIntyre and Dr. Moses point out may be happening in countries with modified guidelines, seems questionable, perhaps we should think differently about our approach.
More than 20 years ago, it was reported that jelly beans could be used as an alternative to the 50-g GDM screening test (Am J Obstet Gynecol. 1999 Nov;181[5 Pt 1]:1154‐7; Am J Obstet Gynecol. 1995 Dec;173[6]:1889‐92); more recently, candy twists were used with similar results (Am J Obstet Gynecol. 2015 Apr;212[4]:522.e1-5). In addition, a number of articles have reported on the utility of capillary whole blood glucose measurements to screen for GDM in developing and resource-limited countries (Diabetes Technol Ther. 2011;13[5]:586‐91; Acta Diabetol. 2016 Feb;53[1]:91‐7; Diabetes Technol Ther. 2012 Feb;14[2]:131-4). Therefore, rather than forgo GDM screening, women could self-administer a jelly bean test at home, measure blood sugar with a glucometer, and depending on the results, have an OGTT. Importantly, this would allow ob.gyns. to maintain medical standards while managing patients via telemedicine.
We have evidence that GDM can establish poor health for generations. We know that people with underlying conditions have greater morbidity and mortality from infectious diseases. We recognize that accurate screening and diagnosis is the key to prevention and management. Rather than accept a “least worst” scenario, as Dr. McIntyre and Dr. Moses state, we must find ways to provide the best possible care under the current circumstances.
E. Albert Reece, MD, PhD, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. He said he had no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
A major concern against the backdrop of COVID-19 is ensuring long-term health while urgent care is – understandably so – being prioritized over preventive care. We can already see the impact that the decrease in primary care has had: Rates of childhood vaccination appear to have dropped; the cancellation or indefinite delay of elective medical procedures has meant a reduction in preventive cancer screenings, such as colonoscopies and mammograms; and concerns about COVID-19 may be keeping those experiencing cardiac events from seeking emergency care.
However, an outcropping of the coronavirus pandemic is an ingenuity to adapt to our new “normal.” Medical licenses have been recognized across state lines to allow much-needed professionals to practice in the hardest-hit areas. Doctors retrofitted a sleep apnea machine to be used as a makeshift ventilator. Those in the wearable device market now have a greater onus to deliver on quality, utility, security, and accuracy.
Obstetricians have had to dramatically change delivery of ante-, intra- and postpartum care. The recent commentary by Dr. McIntyre and Dr. Moses focuses on one particular area of concern: screening, diagnosis, and management of gestational diabetes mellitus (GDM).
Screening and diagnosis are mainstays to reduce the adverse maternal and neonatal outcomes of diabetes in pregnancy. Although there is no universally accepted approach to evaluating GDM, all current methods utilize an oral glucose tolerance test (OGTT), which requires significant time spent in a clinical office setting, thus increasing risk for COVID-19 exposure.
Several countries have adopted modified GDM criteria within the last months. At the time of this writing, the United States has not. Although not testing women for GDM, which is what Dr. McIntyre and Dr. Moses point out may be happening in countries with modified guidelines, seems questionable, perhaps we should think differently about our approach.
More than 20 years ago, it was reported that jelly beans could be used as an alternative to the 50-g GDM screening test (Am J Obstet Gynecol. 1999 Nov;181[5 Pt 1]:1154‐7; Am J Obstet Gynecol. 1995 Dec;173[6]:1889‐92); more recently, candy twists were used with similar results (Am J Obstet Gynecol. 2015 Apr;212[4]:522.e1-5). In addition, a number of articles have reported on the utility of capillary whole blood glucose measurements to screen for GDM in developing and resource-limited countries (Diabetes Technol Ther. 2011;13[5]:586‐91; Acta Diabetol. 2016 Feb;53[1]:91‐7; Diabetes Technol Ther. 2012 Feb;14[2]:131-4). Therefore, rather than forgo GDM screening, women could self-administer a jelly bean test at home, measure blood sugar with a glucometer, and depending on the results, have an OGTT. Importantly, this would allow ob.gyns. to maintain medical standards while managing patients via telemedicine.
We have evidence that GDM can establish poor health for generations. We know that people with underlying conditions have greater morbidity and mortality from infectious diseases. We recognize that accurate screening and diagnosis is the key to prevention and management. Rather than accept a “least worst” scenario, as Dr. McIntyre and Dr. Moses state, we must find ways to provide the best possible care under the current circumstances.
E. Albert Reece, MD, PhD, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. He said he had no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
A major concern against the backdrop of COVID-19 is ensuring long-term health while urgent care is – understandably so – being prioritized over preventive care. We can already see the impact that the decrease in primary care has had: Rates of childhood vaccination appear to have dropped; the cancellation or indefinite delay of elective medical procedures has meant a reduction in preventive cancer screenings, such as colonoscopies and mammograms; and concerns about COVID-19 may be keeping those experiencing cardiac events from seeking emergency care.
However, an outcropping of the coronavirus pandemic is an ingenuity to adapt to our new “normal.” Medical licenses have been recognized across state lines to allow much-needed professionals to practice in the hardest-hit areas. Doctors retrofitted a sleep apnea machine to be used as a makeshift ventilator. Those in the wearable device market now have a greater onus to deliver on quality, utility, security, and accuracy.
Obstetricians have had to dramatically change delivery of ante-, intra- and postpartum care. The recent commentary by Dr. McIntyre and Dr. Moses focuses on one particular area of concern: screening, diagnosis, and management of gestational diabetes mellitus (GDM).
Screening and diagnosis are mainstays to reduce the adverse maternal and neonatal outcomes of diabetes in pregnancy. Although there is no universally accepted approach to evaluating GDM, all current methods utilize an oral glucose tolerance test (OGTT), which requires significant time spent in a clinical office setting, thus increasing risk for COVID-19 exposure.
Several countries have adopted modified GDM criteria within the last months. At the time of this writing, the United States has not. Although not testing women for GDM, which is what Dr. McIntyre and Dr. Moses point out may be happening in countries with modified guidelines, seems questionable, perhaps we should think differently about our approach.
More than 20 years ago, it was reported that jelly beans could be used as an alternative to the 50-g GDM screening test (Am J Obstet Gynecol. 1999 Nov;181[5 Pt 1]:1154‐7; Am J Obstet Gynecol. 1995 Dec;173[6]:1889‐92); more recently, candy twists were used with similar results (Am J Obstet Gynecol. 2015 Apr;212[4]:522.e1-5). In addition, a number of articles have reported on the utility of capillary whole blood glucose measurements to screen for GDM in developing and resource-limited countries (Diabetes Technol Ther. 2011;13[5]:586‐91; Acta Diabetol. 2016 Feb;53[1]:91‐7; Diabetes Technol Ther. 2012 Feb;14[2]:131-4). Therefore, rather than forgo GDM screening, women could self-administer a jelly bean test at home, measure blood sugar with a glucometer, and depending on the results, have an OGTT. Importantly, this would allow ob.gyns. to maintain medical standards while managing patients via telemedicine.
We have evidence that GDM can establish poor health for generations. We know that people with underlying conditions have greater morbidity and mortality from infectious diseases. We recognize that accurate screening and diagnosis is the key to prevention and management. Rather than accept a “least worst” scenario, as Dr. McIntyre and Dr. Moses state, we must find ways to provide the best possible care under the current circumstances.
E. Albert Reece, MD, PhD, who specializes in maternal-fetal medicine, is executive vice president for medical affairs at the University of Maryland, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. He said he had no relevant financial disclosures. He is a member of the Ob.Gyn. News editorial advisory board.
Clinicians and pregnant women are less likely to prescribe and undergo the oral glucose tolerance test (OGTT) to diagnose gestational diabetes in the context of the COVID-19 pandemic, according to a review by H. David McIntyre, MD, of the University of Queensland, Brisbane, Australia, and Robert G. Moses, MD, of Wollongong (Australia) Hospital.
National and international discussions of whether a one- or two-step test for gestational diabetes mellitus (GDM) is optimal, and which women should be tested are ongoing, but the potential for exposure risks to COVID-19 are impacting the test process, they wrote in a commentary published in Diabetes Care.
“Any national or local guidelines should be developed with the primary aim of being protective for pregnant women and workable in the current health crisis,” they wrote.
Key concerns expressed by women and health care providers include the need for travel to be tested, the possible need for two visits, and the several hours spent in a potentially high-risk specimen collection center.
“Further, a GDM diagnosis generally involves additional health service visits for diabetes education, glucose monitoring review, and fetal ultrasonography, all of which carry exposure risks during a pandemic,” Dr. McIntyre and Dr. Moses noted.
Professional societies in the United Kingdom, Canada, and Australia have issued guidance to clinicians for modifying GDM diagnoses criteria during the pandemic that aim to reduce the need for the oral glucose tolerance test both during and after pregnancy.
Pandemic guidelines for all three of these countries support the identification of GDM using early pregnancy hemoglobin A1c (HbA1c) of at least 41 mmol/mol (5.9%).
Then, professionals in the United Kingdom recommend testing based on risk factors and diagnosing GDM based on any of these criteria: HbA1c of at least 39 mmol/mol (5.7%), fasting venous plasma glucose of at least 5.6 mmol/L (preferred), or random VPG of at least 9.0 mmol/L.
The revised testing pathway for Canada accepts an HbA1c of at least 39 mmol/mol (5.7%) and/or random VPG of at least 11.1 mmol/L.
“The revised Australian pathway does not include HbA1c but recommends a fasting VPG with progression to OGTT only if this result is 4.7-5.0 mmol/L,” Dr. McIntyre and Dr. Moses explained.
Overall, the revised guidelines for GDM testing will likely miss some women and only identify those with higher levels of hyperglycemia, the authors wrote. In addition, “the evidence base for these revised pathways is limited and that each alternative strategy should be evaluated over the course of the current pandemic.”
Validation of new testing strategies are needed, and the pandemic may provide and opportunity to adopt an alternative to the OGTT. The World Health Organization has not issued revised guidance for other methods of testing, but fasting VPG alone may be the simplest and most cost effective, at least for the short term, they noted.
“In this ‘new COVID world,’ GDM should not be ignored but pragmatically merits a lower priority than the avoidance of exposure to the COVID-19 virus,” although no single alternative strategy applies in all countries and situations, the authors concluded. Pragmatic measures and documentation of outcomes at the local level will offer the “least worst” solution while the pandemic continues.
The authors had no relevant financial disclosures.
SOURCE: McIntyre HD, Moses RG. Diabetes Care. 2020 May. doi: 10.2337/dci20-0026.
Clinicians and pregnant women are less likely to prescribe and undergo the oral glucose tolerance test (OGTT) to diagnose gestational diabetes in the context of the COVID-19 pandemic, according to a review by H. David McIntyre, MD, of the University of Queensland, Brisbane, Australia, and Robert G. Moses, MD, of Wollongong (Australia) Hospital.
National and international discussions of whether a one- or two-step test for gestational diabetes mellitus (GDM) is optimal, and which women should be tested are ongoing, but the potential for exposure risks to COVID-19 are impacting the test process, they wrote in a commentary published in Diabetes Care.
“Any national or local guidelines should be developed with the primary aim of being protective for pregnant women and workable in the current health crisis,” they wrote.
Key concerns expressed by women and health care providers include the need for travel to be tested, the possible need for two visits, and the several hours spent in a potentially high-risk specimen collection center.
“Further, a GDM diagnosis generally involves additional health service visits for diabetes education, glucose monitoring review, and fetal ultrasonography, all of which carry exposure risks during a pandemic,” Dr. McIntyre and Dr. Moses noted.
Professional societies in the United Kingdom, Canada, and Australia have issued guidance to clinicians for modifying GDM diagnoses criteria during the pandemic that aim to reduce the need for the oral glucose tolerance test both during and after pregnancy.
Pandemic guidelines for all three of these countries support the identification of GDM using early pregnancy hemoglobin A1c (HbA1c) of at least 41 mmol/mol (5.9%).
Then, professionals in the United Kingdom recommend testing based on risk factors and diagnosing GDM based on any of these criteria: HbA1c of at least 39 mmol/mol (5.7%), fasting venous plasma glucose of at least 5.6 mmol/L (preferred), or random VPG of at least 9.0 mmol/L.
The revised testing pathway for Canada accepts an HbA1c of at least 39 mmol/mol (5.7%) and/or random VPG of at least 11.1 mmol/L.
“The revised Australian pathway does not include HbA1c but recommends a fasting VPG with progression to OGTT only if this result is 4.7-5.0 mmol/L,” Dr. McIntyre and Dr. Moses explained.
Overall, the revised guidelines for GDM testing will likely miss some women and only identify those with higher levels of hyperglycemia, the authors wrote. In addition, “the evidence base for these revised pathways is limited and that each alternative strategy should be evaluated over the course of the current pandemic.”
Validation of new testing strategies are needed, and the pandemic may provide and opportunity to adopt an alternative to the OGTT. The World Health Organization has not issued revised guidance for other methods of testing, but fasting VPG alone may be the simplest and most cost effective, at least for the short term, they noted.
“In this ‘new COVID world,’ GDM should not be ignored but pragmatically merits a lower priority than the avoidance of exposure to the COVID-19 virus,” although no single alternative strategy applies in all countries and situations, the authors concluded. Pragmatic measures and documentation of outcomes at the local level will offer the “least worst” solution while the pandemic continues.
The authors had no relevant financial disclosures.
SOURCE: McIntyre HD, Moses RG. Diabetes Care. 2020 May. doi: 10.2337/dci20-0026.
Can you catch COVID-19 through your eyes?
You can catch COVID-19 if an infected person coughs or sneezes and contagious droplets enter your nose or mouth. But can you become ill if the virus lands in your eyes?
Virologist Joseph Fair, PhD, an NBC News contributor, raised that concern when he became critically ill with COVID-19, the disease caused by the coronavirus. From a hospital bed in his hometown of New Orleans, he told the network that he had flown on a crowded plane where flight attendants weren’t wearing masks. He wore a mask and gloves, but no eye protection.
“My best guess,” he told the interviewer, “was that it came through the eye route.”
Asked if people should start wearing eye protection, Dr. Fair replied, “In my opinion, yes.”
While Dr. Fair is convinced that eye protection helps, other experts aren’t sure. So much remains unknown about the new coronavirus, SARS-CoV-2, that researchers are still trying to establish whether infection can actually happen through the eyes.
“I don’t think we can answer that question with 100% confidence at this time,” said H. Nida Sen, MD, director of the uveitis clinic at the National Eye Institute in Bethesda, Md., and a clinical investigator who is studying the effects of COVID-19 on the eye. But, she says, “I think it is biologically plausible.”
Some research has begun pointing in that direction, according to Elia Duh, MD, a researcher and professor of ophthalmology at Johns Hopkins University in Baltimore.
The clear tissue that covers the white of the eye and lines the inside of the eyelid, known as the conjunctiva, “can be infected by other viruses, such as adenoviruses associated with the common cold and the herpes simplex virus,” he said.
There’s the same chance of infection with SARS-CoV-2, said Dr. Duh. “ just like the nasal passages are exposed. In addition, people rub and touch their eyes a lot. So there’s certainly already the vulnerability.”
To study whether SARS-CoV-2 could infect the eyes, Dr. Duh and fellow researchers at Johns Hopkins looked at whether the eye’s surface cells possess key factors that make the virus more likely to enter and infect them.
In their study (BioRxiv. 2020 May 9. doi: 10.1101/2020.05.09.086165), which is now being peer-reviewed, the team examined 10 postmortem eyes and five surgical samples of conjunctiva from patients who did not have the coronavirus. They wanted to see whether the eyes’ surface cells produced the key receptor for coronavirus, the ACE2 receptor.
For SARS-CoV-2 to enter a cell, “the cell has to have ACE2 on its surface so that the coronavirus can latch onto it and gain entry into the cell,” Dr. Duh said.
Not much research existed on ACE2 and the eye’s surface cells, he said. “We were really struck that ACE2 was clearly present in the surface cells of all of the specimens.” In addition, the researchers found that the eye’s surface cells also produce TMPRSS2, an enzyme that helps the virus enter the cell.
More research is needed for a definitive answer, Dr. Duh said. But “all of this evidence together seems to suggest that there’s a good likelihood that the ocular surface cells are susceptible to infection by coronavirus.”
If that’s the case, the virus then could be transmitted through the tear ducts that connect the eyes to the nasal cavity and subsequently infect the respiratory cells, he said.
Edward E. Manche, MD, professor of ophthalmology at Stanford (Calif.) University, said that while doctors don’t know for sure, many think eye infection can happen. “I think it’s widely believed now that you can acquire it through the eye. The way the virus works, it’s most commonly transmitted through the mouth and nasal passages. We have mucosal tissues where it can get in.”
Dr. Manche said the eyes would be “the least common mode of transmission.”
Besides looking at the eyes as an entryway, researchers are exploring whether people with SARS-CoV-2 in their eyes could infect others through their tears or eye secretions.
“The virus has been detected in tears and conjunctival swab specimens from individuals with COVID-19,” Dr. Duh said. “If someone rubs their eyes and then touches someone else or touches a surface, that kind of transmission mechanism could occur.
“It again highlights how contagious the coronavirus is and how stealthy it can be in its contagiousness,” he said.
If it turns out that the coronavirus can infect the eyes, the virus could persist there as a source of contagion, Dr. Duh said. “The eyes and tears could serve as a source of infection to others for longer.” He noted a case of a COVID-infected woman with conjunctivitis who still had detectable virus in her eyes 3 weeks after her symptoms started.
Conjunctivitis, commonly called pink eye, could be a symptom of COVID-19, said Dr. Sen, who is an ophthalmologist. She recommends that people get tested for COVID-19 if they have this condition, which is marked by redness, itchiness, tearing, discharge, and a gritty sensation in the eye.
Dr. Fair, the virologist, was released from the hospital to recover at home and continued to urge eye protection. “People like to call people like me fearmongers ... but the reality is, we’re just trying to keep them safe,” he told NBC News.
The CDC hasn’t issued such advice. In an email, the agency said it “does not have specific recommendations for the public regarding eye protection. However, in health care settings, the CDC does recommend eye protection for health care workers to prevent transmission via droplets.”
Dr. Sen agrees. “For the general public, I don’t think we have enough data to suggest that they should be covering the eyes in some form,” she said.
When she goes to the grocery store, she doesn’t wear eye protection. “I am only wearing goggles when I’m seeing ophthalmology patients up close, basically because I’m 4 or 5 inches away from them.”
But fuller protection – a mask, gloves, and even eye protection, such as goggles – might help those taking care of a COVID-19 patient at home, Dr. Manche said. “If you’re caring for somebody, that’s a much higher risk because they’re shedding viral load. You lessen the chance of transmission.”
For the public, Dr. Sen stresses the continued importance of hand hygiene. “In an abundance of caution, I would still encourage handwashing and not touching the eye for many reasons, not just COVID. You can transmit simple infections to your eye. We have other viruses and bacteria that are circulating in the environment and in our bodies elsewhere, so we can easily carry those to the eyes.”
Switching from contact lenses to eyeglasses could help cut down on touching the eyes, she says. Eyeglasses can also be a “mechanical barrier” to keep hands away.
Eyeglasses might block some droplets if someone nearby sneezes or coughs, Dr. Manche said, although they “aren’t sealed around the edges. They’re not like true medical goggles that are going to keep out the virus.”
Dr. Duh agrees that health care workers must don eye protection, but he said the public doesn’t need to start wearing goggles, face shields, or other eye protection. “I still think the major mode of transmission is through the nasal passages and the respiratory system,” he said.
It’s unclear whether eye protection is warranted for airplane passengers, Dr. Manche said. “It probably wouldn’t hurt, but I think the more important thing would be to take precautions: wearing a face mask, washing your hands, cleaning the seats and tray tables in front of you, and not touching things and touching your face and eyes.”
A version of this article originally appeared on WebMD.com.
You can catch COVID-19 if an infected person coughs or sneezes and contagious droplets enter your nose or mouth. But can you become ill if the virus lands in your eyes?
Virologist Joseph Fair, PhD, an NBC News contributor, raised that concern when he became critically ill with COVID-19, the disease caused by the coronavirus. From a hospital bed in his hometown of New Orleans, he told the network that he had flown on a crowded plane where flight attendants weren’t wearing masks. He wore a mask and gloves, but no eye protection.
“My best guess,” he told the interviewer, “was that it came through the eye route.”
Asked if people should start wearing eye protection, Dr. Fair replied, “In my opinion, yes.”
While Dr. Fair is convinced that eye protection helps, other experts aren’t sure. So much remains unknown about the new coronavirus, SARS-CoV-2, that researchers are still trying to establish whether infection can actually happen through the eyes.
“I don’t think we can answer that question with 100% confidence at this time,” said H. Nida Sen, MD, director of the uveitis clinic at the National Eye Institute in Bethesda, Md., and a clinical investigator who is studying the effects of COVID-19 on the eye. But, she says, “I think it is biologically plausible.”
Some research has begun pointing in that direction, according to Elia Duh, MD, a researcher and professor of ophthalmology at Johns Hopkins University in Baltimore.
The clear tissue that covers the white of the eye and lines the inside of the eyelid, known as the conjunctiva, “can be infected by other viruses, such as adenoviruses associated with the common cold and the herpes simplex virus,” he said.
There’s the same chance of infection with SARS-CoV-2, said Dr. Duh. “ just like the nasal passages are exposed. In addition, people rub and touch their eyes a lot. So there’s certainly already the vulnerability.”
To study whether SARS-CoV-2 could infect the eyes, Dr. Duh and fellow researchers at Johns Hopkins looked at whether the eye’s surface cells possess key factors that make the virus more likely to enter and infect them.
In their study (BioRxiv. 2020 May 9. doi: 10.1101/2020.05.09.086165), which is now being peer-reviewed, the team examined 10 postmortem eyes and five surgical samples of conjunctiva from patients who did not have the coronavirus. They wanted to see whether the eyes’ surface cells produced the key receptor for coronavirus, the ACE2 receptor.
For SARS-CoV-2 to enter a cell, “the cell has to have ACE2 on its surface so that the coronavirus can latch onto it and gain entry into the cell,” Dr. Duh said.
Not much research existed on ACE2 and the eye’s surface cells, he said. “We were really struck that ACE2 was clearly present in the surface cells of all of the specimens.” In addition, the researchers found that the eye’s surface cells also produce TMPRSS2, an enzyme that helps the virus enter the cell.
More research is needed for a definitive answer, Dr. Duh said. But “all of this evidence together seems to suggest that there’s a good likelihood that the ocular surface cells are susceptible to infection by coronavirus.”
If that’s the case, the virus then could be transmitted through the tear ducts that connect the eyes to the nasal cavity and subsequently infect the respiratory cells, he said.
Edward E. Manche, MD, professor of ophthalmology at Stanford (Calif.) University, said that while doctors don’t know for sure, many think eye infection can happen. “I think it’s widely believed now that you can acquire it through the eye. The way the virus works, it’s most commonly transmitted through the mouth and nasal passages. We have mucosal tissues where it can get in.”
Dr. Manche said the eyes would be “the least common mode of transmission.”
Besides looking at the eyes as an entryway, researchers are exploring whether people with SARS-CoV-2 in their eyes could infect others through their tears or eye secretions.
“The virus has been detected in tears and conjunctival swab specimens from individuals with COVID-19,” Dr. Duh said. “If someone rubs their eyes and then touches someone else or touches a surface, that kind of transmission mechanism could occur.
“It again highlights how contagious the coronavirus is and how stealthy it can be in its contagiousness,” he said.
If it turns out that the coronavirus can infect the eyes, the virus could persist there as a source of contagion, Dr. Duh said. “The eyes and tears could serve as a source of infection to others for longer.” He noted a case of a COVID-infected woman with conjunctivitis who still had detectable virus in her eyes 3 weeks after her symptoms started.
Conjunctivitis, commonly called pink eye, could be a symptom of COVID-19, said Dr. Sen, who is an ophthalmologist. She recommends that people get tested for COVID-19 if they have this condition, which is marked by redness, itchiness, tearing, discharge, and a gritty sensation in the eye.
Dr. Fair, the virologist, was released from the hospital to recover at home and continued to urge eye protection. “People like to call people like me fearmongers ... but the reality is, we’re just trying to keep them safe,” he told NBC News.
The CDC hasn’t issued such advice. In an email, the agency said it “does not have specific recommendations for the public regarding eye protection. However, in health care settings, the CDC does recommend eye protection for health care workers to prevent transmission via droplets.”
Dr. Sen agrees. “For the general public, I don’t think we have enough data to suggest that they should be covering the eyes in some form,” she said.
When she goes to the grocery store, she doesn’t wear eye protection. “I am only wearing goggles when I’m seeing ophthalmology patients up close, basically because I’m 4 or 5 inches away from them.”
But fuller protection – a mask, gloves, and even eye protection, such as goggles – might help those taking care of a COVID-19 patient at home, Dr. Manche said. “If you’re caring for somebody, that’s a much higher risk because they’re shedding viral load. You lessen the chance of transmission.”
For the public, Dr. Sen stresses the continued importance of hand hygiene. “In an abundance of caution, I would still encourage handwashing and not touching the eye for many reasons, not just COVID. You can transmit simple infections to your eye. We have other viruses and bacteria that are circulating in the environment and in our bodies elsewhere, so we can easily carry those to the eyes.”
Switching from contact lenses to eyeglasses could help cut down on touching the eyes, she says. Eyeglasses can also be a “mechanical barrier” to keep hands away.
Eyeglasses might block some droplets if someone nearby sneezes or coughs, Dr. Manche said, although they “aren’t sealed around the edges. They’re not like true medical goggles that are going to keep out the virus.”
Dr. Duh agrees that health care workers must don eye protection, but he said the public doesn’t need to start wearing goggles, face shields, or other eye protection. “I still think the major mode of transmission is through the nasal passages and the respiratory system,” he said.
It’s unclear whether eye protection is warranted for airplane passengers, Dr. Manche said. “It probably wouldn’t hurt, but I think the more important thing would be to take precautions: wearing a face mask, washing your hands, cleaning the seats and tray tables in front of you, and not touching things and touching your face and eyes.”
A version of this article originally appeared on WebMD.com.
You can catch COVID-19 if an infected person coughs or sneezes and contagious droplets enter your nose or mouth. But can you become ill if the virus lands in your eyes?
Virologist Joseph Fair, PhD, an NBC News contributor, raised that concern when he became critically ill with COVID-19, the disease caused by the coronavirus. From a hospital bed in his hometown of New Orleans, he told the network that he had flown on a crowded plane where flight attendants weren’t wearing masks. He wore a mask and gloves, but no eye protection.
“My best guess,” he told the interviewer, “was that it came through the eye route.”
Asked if people should start wearing eye protection, Dr. Fair replied, “In my opinion, yes.”
While Dr. Fair is convinced that eye protection helps, other experts aren’t sure. So much remains unknown about the new coronavirus, SARS-CoV-2, that researchers are still trying to establish whether infection can actually happen through the eyes.
“I don’t think we can answer that question with 100% confidence at this time,” said H. Nida Sen, MD, director of the uveitis clinic at the National Eye Institute in Bethesda, Md., and a clinical investigator who is studying the effects of COVID-19 on the eye. But, she says, “I think it is biologically plausible.”
Some research has begun pointing in that direction, according to Elia Duh, MD, a researcher and professor of ophthalmology at Johns Hopkins University in Baltimore.
The clear tissue that covers the white of the eye and lines the inside of the eyelid, known as the conjunctiva, “can be infected by other viruses, such as adenoviruses associated with the common cold and the herpes simplex virus,” he said.
There’s the same chance of infection with SARS-CoV-2, said Dr. Duh. “ just like the nasal passages are exposed. In addition, people rub and touch their eyes a lot. So there’s certainly already the vulnerability.”
To study whether SARS-CoV-2 could infect the eyes, Dr. Duh and fellow researchers at Johns Hopkins looked at whether the eye’s surface cells possess key factors that make the virus more likely to enter and infect them.
In their study (BioRxiv. 2020 May 9. doi: 10.1101/2020.05.09.086165), which is now being peer-reviewed, the team examined 10 postmortem eyes and five surgical samples of conjunctiva from patients who did not have the coronavirus. They wanted to see whether the eyes’ surface cells produced the key receptor for coronavirus, the ACE2 receptor.
For SARS-CoV-2 to enter a cell, “the cell has to have ACE2 on its surface so that the coronavirus can latch onto it and gain entry into the cell,” Dr. Duh said.
Not much research existed on ACE2 and the eye’s surface cells, he said. “We were really struck that ACE2 was clearly present in the surface cells of all of the specimens.” In addition, the researchers found that the eye’s surface cells also produce TMPRSS2, an enzyme that helps the virus enter the cell.
More research is needed for a definitive answer, Dr. Duh said. But “all of this evidence together seems to suggest that there’s a good likelihood that the ocular surface cells are susceptible to infection by coronavirus.”
If that’s the case, the virus then could be transmitted through the tear ducts that connect the eyes to the nasal cavity and subsequently infect the respiratory cells, he said.
Edward E. Manche, MD, professor of ophthalmology at Stanford (Calif.) University, said that while doctors don’t know for sure, many think eye infection can happen. “I think it’s widely believed now that you can acquire it through the eye. The way the virus works, it’s most commonly transmitted through the mouth and nasal passages. We have mucosal tissues where it can get in.”
Dr. Manche said the eyes would be “the least common mode of transmission.”
Besides looking at the eyes as an entryway, researchers are exploring whether people with SARS-CoV-2 in their eyes could infect others through their tears or eye secretions.
“The virus has been detected in tears and conjunctival swab specimens from individuals with COVID-19,” Dr. Duh said. “If someone rubs their eyes and then touches someone else or touches a surface, that kind of transmission mechanism could occur.
“It again highlights how contagious the coronavirus is and how stealthy it can be in its contagiousness,” he said.
If it turns out that the coronavirus can infect the eyes, the virus could persist there as a source of contagion, Dr. Duh said. “The eyes and tears could serve as a source of infection to others for longer.” He noted a case of a COVID-infected woman with conjunctivitis who still had detectable virus in her eyes 3 weeks after her symptoms started.
Conjunctivitis, commonly called pink eye, could be a symptom of COVID-19, said Dr. Sen, who is an ophthalmologist. She recommends that people get tested for COVID-19 if they have this condition, which is marked by redness, itchiness, tearing, discharge, and a gritty sensation in the eye.
Dr. Fair, the virologist, was released from the hospital to recover at home and continued to urge eye protection. “People like to call people like me fearmongers ... but the reality is, we’re just trying to keep them safe,” he told NBC News.
The CDC hasn’t issued such advice. In an email, the agency said it “does not have specific recommendations for the public regarding eye protection. However, in health care settings, the CDC does recommend eye protection for health care workers to prevent transmission via droplets.”
Dr. Sen agrees. “For the general public, I don’t think we have enough data to suggest that they should be covering the eyes in some form,” she said.
When she goes to the grocery store, she doesn’t wear eye protection. “I am only wearing goggles when I’m seeing ophthalmology patients up close, basically because I’m 4 or 5 inches away from them.”
But fuller protection – a mask, gloves, and even eye protection, such as goggles – might help those taking care of a COVID-19 patient at home, Dr. Manche said. “If you’re caring for somebody, that’s a much higher risk because they’re shedding viral load. You lessen the chance of transmission.”
For the public, Dr. Sen stresses the continued importance of hand hygiene. “In an abundance of caution, I would still encourage handwashing and not touching the eye for many reasons, not just COVID. You can transmit simple infections to your eye. We have other viruses and bacteria that are circulating in the environment and in our bodies elsewhere, so we can easily carry those to the eyes.”
Switching from contact lenses to eyeglasses could help cut down on touching the eyes, she says. Eyeglasses can also be a “mechanical barrier” to keep hands away.
Eyeglasses might block some droplets if someone nearby sneezes or coughs, Dr. Manche said, although they “aren’t sealed around the edges. They’re not like true medical goggles that are going to keep out the virus.”
Dr. Duh agrees that health care workers must don eye protection, but he said the public doesn’t need to start wearing goggles, face shields, or other eye protection. “I still think the major mode of transmission is through the nasal passages and the respiratory system,” he said.
It’s unclear whether eye protection is warranted for airplane passengers, Dr. Manche said. “It probably wouldn’t hurt, but I think the more important thing would be to take precautions: wearing a face mask, washing your hands, cleaning the seats and tray tables in front of you, and not touching things and touching your face and eyes.”
A version of this article originally appeared on WebMD.com.
Severe disease not uncommon in children hospitalized with COVID-19
Children with COVID-19 are more likely to develop severe illness and require intensive care than previously realized, data from a single-center study suggest.
Jerry Y. Chao, MD, of the department of anesthesiology, Albert Einstein College of Medicine, New York, and colleagues reported their findings in an article published online May 11 in the Journal of Pediatrics.
“Thankfully most children with COVID-19 fare well, and some do not have any symptoms at all, but this research is a sobering reminder that children are not immune to this virus and some do require a higher level of care,” senior author Shivanand S. Medar, MD, FAAP, attending physician, Cardiac Intensive Care, Children’s Hospital at Montefiore, and assistant professor of pediatrics, Albert Einstein College of Medicine, said in a Montefiore Medical Center news release.
The study included 67 patients aged 1 month to 21 years (median, 13.1 years) who were treated for COVID-19 at a tertiary care children’s hospital between March 15 and April 13. Of those, 21 (31.3%) were treated as outpatients.
“As the number of patients screened for COVID-19 was restricted during the first weeks of the outbreak because of limited testing availability, the number of mildly symptomatic patients is not known, and therefore these 21 patients are not included in the analysis,” the authors wrote.
Of the 46 hospitalized patients, 33 (72%) were admitted to a general pediatric medical ward, and 13 (28%) were admitted to the pediatric intensive care unit (PICU).
Almost one-third (14 children; 30.4%) of the admitted patients were obese, and almost one-quarter (11 children; 24.4%) had asthma, but neither factor was associated with an increased risk for PICU admission.
“We know that in adults, obesity is a risk factor for more severe disease, however, surprisingly, our study found that children admitted to the intensive care unit did not have a higher prevalence of obesity than those on the general unit,” Dr. Chao said in the news release.
Three of the PICU patients (25%) had preexisting seizure disorders, as did one (3%) patient on the general medical unit. “There was no significant difference in the usage of ibuprofen prior to hospitalization among patients admitted to medical unit compared with those admitted to the PICU,” the authors wrote.
Platelet counts were lower in patients admitted to the PICU compared with those on the general medical unit; however, C-reactive protein, procalcitonin, and pro–brain natriuretic peptide levels were all elevated in patients admitted to the PICU compared with those admitted to the general medical unit.
Patients admitted to the PICU were more likely to need high-flow nasal cannula. Ten (77%) patients in the PICU developed acute respiratory distress syndrome (ARDS), and six (46.2%) of them needed “invasive mechanical ventilation for a median of 9 days.”
The only clinical symptom significantly linked to PICU admission was shortness of breath (92.3% vs 30.3%; P < .001).
Eight (61.5%) of the 13 patients treated in the PICU were discharged to home; four (30.7%) were still hospitalized and receiving ventilatory support on day 14. One patient had metastatic cancer and died as a result of the cancer after life-sustaining therapy was withdrawn.
Those admitted to the PICU were more likely to receive treatment with remdesivir via compassionate use compared with those treated in the general medical unit. Seven (53.8%) patients in the PICU developed severe sepsis and septic shock syndromes.
The average hospital stay was 4 days longer for the children admitted to the PICU than for the children admitted to the general medical unit.
Cough (63%) and fever (60.9%) were the most frequently reported symptoms at admission. The median duration of symptoms before admission was 3 days. None of the children had traveled to an area affected by COVID-19 before becoming ill, and only 20 (43.5%) children were confirmed to have had contact with someone with COVID-19. “The lack of a known sick contact reported in our study may have implications for how healthcare providers identify and screen for potential cases,” the authors explained.
Although children are believed to experience milder SARS-CoV-2 illness, these results and those of an earlier study suggest that some pediatric patients develop illness severe enough to require PICU admission. “This subset had significantly higher markers of inflammation (CRP, pro-BNP, procalcitonin) compared with patients in the medical unit. Inflammation likely contributed to the high rate of ARDS we observed, although serum levels of IL-6 and other cytokines linked to ARDS were not determined,” the authors wrote.
A retrospective cohort study found that of 177 children and young adults treated in a single center, patients younger than 1 year and older than 15 years were more likely to become critically ill with COVID-19 (J Pediatr. 2020 May. doi: 10.1016/j.jpeds.2020.05.007).
Each of the two age groups accounted for 32% of the hospitalized patients.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Children with COVID-19 are more likely to develop severe illness and require intensive care than previously realized, data from a single-center study suggest.
Jerry Y. Chao, MD, of the department of anesthesiology, Albert Einstein College of Medicine, New York, and colleagues reported their findings in an article published online May 11 in the Journal of Pediatrics.
“Thankfully most children with COVID-19 fare well, and some do not have any symptoms at all, but this research is a sobering reminder that children are not immune to this virus and some do require a higher level of care,” senior author Shivanand S. Medar, MD, FAAP, attending physician, Cardiac Intensive Care, Children’s Hospital at Montefiore, and assistant professor of pediatrics, Albert Einstein College of Medicine, said in a Montefiore Medical Center news release.
The study included 67 patients aged 1 month to 21 years (median, 13.1 years) who were treated for COVID-19 at a tertiary care children’s hospital between March 15 and April 13. Of those, 21 (31.3%) were treated as outpatients.
“As the number of patients screened for COVID-19 was restricted during the first weeks of the outbreak because of limited testing availability, the number of mildly symptomatic patients is not known, and therefore these 21 patients are not included in the analysis,” the authors wrote.
Of the 46 hospitalized patients, 33 (72%) were admitted to a general pediatric medical ward, and 13 (28%) were admitted to the pediatric intensive care unit (PICU).
Almost one-third (14 children; 30.4%) of the admitted patients were obese, and almost one-quarter (11 children; 24.4%) had asthma, but neither factor was associated with an increased risk for PICU admission.
“We know that in adults, obesity is a risk factor for more severe disease, however, surprisingly, our study found that children admitted to the intensive care unit did not have a higher prevalence of obesity than those on the general unit,” Dr. Chao said in the news release.
Three of the PICU patients (25%) had preexisting seizure disorders, as did one (3%) patient on the general medical unit. “There was no significant difference in the usage of ibuprofen prior to hospitalization among patients admitted to medical unit compared with those admitted to the PICU,” the authors wrote.
Platelet counts were lower in patients admitted to the PICU compared with those on the general medical unit; however, C-reactive protein, procalcitonin, and pro–brain natriuretic peptide levels were all elevated in patients admitted to the PICU compared with those admitted to the general medical unit.
Patients admitted to the PICU were more likely to need high-flow nasal cannula. Ten (77%) patients in the PICU developed acute respiratory distress syndrome (ARDS), and six (46.2%) of them needed “invasive mechanical ventilation for a median of 9 days.”
The only clinical symptom significantly linked to PICU admission was shortness of breath (92.3% vs 30.3%; P < .001).
Eight (61.5%) of the 13 patients treated in the PICU were discharged to home; four (30.7%) were still hospitalized and receiving ventilatory support on day 14. One patient had metastatic cancer and died as a result of the cancer after life-sustaining therapy was withdrawn.
Those admitted to the PICU were more likely to receive treatment with remdesivir via compassionate use compared with those treated in the general medical unit. Seven (53.8%) patients in the PICU developed severe sepsis and septic shock syndromes.
The average hospital stay was 4 days longer for the children admitted to the PICU than for the children admitted to the general medical unit.
Cough (63%) and fever (60.9%) were the most frequently reported symptoms at admission. The median duration of symptoms before admission was 3 days. None of the children had traveled to an area affected by COVID-19 before becoming ill, and only 20 (43.5%) children were confirmed to have had contact with someone with COVID-19. “The lack of a known sick contact reported in our study may have implications for how healthcare providers identify and screen for potential cases,” the authors explained.
Although children are believed to experience milder SARS-CoV-2 illness, these results and those of an earlier study suggest that some pediatric patients develop illness severe enough to require PICU admission. “This subset had significantly higher markers of inflammation (CRP, pro-BNP, procalcitonin) compared with patients in the medical unit. Inflammation likely contributed to the high rate of ARDS we observed, although serum levels of IL-6 and other cytokines linked to ARDS were not determined,” the authors wrote.
A retrospective cohort study found that of 177 children and young adults treated in a single center, patients younger than 1 year and older than 15 years were more likely to become critically ill with COVID-19 (J Pediatr. 2020 May. doi: 10.1016/j.jpeds.2020.05.007).
Each of the two age groups accounted for 32% of the hospitalized patients.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Children with COVID-19 are more likely to develop severe illness and require intensive care than previously realized, data from a single-center study suggest.
Jerry Y. Chao, MD, of the department of anesthesiology, Albert Einstein College of Medicine, New York, and colleagues reported their findings in an article published online May 11 in the Journal of Pediatrics.
“Thankfully most children with COVID-19 fare well, and some do not have any symptoms at all, but this research is a sobering reminder that children are not immune to this virus and some do require a higher level of care,” senior author Shivanand S. Medar, MD, FAAP, attending physician, Cardiac Intensive Care, Children’s Hospital at Montefiore, and assistant professor of pediatrics, Albert Einstein College of Medicine, said in a Montefiore Medical Center news release.
The study included 67 patients aged 1 month to 21 years (median, 13.1 years) who were treated for COVID-19 at a tertiary care children’s hospital between March 15 and April 13. Of those, 21 (31.3%) were treated as outpatients.
“As the number of patients screened for COVID-19 was restricted during the first weeks of the outbreak because of limited testing availability, the number of mildly symptomatic patients is not known, and therefore these 21 patients are not included in the analysis,” the authors wrote.
Of the 46 hospitalized patients, 33 (72%) were admitted to a general pediatric medical ward, and 13 (28%) were admitted to the pediatric intensive care unit (PICU).
Almost one-third (14 children; 30.4%) of the admitted patients were obese, and almost one-quarter (11 children; 24.4%) had asthma, but neither factor was associated with an increased risk for PICU admission.
“We know that in adults, obesity is a risk factor for more severe disease, however, surprisingly, our study found that children admitted to the intensive care unit did not have a higher prevalence of obesity than those on the general unit,” Dr. Chao said in the news release.
Three of the PICU patients (25%) had preexisting seizure disorders, as did one (3%) patient on the general medical unit. “There was no significant difference in the usage of ibuprofen prior to hospitalization among patients admitted to medical unit compared with those admitted to the PICU,” the authors wrote.
Platelet counts were lower in patients admitted to the PICU compared with those on the general medical unit; however, C-reactive protein, procalcitonin, and pro–brain natriuretic peptide levels were all elevated in patients admitted to the PICU compared with those admitted to the general medical unit.
Patients admitted to the PICU were more likely to need high-flow nasal cannula. Ten (77%) patients in the PICU developed acute respiratory distress syndrome (ARDS), and six (46.2%) of them needed “invasive mechanical ventilation for a median of 9 days.”
The only clinical symptom significantly linked to PICU admission was shortness of breath (92.3% vs 30.3%; P < .001).
Eight (61.5%) of the 13 patients treated in the PICU were discharged to home; four (30.7%) were still hospitalized and receiving ventilatory support on day 14. One patient had metastatic cancer and died as a result of the cancer after life-sustaining therapy was withdrawn.
Those admitted to the PICU were more likely to receive treatment with remdesivir via compassionate use compared with those treated in the general medical unit. Seven (53.8%) patients in the PICU developed severe sepsis and septic shock syndromes.
The average hospital stay was 4 days longer for the children admitted to the PICU than for the children admitted to the general medical unit.
Cough (63%) and fever (60.9%) were the most frequently reported symptoms at admission. The median duration of symptoms before admission was 3 days. None of the children had traveled to an area affected by COVID-19 before becoming ill, and only 20 (43.5%) children were confirmed to have had contact with someone with COVID-19. “The lack of a known sick contact reported in our study may have implications for how healthcare providers identify and screen for potential cases,” the authors explained.
Although children are believed to experience milder SARS-CoV-2 illness, these results and those of an earlier study suggest that some pediatric patients develop illness severe enough to require PICU admission. “This subset had significantly higher markers of inflammation (CRP, pro-BNP, procalcitonin) compared with patients in the medical unit. Inflammation likely contributed to the high rate of ARDS we observed, although serum levels of IL-6 and other cytokines linked to ARDS were not determined,” the authors wrote.
A retrospective cohort study found that of 177 children and young adults treated in a single center, patients younger than 1 year and older than 15 years were more likely to become critically ill with COVID-19 (J Pediatr. 2020 May. doi: 10.1016/j.jpeds.2020.05.007).
Each of the two age groups accounted for 32% of the hospitalized patients.
The authors have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
COVID-19: Psychiatrists assess geriatric harm from social distancing
One of the greatest tragedies of the first wave of the COVID-19 pandemic has been the failure of health policy makers to anticipate and mitigate the enormous havoc the policy of social distancing would wreak on mental health and cognitive function in older persons, speakers agreed at a webinar on COVID-19, social distancing, and its impact on social and mental health in the elderly hosted by the International Psychogeriatric Association in collaboration with INTERDEM.
“Social distancing” is a two-edged sword: It is for now and the foreseeable future the only available effective strategy for protecting against infection in the older population most vulnerable to severe forms of COVID-19. Yet social distancing also has caused many elderly – particularly those in nursing homes and other long-term care facilities – to plunge into a profound experience of loneliness, isolation, distress, feelings of abandonment, anxiety, depression, and accelerated cognitive deterioration. And this needn’t have happened, the mental health professionals asserted.
“When are we going to get rid of the term ‘social distancing?’ ” asked IPA President William E. Reichman, MD. “Many have appreciated – including the World Health Organization – that the real issue is physical distancing to prevent contagion. And physical distancing doesn’t have to mean social distancing.”
Social connectedness between elderly persons and their peers and family members can be maintained and should be emphatically encouraged during the physical distancing required by the pandemic, said Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers.
This can be achieved using readily available technologies, including the telephone and videoconferencing, as well as by creating opportunities for supervised masked visits between a family member and an elderly loved one in outdoor courtyards or gardens within long-term care facilities. And yet, as the pandemic seized hold in many parts of the world, family members were blocked from entry to these facilities, she observed.
Impact on mental health, cognition
Dr. Vernooij-Dassen noted that studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly.
“
INTERDEM is backing two ongoing studies evaluating the hypothesis that interventions fostering increased social interaction among elderly individuals can delay onset of dementia or favorably affect its course. The proposed mechanism of benefit is stimulation of brain plasticity to enhance cognitive reserve.
“This is a hypothesis of hope. We know that social interaction for humans is like water to plants – we really, really need it,” she explained.
Diego de Leo, MD, PhD, emeritus professor of psychiatry and former director of the Australian Institute for Suicide Research and Prevention at Griffith University in Brisbane, was living in hard-hit Padua, Italy, during the first surge of COVID-19. He described his anecdotal experience.
“What I hear from many Italian colleagues and friends and directors of mental health services is that emergency admissions related to mental disorders declined during the first wave of the COVID pandemic. For example, not many people attended emergency departments due to suicide attempts; there was a very marked decrease in the number of suicide attempts during the worst days of the pandemic,” he said.
People with psychiatric conditions were afraid to go to the hospital because they thought they would contract the infection and die there. That’s changing now, however.
“Now there is an increased number of admissions to mental health units. A new wave. It has been a U-shaped curve. And we’re now witnessing an increasing number of fatal suicides due to persistent fears, due to people imagining that there is no more room for them, and no more future for them from a financial point of view – which is the major negative outcome of this crisis. It will be a disaster for many families,” the psychiatrist continued.
A noteworthy phenomenon in northern Italy was that, when tablets were made available to nursing home residents in an effort to enhance their connectedness to the outside world, those with dementia often became so frustrated and confused by their difficulty in using the devices that they developed a hypokinetic delirium marked by refusal to eat or leave their bed, he reported.
It’s far too early to have reliable data on suicide trends in response to the pandemic, according to Dr. de Leo. But one thing is for sure: The strategy of social distancing employed to curb COVID-19 has increased the prevalence of known risk factors for suicide in older individuals, including loneliness, anxiety, and depression; increased alcohol use; and a perception of being a burden on society. Dr. de Leo directs a foundation dedicated to helping people experiencing traumatic bereavement, and in one recent week, the foundation was contacted by eight families in the province of Padua with a recent death by suicide apparently related to fallout from the COVID-19 pandemic. That’s an unusually high spike in suicide in a province with a population of 1 million.
“People probably preferred to end the agitation, the fear, the extreme anxiety about their destiny by deciding to prematurely truncate their life. That has been reported by nursing staff,” he said.
The Italian government has determined that, to date, 36% of all COVID-related deaths have occurred in people aged 85 years or older, and 84% of deaths were in individuals aged at least 70 years. And in Milan and the surrounding province of Lombardy, it’s estimated that COVID-19 has taken the lives of 25% of all nursing home residents. The North American experience has been uncomfortably similar.
“Almost 80% of COVID deaths in Canada have occurred in congregate settings,” observed Dr. Reichman, professor of psychiatry at the University of Toronto, and president and CEO of Baycrest Health Sciences, a geriatric research center.
“Certainly, the appalling number of deaths in nursing homes is the No. 1 horror of the pandemic,” declared Carmelle Peisah, MBBS, MD, a psychiatrist at the University of New South Wales in Kensington, Australia.
The fire next time
The conventional wisdom holds that COVID-19 has caused all sorts of mayhem in the delivery of elder care. Not so, in Dr. Reichman’s view.
“I would suggest that the pandemic has not caused many of the problems we talk about, it’s actually revealed problems that have always been there under the surface. For example, many older people, even before COVID-19, were socially isolated, socially distant. They had difficulty connecting with their relatives, difficulty accessing transportation to get to the store to buy food and see their doctors, and to interact with other older people,” the psychiatrist said.
“I would say as well that the pandemic didn’t cause the problems we’ve seen in long-term congregate senior care. The pandemic revealed them. We’ve had facilities where older people were severely crowded together, which compromises their quality of life, even when there’s not a pandemic. We’ve had difficulty staffing these kinds of environments with people that are paid an honest wage for the very hard work that they do. In many of these settings they’re inadequately trained, not only in infection prevention and control but in all other aspects of care. And the pandemic has revealed that many of these organizations are not properly funded. The government doesn’t support them well enough across jurisdictions, and they can’t raise enough philanthropic funds to provide the kind of quality of life that residents demand,” Dr. Reichman continued.
Could the pandemic spur improved elder care? His hope is that health care professionals, politicians, and society at large will learn from the devastation left by the first surge of the pandemic and will lobby for the resources necessary for much-needed improvements in geriatric care.
“We need to be better prepared should there be not only a second wave of this pandemic, but for other pandemics to come,” Dr. Reichman concluded.
The speakers indicated they had no financial conflicts regarding their presentations.
One of the greatest tragedies of the first wave of the COVID-19 pandemic has been the failure of health policy makers to anticipate and mitigate the enormous havoc the policy of social distancing would wreak on mental health and cognitive function in older persons, speakers agreed at a webinar on COVID-19, social distancing, and its impact on social and mental health in the elderly hosted by the International Psychogeriatric Association in collaboration with INTERDEM.
“Social distancing” is a two-edged sword: It is for now and the foreseeable future the only available effective strategy for protecting against infection in the older population most vulnerable to severe forms of COVID-19. Yet social distancing also has caused many elderly – particularly those in nursing homes and other long-term care facilities – to plunge into a profound experience of loneliness, isolation, distress, feelings of abandonment, anxiety, depression, and accelerated cognitive deterioration. And this needn’t have happened, the mental health professionals asserted.
“When are we going to get rid of the term ‘social distancing?’ ” asked IPA President William E. Reichman, MD. “Many have appreciated – including the World Health Organization – that the real issue is physical distancing to prevent contagion. And physical distancing doesn’t have to mean social distancing.”
Social connectedness between elderly persons and their peers and family members can be maintained and should be emphatically encouraged during the physical distancing required by the pandemic, said Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers.
This can be achieved using readily available technologies, including the telephone and videoconferencing, as well as by creating opportunities for supervised masked visits between a family member and an elderly loved one in outdoor courtyards or gardens within long-term care facilities. And yet, as the pandemic seized hold in many parts of the world, family members were blocked from entry to these facilities, she observed.
Impact on mental health, cognition
Dr. Vernooij-Dassen noted that studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly.
“
INTERDEM is backing two ongoing studies evaluating the hypothesis that interventions fostering increased social interaction among elderly individuals can delay onset of dementia or favorably affect its course. The proposed mechanism of benefit is stimulation of brain plasticity to enhance cognitive reserve.
“This is a hypothesis of hope. We know that social interaction for humans is like water to plants – we really, really need it,” she explained.
Diego de Leo, MD, PhD, emeritus professor of psychiatry and former director of the Australian Institute for Suicide Research and Prevention at Griffith University in Brisbane, was living in hard-hit Padua, Italy, during the first surge of COVID-19. He described his anecdotal experience.
“What I hear from many Italian colleagues and friends and directors of mental health services is that emergency admissions related to mental disorders declined during the first wave of the COVID pandemic. For example, not many people attended emergency departments due to suicide attempts; there was a very marked decrease in the number of suicide attempts during the worst days of the pandemic,” he said.
People with psychiatric conditions were afraid to go to the hospital because they thought they would contract the infection and die there. That’s changing now, however.
“Now there is an increased number of admissions to mental health units. A new wave. It has been a U-shaped curve. And we’re now witnessing an increasing number of fatal suicides due to persistent fears, due to people imagining that there is no more room for them, and no more future for them from a financial point of view – which is the major negative outcome of this crisis. It will be a disaster for many families,” the psychiatrist continued.
A noteworthy phenomenon in northern Italy was that, when tablets were made available to nursing home residents in an effort to enhance their connectedness to the outside world, those with dementia often became so frustrated and confused by their difficulty in using the devices that they developed a hypokinetic delirium marked by refusal to eat or leave their bed, he reported.
It’s far too early to have reliable data on suicide trends in response to the pandemic, according to Dr. de Leo. But one thing is for sure: The strategy of social distancing employed to curb COVID-19 has increased the prevalence of known risk factors for suicide in older individuals, including loneliness, anxiety, and depression; increased alcohol use; and a perception of being a burden on society. Dr. de Leo directs a foundation dedicated to helping people experiencing traumatic bereavement, and in one recent week, the foundation was contacted by eight families in the province of Padua with a recent death by suicide apparently related to fallout from the COVID-19 pandemic. That’s an unusually high spike in suicide in a province with a population of 1 million.
“People probably preferred to end the agitation, the fear, the extreme anxiety about their destiny by deciding to prematurely truncate their life. That has been reported by nursing staff,” he said.
The Italian government has determined that, to date, 36% of all COVID-related deaths have occurred in people aged 85 years or older, and 84% of deaths were in individuals aged at least 70 years. And in Milan and the surrounding province of Lombardy, it’s estimated that COVID-19 has taken the lives of 25% of all nursing home residents. The North American experience has been uncomfortably similar.
“Almost 80% of COVID deaths in Canada have occurred in congregate settings,” observed Dr. Reichman, professor of psychiatry at the University of Toronto, and president and CEO of Baycrest Health Sciences, a geriatric research center.
“Certainly, the appalling number of deaths in nursing homes is the No. 1 horror of the pandemic,” declared Carmelle Peisah, MBBS, MD, a psychiatrist at the University of New South Wales in Kensington, Australia.
The fire next time
The conventional wisdom holds that COVID-19 has caused all sorts of mayhem in the delivery of elder care. Not so, in Dr. Reichman’s view.
“I would suggest that the pandemic has not caused many of the problems we talk about, it’s actually revealed problems that have always been there under the surface. For example, many older people, even before COVID-19, were socially isolated, socially distant. They had difficulty connecting with their relatives, difficulty accessing transportation to get to the store to buy food and see their doctors, and to interact with other older people,” the psychiatrist said.
“I would say as well that the pandemic didn’t cause the problems we’ve seen in long-term congregate senior care. The pandemic revealed them. We’ve had facilities where older people were severely crowded together, which compromises their quality of life, even when there’s not a pandemic. We’ve had difficulty staffing these kinds of environments with people that are paid an honest wage for the very hard work that they do. In many of these settings they’re inadequately trained, not only in infection prevention and control but in all other aspects of care. And the pandemic has revealed that many of these organizations are not properly funded. The government doesn’t support them well enough across jurisdictions, and they can’t raise enough philanthropic funds to provide the kind of quality of life that residents demand,” Dr. Reichman continued.
Could the pandemic spur improved elder care? His hope is that health care professionals, politicians, and society at large will learn from the devastation left by the first surge of the pandemic and will lobby for the resources necessary for much-needed improvements in geriatric care.
“We need to be better prepared should there be not only a second wave of this pandemic, but for other pandemics to come,” Dr. Reichman concluded.
The speakers indicated they had no financial conflicts regarding their presentations.
One of the greatest tragedies of the first wave of the COVID-19 pandemic has been the failure of health policy makers to anticipate and mitigate the enormous havoc the policy of social distancing would wreak on mental health and cognitive function in older persons, speakers agreed at a webinar on COVID-19, social distancing, and its impact on social and mental health in the elderly hosted by the International Psychogeriatric Association in collaboration with INTERDEM.
“Social distancing” is a two-edged sword: It is for now and the foreseeable future the only available effective strategy for protecting against infection in the older population most vulnerable to severe forms of COVID-19. Yet social distancing also has caused many elderly – particularly those in nursing homes and other long-term care facilities – to plunge into a profound experience of loneliness, isolation, distress, feelings of abandonment, anxiety, depression, and accelerated cognitive deterioration. And this needn’t have happened, the mental health professionals asserted.
“When are we going to get rid of the term ‘social distancing?’ ” asked IPA President William E. Reichman, MD. “Many have appreciated – including the World Health Organization – that the real issue is physical distancing to prevent contagion. And physical distancing doesn’t have to mean social distancing.”
Social connectedness between elderly persons and their peers and family members can be maintained and should be emphatically encouraged during the physical distancing required by the pandemic, said Myrra Vernooij-Dassen, PhD, of Radboud University in Nigmegen, the Netherlands, and chair of INTERDEM, a pan-European network of dementia researchers.
This can be achieved using readily available technologies, including the telephone and videoconferencing, as well as by creating opportunities for supervised masked visits between a family member and an elderly loved one in outdoor courtyards or gardens within long-term care facilities. And yet, as the pandemic seized hold in many parts of the world, family members were blocked from entry to these facilities, she observed.
Impact on mental health, cognition
Dr. Vernooij-Dassen noted that studies of previous quarantine periods as well as preliminary findings during the COVID-19 pandemic demonstrate an inverse relationship between social isolation measures and cognitive functioning in the elderly.
“
INTERDEM is backing two ongoing studies evaluating the hypothesis that interventions fostering increased social interaction among elderly individuals can delay onset of dementia or favorably affect its course. The proposed mechanism of benefit is stimulation of brain plasticity to enhance cognitive reserve.
“This is a hypothesis of hope. We know that social interaction for humans is like water to plants – we really, really need it,” she explained.
Diego de Leo, MD, PhD, emeritus professor of psychiatry and former director of the Australian Institute for Suicide Research and Prevention at Griffith University in Brisbane, was living in hard-hit Padua, Italy, during the first surge of COVID-19. He described his anecdotal experience.
“What I hear from many Italian colleagues and friends and directors of mental health services is that emergency admissions related to mental disorders declined during the first wave of the COVID pandemic. For example, not many people attended emergency departments due to suicide attempts; there was a very marked decrease in the number of suicide attempts during the worst days of the pandemic,” he said.
People with psychiatric conditions were afraid to go to the hospital because they thought they would contract the infection and die there. That’s changing now, however.
“Now there is an increased number of admissions to mental health units. A new wave. It has been a U-shaped curve. And we’re now witnessing an increasing number of fatal suicides due to persistent fears, due to people imagining that there is no more room for them, and no more future for them from a financial point of view – which is the major negative outcome of this crisis. It will be a disaster for many families,” the psychiatrist continued.
A noteworthy phenomenon in northern Italy was that, when tablets were made available to nursing home residents in an effort to enhance their connectedness to the outside world, those with dementia often became so frustrated and confused by their difficulty in using the devices that they developed a hypokinetic delirium marked by refusal to eat or leave their bed, he reported.
It’s far too early to have reliable data on suicide trends in response to the pandemic, according to Dr. de Leo. But one thing is for sure: The strategy of social distancing employed to curb COVID-19 has increased the prevalence of known risk factors for suicide in older individuals, including loneliness, anxiety, and depression; increased alcohol use; and a perception of being a burden on society. Dr. de Leo directs a foundation dedicated to helping people experiencing traumatic bereavement, and in one recent week, the foundation was contacted by eight families in the province of Padua with a recent death by suicide apparently related to fallout from the COVID-19 pandemic. That’s an unusually high spike in suicide in a province with a population of 1 million.
“People probably preferred to end the agitation, the fear, the extreme anxiety about their destiny by deciding to prematurely truncate their life. That has been reported by nursing staff,” he said.
The Italian government has determined that, to date, 36% of all COVID-related deaths have occurred in people aged 85 years or older, and 84% of deaths were in individuals aged at least 70 years. And in Milan and the surrounding province of Lombardy, it’s estimated that COVID-19 has taken the lives of 25% of all nursing home residents. The North American experience has been uncomfortably similar.
“Almost 80% of COVID deaths in Canada have occurred in congregate settings,” observed Dr. Reichman, professor of psychiatry at the University of Toronto, and president and CEO of Baycrest Health Sciences, a geriatric research center.
“Certainly, the appalling number of deaths in nursing homes is the No. 1 horror of the pandemic,” declared Carmelle Peisah, MBBS, MD, a psychiatrist at the University of New South Wales in Kensington, Australia.
The fire next time
The conventional wisdom holds that COVID-19 has caused all sorts of mayhem in the delivery of elder care. Not so, in Dr. Reichman’s view.
“I would suggest that the pandemic has not caused many of the problems we talk about, it’s actually revealed problems that have always been there under the surface. For example, many older people, even before COVID-19, were socially isolated, socially distant. They had difficulty connecting with their relatives, difficulty accessing transportation to get to the store to buy food and see their doctors, and to interact with other older people,” the psychiatrist said.
“I would say as well that the pandemic didn’t cause the problems we’ve seen in long-term congregate senior care. The pandemic revealed them. We’ve had facilities where older people were severely crowded together, which compromises their quality of life, even when there’s not a pandemic. We’ve had difficulty staffing these kinds of environments with people that are paid an honest wage for the very hard work that they do. In many of these settings they’re inadequately trained, not only in infection prevention and control but in all other aspects of care. And the pandemic has revealed that many of these organizations are not properly funded. The government doesn’t support them well enough across jurisdictions, and they can’t raise enough philanthropic funds to provide the kind of quality of life that residents demand,” Dr. Reichman continued.
Could the pandemic spur improved elder care? His hope is that health care professionals, politicians, and society at large will learn from the devastation left by the first surge of the pandemic and will lobby for the resources necessary for much-needed improvements in geriatric care.
“We need to be better prepared should there be not only a second wave of this pandemic, but for other pandemics to come,” Dr. Reichman concluded.
The speakers indicated they had no financial conflicts regarding their presentations.
More evidence hydroxychloroquine is ineffective, harmful in COVID-19
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Immunotherapy, steroids had positive outcomes in COVID-19–associated multisystem inflammatory syndrome
According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”
Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m2 (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.
Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.
“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”
They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”
Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”
The researchers and Dr. Goldberg reported having no disclosures.
SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.
According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”
Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m2 (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.
Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.
“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”
They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”
Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”
The researchers and Dr. Goldberg reported having no disclosures.
SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.
According to study of a cluster of patients in France and Switzerland, children may experience an acute cardiac decompensation from the severe inflammatory state following SARS-CoV-2 infection, termed multisystem inflammatory syndrome in children (MIS-C). Treatment with immunoglobulin appears to be associated with recovery of left ventricular systolic function.
“The pediatric and cardiology communities should be acutely aware of this new disease probably related to SARS-CoV-2 infection (MIS-C), that shares similarities with Kawasaki disease but has specificities in its presentation,” researchers led by Zahra Belhadjer, MD, of Necker-Enfants Malades Hospital in Paris, wrote in a cases series report published online in Circulation “Early diagnosis and management appear to lead to favorable outcome using classical therapies. Elucidating the immune mechanisms of this disease will afford further insights for treatment and potential global prevention of severe forms.”
Over a 2-month period that coincided with the SARS-CoV-2 pandemic in France and Switzerland, the researchers retrospectively collected clinical, biological, therapeutic, and early-outcomes data in 35 children who were admitted to pediatric ICUs in 14 centers for cardiogenic shock, left ventricular dysfunction, and severe inflammatory state. Their median age was 10 years, all presented with a fever, 80% had gastrointestinal symptoms of abdominal pain, vomiting, or diarrhea, and 28% had comorbidities that included body mass index of greater than 25 kg/m2 (17%), asthma (9%), and lupus (3%), and overweight. Only 17% presented with chest pain. The researchers observed that left ventricular ejection fraction was less than 30% in 28% of patients, and 80% required inotropic support with 28% treated with extracorporeal membrane oxygenation (ECMO). All patients presented with a severe inflammatory state evidenced by elevated C-reactive protein and d-dimer. Interleukin 6 was elevated to a median of 135 pg/mL in 13 of the patients. Elevation of troponin I was constant but mild to moderate, and NT-proBNP or BNP elevation was present in all children.
Nearly all patients 35 (88%) patients tested positive for SARS-CoV-2 infection by polymerase chain reaction of nasopharyngeal swab or serology. Most patients (80%) received IV inotropic support, 71% received first-line IV immunoglobulin, 65% received anticoagulation with heparin, 34% received IV steroids having been considered high-risk patients with symptoms similar to an incomplete form of Kawasaki disease, and 8% received treatment with an interleukin-1 receptor antagonist because of a persistent severe inflammatory state. Left ventricular function was restored in 71% of those discharged from the intensive care unit. No patient died, and all patients treated with ECMO were successfully weaned after a median of 4.5 days.
“Some aspects of this emerging pediatric disease (MIS-C) are similar to those of Kawasaki disease: prolonged fever, multisystem inflammation with skin rash, lymphadenopathy, diarrhea, meningism, and high levels of inflammatory biomarkers,” the researchers wrote. “But differences are important and raise the question as to whether this syndrome is Kawasaki disease with SARS-CoV-2 as the triggering agent, or represents a different syndrome (MIS-C). Kawasaki disease predominantly affects young children younger than 5 years, whereas the median age in our series is 10 years. Incomplete forms of Kawasaki disease occur in infants who may have fever as the sole clinical finding, whereas older patients are more prone to exhibit the complete form.”
They went on to note that the overlapping features between MIS-C and Kawasaki disease “may be due to similar pathophysiology. The etiologic agent of Kawasaki disease is unknown but likely to be ubiquitous, causing asymptomatic childhood infection but triggering the immunologic cascade of Kawasaki disease in genetically susceptible individuals. Please note that infection with a novel RNA virus that enters through the upper respiratory tract has been proposed to be the cause of the disease (see PLoS One. 2008 Feb 13;3:e1582 and J Infect Dis. 2011 Apr 1;203:1021-30).”
Based on the work of authors, it appears that a high index of suspicion for MIS-C is important for children who develop Kawasaki-like symptoms, David J. Goldberg, MD, said in an interview. “Although children have largely been spared from the acute respiratory presentation of the SARS-CoV-2 pandemic, the recognition and understanding of what appears to be a postviral inflammatory response is a critical first step in developing treatment algorithms for this disease process,” said Dr. Goldberg, a board-certified attending cardiologist in the cardiac center and fetal heart program at Children’s Hospital of Philadelphia. “If inflammatory markers are elevated, particularly if there are accompanying gastrointestinal symptoms, the possibility of cardiac involvement suggests the utility of screening echocardiography. Given the potential need for inotropic or mechanical circulatory support, the presence of myocardial dysfunction dictates care in an intensive care unit capable of providing advanced therapies. While the evidence from Dr. Belhadjer’s cohort suggests that full recovery is probable, there is still much to be learned about this unique inflammatory syndrome and the alarm has rightly been sounded.”
The researchers and Dr. Goldberg reported having no disclosures.
SOURCE: Belhadjer Z et al. Circulation 2020 May 17; doi: 10.1161/circulationaha.120.048360.
FROM CIRCULATION
Today’s top news highlights: Remdesivir data dive, FDA approves contraceptive gel
:
Remdesivir trial data published
Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.
FDA approves contraceptive gel
The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.
COVID-19 lessons from one cancer center
Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.
Convalescent plasma: Hope or hype?
There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.
New rosacea treatment guidelines
Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
:
Remdesivir trial data published
Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.
FDA approves contraceptive gel
The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.
COVID-19 lessons from one cancer center
Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.
Convalescent plasma: Hope or hype?
There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.
New rosacea treatment guidelines
Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
:
Remdesivir trial data published
Weeks after topline remdesivir data appeared in the press, investigators published their full experience using the drug to treat COVID-19 patients. The study, published in the New England Journal of Medicine, showed the drug reduced recovery time from 15 to 11 days, compared with placebo. Patients receiving oxygen seemed to fare best from treatment with remdesivir. “There is clear and consistent evidence of clinically significant benefit for those hospitalized on oxygen but not yet requiring mechanical ventilation,” Daniel Kaul, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, said after seeing the published results. “Surprisingly, early dosing as measured from time to onset of symptoms did not seem to make a difference.” READ MORE.
FDA approves contraceptive gel
The Food and Drug Administration approved Phexxi (lactic acid, citric acid, and potassium bitartrate) vaginal gel to prevent pregnancy in women of reproductive potential. It’s the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5. READ MORE.
COVID-19 lessons from one cancer center
Physicians at Levine Cancer Institute in Charlotte, N.C., largely have been able to keep hematologic oncology patients on their treatment regimens and continue to care for inpatients during the early months of the COVID-19 pandemic. How have they kept the situation managable? Strict infection control, liberal testing, and a proactive plan to defer and temporarily replace infusion care when medically appropriate were all part of the strategy. “My impression is that the incidence has been low partly because our patients, especially those with hematologic malignancies including those on active chemotherapy, were already getting warned to be cautious, even before the coronavirus, using distancing, masking, and meticulous hand hygiene,” said Peter Voorhees, MD, professor of medicine and director of Medical Operations and Outreach Services in Levine Cancer Institute’s Department of Hematologic Oncology and Blood Disorders. READ MORE.
Convalescent plasma: Hope or hype?
There are currently more than two dozen trials of convalescent plasma in the United States and elsewhere but most are single-arm trials to determine if one infusion can decrease the need for intubation or help patients on a ventilator to improve. Others researchers are investigating whether convalescent plasma might be used before severe disease sets in. Meanwhile, about 2,200 hospitals are participating in an expanded access program being led by the Mayo Clinic nationwide. The National Institutes of Health recently said that “there are insufficient clinical data to recommend either for or against” its use for COVID-19. READ MORE.
New rosacea treatment guidelines
Patients with rosacea should receive treatments based on their phenotype and specific symptoms, rather than being assigned into distinct subtype categories, according to updated guidance published in the Journal of the American Academy of Dermatology. The update comes from the National Rosacea Society Expert Committee and is based on a review of the evidence. Patients “shouldn’t be classified as having a certain subtype of rosacea” since “many patients have features that overlap more than one subtype,” said Diane Thiboutot, MD, lead author of the update and a professor of dermatology and associate dean of clinical and translational research education at Penn State University, Hershey. READ MORE.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Is HIPAA critical?
Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.
Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?
What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?
Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?
My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.
Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.
Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.
Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.
Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?
What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?
Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?
My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.
Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.
Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.
Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
Ignorance may be bliss for some. But as I sit here in my scenic social isolation on the Maine coast I find that, like most people, what I don’t know unsettles me. How is the COVID-19 virus spread? Does my wife’s wipe down of the doorknobs after I return from the grocery store really make us any less likely to contract the virus? Is wearing my homemade bandana face mask doing anything to protect me? I suspect not, but I wear it as a statement of courtesy and solidarity to my fellow community members.
Does the 6-foot rule make any sense? I’ve read that it is based on a study dating back to the 1930s. I’ve seen images of the 25-foot droplet plume blasting out from a sneeze and understand that, as a bicyclist, I may be generating a shower of droplets in my wake. But, are those droplets a threat to anyone I pedal by if I am symptom free? What does being a carrier mean when we are talking about COVID-19?
What makes me more vulnerable to this particular virus as an apparently healthy septuagenarian? What collection of misfortunes have fallen on those younger victims of the pandemic? How often was it genetic?
Of course, none of us has the information yet that can provide us answers. This vacuum has attracted scores of “experts” bold enough or careless enough to venture an opinion. They may have also issued a caveat, but how often have the media failed to include it in the report or buried it in the fine print at the end of the story?
My discomfort with this information void has left me and you and everyone else to our imaginations to craft our own explanations. So, I try to piece together a construct based on what I can glean from what I read and see in the news because like most people I fortunately have no first-hand information about even a single case. The number of deaths is horrifying, but may not have hit close to home and given most of us a real personal sense of the illness and its character.
Maine is a small state with just over a million inhabitants, and most of us have some connection to one another. It may be that a person is the second cousin of someone who used to live 2 miles down the road. But, there is some feeling of familiarity. We have had deaths related to COVID-19, but very scanty information other than the county about where they occurred and whether the victim was a resident of an extended care facility. We are told very little if any details about exposure as officials invoke HIPAA regulations that leave us in the dark. Other than one vague reference to a “traveling salesman” who may have introduced the virus to several nursing homes, there has been very little information about how the virus may have been spread here in Maine. Even national reports of the deaths of high-profile entertainers and retired athletes are usually draped in the same haze of privacy.
Most of us don’t need to know the names and street addresses of the victims but a few anonymous narratives that include some general information on how epidemiologists believe clusters began and propagated would help us understand our risks with just a glimmer of clarity.
Of course the epidemiologists may not have the answers we are seeking because they too are struggling to untangle connections hampered by concerns of privacy. There is no question that privacy must remain an important part of the physician-patient relationship. But a pandemic has thrown us into a situation where common sense demands that HIPAA be interpreted with an emphasis on the greater good. Finding that balance between privacy and public knowledge will continue to be one of our greatest challenges.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.
FDA approves Phexxi for use as an on-demand contraceptive
Evofem Biosciences expects to release Phexxi – the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5 – in September 2020 alongside the Phexxi Concierge Experience, a comprehensive patient and health care provider telemedicine support system, according to the company’s press release. The service is designed to provide physicians with on-demand educational support, and to speed and simplify women’s access to Phexxi.
In an open-label multicenter trial, women aged 18-35 with regular menstrual cycles intravaginally administered a 5-gram dose of Phexxi vaginal gel up to 1 hour prior to intercourse; they did so for up to seven cycles. There were 101 pregnancies in 1,183 subjects during 4,769 cycles. The 7-cycle cumulative pregnancy rate was 14% (95% confidence interval: 10.0%, 17.5%).
The most common adverse events associated with Phexxi were vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, bacterial vaginosis, vaginal discharge, dysuria, and vulvovaginal pain.
Evofem Biosciences expects to release Phexxi – the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5 – in September 2020 alongside the Phexxi Concierge Experience, a comprehensive patient and health care provider telemedicine support system, according to the company’s press release. The service is designed to provide physicians with on-demand educational support, and to speed and simplify women’s access to Phexxi.
In an open-label multicenter trial, women aged 18-35 with regular menstrual cycles intravaginally administered a 5-gram dose of Phexxi vaginal gel up to 1 hour prior to intercourse; they did so for up to seven cycles. There were 101 pregnancies in 1,183 subjects during 4,769 cycles. The 7-cycle cumulative pregnancy rate was 14% (95% confidence interval: 10.0%, 17.5%).
The most common adverse events associated with Phexxi were vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, bacterial vaginosis, vaginal discharge, dysuria, and vulvovaginal pain.
Evofem Biosciences expects to release Phexxi – the first nonhormonal, on-demand, vaginal pH regulator contraceptive designed to maintain vaginal pH within the range of 3.5-4.5 – in September 2020 alongside the Phexxi Concierge Experience, a comprehensive patient and health care provider telemedicine support system, according to the company’s press release. The service is designed to provide physicians with on-demand educational support, and to speed and simplify women’s access to Phexxi.
In an open-label multicenter trial, women aged 18-35 with regular menstrual cycles intravaginally administered a 5-gram dose of Phexxi vaginal gel up to 1 hour prior to intercourse; they did so for up to seven cycles. There were 101 pregnancies in 1,183 subjects during 4,769 cycles. The 7-cycle cumulative pregnancy rate was 14% (95% confidence interval: 10.0%, 17.5%).
The most common adverse events associated with Phexxi were vulvovaginal burning sensation, vulvovaginal pruritus, vulvovaginal mycotic infection, urinary tract infection, bacterial vaginosis, vaginal discharge, dysuria, and vulvovaginal pain.
Convalescent plasma: ‘Flavor of the month’ or valid COVID-19 treatment?
On March 31, soon after the Food and Drug Administration authorized emergency use of antibody-packed plasma from recovered patients with COVID-19, Marisa Leuzzi became the first donor at an American Red Cross center. She hoped it could help her aunt, Renee Bannister, who was failing after 3 weeks on a ventilator at Virtua Hospital in Voorhees, N.J.
It may have worked; 11 days after receiving the plasma, Ms. Bannister was weaned off the ventilator and she is now awake and speaking, said Red Cross spokesperson Stephanie Rendon.
This kind of anecdote is fueling demand for the therapy, which can be provided through an expanded access program led by the Mayo Clinic, backed by the FDA, and the plasma paid for by the U.S. Department of Health & Human Services. But while this program is collecting safety and outcomes data, it’s not a randomized, controlled trial.
Others, however, are pursuing that data.
“One of the things I don’t want this to be is the flavor of the month,” Shmuel Shoham, MD, associate professor of medicine at Johns Hopkins University, said in an interview.
Dr. Shoham, principal investigator for a study evaluating convalescent plasma to prevent the infection in high-risk individuals, said some clinicians, desperate for any treatment, have tried potential therapies such as hydroxychloroquine and remdesivir without evidence of safety or efficacy in COVID-19.
The National Institutes of Health recently said something similar for convalescent plasma, that “there are insufficient clinical data to recommend either for or against” its use for COVID-19.
But plasma has promise, according to a Johns Hopkins School of Medicine’s Bloomberg Distinguished Professor, Arturo Casadevall, MD, PhD, in Baltimore, and Liise-anne Pirofski, MD, a professor at Albert Einstein College of Medicine, New York. They lay out the case for convalescent plasma in an article published online March 13 in the Journal of Clinical Investigation. Passive antibody therapy, they wrote, has been used to stem polio, measles, mumps, and influenza, and more recently has shown some success against SARS-CoV-1 and Middle East respiratory syndrome (MERS).
“The special attraction of this modality of treatment is that, unlike vaccines or newly developed drugs, it could, in principle, be made available very rapidly,” said researchers with the National COVID-19 Convalescent Plasma Project, which includes physicians and scientists from 57 institutions in 46 states. But where principle veers from reality is in availability of the plasma itself, and donors are in short supply.
Aiming to prevent infection
So far, the FDA has approved 12 plasma trials – including Dr. Shoham’s – and the NIH’s clinicaltrials.gov lists more than two dozen convalescent plasma studies in the United States and elsewhere.
Most are single-arm trials to determine if one infusion can decrease the need for intubation or help those on a ventilator improve. Two others, one at Johns Hopkins and one at Stanford (Calif.) Hospital are investigating whether convalescent plasma might be used before severe disease sets in.
“A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease,” Dr. Casadevall and Dr. Pirofski wrote.
Stanford’s randomized, double-blind study will evaluate regular versus convalescent plasma in ED patients who are not sick enough to require hospitalization.
The Johns Hopkins trial, which aims to protect against infection in the first place, will begin at Johns Hopkins, Baltimore, and at Hopkins-affiliated hospitals throughout Maryland, Dr. Shoham said. He hopes it will expand nationwide eventually, and said that they expect to enroll the first patients soon.
To start, the prevention study will enroll only 150 patients, each of whom must have had close contact with someone who has COVID-19 within the previous 120 hours and be asymptomatic. The number of subjects is small, compared with the trial size of other potential therapies, and an issue, Shoham said, “that keeps me up at night.” But finding thousands of enrollees for plasma studies is hard, in part because it’s so difficult to recruit donors.
Participants will receive normal plasma (which will act as a placebo) or convalescent plasma.
The primary endpoint is cumulative incidence of COVID-19, defined as symptoms and a polymerase chain reaction–positive test; participants will be tracked for 90 days. Hospitals and health care workers could then decide if they want to use the therapy, he said.
The study will not answer whether participants will continue to have antibodies beyond the 90 days. Convalescent plasma is given as a rapid response to an emergent pathogen – a short-term boost of immunity rather than a long-term therapeutic.
What can we learn from expanded access?
Meanwhile, some 2,200 hospitals are participating in the expanded access program being led by the Mayo Clinic nationwide; more than 9,000 patients had received infusions at press time.
One participant is Northwell Health, a 23-hospital system that sprawls across the U.S. COVID epicenter: four of the five boroughs of New York City and Long Island.
Convalescent plasma is an in-demand therapy, said Christina Brennan, MD, vice president of clinical research at Northwell. “We get patients, family members, they say my family member is at X hospital – if it’s not being offered there, can you have them transferred?” she said in an interview.
When Northwell – through the New York Blood Bank – opened up donor registration, 800 people signed up in the first 24 hours, Dr. Brennan said. As of mid-May, 527 patients had received a transfusion.
Who’s the best donor and when should donation occur?
The Red Cross, hospitals, and independent blood banks are all soliciting donors, who can sign up at the Red Cross website. The FDA recommends that donors have a history of COVID-19 as confirmed by molecular or antibody testing, be symptom free for 14 days, have a negative follow-up molecular test, and be virus free at the time of collection. The FDA also suggests measuring a donor’s SARS-CoV-2 neutralizing antibody titers, if available, with a recommendation of at least 1:160.
But questions remain, such as whether there is a theoretical risk for antibody-dependent enhancement (ADE) of infection with SARS-CoV-2. “Antibodies to one type of coronavirus could enhance infection to another viral strain,” of coronavirus, Dr. Casadevall wrote. ADE has been observed in both severe acute respiratory syndrome (SARS) and MERS.
The other risk is that donors may still be shedding active virus. While the FDA suggests that donors are unlikely to still be infectious 14 days after infection, that is as of yet unproven. Both COVID-19 diagnostics and antibody tests have high rates of false negatives, which raises the specter that infection could be spread via the plasma donation.
Daniele Focosi, MD, PhD, from Pisa (Italy) University Hospital and colleagues raise that concern in a preprint review on convalescent plasma in COVID-19. “Although the recipient is already infected, theoretically transmission of more infectious particles could worsen clinical conditions,” they wrote, noting that “such a concern can be somewhat reduced by treatment with modern pathogen inactivation techniques.”
No evidence exists that SARS-CoV-2 can be transmitted through blood, but “we don’t know for sure,” Dr. Shoham said in an interview. A reassuring point: Even those with severe infection do not have viral RNA in their blood, he said, adding, “We don’t think there’s going to be viral transmission of this particular virus with transfusion.”
For another highly infectious pathogen, the Ebola virus, the World Health Organization recommended in 2014 that potential plasma donors wait at least 28 days after infection.
It’s also not known how long SARS-CoV-2 antibodies persist in the blood; longer viability could mean a longer donation window. Dr. Focosi noted that a previous Chinese study had shown that SARS-specific antibodies in people infected with the first SARS virus, SARS-CoV-1, persisted for 2 years.
Dr. Casadevall and Dr. Pirofski have disclosed no relevant financial relationships. Shoham has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
On March 31, soon after the Food and Drug Administration authorized emergency use of antibody-packed plasma from recovered patients with COVID-19, Marisa Leuzzi became the first donor at an American Red Cross center. She hoped it could help her aunt, Renee Bannister, who was failing after 3 weeks on a ventilator at Virtua Hospital in Voorhees, N.J.
It may have worked; 11 days after receiving the plasma, Ms. Bannister was weaned off the ventilator and she is now awake and speaking, said Red Cross spokesperson Stephanie Rendon.
This kind of anecdote is fueling demand for the therapy, which can be provided through an expanded access program led by the Mayo Clinic, backed by the FDA, and the plasma paid for by the U.S. Department of Health & Human Services. But while this program is collecting safety and outcomes data, it’s not a randomized, controlled trial.
Others, however, are pursuing that data.
“One of the things I don’t want this to be is the flavor of the month,” Shmuel Shoham, MD, associate professor of medicine at Johns Hopkins University, said in an interview.
Dr. Shoham, principal investigator for a study evaluating convalescent plasma to prevent the infection in high-risk individuals, said some clinicians, desperate for any treatment, have tried potential therapies such as hydroxychloroquine and remdesivir without evidence of safety or efficacy in COVID-19.
The National Institutes of Health recently said something similar for convalescent plasma, that “there are insufficient clinical data to recommend either for or against” its use for COVID-19.
But plasma has promise, according to a Johns Hopkins School of Medicine’s Bloomberg Distinguished Professor, Arturo Casadevall, MD, PhD, in Baltimore, and Liise-anne Pirofski, MD, a professor at Albert Einstein College of Medicine, New York. They lay out the case for convalescent plasma in an article published online March 13 in the Journal of Clinical Investigation. Passive antibody therapy, they wrote, has been used to stem polio, measles, mumps, and influenza, and more recently has shown some success against SARS-CoV-1 and Middle East respiratory syndrome (MERS).
“The special attraction of this modality of treatment is that, unlike vaccines or newly developed drugs, it could, in principle, be made available very rapidly,” said researchers with the National COVID-19 Convalescent Plasma Project, which includes physicians and scientists from 57 institutions in 46 states. But where principle veers from reality is in availability of the plasma itself, and donors are in short supply.
Aiming to prevent infection
So far, the FDA has approved 12 plasma trials – including Dr. Shoham’s – and the NIH’s clinicaltrials.gov lists more than two dozen convalescent plasma studies in the United States and elsewhere.
Most are single-arm trials to determine if one infusion can decrease the need for intubation or help those on a ventilator improve. Two others, one at Johns Hopkins and one at Stanford (Calif.) Hospital are investigating whether convalescent plasma might be used before severe disease sets in.
“A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease,” Dr. Casadevall and Dr. Pirofski wrote.
Stanford’s randomized, double-blind study will evaluate regular versus convalescent plasma in ED patients who are not sick enough to require hospitalization.
The Johns Hopkins trial, which aims to protect against infection in the first place, will begin at Johns Hopkins, Baltimore, and at Hopkins-affiliated hospitals throughout Maryland, Dr. Shoham said. He hopes it will expand nationwide eventually, and said that they expect to enroll the first patients soon.
To start, the prevention study will enroll only 150 patients, each of whom must have had close contact with someone who has COVID-19 within the previous 120 hours and be asymptomatic. The number of subjects is small, compared with the trial size of other potential therapies, and an issue, Shoham said, “that keeps me up at night.” But finding thousands of enrollees for plasma studies is hard, in part because it’s so difficult to recruit donors.
Participants will receive normal plasma (which will act as a placebo) or convalescent plasma.
The primary endpoint is cumulative incidence of COVID-19, defined as symptoms and a polymerase chain reaction–positive test; participants will be tracked for 90 days. Hospitals and health care workers could then decide if they want to use the therapy, he said.
The study will not answer whether participants will continue to have antibodies beyond the 90 days. Convalescent plasma is given as a rapid response to an emergent pathogen – a short-term boost of immunity rather than a long-term therapeutic.
What can we learn from expanded access?
Meanwhile, some 2,200 hospitals are participating in the expanded access program being led by the Mayo Clinic nationwide; more than 9,000 patients had received infusions at press time.
One participant is Northwell Health, a 23-hospital system that sprawls across the U.S. COVID epicenter: four of the five boroughs of New York City and Long Island.
Convalescent plasma is an in-demand therapy, said Christina Brennan, MD, vice president of clinical research at Northwell. “We get patients, family members, they say my family member is at X hospital – if it’s not being offered there, can you have them transferred?” she said in an interview.
When Northwell – through the New York Blood Bank – opened up donor registration, 800 people signed up in the first 24 hours, Dr. Brennan said. As of mid-May, 527 patients had received a transfusion.
Who’s the best donor and when should donation occur?
The Red Cross, hospitals, and independent blood banks are all soliciting donors, who can sign up at the Red Cross website. The FDA recommends that donors have a history of COVID-19 as confirmed by molecular or antibody testing, be symptom free for 14 days, have a negative follow-up molecular test, and be virus free at the time of collection. The FDA also suggests measuring a donor’s SARS-CoV-2 neutralizing antibody titers, if available, with a recommendation of at least 1:160.
But questions remain, such as whether there is a theoretical risk for antibody-dependent enhancement (ADE) of infection with SARS-CoV-2. “Antibodies to one type of coronavirus could enhance infection to another viral strain,” of coronavirus, Dr. Casadevall wrote. ADE has been observed in both severe acute respiratory syndrome (SARS) and MERS.
The other risk is that donors may still be shedding active virus. While the FDA suggests that donors are unlikely to still be infectious 14 days after infection, that is as of yet unproven. Both COVID-19 diagnostics and antibody tests have high rates of false negatives, which raises the specter that infection could be spread via the plasma donation.
Daniele Focosi, MD, PhD, from Pisa (Italy) University Hospital and colleagues raise that concern in a preprint review on convalescent plasma in COVID-19. “Although the recipient is already infected, theoretically transmission of more infectious particles could worsen clinical conditions,” they wrote, noting that “such a concern can be somewhat reduced by treatment with modern pathogen inactivation techniques.”
No evidence exists that SARS-CoV-2 can be transmitted through blood, but “we don’t know for sure,” Dr. Shoham said in an interview. A reassuring point: Even those with severe infection do not have viral RNA in their blood, he said, adding, “We don’t think there’s going to be viral transmission of this particular virus with transfusion.”
For another highly infectious pathogen, the Ebola virus, the World Health Organization recommended in 2014 that potential plasma donors wait at least 28 days after infection.
It’s also not known how long SARS-CoV-2 antibodies persist in the blood; longer viability could mean a longer donation window. Dr. Focosi noted that a previous Chinese study had shown that SARS-specific antibodies in people infected with the first SARS virus, SARS-CoV-1, persisted for 2 years.
Dr. Casadevall and Dr. Pirofski have disclosed no relevant financial relationships. Shoham has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
On March 31, soon after the Food and Drug Administration authorized emergency use of antibody-packed plasma from recovered patients with COVID-19, Marisa Leuzzi became the first donor at an American Red Cross center. She hoped it could help her aunt, Renee Bannister, who was failing after 3 weeks on a ventilator at Virtua Hospital in Voorhees, N.J.
It may have worked; 11 days after receiving the plasma, Ms. Bannister was weaned off the ventilator and she is now awake and speaking, said Red Cross spokesperson Stephanie Rendon.
This kind of anecdote is fueling demand for the therapy, which can be provided through an expanded access program led by the Mayo Clinic, backed by the FDA, and the plasma paid for by the U.S. Department of Health & Human Services. But while this program is collecting safety and outcomes data, it’s not a randomized, controlled trial.
Others, however, are pursuing that data.
“One of the things I don’t want this to be is the flavor of the month,” Shmuel Shoham, MD, associate professor of medicine at Johns Hopkins University, said in an interview.
Dr. Shoham, principal investigator for a study evaluating convalescent plasma to prevent the infection in high-risk individuals, said some clinicians, desperate for any treatment, have tried potential therapies such as hydroxychloroquine and remdesivir without evidence of safety or efficacy in COVID-19.
The National Institutes of Health recently said something similar for convalescent plasma, that “there are insufficient clinical data to recommend either for or against” its use for COVID-19.
But plasma has promise, according to a Johns Hopkins School of Medicine’s Bloomberg Distinguished Professor, Arturo Casadevall, MD, PhD, in Baltimore, and Liise-anne Pirofski, MD, a professor at Albert Einstein College of Medicine, New York. They lay out the case for convalescent plasma in an article published online March 13 in the Journal of Clinical Investigation. Passive antibody therapy, they wrote, has been used to stem polio, measles, mumps, and influenza, and more recently has shown some success against SARS-CoV-1 and Middle East respiratory syndrome (MERS).
“The special attraction of this modality of treatment is that, unlike vaccines or newly developed drugs, it could, in principle, be made available very rapidly,” said researchers with the National COVID-19 Convalescent Plasma Project, which includes physicians and scientists from 57 institutions in 46 states. But where principle veers from reality is in availability of the plasma itself, and donors are in short supply.
Aiming to prevent infection
So far, the FDA has approved 12 plasma trials – including Dr. Shoham’s – and the NIH’s clinicaltrials.gov lists more than two dozen convalescent plasma studies in the United States and elsewhere.
Most are single-arm trials to determine if one infusion can decrease the need for intubation or help those on a ventilator improve. Two others, one at Johns Hopkins and one at Stanford (Calif.) Hospital are investigating whether convalescent plasma might be used before severe disease sets in.
“A general principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease,” Dr. Casadevall and Dr. Pirofski wrote.
Stanford’s randomized, double-blind study will evaluate regular versus convalescent plasma in ED patients who are not sick enough to require hospitalization.
The Johns Hopkins trial, which aims to protect against infection in the first place, will begin at Johns Hopkins, Baltimore, and at Hopkins-affiliated hospitals throughout Maryland, Dr. Shoham said. He hopes it will expand nationwide eventually, and said that they expect to enroll the first patients soon.
To start, the prevention study will enroll only 150 patients, each of whom must have had close contact with someone who has COVID-19 within the previous 120 hours and be asymptomatic. The number of subjects is small, compared with the trial size of other potential therapies, and an issue, Shoham said, “that keeps me up at night.” But finding thousands of enrollees for plasma studies is hard, in part because it’s so difficult to recruit donors.
Participants will receive normal plasma (which will act as a placebo) or convalescent plasma.
The primary endpoint is cumulative incidence of COVID-19, defined as symptoms and a polymerase chain reaction–positive test; participants will be tracked for 90 days. Hospitals and health care workers could then decide if they want to use the therapy, he said.
The study will not answer whether participants will continue to have antibodies beyond the 90 days. Convalescent plasma is given as a rapid response to an emergent pathogen – a short-term boost of immunity rather than a long-term therapeutic.
What can we learn from expanded access?
Meanwhile, some 2,200 hospitals are participating in the expanded access program being led by the Mayo Clinic nationwide; more than 9,000 patients had received infusions at press time.
One participant is Northwell Health, a 23-hospital system that sprawls across the U.S. COVID epicenter: four of the five boroughs of New York City and Long Island.
Convalescent plasma is an in-demand therapy, said Christina Brennan, MD, vice president of clinical research at Northwell. “We get patients, family members, they say my family member is at X hospital – if it’s not being offered there, can you have them transferred?” she said in an interview.
When Northwell – through the New York Blood Bank – opened up donor registration, 800 people signed up in the first 24 hours, Dr. Brennan said. As of mid-May, 527 patients had received a transfusion.
Who’s the best donor and when should donation occur?
The Red Cross, hospitals, and independent blood banks are all soliciting donors, who can sign up at the Red Cross website. The FDA recommends that donors have a history of COVID-19 as confirmed by molecular or antibody testing, be symptom free for 14 days, have a negative follow-up molecular test, and be virus free at the time of collection. The FDA also suggests measuring a donor’s SARS-CoV-2 neutralizing antibody titers, if available, with a recommendation of at least 1:160.
But questions remain, such as whether there is a theoretical risk for antibody-dependent enhancement (ADE) of infection with SARS-CoV-2. “Antibodies to one type of coronavirus could enhance infection to another viral strain,” of coronavirus, Dr. Casadevall wrote. ADE has been observed in both severe acute respiratory syndrome (SARS) and MERS.
The other risk is that donors may still be shedding active virus. While the FDA suggests that donors are unlikely to still be infectious 14 days after infection, that is as of yet unproven. Both COVID-19 diagnostics and antibody tests have high rates of false negatives, which raises the specter that infection could be spread via the plasma donation.
Daniele Focosi, MD, PhD, from Pisa (Italy) University Hospital and colleagues raise that concern in a preprint review on convalescent plasma in COVID-19. “Although the recipient is already infected, theoretically transmission of more infectious particles could worsen clinical conditions,” they wrote, noting that “such a concern can be somewhat reduced by treatment with modern pathogen inactivation techniques.”
No evidence exists that SARS-CoV-2 can be transmitted through blood, but “we don’t know for sure,” Dr. Shoham said in an interview. A reassuring point: Even those with severe infection do not have viral RNA in their blood, he said, adding, “We don’t think there’s going to be viral transmission of this particular virus with transfusion.”
For another highly infectious pathogen, the Ebola virus, the World Health Organization recommended in 2014 that potential plasma donors wait at least 28 days after infection.
It’s also not known how long SARS-CoV-2 antibodies persist in the blood; longer viability could mean a longer donation window. Dr. Focosi noted that a previous Chinese study had shown that SARS-specific antibodies in people infected with the first SARS virus, SARS-CoV-1, persisted for 2 years.
Dr. Casadevall and Dr. Pirofski have disclosed no relevant financial relationships. Shoham has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.