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‘COVID toes’ chilblain-like lesions not related to COVID-19
from Italy.
These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.
“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.
The study was published online June 10, 2021, in JAMA Network Open.
‘COVID toes’ a fallacy?
The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.
For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.
None had evidence of current, past, or local SARS-CoV-2 infection.
“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.
The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.
Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.
None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.
Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.
In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.
Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.
Don’t blame it on ischemia, clots
Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.
Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.
Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”
Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.
“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.
Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.
The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.
The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.
In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.
In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.
“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.
This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
from Italy.
These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.
“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.
The study was published online June 10, 2021, in JAMA Network Open.
‘COVID toes’ a fallacy?
The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.
For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.
None had evidence of current, past, or local SARS-CoV-2 infection.
“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.
The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.
Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.
None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.
Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.
In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.
Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.
Don’t blame it on ischemia, clots
Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.
Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.
Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”
Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.
“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.
Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.
The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.
The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.
In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.
In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.
“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.
This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
from Italy.
These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.
“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.
The study was published online June 10, 2021, in JAMA Network Open.
‘COVID toes’ a fallacy?
The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.
For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.
None had evidence of current, past, or local SARS-CoV-2 infection.
“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.
The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.
Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.
None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.
Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.
In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.
Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.
Don’t blame it on ischemia, clots
Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.
Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.
Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”
Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.
“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.
Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.
The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.
The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.
In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.
In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.
“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.
This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
As new cases fall, U.S. passes 4 million children with COVID-19
Even as the number of new COVID-19 cases continues to drop, the United States reached the 4-million mark for infected children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
. That weekly total, the lowest since June of 2020, comes from 49 states (excluding N.Y.), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
Children represent 14.1% of all COVID-19 cases since the beginning of the pandemic, while the corresponding figure for the week ending June 10 was 19.0%. That weekly proportion of cases among children had been rising pretty steadily through the winter and early spring, but the situation has become much more volatile over the last month, the AAP/CHA data show.
Use of the Pfizer-BioNTech vaccine in children aged 16-17 years, of course, didn’t begin until April, and the vaccine wasn’t authorized for children aged 12-15 years until mid-May. The Moderna and Johnson & Johnson vaccines have not received such authorization yet, but Moderna is in the process of seeking an emergency-use recommendation from the Food and Drug Administration.
In the younger group of children who are currently eligible, completion of the vaccine regimen took a big jump in the week ending June 14, according to the Centers for Disease Control and Prevention. The cumulative share of those aged 12-15 years who had received a second dose jumped from 4.1% on June 7 to 11.4% on June 14, with comparable numbers for 16- and 17-year-olds coming in at 26.4% and 29.1%.
Activity over just the last 14 days, however, shows a slight decrease in children aged 12-15 getting a first dose: For just the 2 weeks ending June 7, 17.9% of all children in the age group initiated a first dose, but for the 14 days ending June 14, only 17.1% of the age group did so, the CDC said on its COVID Data Tracker site.
For children aged 16-17 years – of whom less than 30% have reached full vaccination – activity seems to have stagnated: 4.8% of all 16- to 17-year-olds initiated a first vaccination during the 14 days ending June 7, compared with 4.7% who did so during the 14 days ending June 14, the CDC reported.
Older age groups with higher completion rates are still producing greater vaccine initiation. As of June 14, those aged 25-39 years had a completion rate of 41.9% and 24.0% of the age group had received a first dose in the previous 2 weeks, while 61.4% of those aged 50-64 were fully vaccinated, and 18.0% had gotten their first dose, the CDC data indicate.
Even as the number of new COVID-19 cases continues to drop, the United States reached the 4-million mark for infected children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
. That weekly total, the lowest since June of 2020, comes from 49 states (excluding N.Y.), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
Children represent 14.1% of all COVID-19 cases since the beginning of the pandemic, while the corresponding figure for the week ending June 10 was 19.0%. That weekly proportion of cases among children had been rising pretty steadily through the winter and early spring, but the situation has become much more volatile over the last month, the AAP/CHA data show.
Use of the Pfizer-BioNTech vaccine in children aged 16-17 years, of course, didn’t begin until April, and the vaccine wasn’t authorized for children aged 12-15 years until mid-May. The Moderna and Johnson & Johnson vaccines have not received such authorization yet, but Moderna is in the process of seeking an emergency-use recommendation from the Food and Drug Administration.
In the younger group of children who are currently eligible, completion of the vaccine regimen took a big jump in the week ending June 14, according to the Centers for Disease Control and Prevention. The cumulative share of those aged 12-15 years who had received a second dose jumped from 4.1% on June 7 to 11.4% on June 14, with comparable numbers for 16- and 17-year-olds coming in at 26.4% and 29.1%.
Activity over just the last 14 days, however, shows a slight decrease in children aged 12-15 getting a first dose: For just the 2 weeks ending June 7, 17.9% of all children in the age group initiated a first dose, but for the 14 days ending June 14, only 17.1% of the age group did so, the CDC said on its COVID Data Tracker site.
For children aged 16-17 years – of whom less than 30% have reached full vaccination – activity seems to have stagnated: 4.8% of all 16- to 17-year-olds initiated a first vaccination during the 14 days ending June 7, compared with 4.7% who did so during the 14 days ending June 14, the CDC reported.
Older age groups with higher completion rates are still producing greater vaccine initiation. As of June 14, those aged 25-39 years had a completion rate of 41.9% and 24.0% of the age group had received a first dose in the previous 2 weeks, while 61.4% of those aged 50-64 were fully vaccinated, and 18.0% had gotten their first dose, the CDC data indicate.
Even as the number of new COVID-19 cases continues to drop, the United States reached the 4-million mark for infected children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
. That weekly total, the lowest since June of 2020, comes from 49 states (excluding N.Y.), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.
Children represent 14.1% of all COVID-19 cases since the beginning of the pandemic, while the corresponding figure for the week ending June 10 was 19.0%. That weekly proportion of cases among children had been rising pretty steadily through the winter and early spring, but the situation has become much more volatile over the last month, the AAP/CHA data show.
Use of the Pfizer-BioNTech vaccine in children aged 16-17 years, of course, didn’t begin until April, and the vaccine wasn’t authorized for children aged 12-15 years until mid-May. The Moderna and Johnson & Johnson vaccines have not received such authorization yet, but Moderna is in the process of seeking an emergency-use recommendation from the Food and Drug Administration.
In the younger group of children who are currently eligible, completion of the vaccine regimen took a big jump in the week ending June 14, according to the Centers for Disease Control and Prevention. The cumulative share of those aged 12-15 years who had received a second dose jumped from 4.1% on June 7 to 11.4% on June 14, with comparable numbers for 16- and 17-year-olds coming in at 26.4% and 29.1%.
Activity over just the last 14 days, however, shows a slight decrease in children aged 12-15 getting a first dose: For just the 2 weeks ending June 7, 17.9% of all children in the age group initiated a first dose, but for the 14 days ending June 14, only 17.1% of the age group did so, the CDC said on its COVID Data Tracker site.
For children aged 16-17 years – of whom less than 30% have reached full vaccination – activity seems to have stagnated: 4.8% of all 16- to 17-year-olds initiated a first vaccination during the 14 days ending June 7, compared with 4.7% who did so during the 14 days ending June 14, the CDC reported.
Older age groups with higher completion rates are still producing greater vaccine initiation. As of June 14, those aged 25-39 years had a completion rate of 41.9% and 24.0% of the age group had received a first dose in the previous 2 weeks, while 61.4% of those aged 50-64 were fully vaccinated, and 18.0% had gotten their first dose, the CDC data indicate.
Third COVID-19 vaccine dose helped some transplant recipients
All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.
Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.
The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
Third dose results
In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.
Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.
Two of the participants had low-positive titers, and 16 were negative.
“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.
“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.
Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.
“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”
Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
Welcome news, but larger studies needed
“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”
He added, “We just want studies to confirm that – larger studies.”
Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.
Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.
“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving. For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”
He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.
“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.
“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses. This will allow primary care clinicians to tackle their many complex jobs.”
Possible solutions for those with low antibody responses
Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.
“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”
Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.
“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
Participant details
None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.
Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.
Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.
All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.
Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.
The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
Third dose results
In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.
Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.
Two of the participants had low-positive titers, and 16 were negative.
“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.
“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.
Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.
“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”
Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
Welcome news, but larger studies needed
“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”
He added, “We just want studies to confirm that – larger studies.”
Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.
Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.
“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving. For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”
He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.
“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.
“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses. This will allow primary care clinicians to tackle their many complex jobs.”
Possible solutions for those with low antibody responses
Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.
“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”
Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.
“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
Participant details
None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.
Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.
Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.
All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.
Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.
The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
Third dose results
In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.
Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.
Two of the participants had low-positive titers, and 16 were negative.
“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.
“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.
Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.
“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”
Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
Welcome news, but larger studies needed
“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”
He added, “We just want studies to confirm that – larger studies.”
Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.
Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.
“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving. For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”
He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.
“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.
“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses. This will allow primary care clinicians to tackle their many complex jobs.”
Possible solutions for those with low antibody responses
Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.
“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”
Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.
“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
Participant details
None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.
Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.
Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.
Judge tosses hospital staff suit over vaccine mandate
A federal judge in Texas has dismissed a lawsuit from 117 Houston Methodist Hospital workers who refused to get a COVID-19 vaccine and said it was illegal to require them to do so.
In the ruling issued June 12, U.S. District Judge Lynn Hughes upheld the hospital’s policy and said the vaccination requirement didn’t break any federal laws.
“This is not coercion,” Judge Hughes wrote in the ruling.
“Methodist is trying to do their business of saving lives without giving them the COVID-19 virus,” he wrote. “It is a choice made to keep staff, patients, and their families safer.”
In April, the Houston Methodist Hospital system announced a policy that required employees to be vaccinated by June 7 or request an exemption. After the deadline, 178 of 26,000 employees refused to get inoculated and were placed on suspension without pay. The employees said the vaccine was unsafe and “experimental.” In his ruling, Judge Hughes said their claim was false and irrelevant.
“Texas law only protects employees from being terminated for refusing to commit an act carrying criminal penalties to the worker,” he wrote. “Receiving a COVID-19 vaccination is not an illegal act, and it carries no criminal penalties.”
He denounced the “press-release style of the complaint” and the comparison of the hospital’s vaccine policy to forced experimentation by the Nazis against Jewish people during the Holocaust.
“Equating the injection requirement to medical experimentation in concentration camps is reprehensible,” he wrote. “Nazi doctors conducted medical experiments on victims that caused pain, mutilation, permanent disability, and in many cases, death.”
Judge Hughes also said that employees can “freely choose” to accept or refuse a COVID-19 vaccine. If they refuse, they “simply need to work somewhere else,” he wrote.
“If a worker refuses an assignment, changed office, earlier start time, or other directive, he may be properly fired,” Judge Hughes said. “Every employment includes limits on the worker’s behavior in exchange for his remuneration. This is all part of the bargain.”
The ruling could set a precedent for similar COVID-19 vaccine lawsuits across the country, NPR reported. Houston Methodist was one of the first hospitals to require staff to be vaccinated. After the ruling on June 12, the hospital system wrote in a statement that it was “pleased and reassured” that Judge Hughes dismissed a “frivolous lawsuit.”
The hospital system will begin to terminate the 178 employees who were suspended if they don’t get a vaccine by June 21.
Jennifer Bridges, a nurse who has led the campaign against the vaccine policy, said she and the other plaintiffs will appeal the decision, according to KHOU.
“We’re OK with this decision. We are appealing. This will be taken all the way to the Supreme Court,” she told the news station. “This is far from over. This is literally only the beginning.”
A version of this article first appeared on WebMD.com.
A federal judge in Texas has dismissed a lawsuit from 117 Houston Methodist Hospital workers who refused to get a COVID-19 vaccine and said it was illegal to require them to do so.
In the ruling issued June 12, U.S. District Judge Lynn Hughes upheld the hospital’s policy and said the vaccination requirement didn’t break any federal laws.
“This is not coercion,” Judge Hughes wrote in the ruling.
“Methodist is trying to do their business of saving lives without giving them the COVID-19 virus,” he wrote. “It is a choice made to keep staff, patients, and their families safer.”
In April, the Houston Methodist Hospital system announced a policy that required employees to be vaccinated by June 7 or request an exemption. After the deadline, 178 of 26,000 employees refused to get inoculated and were placed on suspension without pay. The employees said the vaccine was unsafe and “experimental.” In his ruling, Judge Hughes said their claim was false and irrelevant.
“Texas law only protects employees from being terminated for refusing to commit an act carrying criminal penalties to the worker,” he wrote. “Receiving a COVID-19 vaccination is not an illegal act, and it carries no criminal penalties.”
He denounced the “press-release style of the complaint” and the comparison of the hospital’s vaccine policy to forced experimentation by the Nazis against Jewish people during the Holocaust.
“Equating the injection requirement to medical experimentation in concentration camps is reprehensible,” he wrote. “Nazi doctors conducted medical experiments on victims that caused pain, mutilation, permanent disability, and in many cases, death.”
Judge Hughes also said that employees can “freely choose” to accept or refuse a COVID-19 vaccine. If they refuse, they “simply need to work somewhere else,” he wrote.
“If a worker refuses an assignment, changed office, earlier start time, or other directive, he may be properly fired,” Judge Hughes said. “Every employment includes limits on the worker’s behavior in exchange for his remuneration. This is all part of the bargain.”
The ruling could set a precedent for similar COVID-19 vaccine lawsuits across the country, NPR reported. Houston Methodist was one of the first hospitals to require staff to be vaccinated. After the ruling on June 12, the hospital system wrote in a statement that it was “pleased and reassured” that Judge Hughes dismissed a “frivolous lawsuit.”
The hospital system will begin to terminate the 178 employees who were suspended if they don’t get a vaccine by June 21.
Jennifer Bridges, a nurse who has led the campaign against the vaccine policy, said she and the other plaintiffs will appeal the decision, according to KHOU.
“We’re OK with this decision. We are appealing. This will be taken all the way to the Supreme Court,” she told the news station. “This is far from over. This is literally only the beginning.”
A version of this article first appeared on WebMD.com.
A federal judge in Texas has dismissed a lawsuit from 117 Houston Methodist Hospital workers who refused to get a COVID-19 vaccine and said it was illegal to require them to do so.
In the ruling issued June 12, U.S. District Judge Lynn Hughes upheld the hospital’s policy and said the vaccination requirement didn’t break any federal laws.
“This is not coercion,” Judge Hughes wrote in the ruling.
“Methodist is trying to do their business of saving lives without giving them the COVID-19 virus,” he wrote. “It is a choice made to keep staff, patients, and their families safer.”
In April, the Houston Methodist Hospital system announced a policy that required employees to be vaccinated by June 7 or request an exemption. After the deadline, 178 of 26,000 employees refused to get inoculated and were placed on suspension without pay. The employees said the vaccine was unsafe and “experimental.” In his ruling, Judge Hughes said their claim was false and irrelevant.
“Texas law only protects employees from being terminated for refusing to commit an act carrying criminal penalties to the worker,” he wrote. “Receiving a COVID-19 vaccination is not an illegal act, and it carries no criminal penalties.”
He denounced the “press-release style of the complaint” and the comparison of the hospital’s vaccine policy to forced experimentation by the Nazis against Jewish people during the Holocaust.
“Equating the injection requirement to medical experimentation in concentration camps is reprehensible,” he wrote. “Nazi doctors conducted medical experiments on victims that caused pain, mutilation, permanent disability, and in many cases, death.”
Judge Hughes also said that employees can “freely choose” to accept or refuse a COVID-19 vaccine. If they refuse, they “simply need to work somewhere else,” he wrote.
“If a worker refuses an assignment, changed office, earlier start time, or other directive, he may be properly fired,” Judge Hughes said. “Every employment includes limits on the worker’s behavior in exchange for his remuneration. This is all part of the bargain.”
The ruling could set a precedent for similar COVID-19 vaccine lawsuits across the country, NPR reported. Houston Methodist was one of the first hospitals to require staff to be vaccinated. After the ruling on June 12, the hospital system wrote in a statement that it was “pleased and reassured” that Judge Hughes dismissed a “frivolous lawsuit.”
The hospital system will begin to terminate the 178 employees who were suspended if they don’t get a vaccine by June 21.
Jennifer Bridges, a nurse who has led the campaign against the vaccine policy, said she and the other plaintiffs will appeal the decision, according to KHOU.
“We’re OK with this decision. We are appealing. This will be taken all the way to the Supreme Court,” she told the news station. “This is far from over. This is literally only the beginning.”
A version of this article first appeared on WebMD.com.
Is your patient having an existential crisis?
The news is portraying our modern time as an existential crisis as though our very existence is threatened. An existential crisis is a profound feeling of lack of meaning, choice, or freedom in one’s life that makes even existing seem worthless. It can emerge as early as 5 years old, especially in introspective, gifted children, when they realize that death is permanent and universal, after a real loss or a story of a loss or failure, or from a sense of guilt.
The past 18 months of COVID-19 have been a perfect storm for developing an existential crisis. One of the main sources of life meaning for children is friendships. COVID-19 has reduced or blocked access to old and new friends. Younger children, when asked what makes a friend, will say “we like to do the same things.” Virtual play dates help but don’t replace shared experiences.
School provides meaning for children not only from socializing but also from accomplishing academic tasks – fulfilling Erickson’s stages of “mastery” and “productivity.” Teachers were better able to carry out hands-on activities, group assignments, and field trips in person so that all children and learning styles were engaged and successful. Not having in-person school has also meant loss of extracurricular activities, sports, and clubs as sources of mastery.
Loss of the structure of daily life, common during COVID-19, for waking, dressing, meals, chores, homework time, bathing, or bedtime can be profoundly disorienting.
For adolescents, opportunities to contribute to society and become productive by volunteering or being employed have been stunted by quarantine and social distancing. Some teens have had to care for relatives at home so that parents can earn a living, which, while meaningful, blocks age-essential socializing.
Meaning can also be created at any age by community structures and agreed upon beliefs such as religion. While religious membership is low in the United States, members have been largely unable to attend services. Following sports teams, an alternate “religion” and source of identity, was on hold for many months.
Existential despair can also come from major life losses. COVID-19 has taken a terrible toll of lives, homes, and jobs for millions. As short-term thinkers, when children see so many of their plans and dreams for making the team, having a girlfriend, going to prom, attending summer camp, or graduating, it feels like the end of the world they had imagined. Even the most important source of meaning – connection to family – has been disrupted by lockdown, illness, or loss.
The loss of choice and freedom goes beyond being stuck indoors. Advanced classes and exams, as well as resume-building jobs or volunteering, which teens saw as essential to college, disappeared; sometimes also the money needed was exhausted by COVID-19 unemployment. Work-at-home parents supervising virtual school see their children’s malaise or panic and pressure them to work harder, which is impossible for despairing children. Observing a parent losing his or her job makes a teen’s own career aspirations uncertain. Teen depression and suicidal ideation/acts have shot up from hopelessness, with loss of meaning at the core.
A profound sense of powerlessness has taken over. COVID-19, an invisible threat, has taken down lives. Even with amazingly effective vaccines available, fear and helplessness have burned into our brains. Helplessness to stop structural racism and the arbitrary killings of our own Black citizens by police has finally registered. And climate change is now reported as an impending disaster that may not be stoppable.
So this must be the worst time in history, right? Actually, no. The past 60 years have been a period of historically remarkable stability of government, economy, and natural forces. Perhaps knowing no other world has made these problems appear unsolvable to the parents of our patients. Their own sense of meaning has been challenged in a way similar to that of their children. Perhaps from lack of privacy or peers, parents have been sharing their own sense of powerlessness with their children directly or indirectly, making it harder to reassure them.
With COVID-19 waning in the United States, many of the sources of meaning just discussed can be reinstated by way of in-person play dates, school, sports, socializing, practicing religion, volunteering, and getting jobs. Although there is “existential therapy,” what our children need most is adult leadership showing confidence in life’s meaning, even if we have to hide our own worries. Parents can point out that, even if it takes years, people have made it through difficult times in the past, and there are many positive alternatives for education and employment.
Children need to repeatedly hear about ways they are valued that are not dependent on accomplishments. Thanking them for and telling others about their effort, ideas, curiosity, integrity, love, and kindness point out meaning for their existence independent of world events. Parents need to establish routines and rules for children to demonstrate that life goes on as usual. Chores helpful to the family are a practical contribution. Family activities that are challenging and unpredictable set up for discussing, modeling, and building resilience; for example, visiting new places, camping, hiking, trying a new sport, or adopting a pet give opportunities to say: “Oh, well, we’ll find another way.”
Parents can share stories or books about people who made it through tougher times, such as Abraham Lincoln, or better, personal, or family experiences overcoming challenges. Recalling and nicknaming instances of the child’s own resilience is valuable. Books such as “The Little Engine That Could,” “Chicken Little,” and fairy tales of overcoming doubts when facing challenges can be helpful. “Stay calm and carry on,” a saying from the British when they were being bombed during World War II, has become a meme.
As clinicians we need to sort out significant complicated grief, anxiety, obsessive compulsive disorder, depression, or suicidal ideation, and provide assessment and treatment. But when children get stuck in existential futility, in addition to engaging them in meaningful activities, we can advise parents to coach them to distract themselves, “put the thoughts in a box in your head” to consider later, and/or write down or photograph things that make them grateful. Good lessons for us all to reinvent meaning in our lives.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at [email protected].
The news is portraying our modern time as an existential crisis as though our very existence is threatened. An existential crisis is a profound feeling of lack of meaning, choice, or freedom in one’s life that makes even existing seem worthless. It can emerge as early as 5 years old, especially in introspective, gifted children, when they realize that death is permanent and universal, after a real loss or a story of a loss or failure, or from a sense of guilt.
The past 18 months of COVID-19 have been a perfect storm for developing an existential crisis. One of the main sources of life meaning for children is friendships. COVID-19 has reduced or blocked access to old and new friends. Younger children, when asked what makes a friend, will say “we like to do the same things.” Virtual play dates help but don’t replace shared experiences.
School provides meaning for children not only from socializing but also from accomplishing academic tasks – fulfilling Erickson’s stages of “mastery” and “productivity.” Teachers were better able to carry out hands-on activities, group assignments, and field trips in person so that all children and learning styles were engaged and successful. Not having in-person school has also meant loss of extracurricular activities, sports, and clubs as sources of mastery.
Loss of the structure of daily life, common during COVID-19, for waking, dressing, meals, chores, homework time, bathing, or bedtime can be profoundly disorienting.
For adolescents, opportunities to contribute to society and become productive by volunteering or being employed have been stunted by quarantine and social distancing. Some teens have had to care for relatives at home so that parents can earn a living, which, while meaningful, blocks age-essential socializing.
Meaning can also be created at any age by community structures and agreed upon beliefs such as religion. While religious membership is low in the United States, members have been largely unable to attend services. Following sports teams, an alternate “religion” and source of identity, was on hold for many months.
Existential despair can also come from major life losses. COVID-19 has taken a terrible toll of lives, homes, and jobs for millions. As short-term thinkers, when children see so many of their plans and dreams for making the team, having a girlfriend, going to prom, attending summer camp, or graduating, it feels like the end of the world they had imagined. Even the most important source of meaning – connection to family – has been disrupted by lockdown, illness, or loss.
The loss of choice and freedom goes beyond being stuck indoors. Advanced classes and exams, as well as resume-building jobs or volunteering, which teens saw as essential to college, disappeared; sometimes also the money needed was exhausted by COVID-19 unemployment. Work-at-home parents supervising virtual school see their children’s malaise or panic and pressure them to work harder, which is impossible for despairing children. Observing a parent losing his or her job makes a teen’s own career aspirations uncertain. Teen depression and suicidal ideation/acts have shot up from hopelessness, with loss of meaning at the core.
A profound sense of powerlessness has taken over. COVID-19, an invisible threat, has taken down lives. Even with amazingly effective vaccines available, fear and helplessness have burned into our brains. Helplessness to stop structural racism and the arbitrary killings of our own Black citizens by police has finally registered. And climate change is now reported as an impending disaster that may not be stoppable.
So this must be the worst time in history, right? Actually, no. The past 60 years have been a period of historically remarkable stability of government, economy, and natural forces. Perhaps knowing no other world has made these problems appear unsolvable to the parents of our patients. Their own sense of meaning has been challenged in a way similar to that of their children. Perhaps from lack of privacy or peers, parents have been sharing their own sense of powerlessness with their children directly or indirectly, making it harder to reassure them.
With COVID-19 waning in the United States, many of the sources of meaning just discussed can be reinstated by way of in-person play dates, school, sports, socializing, practicing religion, volunteering, and getting jobs. Although there is “existential therapy,” what our children need most is adult leadership showing confidence in life’s meaning, even if we have to hide our own worries. Parents can point out that, even if it takes years, people have made it through difficult times in the past, and there are many positive alternatives for education and employment.
Children need to repeatedly hear about ways they are valued that are not dependent on accomplishments. Thanking them for and telling others about their effort, ideas, curiosity, integrity, love, and kindness point out meaning for their existence independent of world events. Parents need to establish routines and rules for children to demonstrate that life goes on as usual. Chores helpful to the family are a practical contribution. Family activities that are challenging and unpredictable set up for discussing, modeling, and building resilience; for example, visiting new places, camping, hiking, trying a new sport, or adopting a pet give opportunities to say: “Oh, well, we’ll find another way.”
Parents can share stories or books about people who made it through tougher times, such as Abraham Lincoln, or better, personal, or family experiences overcoming challenges. Recalling and nicknaming instances of the child’s own resilience is valuable. Books such as “The Little Engine That Could,” “Chicken Little,” and fairy tales of overcoming doubts when facing challenges can be helpful. “Stay calm and carry on,” a saying from the British when they were being bombed during World War II, has become a meme.
As clinicians we need to sort out significant complicated grief, anxiety, obsessive compulsive disorder, depression, or suicidal ideation, and provide assessment and treatment. But when children get stuck in existential futility, in addition to engaging them in meaningful activities, we can advise parents to coach them to distract themselves, “put the thoughts in a box in your head” to consider later, and/or write down or photograph things that make them grateful. Good lessons for us all to reinvent meaning in our lives.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at [email protected].
The news is portraying our modern time as an existential crisis as though our very existence is threatened. An existential crisis is a profound feeling of lack of meaning, choice, or freedom in one’s life that makes even existing seem worthless. It can emerge as early as 5 years old, especially in introspective, gifted children, when they realize that death is permanent and universal, after a real loss or a story of a loss or failure, or from a sense of guilt.
The past 18 months of COVID-19 have been a perfect storm for developing an existential crisis. One of the main sources of life meaning for children is friendships. COVID-19 has reduced or blocked access to old and new friends. Younger children, when asked what makes a friend, will say “we like to do the same things.” Virtual play dates help but don’t replace shared experiences.
School provides meaning for children not only from socializing but also from accomplishing academic tasks – fulfilling Erickson’s stages of “mastery” and “productivity.” Teachers were better able to carry out hands-on activities, group assignments, and field trips in person so that all children and learning styles were engaged and successful. Not having in-person school has also meant loss of extracurricular activities, sports, and clubs as sources of mastery.
Loss of the structure of daily life, common during COVID-19, for waking, dressing, meals, chores, homework time, bathing, or bedtime can be profoundly disorienting.
For adolescents, opportunities to contribute to society and become productive by volunteering or being employed have been stunted by quarantine and social distancing. Some teens have had to care for relatives at home so that parents can earn a living, which, while meaningful, blocks age-essential socializing.
Meaning can also be created at any age by community structures and agreed upon beliefs such as religion. While religious membership is low in the United States, members have been largely unable to attend services. Following sports teams, an alternate “religion” and source of identity, was on hold for many months.
Existential despair can also come from major life losses. COVID-19 has taken a terrible toll of lives, homes, and jobs for millions. As short-term thinkers, when children see so many of their plans and dreams for making the team, having a girlfriend, going to prom, attending summer camp, or graduating, it feels like the end of the world they had imagined. Even the most important source of meaning – connection to family – has been disrupted by lockdown, illness, or loss.
The loss of choice and freedom goes beyond being stuck indoors. Advanced classes and exams, as well as resume-building jobs or volunteering, which teens saw as essential to college, disappeared; sometimes also the money needed was exhausted by COVID-19 unemployment. Work-at-home parents supervising virtual school see their children’s malaise or panic and pressure them to work harder, which is impossible for despairing children. Observing a parent losing his or her job makes a teen’s own career aspirations uncertain. Teen depression and suicidal ideation/acts have shot up from hopelessness, with loss of meaning at the core.
A profound sense of powerlessness has taken over. COVID-19, an invisible threat, has taken down lives. Even with amazingly effective vaccines available, fear and helplessness have burned into our brains. Helplessness to stop structural racism and the arbitrary killings of our own Black citizens by police has finally registered. And climate change is now reported as an impending disaster that may not be stoppable.
So this must be the worst time in history, right? Actually, no. The past 60 years have been a period of historically remarkable stability of government, economy, and natural forces. Perhaps knowing no other world has made these problems appear unsolvable to the parents of our patients. Their own sense of meaning has been challenged in a way similar to that of their children. Perhaps from lack of privacy or peers, parents have been sharing their own sense of powerlessness with their children directly or indirectly, making it harder to reassure them.
With COVID-19 waning in the United States, many of the sources of meaning just discussed can be reinstated by way of in-person play dates, school, sports, socializing, practicing religion, volunteering, and getting jobs. Although there is “existential therapy,” what our children need most is adult leadership showing confidence in life’s meaning, even if we have to hide our own worries. Parents can point out that, even if it takes years, people have made it through difficult times in the past, and there are many positive alternatives for education and employment.
Children need to repeatedly hear about ways they are valued that are not dependent on accomplishments. Thanking them for and telling others about their effort, ideas, curiosity, integrity, love, and kindness point out meaning for their existence independent of world events. Parents need to establish routines and rules for children to demonstrate that life goes on as usual. Chores helpful to the family are a practical contribution. Family activities that are challenging and unpredictable set up for discussing, modeling, and building resilience; for example, visiting new places, camping, hiking, trying a new sport, or adopting a pet give opportunities to say: “Oh, well, we’ll find another way.”
Parents can share stories or books about people who made it through tougher times, such as Abraham Lincoln, or better, personal, or family experiences overcoming challenges. Recalling and nicknaming instances of the child’s own resilience is valuable. Books such as “The Little Engine That Could,” “Chicken Little,” and fairy tales of overcoming doubts when facing challenges can be helpful. “Stay calm and carry on,” a saying from the British when they were being bombed during World War II, has become a meme.
As clinicians we need to sort out significant complicated grief, anxiety, obsessive compulsive disorder, depression, or suicidal ideation, and provide assessment and treatment. But when children get stuck in existential futility, in addition to engaging them in meaningful activities, we can advise parents to coach them to distract themselves, “put the thoughts in a box in your head” to consider later, and/or write down or photograph things that make them grateful. Good lessons for us all to reinvent meaning in our lives.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. Email her at [email protected].
OSHA issues new rules on COVID-19 safety for health care workers
The U.S. Occupational Safety and Health Administration issued its long-awaited Emergency Temporary Standard (ETS) for COVID-19 June 10, surprising many by including only health care workers in the new emergency workplace safety rules.
“The ETS is an overdue step toward protecting health care workers, especially those working in long-term care facilities and home health care who are at greatly increased risk of infection,” said George Washington University, Washington, professor and former Obama administration Assistant Secretary of Labor David Michaels, PhD, MPH. “OSHA’s failure to issue a COVID-specific standard in other high-risk industries, like meat and poultry processing, corrections, homeless shelters, and retail establishments is disappointing. If exposure is not controlled in these workplaces, they will continue to be important drivers of infections.”
With the new regulations in place, about 10.3 million health care workers at hospitals, nursing homes, and assisted living facilities, as well as emergency responders and home health care workers, should be guaranteed protection standards that replace former guidance.
The new protections include supplying personal protective equipment and ensuring proper usage (for example, mandatory seal checks on respirators); screening everyone who enters the facility for COVID-19; ensuring proper ventilation; and establishing physical distancing requirements (6 feet) for unvaccinated workers. It also requires employers to give workers time off for vaccination. An antiretaliation clause could shield workers who complain about unsafe conditions.
“The science tells us that health care workers, particularly those who come into regular contact with the virus, are most at risk at this point in the pandemic,” Labor Secretary Marty Walsh said on a press call. “So following an extensive review of the science and data, OSHA determined that a health care–specific safety requirement will make the biggest impact.”
But questions remain, said James Brudney, JD, a professor at Fordham Law School in New York and former chief counsel of the U.S. Senate Subcommittee on Labor. The standard doesn’t amplify or address existing rules regarding a right to refuse unsafe work, for example, so employees may still feel they are risking their jobs to complain, despite the antiretaliation clause.
And although vaccinated employees don’t have to adhere to the same distancing and masking standards in many instances, the standard doesn’t spell out how employers should determine their workers’ vaccination status – instead leaving that determination to employers through their own policies and procedures. (California’s state OSHA office rules specify the mechanism for documentation of vaccination.)
The Trump administration did not issue an ETS, saying OSHA’s general duty clause sufficed. President Joe Biden took the opposite approach, calling for an investigation into an ETS on his first day in office. But the process took months longer than promised.
“I know it’s been a long time coming,” Mr. Walsh acknowledged. “Our health care workers from the very beginning have been put at risk.
While health care unions had asked for mandated safety standards sooner, National Nurses United, the country’s largest labor union for registered nurses, still welcomed the rules.
“An ETS is a major step toward requiring accountability for hospitals who consistently put their budget goals and profits over our health and safety,” Zenei Triunfo-Cortez, RN, one of NNU’s three presidents, said in a statement June 9 anticipating the publication of the rules.
The rules do not apply to retail pharmacies, ambulatory care settings that screen nonemployees for COVID-19, or certain other settings in which all employees are vaccinated and people with suspected or confirmed COVID-19 cannot enter.
The agency said it will work with states that have already issued local regulations, including two states that issued temporary standards of their own, Virginia and California.
Employers will have 2 weeks to comply with most of the regulations after they’re published in the Federal Register. The standards will expire in 6 months but could then become permanent, as Virginia’s did in January.
A version of this article first appeared on Medscape.com.
The U.S. Occupational Safety and Health Administration issued its long-awaited Emergency Temporary Standard (ETS) for COVID-19 June 10, surprising many by including only health care workers in the new emergency workplace safety rules.
“The ETS is an overdue step toward protecting health care workers, especially those working in long-term care facilities and home health care who are at greatly increased risk of infection,” said George Washington University, Washington, professor and former Obama administration Assistant Secretary of Labor David Michaels, PhD, MPH. “OSHA’s failure to issue a COVID-specific standard in other high-risk industries, like meat and poultry processing, corrections, homeless shelters, and retail establishments is disappointing. If exposure is not controlled in these workplaces, they will continue to be important drivers of infections.”
With the new regulations in place, about 10.3 million health care workers at hospitals, nursing homes, and assisted living facilities, as well as emergency responders and home health care workers, should be guaranteed protection standards that replace former guidance.
The new protections include supplying personal protective equipment and ensuring proper usage (for example, mandatory seal checks on respirators); screening everyone who enters the facility for COVID-19; ensuring proper ventilation; and establishing physical distancing requirements (6 feet) for unvaccinated workers. It also requires employers to give workers time off for vaccination. An antiretaliation clause could shield workers who complain about unsafe conditions.
“The science tells us that health care workers, particularly those who come into regular contact with the virus, are most at risk at this point in the pandemic,” Labor Secretary Marty Walsh said on a press call. “So following an extensive review of the science and data, OSHA determined that a health care–specific safety requirement will make the biggest impact.”
But questions remain, said James Brudney, JD, a professor at Fordham Law School in New York and former chief counsel of the U.S. Senate Subcommittee on Labor. The standard doesn’t amplify or address existing rules regarding a right to refuse unsafe work, for example, so employees may still feel they are risking their jobs to complain, despite the antiretaliation clause.
And although vaccinated employees don’t have to adhere to the same distancing and masking standards in many instances, the standard doesn’t spell out how employers should determine their workers’ vaccination status – instead leaving that determination to employers through their own policies and procedures. (California’s state OSHA office rules specify the mechanism for documentation of vaccination.)
The Trump administration did not issue an ETS, saying OSHA’s general duty clause sufficed. President Joe Biden took the opposite approach, calling for an investigation into an ETS on his first day in office. But the process took months longer than promised.
“I know it’s been a long time coming,” Mr. Walsh acknowledged. “Our health care workers from the very beginning have been put at risk.
While health care unions had asked for mandated safety standards sooner, National Nurses United, the country’s largest labor union for registered nurses, still welcomed the rules.
“An ETS is a major step toward requiring accountability for hospitals who consistently put their budget goals and profits over our health and safety,” Zenei Triunfo-Cortez, RN, one of NNU’s three presidents, said in a statement June 9 anticipating the publication of the rules.
The rules do not apply to retail pharmacies, ambulatory care settings that screen nonemployees for COVID-19, or certain other settings in which all employees are vaccinated and people with suspected or confirmed COVID-19 cannot enter.
The agency said it will work with states that have already issued local regulations, including two states that issued temporary standards of their own, Virginia and California.
Employers will have 2 weeks to comply with most of the regulations after they’re published in the Federal Register. The standards will expire in 6 months but could then become permanent, as Virginia’s did in January.
A version of this article first appeared on Medscape.com.
The U.S. Occupational Safety and Health Administration issued its long-awaited Emergency Temporary Standard (ETS) for COVID-19 June 10, surprising many by including only health care workers in the new emergency workplace safety rules.
“The ETS is an overdue step toward protecting health care workers, especially those working in long-term care facilities and home health care who are at greatly increased risk of infection,” said George Washington University, Washington, professor and former Obama administration Assistant Secretary of Labor David Michaels, PhD, MPH. “OSHA’s failure to issue a COVID-specific standard in other high-risk industries, like meat and poultry processing, corrections, homeless shelters, and retail establishments is disappointing. If exposure is not controlled in these workplaces, they will continue to be important drivers of infections.”
With the new regulations in place, about 10.3 million health care workers at hospitals, nursing homes, and assisted living facilities, as well as emergency responders and home health care workers, should be guaranteed protection standards that replace former guidance.
The new protections include supplying personal protective equipment and ensuring proper usage (for example, mandatory seal checks on respirators); screening everyone who enters the facility for COVID-19; ensuring proper ventilation; and establishing physical distancing requirements (6 feet) for unvaccinated workers. It also requires employers to give workers time off for vaccination. An antiretaliation clause could shield workers who complain about unsafe conditions.
“The science tells us that health care workers, particularly those who come into regular contact with the virus, are most at risk at this point in the pandemic,” Labor Secretary Marty Walsh said on a press call. “So following an extensive review of the science and data, OSHA determined that a health care–specific safety requirement will make the biggest impact.”
But questions remain, said James Brudney, JD, a professor at Fordham Law School in New York and former chief counsel of the U.S. Senate Subcommittee on Labor. The standard doesn’t amplify or address existing rules regarding a right to refuse unsafe work, for example, so employees may still feel they are risking their jobs to complain, despite the antiretaliation clause.
And although vaccinated employees don’t have to adhere to the same distancing and masking standards in many instances, the standard doesn’t spell out how employers should determine their workers’ vaccination status – instead leaving that determination to employers through their own policies and procedures. (California’s state OSHA office rules specify the mechanism for documentation of vaccination.)
The Trump administration did not issue an ETS, saying OSHA’s general duty clause sufficed. President Joe Biden took the opposite approach, calling for an investigation into an ETS on his first day in office. But the process took months longer than promised.
“I know it’s been a long time coming,” Mr. Walsh acknowledged. “Our health care workers from the very beginning have been put at risk.
While health care unions had asked for mandated safety standards sooner, National Nurses United, the country’s largest labor union for registered nurses, still welcomed the rules.
“An ETS is a major step toward requiring accountability for hospitals who consistently put their budget goals and profits over our health and safety,” Zenei Triunfo-Cortez, RN, one of NNU’s three presidents, said in a statement June 9 anticipating the publication of the rules.
The rules do not apply to retail pharmacies, ambulatory care settings that screen nonemployees for COVID-19, or certain other settings in which all employees are vaccinated and people with suspected or confirmed COVID-19 cannot enter.
The agency said it will work with states that have already issued local regulations, including two states that issued temporary standards of their own, Virginia and California.
Employers will have 2 weeks to comply with most of the regulations after they’re published in the Federal Register. The standards will expire in 6 months but could then become permanent, as Virginia’s did in January.
A version of this article first appeared on Medscape.com.
COVID-19 death toll higher for international medical graduates
researchers report.
“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”
IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.
IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.
To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.
The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.
Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.
After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).
New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.
Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.
Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.
In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.
Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.
IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.
In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”
The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.
A version of this article first appeared on Medscape.com.
researchers report.
“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”
IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.
IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.
To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.
The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.
Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.
After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).
New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.
Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.
Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.
In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.
Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.
IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.
In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”
The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.
A version of this article first appeared on Medscape.com.
researchers report.
“I’ve always felt that international medical graduates [IMGs] in America are largely invisible,” said senior author Abraham Verghese, MD, MFA, an infectious disease specialist at Stanford (Calif.) University. “Everyone is aware that there are foreign doctors, but very few are aware of how many there are and also how vital they are to providing health care in America.”
IMGs made up 25% of all U.S. physicians in 2020 but accounted for 45% of those whose deaths had been attributed to COVID-19 through Nov. 23, 2020, Deendayal Dinakarpandian, MD, PhD, clinical associate professor of medicine at Stanford (Calif.) University, and colleagues report in JAMA Network Open.
IMGs are more likely to work in places where the incidence of COVID-19 is high and in facilities with fewer resources, Dr. Verghese said in an interview. “So, it’s not surprising that they were on the front lines when this thing came along,” he said.
To see whether their vulnerability affected their risk for death, Dr. Dinakarpandian and colleagues collected data from Nov. 23, 2020, from three sources of information regarding deaths among physicians: MedPage Today, which used investigative and voluntary reporting; Medscape, which used voluntary reporting of verifiable information; and a collaboration of The Guardian and Kaiser Health News, which used investigative reporting.
The Medscape project was launched on April 1, 2020. The MedPage Today and The Guardian/Kaiser Health News projects were launched on April 8, 2020.
Dr. Verghese and colleagues researched obituaries and news articles referenced by the three projects to verify their data. They used DocInfo to ascertain the deceased physicians’ medical schools.
After eliminating duplications from the lists, the researchers counted 132 physician deaths in 28 states. Of these, 59 physicians had graduated from medical schools outside the United States, a death toll 1.8 times higher than the proportion of IMGs among U.S. physicians (95% confidence interval, 1.52-2.21; P < .001).
New York, New Jersey, and Florida accounted for 66% of the deaths among IMGs but for only 45% of the deaths among U.S. medical school graduates.
Within each state, the proportion of IMGs among deceased physicians was not statistically different from their proportion among physicians in those states, with the exception of New York.
Two-thirds of the physicians’ deaths occurred in states where IMGs make up a larger proportion of physicians than in the nation as a whole. In these states, the incidence of COVID-19 was high at the start of the pandemic.
In New York, IMGs accounted for 60% of physician deaths, which was 1.62 times higher (95% CI, 1.26-2.09; P = .005) than the 37% among New York physicians overall.
Physicians who were trained abroad frequently can’t get into the most prestigious residency programs or into the highest paid specialties and are more likely to serve in primary care, Dr. Verghese said. Overall, 60% of the physicians who died of COVID-19 worked in primary care.
IMGs often staff hospitals serving low-income communities and communities of color, which were hardest hit by the pandemic and where personal protective equipment was hard to obtain, said Dr. Verghese.
In addition to these risks, IMGs sometimes endure racism, said Dr. Verghese, who obtained his medical degree at Madras Medical College, Chennai, India. “We’ve actually seen in the COVID era, in keeping with the sort of political tone that was set in Washington, that there’s been a lot more abuses of both foreign physicians and foreign looking physicians – even if they’re not foreign trained – and nurses by patients who have been given license. And I want to acknowledge the heroism of all these physicians.”
The study was partially funded by the Presence Center at Stanford. Dr. Verghese is a regular contributor to Medscape. He served on the advisory board for Gilead Sciences, serves as a speaker or a member of a speakers bureau for Leigh Bureau, and receives royalties from Penguin Random House and Simon & Schuster.
A version of this article first appeared on Medscape.com.
More evidence links COVID vaccines to rare cases of myocarditis in youth
a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.
The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.
Telltale symptoms include chest pain, shortness of breath, and fever.
William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.
“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.
The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children.
Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization. Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.
“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.
Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
Adverse events reports
The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials.
But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.
But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get.
Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.
The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.
Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.
The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
More study needed
Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.
“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee.
“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.
Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.
“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.
The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.
In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.
The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.
A version of this article first appeared on Medscape.com.
a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.
The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.
Telltale symptoms include chest pain, shortness of breath, and fever.
William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.
“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.
The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children.
Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization. Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.
“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.
Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
Adverse events reports
The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials.
But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.
But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get.
Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.
The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.
Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.
The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
More study needed
Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.
“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee.
“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.
Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.
“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.
The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.
In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.
The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.
A version of this article first appeared on Medscape.com.
a Centers for Disease Control and Prevention expert reported on June 10, detailing data on cases of myocarditis and pericarditis detected through a government safety system.
The side effect seems to be more common in teen boys and young men than in older adults and women and may occur in 16 cases for every 1 million people who got a second dose, said Tom Shimabukuro, MD, MPH, deputy director of the CDC’s Immunization Safety Office, who presented information on the cases at a meeting of an expert panel that advises the U.S. Food and Drug Administration on vaccines.
Telltale symptoms include chest pain, shortness of breath, and fever.
William Schaffner, MD, an infectious diseases specialist from Vanderbilt University, Nashville, Tenn., thinks certain characteristics are pointing toward a “rare, but real” signal. First, the events are clustering, occurring within days of vaccination. Second, they tend to be more common in males and younger people. Third, he says, the number of events is above the so-called “background rate” – the cases that could be expected in this age group even without vaccination.
“I don’t think we’re quite there yet. We haven’t tied a ribbon around it, but I think the data are trending in that direction,” he said.
The issue of myocarditis weighed heavily on the Vaccines and Related Biological Products Advisory Committee’s considerations of what kind and how much data might be needed to green light use of a vaccine for COVID in children.
Because the rates of hospitalization for COVID are low in kids, some felt that the FDA should require at least a year of study of the vaccines in clinical trials, the amount of data typically required for full approval, instead of the 2 months currently required for emergency use authorization. Others wondered whether the risks of vaccination – as low as they are – might outweigh the benefits in this age group.
“I don’t really see this as an emergency in children,” said committee member Michael Kurilla, MD, PhD, the director of clinical innovation at the National Institutes of Health. Dr. Kurilla, however, did say he thought having an expanded access program for children at high risk might make sense.
Most of the young adults who experienced myocarditis recovered quickly, though three needed intensive care and rehabilitation after their episodes. Among cases with known outcomes, 81% got better and 19% still have ongoing symptoms.
Adverse events reports
The data on myocarditis come from the Vaccine Adverse Events Reporting System, or VAERS, a database of health problems reported after vaccination. This reporting system, open to anyone, has benefits and limits. It gives the CDC and FDA the ability to rapidly detect potential safety issues, and it is large enough that it can detect rare events, something that’s beyond the power of even large clinical trials.
But it is observational, so that there’s no way to know if problems reported were caused by the vaccines or a coincidence.
But because VAERS works on an honor system, it can also be spammed, and it carries the bias of the person who’s doing the reporting, from clinicians to average patients. For that reason, Dr. Shimabukuro said they are actively investigating and confirming each report they get.
Out of more than 12 million doses administered to youth ages 16-24, the CDC says it has 275 reports of heart inflammation following vaccination in this age group. The CDC has analyzed a total 475 cases of myocarditis after vaccination in people under age 30 that were reported to VAERS.
The vaccines linked to the events are the mRNA vaccines made by Pfizer and Moderna. The only vaccines currently authorized for use in adolescents are made by Pfizer. Because the Pfizer vaccine was authorized for use in kids as young as 12 last month, there’s not yet enough data to draw conclusions about the risk of myocarditis in kids ages 12-15.
Younger age groups have only received about 9% of the total doses of the vaccine so far, but they represent about 50% of the myocarditis cases reported after vaccination. “We clearly have an imbalance there,” Dr. Shimabukuro said.
The number of events in this age group appears to be above the rate that would be expected for these age groups without vaccines in the picture, he said, explaining that the number of events are in line with similar adverse events seen in young people in Israel and reported by the Department of Defense. Israel found the incidence of myocarditis after vaccination was 50 cases per million for men ages 18-30.
More study needed
Another system tracking adverse events through hospitals, the Vaccine Safety Datalink, didn’t show reports of heart inflammation above numbers that are normally seen in the population, but it did show that inflammation was more likely after a second dose of the vaccine.
“Should this be included in informed consent?” asked Cody Meissner, MD, a pediatric infectious disease specialist at Tufts University, Boston, and a member of the FDA committee.
“I think it’s hard to deny there seem to be some [events that seem] to be occurring in terms of myocarditis,” he said.
Dr. Meissner said later in the committee’s discussion that his own hospital had recently admitted a 12-year-old boy who developed heart swelling 2 days after the second dose of vaccine with a high level of troponin, an enzyme that indicates damage to the heart. His level was over 9. “A very high level,” Dr. Meissner said.
“Will there be scarring to the myocardium? Will there be a predisposition to arrhythmias later on? Will there be an early onset of heart failure? We think that’s unlikely, but [we] don’t know that,” he said.
The CDC has scheduled an emergency meeting next week to convene an expert panel on immunization practices to further review the events.
In addition to the information presented at the FDA’s meeting, doctors at Oregon Health & Science University, Portland, recently described seven cases in teens – all boys – who developed heart inflammation within 4 days of getting the second dose of the Pfizer vaccine.
The study was published June 10 in Pediatrics. All the boys were hospitalized and treated with anti-inflammatory medications including NSAIDs and steroids. Most were discharged within a few days and all recovered from their symptoms.
A version of this article first appeared on Medscape.com.
Migraine linked to more COVID-19 infections, symptoms but less health care utilization
, according to a study presented at the American Headache Society’s 2021 annual meeting.
“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”
In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.
Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.
Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.
For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).
The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).
Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).
Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:
- Difficulty breathing or shortness of breath (P = .005).
- Fever.
- Headache, sore throat, and/or congestion.
- Fatigue.
- Loss of smell and taste.
- Chills and body aches.
- Persistent pain or pressure in the chest.
- Confusion or inability to arouse.
- Digestive issues (P = .005).
- Bluish lips or face.
For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
Changes in health care utilization
“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.
Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).
Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”
Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.
Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.
“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”
The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.
, according to a study presented at the American Headache Society’s 2021 annual meeting.
“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”
In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.
Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.
Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.
For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).
The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).
Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).
Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:
- Difficulty breathing or shortness of breath (P = .005).
- Fever.
- Headache, sore throat, and/or congestion.
- Fatigue.
- Loss of smell and taste.
- Chills and body aches.
- Persistent pain or pressure in the chest.
- Confusion or inability to arouse.
- Digestive issues (P = .005).
- Bluish lips or face.
For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
Changes in health care utilization
“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.
Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).
Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”
Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.
Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.
“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”
The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.
, according to a study presented at the American Headache Society’s 2021 annual meeting.
“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”
In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.
Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.
Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.
For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).
The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).
Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).
Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:
- Difficulty breathing or shortness of breath (P = .005).
- Fever.
- Headache, sore throat, and/or congestion.
- Fatigue.
- Loss of smell and taste.
- Chills and body aches.
- Persistent pain or pressure in the chest.
- Confusion or inability to arouse.
- Digestive issues (P = .005).
- Bluish lips or face.
For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
Changes in health care utilization
“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.
Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).
Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”
Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.
Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.
“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”
The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.
FROM AHS 2021
Mavrilimumab may aid severe COVID-19 recovery
Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.
There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.
The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.
Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).
Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.
Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.
In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.
“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.
“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”
Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia
“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.
She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”
The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.
“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.
Study details and other outcome results
The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.
Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.
The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.
Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.
“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).
“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.
There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).
Timing of mavrilimumab administration and safety
Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”
Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”
No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.
Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.
“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.
“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.
Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.
Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.
Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.
Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.
There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.
The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.
Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).
Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.
Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.
In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.
“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.
“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”
Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia
“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.
She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”
The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.
“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.
Study details and other outcome results
The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.
Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.
The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.
Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.
“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).
“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.
There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).
Timing of mavrilimumab administration and safety
Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”
Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”
No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.
Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.
“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.
“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.
Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.
Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.
Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.
Inhibiting granulocyte/macrophage–colony stimulating factor (GM-CSF) with mavrilimumab prevented some patients with severe COVID-19 pneumonia and hyperinflammation from needing mechanical ventilation and reduced their risk of dying versus placebo in a phase 2 study.
There was no difference in outcomes between the two doses of mavrilimumab used in the trial (6 mg/kg or 10 mg/kg) and combined data showed a higher percentage of patients achieving the primary endpoint of being alive and free of mechanical ventilation at 29 days, at 87%, versus placebo, at 74%.
The P value was 0.12, “which achieved the prespecified evidentiary standard of 0.2,” according to Lara Pupim, MD, vice president of clinical research and development at Kiniksa Pharmaceuticals in Lexington, Mass.
Importantly, there was a 61% reduction in the risk of dying if patients had received mavrilimumab rather than placebo, she reported at the annual European Congress of Rheumatology. Mortality at day 29 was 21% in the placebo arm but just 8% in the combined mavrilimumab arms (P = .07).
Hendrik Schulze-Koops, MD, called it a “surprising study” and that “the outcome is very spectacular” in his short appraisal of the study during the Clinical Highlights session on the final day of the congress.
Mavrilimumab was “a compound that we would not have thought that would have such an impact on the outcome of COVID-19 infected patients,” Dr. Schulze-Koops of Ludwig Maximilian University of Munich added.
In this small study, “there was a consistent suggestion of a biological effect across key endpoints,” Richard Conway, MBChB, PhD, a consultant rheumatologist at St. James’s Hospital in Dublin, pointed out in an interview.
“Similar to tocilizumab, the benefits with mavrilimumab appear to be in addition to those seen with glucocorticoids, as 96% of patients received dexamethasone,” Dr. Conway observed. Furthermore, nearly one-third received antiviral or remdesivir treatment.
“This study was likely underpowered to assess a clinically meaningful benefit,” he said, adding that “there is insufficient evidence at present to begin using mavrilimumab as an alternative to currently available agents.” That said, “these results are promising for future studies.”
Rationale for GM-CSF inhibition with mavrilimumab in COVID-19 pneumonia
“The cytokine GM-CSF is vital to both lung homeostasis and regulation of inflammation in autoimmunity,” Dr. Pupim explained.
She added that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”
The efficacy and safety of blocking GM-CSF with mavrilimumab have been shown previously in phase 2 studies in other diseases, Dr. Pupim noted. This includes patients with rheumatoid arthritis and those with giant cell arteritis.
“It was hypothesized that GM-CSF receptor–alpha blockade may reduce infiltration of pathogenic cells into the lung and may suppress inflammation in COVID-19 pneumonia in hyperinflammation,” she explained.
Study details and other outcome results
The study presented by Dr. Pupim was a phase 2/3 double-blind, placebo-controlled trial predominantly conducted in Brazil, the United States, and South Africa, with some participation in Peru and Chile.
Patients were eligible for inclusion if they had had a positive COVID-19 test within 14 days of randomization and had been hospitalized but not ventilated. Evidence of bilateral pneumonia on chest x-ray or CT scan and clinical laboratory evidence indicative of hyperinflammation were also prerequisites for study enrollment.
The ongoing study comprised two cohorts, Dr. Pupim explained: patients who have not been ventilated and those who have recently been ventilated. Dr. Pupim presented the data on the nonventilated cohort, noting that there was a total of 116 patients aged a mean of 57 years.
Patients were randomized to one of three treatment arms: two groups received a single intravenous infusion of mavrilimumab, either 6 mg/kg or 10 mg/kg, and the third group got a placebo.
“Using a time-to-event approach, looking at mechanical ventilation-free survival, mavrilimumab recipients experienced a 65% reduction in the risk of mechanical ventilation or death,” Dr. Pupim said (P = .0175).
“Separation in the Kaplan-Meier curves was evident very early after study drug administration,” she added.
There were trends toward a faster benefit with mavrilimumab than placebo in two other key secondary endpoints: the median time to achieving a two-point clinical improvement (7 vs. 11 days) and the median time to room air (7 vs. 9 days).
Timing of mavrilimumab administration and safety
Study coauthor and chief clinical development officer at Kiniksa, Arian Pano, MD, answered questions on the presentation. When asked about the timing of giving mavrilimumab, he said: “Based on these data it is before they go to ventilation, as soon as you have symptoms of hyperinflammation and a need for oxygen.”
Mavrilimumab is given as a single infusion “and has been well tolerated; virtually no interruptions occurred in this study.”
No serious adverse events related to mavrilimumab were seen, and adverse events, including secondary infections, which are known complications of COVID-19, occurred less frequently in mavrilimumab recipients, compared with placebo.
Dr. Pupim reported that there was a case of tuberculosis in one patient treated with mavrilimumab (10 mg/kg). That case had occurred in an “endemic area for tuberculosis,” and the patient had been screened before entry but only via a sputum sample.
“Prior to these events, the patient received high-dose corticosteroids, a known risk factor for reactivation of TB, and thus the potential additive contribution of mavrilimumab, if any, is uncertain.” Dr. Pupim said.
“Thrombotic events, another known complication of COVID-19, occurred in the placebo arm only,” she added.
Dr. Pano commented that the study has now “seamlessly continued to phase 3. So, basically, we did not stop the study. At the end of phase 2, we just locked the database and collected the data.” Both the 6 mg/kg and 10 mg/kg are being studied, but it’s “very likely [that] 6 mg/kg could be the dose that we may bring forward to the clinic in terms of registration, but that’s at this point in time. We will need to wait for the phase 3 data,” he observed. Those findings will hopefully be available later this year.
Kiniksa funded the study. Dr. Pupim, Dr. Pano, and multiple study coinvestigators are employees of the company.
Dr. Schulze-Koops was not involved in the study and had no specific disclosures. Dr. Conway had no financial disclosures to make in relation to his comments.
FROM EULAR 2021 CONGRESS