User login
Does COVID-19 induce type 1 diabetes in kids? Jury still out
Two new studies from different parts of the world have identified an increase in the incidence of type 1 diabetes in children since the COVID-19 pandemic began, but the reasons still aren’t clear.
The findings from the two studies, in Germany and the United States, align closely, endocrinologist Jane J. Kim, MD, professor of pediatrics and principal investigator of the U.S. study, told this news organization. “I think that the general conclusion based on their data and our data is that there appears to be an increased rate of new type 1 diabetes diagnoses in children since the onset of the pandemic.”
Dr. Kim noted that because her group’s data pertain to just a single center, she is “heartened to see that the [German team’s] general conclusions are the same as ours.” Moreover, she pointed out that other studies examining this question came from Europe early in the pandemic, whereas “now both they [the German group] and we have had the opportunity to look at what’s happening over a longer period of time.”
But the reason for the association remains unclear. Some answers may be forthcoming from a database designed in mid-2020 specifically to examine the relationship between COVID-19 and new-onset diabetes. Called CoviDiab, the registry aims “to establish the extent and characteristics of new-onset, COVID-19–related diabetes and to investigate its pathogenesis, management, and outcomes,” according to the website.
The first new study, a multicenter German diabetes registry study, was published online Jan. 17 in Diabetes Care by Clemens Kamrath, MD, of Justus Liebig University, Giessen, Germany, and colleagues.
The other, from Rady Children’s Hospital of San Diego, was published online Jan. 24 in JAMA Pediatrics by Bethany L. Gottesman, MD, and colleagues, all with the University of California, San Diego.
Mechanisms likely to differ for type 1 versus type 2 diabetes
Neither the German nor the U.S. investigators were able to directly correlate current or prior SARS-CoV-2 infection in children with the subsequent development of type 1 diabetes.
Earlier this month, a study from the U.S. Centers for Disease Control and Prevention did examine that issue, but it also included youth with type 2 diabetes and did not separate out the two groups.
Dr. Kim said her institution has also seen an increase in type 2 diabetes among youth since the COVID-19 pandemic began but did not include that in their current article.
“When we started looking at our data, diabetes and COVID-19 in adults had been relatively well established. To see an increase in type 2 [diabetes] was not so surprising to our group. But we had the sense we were seeing more patients with type 1, and when we looked at our hospital that was very much the case. I think that was a surprise to people,” said Dr. Kim.
Although a direct effect of SARS-CoV-2 on pancreatic beta cells has been proposed, in both the German and San Diego datasets the diagnosis of type 1 diabetes was confirmed with autoantibodies that are typically present years prior to the onset of clinical symptoms.
The German group suggests possible other explanations for the link, including the lack of immune system exposure to other common pediatric infections during pandemic-necessitated social distancing – the so-called hygiene hypothesis – as well as the possible role of psychological stress, which several studies have linked to type 1 diabetes.
But as of now, Dr. Kim said, “Nobody really knows.”
Is the effect direct or indirect?
Using data from the multicenter German Diabetes Prospective Follow-up Registry, Dr. Kamrath and colleagues compared the incidence of type 1 diabetes in children and adolescents from Jan. 1, 2020 through June 30, 2021 with the incidence in 2011-2019.
During the pandemic period, a total of 5,162 youth were newly diagnosed with type 1 diabetes at 236 German centers. That incidence, 24.4 per 100,000 patient-years, was significantly higher than the 21.2 per 100,000 patient-years expected based on the prior decade, with an incidence rate ratio of 1.15 (P < .001). The increase was similar in both males and females.
There was a difference by age, however, as the phenomenon appeared to be limited to the preadolescent age groups. The incidence rate ratios (IRRs) for ages below 6 years and 6-11 years were 1.23 and 1.18 (both P < .001), respectively, compared to a nonsignificant IRR of 1.06 (P = .13) in those aged 12-17 years.
Compared with the expected monthly incidence, the observed incidence was significantly higher in June 2020 (IRR, 1.43; P = .003), July 2020 (IRR, 1.48; P < 0.001), March 2021 (IRR, 1.29; P = .028), and June 2021 (IRR, 1.39; P = .01).
Among the 3,851 patients for whom data on type 1 diabetes-associated autoantibodies were available, the adjusted rates of autoantibody negativity did not differ from 2018-2019 during the entire pandemic period or during the year 2020 or the first half of 2021.
“Therefore, the increase in the incidence of type 1 diabetes in children appears to be due to immune-mediated type 1 diabetes. However, because autoimmunity and progressive beta-cell destruction typically begin long before the clinical diagnosis of type 1 diabetes, we were surprised to see the incidence of type 1 diabetes followed the peak incidence of COVID-19 and also the pandemic containment measures by only approximately 3 months,” Dr. Kamrath and colleagues write.
Taken together, they say, the data suggest that “the impact on type 1 diabetes incidence is not due to infection with SARS-CoV-2 but rather a consequence of environmental changes resulting from the pandemic itself or pandemic containment measures.”
Similar findings at a U.S. children’s hospital
In the cross-sectional study in San Diego, Dr. Gottesman and colleagues looked at the electronic medical records (EMRs) at Rady Children’s Hospital for patients aged younger than 19 years with at least one positive type 1 diabetes antibody titer.
During March 19, 2020 to March 18, 2021, a total of 187 children were admitted for new-onset type 1 diabetes, compared with just 119 the previous year, a 57% increase.
From July 2020 through February 2021, the number of new type 1 diabetes diagnoses significantly exceeded the number expected based on a quarterly moving average of each of the preceding 5 years.
Only four of the 187 patients (2.1%) diagnosed during the pandemic period had a COVID-19 infection at the time of presentation. Antibody testing to assess prior infection wasn’t feasible, and now that children are receiving the vaccine – and therefore most will have antibodies – “we’ve lost our window of opportunity to look at that question,” Dr. Kim noted.
As has been previously shown, there was an increase in the percentage of patients presenting with diabetic ketoacidosis during the pandemic compared with the prior 5 years (49.7% vs. 40.7% requiring insulin infusion). However, there was no difference in mean age at presentation, body mass index, A1c, or percentage requiring admission to intensive care.
Because these data only go through March 2021, Dr. Kim noted, “We need to see what’s happening with these different variants. We’ll have a chance to look in a month or two to see the effects of Omicron on the rates of diabetes in the hospital.”
Will CoviDiab answer the question?
Data from CoviDiab will include diabetes type in adults and children, registry coprincipal investigator Francesco Rubino, MD, of King’s College London, told this news organization.
“We aimed at having as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c. By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19 as this also speaks about mechanisms of action.”
Dr. Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or that the hyperglycemia may be stress-induced and temporary.
“We’re looking at this question with a skeptical eye ... Is it just an association, or does the virus have a role in inducing diabetes from scratch, or can the virus advance pathophysiology in a way that it ends up in full-blown diabetes in predisposed individuals?”
While no single study will prove that SARS-CoV-2 causes diabetes, “combining observations from various studies and approaches we may get a higher degree of certainty,” Dr. Rubino said, noting that the CoviDiab team plans to publish data from the first 800 cases “soon.”
Dr. Kim has reported no relevant financial relationships. Dr. Rubino has reported receiving grants from Ethicon and Medtronic, personal fees from GI Dynamic, Keyron, Novo Nordisk, Ethicon, and Medtronic.
A version of this article first appeared on Medscape.com.
Two new studies from different parts of the world have identified an increase in the incidence of type 1 diabetes in children since the COVID-19 pandemic began, but the reasons still aren’t clear.
The findings from the two studies, in Germany and the United States, align closely, endocrinologist Jane J. Kim, MD, professor of pediatrics and principal investigator of the U.S. study, told this news organization. “I think that the general conclusion based on their data and our data is that there appears to be an increased rate of new type 1 diabetes diagnoses in children since the onset of the pandemic.”
Dr. Kim noted that because her group’s data pertain to just a single center, she is “heartened to see that the [German team’s] general conclusions are the same as ours.” Moreover, she pointed out that other studies examining this question came from Europe early in the pandemic, whereas “now both they [the German group] and we have had the opportunity to look at what’s happening over a longer period of time.”
But the reason for the association remains unclear. Some answers may be forthcoming from a database designed in mid-2020 specifically to examine the relationship between COVID-19 and new-onset diabetes. Called CoviDiab, the registry aims “to establish the extent and characteristics of new-onset, COVID-19–related diabetes and to investigate its pathogenesis, management, and outcomes,” according to the website.
The first new study, a multicenter German diabetes registry study, was published online Jan. 17 in Diabetes Care by Clemens Kamrath, MD, of Justus Liebig University, Giessen, Germany, and colleagues.
The other, from Rady Children’s Hospital of San Diego, was published online Jan. 24 in JAMA Pediatrics by Bethany L. Gottesman, MD, and colleagues, all with the University of California, San Diego.
Mechanisms likely to differ for type 1 versus type 2 diabetes
Neither the German nor the U.S. investigators were able to directly correlate current or prior SARS-CoV-2 infection in children with the subsequent development of type 1 diabetes.
Earlier this month, a study from the U.S. Centers for Disease Control and Prevention did examine that issue, but it also included youth with type 2 diabetes and did not separate out the two groups.
Dr. Kim said her institution has also seen an increase in type 2 diabetes among youth since the COVID-19 pandemic began but did not include that in their current article.
“When we started looking at our data, diabetes and COVID-19 in adults had been relatively well established. To see an increase in type 2 [diabetes] was not so surprising to our group. But we had the sense we were seeing more patients with type 1, and when we looked at our hospital that was very much the case. I think that was a surprise to people,” said Dr. Kim.
Although a direct effect of SARS-CoV-2 on pancreatic beta cells has been proposed, in both the German and San Diego datasets the diagnosis of type 1 diabetes was confirmed with autoantibodies that are typically present years prior to the onset of clinical symptoms.
The German group suggests possible other explanations for the link, including the lack of immune system exposure to other common pediatric infections during pandemic-necessitated social distancing – the so-called hygiene hypothesis – as well as the possible role of psychological stress, which several studies have linked to type 1 diabetes.
But as of now, Dr. Kim said, “Nobody really knows.”
Is the effect direct or indirect?
Using data from the multicenter German Diabetes Prospective Follow-up Registry, Dr. Kamrath and colleagues compared the incidence of type 1 diabetes in children and adolescents from Jan. 1, 2020 through June 30, 2021 with the incidence in 2011-2019.
During the pandemic period, a total of 5,162 youth were newly diagnosed with type 1 diabetes at 236 German centers. That incidence, 24.4 per 100,000 patient-years, was significantly higher than the 21.2 per 100,000 patient-years expected based on the prior decade, with an incidence rate ratio of 1.15 (P < .001). The increase was similar in both males and females.
There was a difference by age, however, as the phenomenon appeared to be limited to the preadolescent age groups. The incidence rate ratios (IRRs) for ages below 6 years and 6-11 years were 1.23 and 1.18 (both P < .001), respectively, compared to a nonsignificant IRR of 1.06 (P = .13) in those aged 12-17 years.
Compared with the expected monthly incidence, the observed incidence was significantly higher in June 2020 (IRR, 1.43; P = .003), July 2020 (IRR, 1.48; P < 0.001), March 2021 (IRR, 1.29; P = .028), and June 2021 (IRR, 1.39; P = .01).
Among the 3,851 patients for whom data on type 1 diabetes-associated autoantibodies were available, the adjusted rates of autoantibody negativity did not differ from 2018-2019 during the entire pandemic period or during the year 2020 or the first half of 2021.
“Therefore, the increase in the incidence of type 1 diabetes in children appears to be due to immune-mediated type 1 diabetes. However, because autoimmunity and progressive beta-cell destruction typically begin long before the clinical diagnosis of type 1 diabetes, we were surprised to see the incidence of type 1 diabetes followed the peak incidence of COVID-19 and also the pandemic containment measures by only approximately 3 months,” Dr. Kamrath and colleagues write.
Taken together, they say, the data suggest that “the impact on type 1 diabetes incidence is not due to infection with SARS-CoV-2 but rather a consequence of environmental changes resulting from the pandemic itself or pandemic containment measures.”
Similar findings at a U.S. children’s hospital
In the cross-sectional study in San Diego, Dr. Gottesman and colleagues looked at the electronic medical records (EMRs) at Rady Children’s Hospital for patients aged younger than 19 years with at least one positive type 1 diabetes antibody titer.
During March 19, 2020 to March 18, 2021, a total of 187 children were admitted for new-onset type 1 diabetes, compared with just 119 the previous year, a 57% increase.
From July 2020 through February 2021, the number of new type 1 diabetes diagnoses significantly exceeded the number expected based on a quarterly moving average of each of the preceding 5 years.
Only four of the 187 patients (2.1%) diagnosed during the pandemic period had a COVID-19 infection at the time of presentation. Antibody testing to assess prior infection wasn’t feasible, and now that children are receiving the vaccine – and therefore most will have antibodies – “we’ve lost our window of opportunity to look at that question,” Dr. Kim noted.
As has been previously shown, there was an increase in the percentage of patients presenting with diabetic ketoacidosis during the pandemic compared with the prior 5 years (49.7% vs. 40.7% requiring insulin infusion). However, there was no difference in mean age at presentation, body mass index, A1c, or percentage requiring admission to intensive care.
Because these data only go through March 2021, Dr. Kim noted, “We need to see what’s happening with these different variants. We’ll have a chance to look in a month or two to see the effects of Omicron on the rates of diabetes in the hospital.”
Will CoviDiab answer the question?
Data from CoviDiab will include diabetes type in adults and children, registry coprincipal investigator Francesco Rubino, MD, of King’s College London, told this news organization.
“We aimed at having as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c. By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19 as this also speaks about mechanisms of action.”
Dr. Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or that the hyperglycemia may be stress-induced and temporary.
“We’re looking at this question with a skeptical eye ... Is it just an association, or does the virus have a role in inducing diabetes from scratch, or can the virus advance pathophysiology in a way that it ends up in full-blown diabetes in predisposed individuals?”
While no single study will prove that SARS-CoV-2 causes diabetes, “combining observations from various studies and approaches we may get a higher degree of certainty,” Dr. Rubino said, noting that the CoviDiab team plans to publish data from the first 800 cases “soon.”
Dr. Kim has reported no relevant financial relationships. Dr. Rubino has reported receiving grants from Ethicon and Medtronic, personal fees from GI Dynamic, Keyron, Novo Nordisk, Ethicon, and Medtronic.
A version of this article first appeared on Medscape.com.
Two new studies from different parts of the world have identified an increase in the incidence of type 1 diabetes in children since the COVID-19 pandemic began, but the reasons still aren’t clear.
The findings from the two studies, in Germany and the United States, align closely, endocrinologist Jane J. Kim, MD, professor of pediatrics and principal investigator of the U.S. study, told this news organization. “I think that the general conclusion based on their data and our data is that there appears to be an increased rate of new type 1 diabetes diagnoses in children since the onset of the pandemic.”
Dr. Kim noted that because her group’s data pertain to just a single center, she is “heartened to see that the [German team’s] general conclusions are the same as ours.” Moreover, she pointed out that other studies examining this question came from Europe early in the pandemic, whereas “now both they [the German group] and we have had the opportunity to look at what’s happening over a longer period of time.”
But the reason for the association remains unclear. Some answers may be forthcoming from a database designed in mid-2020 specifically to examine the relationship between COVID-19 and new-onset diabetes. Called CoviDiab, the registry aims “to establish the extent and characteristics of new-onset, COVID-19–related diabetes and to investigate its pathogenesis, management, and outcomes,” according to the website.
The first new study, a multicenter German diabetes registry study, was published online Jan. 17 in Diabetes Care by Clemens Kamrath, MD, of Justus Liebig University, Giessen, Germany, and colleagues.
The other, from Rady Children’s Hospital of San Diego, was published online Jan. 24 in JAMA Pediatrics by Bethany L. Gottesman, MD, and colleagues, all with the University of California, San Diego.
Mechanisms likely to differ for type 1 versus type 2 diabetes
Neither the German nor the U.S. investigators were able to directly correlate current or prior SARS-CoV-2 infection in children with the subsequent development of type 1 diabetes.
Earlier this month, a study from the U.S. Centers for Disease Control and Prevention did examine that issue, but it also included youth with type 2 diabetes and did not separate out the two groups.
Dr. Kim said her institution has also seen an increase in type 2 diabetes among youth since the COVID-19 pandemic began but did not include that in their current article.
“When we started looking at our data, diabetes and COVID-19 in adults had been relatively well established. To see an increase in type 2 [diabetes] was not so surprising to our group. But we had the sense we were seeing more patients with type 1, and when we looked at our hospital that was very much the case. I think that was a surprise to people,” said Dr. Kim.
Although a direct effect of SARS-CoV-2 on pancreatic beta cells has been proposed, in both the German and San Diego datasets the diagnosis of type 1 diabetes was confirmed with autoantibodies that are typically present years prior to the onset of clinical symptoms.
The German group suggests possible other explanations for the link, including the lack of immune system exposure to other common pediatric infections during pandemic-necessitated social distancing – the so-called hygiene hypothesis – as well as the possible role of psychological stress, which several studies have linked to type 1 diabetes.
But as of now, Dr. Kim said, “Nobody really knows.”
Is the effect direct or indirect?
Using data from the multicenter German Diabetes Prospective Follow-up Registry, Dr. Kamrath and colleagues compared the incidence of type 1 diabetes in children and adolescents from Jan. 1, 2020 through June 30, 2021 with the incidence in 2011-2019.
During the pandemic period, a total of 5,162 youth were newly diagnosed with type 1 diabetes at 236 German centers. That incidence, 24.4 per 100,000 patient-years, was significantly higher than the 21.2 per 100,000 patient-years expected based on the prior decade, with an incidence rate ratio of 1.15 (P < .001). The increase was similar in both males and females.
There was a difference by age, however, as the phenomenon appeared to be limited to the preadolescent age groups. The incidence rate ratios (IRRs) for ages below 6 years and 6-11 years were 1.23 and 1.18 (both P < .001), respectively, compared to a nonsignificant IRR of 1.06 (P = .13) in those aged 12-17 years.
Compared with the expected monthly incidence, the observed incidence was significantly higher in June 2020 (IRR, 1.43; P = .003), July 2020 (IRR, 1.48; P < 0.001), March 2021 (IRR, 1.29; P = .028), and June 2021 (IRR, 1.39; P = .01).
Among the 3,851 patients for whom data on type 1 diabetes-associated autoantibodies were available, the adjusted rates of autoantibody negativity did not differ from 2018-2019 during the entire pandemic period or during the year 2020 or the first half of 2021.
“Therefore, the increase in the incidence of type 1 diabetes in children appears to be due to immune-mediated type 1 diabetes. However, because autoimmunity and progressive beta-cell destruction typically begin long before the clinical diagnosis of type 1 diabetes, we were surprised to see the incidence of type 1 diabetes followed the peak incidence of COVID-19 and also the pandemic containment measures by only approximately 3 months,” Dr. Kamrath and colleagues write.
Taken together, they say, the data suggest that “the impact on type 1 diabetes incidence is not due to infection with SARS-CoV-2 but rather a consequence of environmental changes resulting from the pandemic itself or pandemic containment measures.”
Similar findings at a U.S. children’s hospital
In the cross-sectional study in San Diego, Dr. Gottesman and colleagues looked at the electronic medical records (EMRs) at Rady Children’s Hospital for patients aged younger than 19 years with at least one positive type 1 diabetes antibody titer.
During March 19, 2020 to March 18, 2021, a total of 187 children were admitted for new-onset type 1 diabetes, compared with just 119 the previous year, a 57% increase.
From July 2020 through February 2021, the number of new type 1 diabetes diagnoses significantly exceeded the number expected based on a quarterly moving average of each of the preceding 5 years.
Only four of the 187 patients (2.1%) diagnosed during the pandemic period had a COVID-19 infection at the time of presentation. Antibody testing to assess prior infection wasn’t feasible, and now that children are receiving the vaccine – and therefore most will have antibodies – “we’ve lost our window of opportunity to look at that question,” Dr. Kim noted.
As has been previously shown, there was an increase in the percentage of patients presenting with diabetic ketoacidosis during the pandemic compared with the prior 5 years (49.7% vs. 40.7% requiring insulin infusion). However, there was no difference in mean age at presentation, body mass index, A1c, or percentage requiring admission to intensive care.
Because these data only go through March 2021, Dr. Kim noted, “We need to see what’s happening with these different variants. We’ll have a chance to look in a month or two to see the effects of Omicron on the rates of diabetes in the hospital.”
Will CoviDiab answer the question?
Data from CoviDiab will include diabetes type in adults and children, registry coprincipal investigator Francesco Rubino, MD, of King’s College London, told this news organization.
“We aimed at having as many as possible cases of new-onset diabetes for which we can have also a minimum set of clinical data including type of diabetes and A1c. By looking at this information we can infer whether a role of COVID-19 in triggering diabetes is clinically plausible – or not – and what type of diabetes is most frequently associated with COVID-19 as this also speaks about mechanisms of action.”
Dr. Rubino said that the CoviDiab team is approaching the data with the assumption that, at least in adults diagnosed with type 2 diabetes, the explanation might be that the person already had undiagnosed diabetes or that the hyperglycemia may be stress-induced and temporary.
“We’re looking at this question with a skeptical eye ... Is it just an association, or does the virus have a role in inducing diabetes from scratch, or can the virus advance pathophysiology in a way that it ends up in full-blown diabetes in predisposed individuals?”
While no single study will prove that SARS-CoV-2 causes diabetes, “combining observations from various studies and approaches we may get a higher degree of certainty,” Dr. Rubino said, noting that the CoviDiab team plans to publish data from the first 800 cases “soon.”
Dr. Kim has reported no relevant financial relationships. Dr. Rubino has reported receiving grants from Ethicon and Medtronic, personal fees from GI Dynamic, Keyron, Novo Nordisk, Ethicon, and Medtronic.
A version of this article first appeared on Medscape.com.
Could probiotics reduce ‘chemo brain’ in breast cancer patients?
compared with a control group taking placebo capsules, reports the first study of its kind.
“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.
The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.
The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.
The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).
The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.
He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”
“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.
Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.
“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.
“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.
A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
Measuring the effect on ‘chemo brain’
“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.
In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.
The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).
Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).
The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).
The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.
CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.
In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.
There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
How does it work?
The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.
A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.
Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
Benefits reported beyond breast cancer
A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.
And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.
The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.
A version of this article first appeared on Medscape.com.
compared with a control group taking placebo capsules, reports the first study of its kind.
“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.
The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.
The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.
The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).
The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.
He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”
“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.
Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.
“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.
“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.
A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
Measuring the effect on ‘chemo brain’
“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.
In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.
The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).
Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).
The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).
The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.
CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.
In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.
There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
How does it work?
The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.
A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.
Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
Benefits reported beyond breast cancer
A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.
And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.
The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.
A version of this article first appeared on Medscape.com.
compared with a control group taking placebo capsules, reports the first study of its kind.
“Our finding[s] provide a simple, inexpensive, and effective prevention strategy for chemotherapy-related side effects, including cognitive impairment,” senior author Jianbin Tong, MD, PhD, of the department of anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China, said in an interview.
The research “is the first study showing that probiotics supplementation during chemotherapy can prevent chemotherapy-related brain impairment,” he noted.
The double-blind, randomized study was published in the European Journal of Cancer. It involved 159 patients in China with stage I-III breast cancer who required adjuvant chemotherapy between 2018 and 2019. These patients were randomized to receive a regimen of three capsules twice per day containing either probiotics (n = 80) or placebo (n = 79) during their chemotherapy.
The probiotic capsule (Bifico, Sine Pharmaceuticals) contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis (210 mg of each).
The reductions in symptoms seen with the supplementation “exceed our expectations,” Dr. Tong said in an interview.
He speculated that this may have longer-term effects, with the prevention of initial cognitive impairment potentially “changing the neurodegenerative trajectory of patients after chemotherapy.”
“Patients don’t need to take probiotics continuously, but it’s better to take probiotics intermittently,” he said.
Approached for comment, Melanie Sekeres, PhD, Canada Research Chair and assistant professor at the University of Ottawa, said the improvements, such as those seen in delayed recall, are especially of interest.
“This is particularly notable because one of the brain regions that is critically involved in long-term memory processing, the hippocampus, is known to be highly sensitive to chemotherapy-induced neurotoxicity,” she said in an interview.
“The finding that probiotic treatment given alongside chemotherapy is sufficient to, in part, protect against memory disturbances in these patients suggests that there may be some neuroprotection conferred by the probiotic treatment,” she said.
A key question is whether similar results would be seen with other chemotherapy regimens, Dr. Sekeres added. “To better understand the effectiveness of these probiotics in preventing CRCI, they should be tested using other classes of chemotherapies before any broad conclusions can be made.”
Measuring the effect on ‘chemo brain’
“Chemo brain” is commonly reported after chemotherapy, and some 35% of patients report having long-term effects. Key symptoms include deficits in memory, attention, and executive and processing speed skills.
In their study, Dr. Tong and colleagues assessed patients on their cognitive status with a number of validated neuropsychological battery tests 1 day prior to initiating chemotherapy and 21 days after the last cycle of chemotherapy. Tests included the Hopkins Verbal Learning Test–Revised for verbal memory, the Brief Visuospatial Memory Test–Revised for visuospatial memory, and various others.
The team reports that, after adjustment for confounding factors, the total incidence of CRCI was significantly lower in the probiotics group versus the placebo group 21 days post chemotherapy (35% vs. 81%; relative risk, 0.43).
Rates of mild cognitive impairment were also lower in the probiotics group (29% vs 52%; RR, 0.55), as were rates of moderate cognitive impairment (6% vs. 29%; RR, 0.22).
The improvements with probiotics were observed across most other neuropsychological domains, including instantaneous verbal memory and delayed visuospatial memory (for both, P = .003) and visuospatial interference and verbal fluency (for both, P < .001).
The greater improvements in the probiotics group were seen regardless of use of other medications or the type of chemotherapy regimen received, which could have included epirubicin or docetaxel and/or cyclophosphamide.
CRCI was more common in patients who were older and had lower education or a higher body mass index; however, the improvements in the probiotics group were observed regardless of those factors, the authors commented.
In addition to the reduction in cognitive impairment that was seen, the treatment with probiotics was also associated with lower blood glucose (mean, 4.96 vs. 5.30; P = .02) and lower LDL cholesterol (2.61 vs. 2.89; P = .03) versus placebo, while there were no significant differences between the groups prior to chemotherapy.
There were no reports of severe emesis or constipation (grade 3 or higher) in either group; however, the probiotics group did have a significantly lower incidence of both, the authors note.
How does it work?
The potential benefits with probiotics are theorized to result from stabilizing the colonic and bacterial disruptions that are caused by chemotherapy, potentially offsetting the neuroinflammation that is linked to the cancer treatment, the authors speculated.
A subanalysis of 78 stool samples from 20 patients in the study showed no differences in alpha diversity or beta diversity before or after chemotherapy; however, there were significant reductions in the abundance of Streptococcus and Tyzzerella (P = .023 and P = .033, respectively) in the probiotics group after chemotherapy.
Further analysis showed that probiotics supplement modulated the levels of nine plasma metabolites in patients with breast cancer, with the results suggesting that metabolites (including p-mentha-1,8-dien-7-ol) “may be modulators in preventing CRCI by probiotics,” the authors noted.
Benefits reported beyond breast cancer
A subsequent trial conducted by Dr. Tong and colleagues following the CRCI study further showed similar protective benefits with probiotics in the prevention of chemotherapy-related hand-foot syndrome and oral mucositis.
And in a recent study, the research team found evidence of probiotic supplements protecting against cognitive impairment in the elderly following surgery.
The study received support from the National Natural Science Foundation of China, Subproject of the National Key Research and Development Program Project of China, science and technology innovation platform and talent plan of Hunan province and Natural Science Foundation of Hunan Province.
A version of this article first appeared on Medscape.com.
FROM THE EUROPEAN JOURNAL OF CANCER
100 coauthored papers, 10 years: Cancer transplant pioneers model 'team science'
On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.
Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.
Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.
Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”
Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.
Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.
“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”
When it comes to clinical science, however, English is the language of choice.
Global leaders in HSCT
Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.
In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).
However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.
Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).
Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.
The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.
The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.
During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).
The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.
The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.
Impact of the pandemic
When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”
The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.
“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
Something more in common
Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.
“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.
He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.
Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”
“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”
Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”
This article was updated 1/26/22.
On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.
Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.
Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.
Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”
Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.
Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.
“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”
When it comes to clinical science, however, English is the language of choice.
Global leaders in HSCT
Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.
In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).
However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.
Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).
Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.
The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.
The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.
During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).
The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.
The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.
Impact of the pandemic
When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”
The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.
“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
Something more in common
Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.
“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.
He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.
Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”
“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”
Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”
This article was updated 1/26/22.
On July 29, 2021, Sergio Giralt, MD, deputy division head of the division of hematologic malignancies and Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at MSKCC, published their 100th peer-reviewed paper as coauthors. Listing hundreds of such articles on a CV is standard for top-tier physicians, but the pair had gone one better: 100 publications written together in 10 years.
Their centenary article hit scientific newsstands almost exactly a decade after their first joint paper, which appeared in September 2011, not long after they met.
Born in Cuba, Dr. Giralt grew up in Venezuela. From the age of 14, he knew that medicine was his path, and in 1984 he earned a medical degree from the Universidad Central de Venezuela, Caracas. Next came a research position at Harvard Medical School, a residency at the Good Samaritan Hospital, Cincinnati, and a fellowship at the University of Texas MD Anderson Cancer Center, Houston. Dr. Giralt arrived at MSKCC in 2010 as the new chief of the adult bone marrow transplant service. There he was introduced to a new colleague, Dr. Perales. They soon learned that in addition to expertise in hematology, they had second language in common: Spanish.
Dr. Giralt said: “We both have a Spanish background and in a certain sense, there was an affinity there. ... We both have shared experiences.”
Dr. Perales was brought up in Belgium, a European nation with three official languages: French, Dutch, and German. He speaks five tongues in all and learned Spanish from his father, who came from Spain.
Fluency in Spanish enables both physicians to take care of the many New Yorkers who are more comfortable in that language – especially when navigating cancer treatment. However, both Dr. Giralt and Dr. Perales said that a second language is more than a professional tool. They described the enjoyable change of persona that happens when they switch to Spanish.
“People who are multilingual have different roles [as much as] different languages,” said Dr. Perales. “When I’m in Spanish, part of my brain is [thinking back to] summer vacations and hanging out with my cousins.”
When it comes to clinical science, however, English is the language of choice.
Global leaders in HSCT
Dr. Giralt and Dr. Perales are known worldwide in the field of allogeneic HSCT, a potentially curative treatment for an elongating list of both malignant and nonmalignant diseases.
In 1973, MSKCC conducted the first bone-marrow transplant from an unrelated donor. Fifty years on, medical oncologists in the United States conduct approximately 8,500 allogeneic transplants each year, 72% to treat acute leukemias or myelodysplastic syndrome (MDS).
However, stripping the immune system with intensive chemotherapy ‘conditioning,’ then rebuilding it with non-diseased donor hematopoietic cells is a hazardous undertaking. Older patients are less likely to survive the intensive conditioning, so historically have missed out. Also, even with a good human leukocyte antigen (HLA) match, the recipient needs often brutal immunosuppression.
Since Dr. Giralt and Dr. Perales began their partnership in 2010, the goals of their work have not changed: to develop safer, lower-intensity transplantation suitable for older, more vulnerable patients and reduce fearsome posttransplant sequelae such as graft-versus-host disease (GVHD).
Dr. Giralt’s publication list spans more than 600 peer-reviewed papers, articles and book chapters, almost exclusively on HSCT. Dr. Perales has more than 300 publication credits on the topic.
The two paired up on their first paper just months after Dr. Giralt arrived at MSKCC. That article, published in Biology of Blood and Marrow Transplantation, compared umbilical cord blood for HSCT with donor blood in 367 people with a variety of hematologic malignancies, including acute and chronic leukemias, MDS, and lymphoma.
The MSKCC team found that transplant-related mortality in the first 180 days was higher for the cord blood (21%), but thereafter mortality and relapse were much lower than for donated blood, with the result that 2-year progression-free survival of 55% was similar. Dr. Perales, Dr. Giralt and their coauthors concluded that the data provided “strong support” for further work on cord blood as an alternative stem-cell source.
During their first decade of collaboration, Dr. Giralt and Dr. Perales worked on any promising avenue that could improve outcomes and the experience of HSCT recipients, including reduced-intensity conditioning regimens to allow older adults to benefit from curative HSCT and donor T-cell depletion by CD34 selection, to reduce graft-versus-host disease (GVHD).
The CD34 protein is typically found on the surface of early stage and highly active stem cell types. Selecting these cell types using a range of techniques can eliminate many other potentially interfering or inactive cells. This enriches the transplant population with the most effective cells and can lower the risk of GVHD.
The 100th paper on which Dr. Giralt and Dr. Perales were coauthors was published in Blood Advances on July 27, 2021. The retrospective study examined the fate of 58 MSKCC patients with a rare form of chronic lymphocytic leukemia, CLL with Richter’s transformation (CLL-RT). It was the largest such study to date of this rare disease.
M.D. Anderson Cancer Center had shown in 2006 that, despite chemotherapy, overall survival in patients with CLL-RT was approximately 8 months. HSCT improved survival dramatically (75% at 3 years; n = 7). However, with the advent of novel targeted drugs for CLL such as ibrutinib (Imbruvica), venetoclax (Venclexta), or idelalisib (Zydelig), the MSKCC team asked themselves: What was the role of reduced-intensive conditioning HSCT? Was it even safe? Among other findings, Dr. Giralt and Dr. Perales’ 100th paper showed that reduced-intensity HSCT remained a viable alternative after a CLL-RT patient progressed on a novel agent.
Impact of the pandemic
When COVID-19 hit, the team lost many research staff and developed a huge backlog, said Dr. Giralt. He and Dr. Perales realized that they needed to be “thoughtful and careful” about which studies to continue. “For example, the CD-34 selection trials we did not close because these are our workhorse trials,” Dr. Giralt said. “We have people we need to treat, and some of the patients that we need to treat can only be treated on trial.”
The team was also able to pivot some of their work into COVID 19 itself, and they collected crucial information on HSCT in recovered COVID-19 patients, as an example.
“We were living through a critical time, but that doesn’t mean we [aren’t] obligated to continue our mission, our research mission,” said Dr. Giralt. “It really is team science. The way we look at it ... there’s a common thread: We both like to do allogeneic transplant, and we both believe in trying to make CD-34 selection better. So we’re both very much [working on] how can we improve what we call ‘the Memorial way’ of doing transplants. Where we separate is, Miguel does primarily lymphoma. He doesn’t do myeloma [like me]. So in those two areas, we’re helping develop the junior faculty in a different way.”
Something more in common
Right from the start, Dr. Perales and Dr. Giralt also shared a commitment to mentoring. Since 2010, Dr. Perales has mentored 22 up-and-coming junior faculty, including 10 from Europe (8 from Spain) and 2 from Latin America.
“[It makes] the research enterprise much more productive but [these young scientists] really increase the visibility of the program,” said Dr. Giralt.
He cited Dr. Perales’ track record of mentoring as one of the reasons for his promotion to chief of the adult bone marrow transplant service. In March 2020, Dr. Perales seamlessly stepped into Dr. Giralt’s shoes, while Dr. Giralt moved on to his present role as deputy division head of the division of hematologic malignancies.
Dr. Perales said: “The key aspect [of these promotions] is the fantastic working relationship that we’ve had over the years. ... I consider Sergio my mentor, but also a good friend and colleague. And so I think it’s this ability that we’ve had to work together and that relationship of trust, which has been key.”
“Sergio is somebody who lifts people up,” Dr. Perales added. “Many people will tell you that Sergio has helped them in their career. ... And I think that’s a lesson I’ve learned from him: training the next generation. And [that’s] not just in the U.S., but outside. I think that’s a key role that we have. And our responsibility.”
Asked to comment on their 100th-paper milestone, Dr. Perales firmly turned the spotlight from himself and Dr. Giralt to the junior investigators who have passed through the doors of the bone-marrow transplant program: “This body of work represents not just our collaboration but also the many contributions of our team at MSK ... and beyond MSK.”
This article was updated 1/26/22.
Two studies detail the dangers of COVID in pregnancy
Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.
A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.
The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.
Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.
The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.
The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.
The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.
“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”
Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.
The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.
The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.
Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.
“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.
The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.
A version of this article first appeared on WebMD.com.
Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.
A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.
The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.
Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.
The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.
The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.
The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.
“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”
Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.
The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.
The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.
Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.
“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.
The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.
A version of this article first appeared on WebMD.com.
Two new studies show how COVID-19 threatens the health of pregnant people and their newborn infants.
A study conducted in Scotland showed that unvaccinated pregnant people who got COVID were much more likely to have a stillborn infant or one that dies in the first 28 days. The study also found that pregnant women infected with COVID died or needed hospitalization at a much higher rate than vaccinated women who got pregnant.
The University of Edinburgh and Public Health Scotland studied national data in 88,000 pregnancies between Dec. 2020 and Oct. 2021, according to the study published in Nature Medicine.
Overall, 77.4% of infections, 90.9% of COVID-related hospitalizations, and 98% of critical care cases occurred in the unvaccinated people, as did all newborn deaths.
The study said 2,364 babies were born to women infected with COVID, with 2,353 live births. Eleven babies were stillborn and eight live-born babies died within 28 days. Of the live births, 241 were premature.
The problems were more likely if the infection occurred 28 days or less before the delivery date, the researchers said.
The authors said the low vaccination rate among pregnant people was a problem. Only 32% of people giving birth in Oct. 2021 were fully vaccinated, while 77% of the Scottish female population aged 18-44 was fully vaccinated.
“Vaccine hesitancy in pregnancy thus requires addressing, especially in light of new recommendations for booster vaccination administration 3 months after the initial vaccination course to help protect against new variants such as Omicron,” the authors wrote. “Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.”
Vaccinated women who were pregnant had complication rates that were about the same for all pregnant women, the study shows.
The second study, published in The Lancet, found that women who got COVID while pregnant in five Western U.S. states were more likely to have premature births, low birth weights, and stillbirths, even when the COVID cases are mild.
The Institute for Systems Biology researchers in Seattle studied data for women who gave birth in Alaska, California, Montana, Oregon, or Washington from March 5, 2020, to July 4, 2021. About 18,000 of them were tested for COVID, with 882 testing positive. Of the positive tests, 85 came in the first trimester, 226 in the second trimester, and 571 in the third semester. None of the pregnant women had been vaccinated at the time they were infected.
Most of the birth problems occurred with first and second trimester infections, the study noted, and problems occurred even if the pregnant person didn’t have respiratory complications, a major COVID symptom.
“Pregnant people are at an increased risk of adverse outcomes following SARS-CoV-2 infection, even when maternal COVID-19 is less severe, and they may benefit from increased monitoring following infection,” Jennifer Hadlock, MD, an author of the paper, said in a news release.
The study also pointed out continuing inequities in health care, with most of the positive cases occurring among young, non-White people with Medicaid and high body mass index.
A version of this article first appeared on WebMD.com.
Severe outcomes increased in youth hospitalized after positive COVID-19 test
Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.
In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.
However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.
In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).
Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).
The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).
Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.
The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.
However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
Data may inform clinical decisions
“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.
“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.
The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.
However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.
The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.
In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.
However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.
In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).
Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).
The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).
Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.
The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.
However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
Data may inform clinical decisions
“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.
“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.
The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.
However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.
The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.
In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.
However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.
In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).
Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).
The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).
Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.
The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.
However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
Data may inform clinical decisions
“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.
“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.
The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.
However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.
The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.
FROM JAMA NETWORK OPEN
Negative home COVID test no ‘free pass’ for kids, study finds
With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.
Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.
“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.
The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.
Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”
Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.
They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.
The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.
Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”
“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”
Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.
Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.
However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”
Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.
“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”
Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.
With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.
Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.
“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.
The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.
Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”
Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.
They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.
The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.
Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”
“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”
Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.
Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.
However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”
Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.
“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”
Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.
With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.
Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.
“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.
The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.
Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”
Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.
They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.
The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.
Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”
“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”
Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.
Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.
However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”
Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.
“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”
Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.
BMJ EVIDENCE-BASED MEDICINE
Docs pen open letter to support Fauci against partisan ‘attacks’
“We deplore the personal attacks on Dr. Fauci. The criticism is inaccurate, unscientific, ill-founded in the facts and, increasingly, motivated by partisan politics,” reads the letter of support, initiated by Ezekiel Emanuel, MD, and signed by almost 300 scientists and public health and medical professionals, including Nobel Laureates, a former Republican senator, and leadership of medical societies and institutions.
Dr. Fauci has led the National Institute for Allergy and Infectious Diseases since 1984 and serves as President Biden’s top medical advisor on the pandemic.
“Dr. Anthony Fauci has served the U.S.A. with wisdom and integrity for nearly 40 years. Through HIV, Ebola, and now COVID, he has unswervingly served the United States guiding the country to very successful outcomes. He has our unreserved respect and trust as a scientist and a national leader,” the letter reads.
Dr. Fauci has repeatedly faced harsh criticism from congressional Republicans, especially Sen. Rand Paul (R-Ky.) and Sen. Roger Marshall (R-Kan.).
At a particularly contentious congressional hearing earlier this week on the federal government’s response to Omicron, Dr. Fauci fought back, telling Sen. Marshall, “You’re so misinformed, it’s extraordinary.”
Dr. Fauci, who has received death threats and harassment of his family, told Sen. Rand that his “completely untrue” statements and rhetoric “kindles the crazies out there.”
‘Sagacious counsel’
The personal attacks on Dr. Fauci are a “distraction from what should be the national focus – working together to finally overcome a pandemic that is killing about 500,000 people a year. We are grateful for Dr. Fauci’s dedication and tireless efforts to help the country through this pandemic and other health crises,” the letter reads.
“Throughout the COVID-19 pandemic, Dr. Fauci has provided the American political leadership and the public with sagacious counsel in these most difficult of times. His advice has been as well informed as data and the rapidly evolving circumstances allowed,” it states.
“Importantly,” Dr. Fauci has given his advice with “humility, being clear about what we know and what is unknown, but requires judgment. He has consistently emphasized the importance of mask-wearing, social distancing, and vaccination. These are standard and necessary public health measures that we all support,” the letter states.
“We are grateful that Dr. Fauci has consistently stated the science in a way that represents the facts as they emerge, without unwarranted speculation.”
“Sadly, in these politically polarized times where misinformation contaminates the United States’ response to the pandemic, routine public health measures have become unnecessarily controversial, undermining the effectiveness of our country’s response,” the letter reads.
A version of this article first appeared on Medscape.com.
“We deplore the personal attacks on Dr. Fauci. The criticism is inaccurate, unscientific, ill-founded in the facts and, increasingly, motivated by partisan politics,” reads the letter of support, initiated by Ezekiel Emanuel, MD, and signed by almost 300 scientists and public health and medical professionals, including Nobel Laureates, a former Republican senator, and leadership of medical societies and institutions.
Dr. Fauci has led the National Institute for Allergy and Infectious Diseases since 1984 and serves as President Biden’s top medical advisor on the pandemic.
“Dr. Anthony Fauci has served the U.S.A. with wisdom and integrity for nearly 40 years. Through HIV, Ebola, and now COVID, he has unswervingly served the United States guiding the country to very successful outcomes. He has our unreserved respect and trust as a scientist and a national leader,” the letter reads.
Dr. Fauci has repeatedly faced harsh criticism from congressional Republicans, especially Sen. Rand Paul (R-Ky.) and Sen. Roger Marshall (R-Kan.).
At a particularly contentious congressional hearing earlier this week on the federal government’s response to Omicron, Dr. Fauci fought back, telling Sen. Marshall, “You’re so misinformed, it’s extraordinary.”
Dr. Fauci, who has received death threats and harassment of his family, told Sen. Rand that his “completely untrue” statements and rhetoric “kindles the crazies out there.”
‘Sagacious counsel’
The personal attacks on Dr. Fauci are a “distraction from what should be the national focus – working together to finally overcome a pandemic that is killing about 500,000 people a year. We are grateful for Dr. Fauci’s dedication and tireless efforts to help the country through this pandemic and other health crises,” the letter reads.
“Throughout the COVID-19 pandemic, Dr. Fauci has provided the American political leadership and the public with sagacious counsel in these most difficult of times. His advice has been as well informed as data and the rapidly evolving circumstances allowed,” it states.
“Importantly,” Dr. Fauci has given his advice with “humility, being clear about what we know and what is unknown, but requires judgment. He has consistently emphasized the importance of mask-wearing, social distancing, and vaccination. These are standard and necessary public health measures that we all support,” the letter states.
“We are grateful that Dr. Fauci has consistently stated the science in a way that represents the facts as they emerge, without unwarranted speculation.”
“Sadly, in these politically polarized times where misinformation contaminates the United States’ response to the pandemic, routine public health measures have become unnecessarily controversial, undermining the effectiveness of our country’s response,” the letter reads.
A version of this article first appeared on Medscape.com.
“We deplore the personal attacks on Dr. Fauci. The criticism is inaccurate, unscientific, ill-founded in the facts and, increasingly, motivated by partisan politics,” reads the letter of support, initiated by Ezekiel Emanuel, MD, and signed by almost 300 scientists and public health and medical professionals, including Nobel Laureates, a former Republican senator, and leadership of medical societies and institutions.
Dr. Fauci has led the National Institute for Allergy and Infectious Diseases since 1984 and serves as President Biden’s top medical advisor on the pandemic.
“Dr. Anthony Fauci has served the U.S.A. with wisdom and integrity for nearly 40 years. Through HIV, Ebola, and now COVID, he has unswervingly served the United States guiding the country to very successful outcomes. He has our unreserved respect and trust as a scientist and a national leader,” the letter reads.
Dr. Fauci has repeatedly faced harsh criticism from congressional Republicans, especially Sen. Rand Paul (R-Ky.) and Sen. Roger Marshall (R-Kan.).
At a particularly contentious congressional hearing earlier this week on the federal government’s response to Omicron, Dr. Fauci fought back, telling Sen. Marshall, “You’re so misinformed, it’s extraordinary.”
Dr. Fauci, who has received death threats and harassment of his family, told Sen. Rand that his “completely untrue” statements and rhetoric “kindles the crazies out there.”
‘Sagacious counsel’
The personal attacks on Dr. Fauci are a “distraction from what should be the national focus – working together to finally overcome a pandemic that is killing about 500,000 people a year. We are grateful for Dr. Fauci’s dedication and tireless efforts to help the country through this pandemic and other health crises,” the letter reads.
“Throughout the COVID-19 pandemic, Dr. Fauci has provided the American political leadership and the public with sagacious counsel in these most difficult of times. His advice has been as well informed as data and the rapidly evolving circumstances allowed,” it states.
“Importantly,” Dr. Fauci has given his advice with “humility, being clear about what we know and what is unknown, but requires judgment. He has consistently emphasized the importance of mask-wearing, social distancing, and vaccination. These are standard and necessary public health measures that we all support,” the letter states.
“We are grateful that Dr. Fauci has consistently stated the science in a way that represents the facts as they emerge, without unwarranted speculation.”
“Sadly, in these politically polarized times where misinformation contaminates the United States’ response to the pandemic, routine public health measures have become unnecessarily controversial, undermining the effectiveness of our country’s response,” the letter reads.
A version of this article first appeared on Medscape.com.
More vitamin D not better for reducing cancer or CVD incidence
according to a new randomized controlled study.
In the cohort of nearly 2,500 healthy individuals, the researchers found no differences in cancer or CVD incidence over 5 years between the groups randomly assigned to vitamin D supplementation and to placebo.
The findings, published online Jan. 4, 2022, in the American Journal of Clinical Nutrition, may be influenced by the fact that most participants had sufficient vitamin D levels at baseline, and thus received higher than recommended doses of vitamin D during the study.
“Vitamin D3 supplementation with 1600 or 3200 IU/day for 5 years did not reduce the incidence of major CVD events, any invasive cancer, or mortality among generally healthy and mostly vitamin D sufficient older adults in Finland,” write the authors, led by Jyrki Virtanen, RD, PhD, associate professor of nutrition and public health at University of Eastern Finland, Kuopio.
“The low number of subjects with low vitamin D concentrations was a bit of a surprise for us also, but it likely reflects the quite successful food fortification policy in Finland,” Dr. Virtanen told this news organization.
Prior research has found that vitamin D insufficiency is associated with a higher risk of nearly all diseases. Although the evidence on the benefits of vitamin D supplementation remains more limited, a meta-analysis reported a consistent and significant 13% reduction in cancer mortality in those who received vitamin D supplements.
In this study, Dr. Virtanen and colleagues investigated the effects of vitamin D3 supplementation on cancer and CVD incidence in a cohort of 2,495 healthy participants.
Men 60 years or older and women 65 years or older were randomly assigned to one of three groups: placebo, 40 mcg (1,600 IU) of daily vitamin D3, or 80 mcg (3,200 IU) of daily vitamin D3.
Data collected at baseline and throughout the trial included serum 25(OH)D concentrations, nutrition, sun exposure, medication use, mental health, and other factors that could affect the risk of disease.
The study’s primary endpoints were incident of major CVD and invasive cancer. Secondary endpoints included incidence of myocardial infarction, stroke, and CVD mortality as well as site-specific cancers and cancer death.
Follow-up occurred via annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person evaluations. In the sub-cohort, mean serum 25(OH)D concentration was 75 nmol/L (30 ng/mL) at baseline; 9.1% had concentrations less than 50 nmol/L (20 ng/mL) and 50.0% had concentrations of at least 75 nmol/L (30 ng/mL).
The authors identified no major differences between the three arms at baseline, but noted that, compared with the overall study population, those in the subcohort were younger, more likely to use their own vitamin D supplements, and more likely to rate their health as good or excellent.
Among 503 participants that had complete data from baseline, the mean increase in serum 25(OH)D in participants receiving 1,600 IU/day vitamin D3 was 23.4 nmol/L (9.4 ng/mL) and 43.6 nmol/L (17.4 ng/mL) in the arm receiving 3,200 IU/day between baseline and 6 months. The authors observed a small additional increase in levels between the 6-month and 12-month visits, but few changes in vitamin D3 levels in the placebo arm.
At the 5-year follow-up, major CVD events occurred in 4.9% of participants in the placebo arm, 5% in those in the 1,600 IU/d arm (hazard ratio, 0.97), and 4.3% of those in the 3,200 IU/d arm (HR, 0.84; P = .44). Invasive cancer at follow-up was diagnosed in 4.9% of placebo recipients, 5.8% of those on 1,600 IU/d supplementation (HR, 1.14; P = .55), and 4.8% in the 3,200 IU/d group (HR, 0.95; P = .81). No significant differences were observed in the secondary endpoints or in total mortality.
The authors did not conduct a subanalysis in participants who had low 25(OH)D concentrations levels at baseline because “there were too few participants to do any meaningful analyses,” said Dr. Virtanen, who noted that blood samples were available for a representative subgroup of 550 subjects, and only 9% of them had low 25(OH)D concentrations at baseline.
Dr. Virtanen noted that future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status.
The study was supported by funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation. Dr. Virtanen disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new randomized controlled study.
In the cohort of nearly 2,500 healthy individuals, the researchers found no differences in cancer or CVD incidence over 5 years between the groups randomly assigned to vitamin D supplementation and to placebo.
The findings, published online Jan. 4, 2022, in the American Journal of Clinical Nutrition, may be influenced by the fact that most participants had sufficient vitamin D levels at baseline, and thus received higher than recommended doses of vitamin D during the study.
“Vitamin D3 supplementation with 1600 or 3200 IU/day for 5 years did not reduce the incidence of major CVD events, any invasive cancer, or mortality among generally healthy and mostly vitamin D sufficient older adults in Finland,” write the authors, led by Jyrki Virtanen, RD, PhD, associate professor of nutrition and public health at University of Eastern Finland, Kuopio.
“The low number of subjects with low vitamin D concentrations was a bit of a surprise for us also, but it likely reflects the quite successful food fortification policy in Finland,” Dr. Virtanen told this news organization.
Prior research has found that vitamin D insufficiency is associated with a higher risk of nearly all diseases. Although the evidence on the benefits of vitamin D supplementation remains more limited, a meta-analysis reported a consistent and significant 13% reduction in cancer mortality in those who received vitamin D supplements.
In this study, Dr. Virtanen and colleagues investigated the effects of vitamin D3 supplementation on cancer and CVD incidence in a cohort of 2,495 healthy participants.
Men 60 years or older and women 65 years or older were randomly assigned to one of three groups: placebo, 40 mcg (1,600 IU) of daily vitamin D3, or 80 mcg (3,200 IU) of daily vitamin D3.
Data collected at baseline and throughout the trial included serum 25(OH)D concentrations, nutrition, sun exposure, medication use, mental health, and other factors that could affect the risk of disease.
The study’s primary endpoints were incident of major CVD and invasive cancer. Secondary endpoints included incidence of myocardial infarction, stroke, and CVD mortality as well as site-specific cancers and cancer death.
Follow-up occurred via annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person evaluations. In the sub-cohort, mean serum 25(OH)D concentration was 75 nmol/L (30 ng/mL) at baseline; 9.1% had concentrations less than 50 nmol/L (20 ng/mL) and 50.0% had concentrations of at least 75 nmol/L (30 ng/mL).
The authors identified no major differences between the three arms at baseline, but noted that, compared with the overall study population, those in the subcohort were younger, more likely to use their own vitamin D supplements, and more likely to rate their health as good or excellent.
Among 503 participants that had complete data from baseline, the mean increase in serum 25(OH)D in participants receiving 1,600 IU/day vitamin D3 was 23.4 nmol/L (9.4 ng/mL) and 43.6 nmol/L (17.4 ng/mL) in the arm receiving 3,200 IU/day between baseline and 6 months. The authors observed a small additional increase in levels between the 6-month and 12-month visits, but few changes in vitamin D3 levels in the placebo arm.
At the 5-year follow-up, major CVD events occurred in 4.9% of participants in the placebo arm, 5% in those in the 1,600 IU/d arm (hazard ratio, 0.97), and 4.3% of those in the 3,200 IU/d arm (HR, 0.84; P = .44). Invasive cancer at follow-up was diagnosed in 4.9% of placebo recipients, 5.8% of those on 1,600 IU/d supplementation (HR, 1.14; P = .55), and 4.8% in the 3,200 IU/d group (HR, 0.95; P = .81). No significant differences were observed in the secondary endpoints or in total mortality.
The authors did not conduct a subanalysis in participants who had low 25(OH)D concentrations levels at baseline because “there were too few participants to do any meaningful analyses,” said Dr. Virtanen, who noted that blood samples were available for a representative subgroup of 550 subjects, and only 9% of them had low 25(OH)D concentrations at baseline.
Dr. Virtanen noted that future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status.
The study was supported by funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation. Dr. Virtanen disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
according to a new randomized controlled study.
In the cohort of nearly 2,500 healthy individuals, the researchers found no differences in cancer or CVD incidence over 5 years between the groups randomly assigned to vitamin D supplementation and to placebo.
The findings, published online Jan. 4, 2022, in the American Journal of Clinical Nutrition, may be influenced by the fact that most participants had sufficient vitamin D levels at baseline, and thus received higher than recommended doses of vitamin D during the study.
“Vitamin D3 supplementation with 1600 or 3200 IU/day for 5 years did not reduce the incidence of major CVD events, any invasive cancer, or mortality among generally healthy and mostly vitamin D sufficient older adults in Finland,” write the authors, led by Jyrki Virtanen, RD, PhD, associate professor of nutrition and public health at University of Eastern Finland, Kuopio.
“The low number of subjects with low vitamin D concentrations was a bit of a surprise for us also, but it likely reflects the quite successful food fortification policy in Finland,” Dr. Virtanen told this news organization.
Prior research has found that vitamin D insufficiency is associated with a higher risk of nearly all diseases. Although the evidence on the benefits of vitamin D supplementation remains more limited, a meta-analysis reported a consistent and significant 13% reduction in cancer mortality in those who received vitamin D supplements.
In this study, Dr. Virtanen and colleagues investigated the effects of vitamin D3 supplementation on cancer and CVD incidence in a cohort of 2,495 healthy participants.
Men 60 years or older and women 65 years or older were randomly assigned to one of three groups: placebo, 40 mcg (1,600 IU) of daily vitamin D3, or 80 mcg (3,200 IU) of daily vitamin D3.
Data collected at baseline and throughout the trial included serum 25(OH)D concentrations, nutrition, sun exposure, medication use, mental health, and other factors that could affect the risk of disease.
The study’s primary endpoints were incident of major CVD and invasive cancer. Secondary endpoints included incidence of myocardial infarction, stroke, and CVD mortality as well as site-specific cancers and cancer death.
Follow-up occurred via annual study questionnaires and national registry data. A representative subcohort of 551 participants had more detailed in-person evaluations. In the sub-cohort, mean serum 25(OH)D concentration was 75 nmol/L (30 ng/mL) at baseline; 9.1% had concentrations less than 50 nmol/L (20 ng/mL) and 50.0% had concentrations of at least 75 nmol/L (30 ng/mL).
The authors identified no major differences between the three arms at baseline, but noted that, compared with the overall study population, those in the subcohort were younger, more likely to use their own vitamin D supplements, and more likely to rate their health as good or excellent.
Among 503 participants that had complete data from baseline, the mean increase in serum 25(OH)D in participants receiving 1,600 IU/day vitamin D3 was 23.4 nmol/L (9.4 ng/mL) and 43.6 nmol/L (17.4 ng/mL) in the arm receiving 3,200 IU/day between baseline and 6 months. The authors observed a small additional increase in levels between the 6-month and 12-month visits, but few changes in vitamin D3 levels in the placebo arm.
At the 5-year follow-up, major CVD events occurred in 4.9% of participants in the placebo arm, 5% in those in the 1,600 IU/d arm (hazard ratio, 0.97), and 4.3% of those in the 3,200 IU/d arm (HR, 0.84; P = .44). Invasive cancer at follow-up was diagnosed in 4.9% of placebo recipients, 5.8% of those on 1,600 IU/d supplementation (HR, 1.14; P = .55), and 4.8% in the 3,200 IU/d group (HR, 0.95; P = .81). No significant differences were observed in the secondary endpoints or in total mortality.
The authors did not conduct a subanalysis in participants who had low 25(OH)D concentrations levels at baseline because “there were too few participants to do any meaningful analyses,” said Dr. Virtanen, who noted that blood samples were available for a representative subgroup of 550 subjects, and only 9% of them had low 25(OH)D concentrations at baseline.
Dr. Virtanen noted that future vitamin D supplementation trials should focus on recruiting participants with low vitamin D status.
The study was supported by funding from the Academy of Finland, University of Eastern Finland, Juho Vainio Foundation, Medicinska Understödsföreningen Liv och Hälsa, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, and Finnish Cultural Foundation. Dr. Virtanen disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF CLINICAL NUTRITION
What if the National Guard Can’t Help?
What if the National Guard Can’t Help?
In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.
By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.
So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.
However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.
And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.
Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”
In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”
In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.
A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.
Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”
As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).
In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”
Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.
In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get.
In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.
By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.
So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.
However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.
And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.
Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”
In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”
In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.
A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.
Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”
As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).
In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”
Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.
In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get.
In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.
By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.
So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.
However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.
And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.
Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”
In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”
In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.
A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.
Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”
As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).
In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”
Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.
In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get.
What if the National Guard Can’t Help?
What if the National Guard Can’t Help?
COVID-19 vaccination has little impact on menstrual cycle
Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.
Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.
The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.
The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.
In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.
In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.
“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.
In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.
Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.
“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”
According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”
In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.
Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.
“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”
These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.
More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”
This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.
Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.
The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.
The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.
In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.
In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.
“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.
In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.
Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.
“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”
According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”
In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.
Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.
“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”
These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.
More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”
This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
Women may rest a bit easier thanks to results from a study showing that vaccination against the SARS-CoV-2 virus has almost no impact on a woman’s menstrual cycle. The issue is significant, as regular menstruation is a sign of health and fertility, and fears of disturbances might increase vaccination hesitancy as COVID-19 cases continue to surge.
Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University, Portland, led a group studying prospective data on almost 24,000 menstrual cycles reported by almost 4,000 U.S. women.
The investigators found that COVID-19 vaccination was associated with a less than 1-day change in cycle length for the menstrual cycles after the first and second inoculations, compared with prevaccine cycles. Vaccination had no effect on the actual number of days menstrual bleeding lasted.
The study looked at the menstrual patterns of women aged 18-45 years with normal cycle lengths of 24-38 days for the three consecutive cycles before the first vaccine dose and for three consecutive postvaccine cycles. The final sample included 2,403 vaccinated and 1,556 unvaccinated individuals.
In vaccinated women, the study initially found a slight average increase in cycle length after dose one of 71% of a day and 91% of a day after dose two. Following adjustments, those increases dropped to 64% of a day after the first dose and 79% of a day after the second dose.
In unvaccinated women, the study looked at six cycles over a similar time period and found no significant changes from baseline.
“Coronavirus disease 2019 vaccination is associated with a small change in cycle length but not menses length,” Dr. Edelman’s group concluded in Obstetrics and Gynecology.
In the rare instance that a woman received two vaccine doses within the same menstrual cycle, the change in length could increase to 2 days. These variations appear to resolve quickly, possibly as soon as the next cycle after vaccination and do not indicate any cause for long-term physical or reproductive health concern, according to the authors.
Reports by women on social media, however, have suggested that postvaccine menstrual disruptions are more common with, for example, heavier and breakthrough bleeding. But it appears such changes are temporary and resolve quickly.
“These findings are reassuring and validating,” Dr. Edelman said in an interview. On a population level, the changes indicate no cause for concern for long-term physical or reproductive health and no reason to avoid vaccination. “On a personal level, people want this information so they know what to expect when they get vaccinated, and not worry about a pregnancy scare or be disappointed if they were trying for pregnancy.”
According to the International Federation of Gynecologists and Obstetricians, variations in cycle length of fewer than 8 days are considered normal, said Christine Metz, PhD, a research biologist and a professor of molecular medicine at the Feinstein Institutes for Medical Research in Manhasset, N.Y. “Thus, the extra 17 hours added to the menstrual cycle length in the vaccination group in this study is well within the ‘normal’ range.”
In a group of about 1,600 menstruating women being studied at Dr. Metz’s center, some have anecdotally reported transient cycle changes post vaccination for COVID-19, including delays in menstruation onset and changes in bleeding patterns.
Exactly how vaccination might alter menstrual cycle length is not known and has not been studied with vaccination against other infections such as influenza and meningococcal disease.
“Many factors are known to affect menstrual cycle length including changes in diet, sleep, and exercise, as well as sickness, travel, and stress,” Dr. Metz said. The COVID-19 vaccines have affected people in different ways, with side effects ranging from injection-site pain to nausea, aches, fever, and fatigue. “Vaccination side effects, particularly if severe, could lead to changes in diet, exercise, and sleep, and feelings of sickness and/or stress.”
These stressors can alter hormone production and stability, as well as the body’s response to hormones such as estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and other hormones associated with female reproduction. “Because these hormones regulate the menstrual cycle, variations in these hormones can either shorten or lengthen the cycle,” Dr. Metz explained.
More research needs to be done at the global level, according to the authors. “Questions remain about other possible changes in menstrual cycles, such as menstrual symptoms, unscheduled bleeding, and changes in the quality and quantity of menstrual bleeding.”
This research was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health’s Office of Research on Women’s Health. Dr. Edelman reported support from the American College of Obstetrics and Gynecology, the World Health Organization, Gynuity, and the Karolinska Institute as well as royalties from UpToDate. Other study authors reported similar relationships with not-for-profit and private-sector companies. Three coauthors are employees of Natural Cycles, a fertility tracking device that was used in the study. Dr. Metz disclosed no conflicts of interest with regard to her comments.
FROM OBSTETRICS & GYNECOLOGY