In England, COVID-19 Transmission Risk Was Child's Play

 During the second wave of COVID-19 infections in England last year, households with children had higher risk of infection and hospitalization, but not death, versus households without children, a large population-based study found.

From September to December 2020, adults younger than 65 living with children ages 12-18 showed increased risk of SARS-CoV-2 infection (adjusted HR 1.22, 95% CI 1.20-1.24) and COVID-19 hospitalization (adjusted HR 1.26, 95% CI 1.12-1.40), with slightly smaller risks associated with children ages 0-11, reported Ben Goldacre, MBBS, of the University of Oxford, and colleagues.

However, adults with children did not have increased risk of infection, hospitalization, or death during the first wave of COVID-19 from February to August 2020, the authors wrote in their study online in The BMJ.

During that first wave, schools were largely closed, but they were open in England throughout the fall. As well, the more transmissible U.K. variant, B.1.1.7, was first detected in September, according to media reports. Early evidence indicated this variant was responsible for a larger share of cases among kids under 20 than the original virus.

Goldacre's group analyzed data from the OpenSAFELY study, a population-based cohort study on behalf of NHS England, including primary care data and linked hospital and ICU admissions and death records during wave 1 (February-August) and wave 2 (September-December) last year.

The cohort included about 9.3 million adults ages 65 and younger and about 2.7 million adults older than 65. About 63% of the cohort did not live with children, 20% lived with only children ages 0-11, and 10% lived with only children ages 12-18. Among adults older than 65, there were 97% who did not live with children.

Interestingly, for adults older than 65 living with children, there was an increased risk of infection tied to living with children, and an increased risk of ICU admission and death for those living with children ages 0-11 and 12-18.

For adults younger than 65, living with children ages 0-11 was tied to a reduced risk of COVID-19 death during both waves, but during wave 2, the authors found "no increase in risk of death for those living with older children."

Living with children was also not associated with increased risk of ICU admission in this population.

Limitations to the data, the researchers said, included lack of generalizability to the overall British population (or others elsewhere), and that the study could not examine the direct association between children and adults within a household testing positive for the virus, "as a substantial proportion of infections in this age group will be asymptomatic or undiagnosed."

"Data from population-based studies show that the reopening of schools was temporally associated with progressively increasing prevalence of SARS-CoV-2 among children of all ages," the researchers wrote, adding that there is a possibility that "widespread school attendance may have led to increased risks in households."

Disclosures

The study was supported by the Medical Research Council, the Wellcome Trust, the NIHR Oxford Biomedical Research Centre, the NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn Westlake Foundation, NHS England, and the Health Foundation.

Goldacre disclosed support from the Laura and John Arnold Foundation, the Wellcome Trust, the NIHR Oxford Biomedical Research Centre, the NHS National Institute for Health Research School of Primary Care Research, the Mohn Westlake Foundation, Health Data Research UK, the Good Thinking Foundation, the Health Foundation, and the World Health Organization, as well as support from speaking and writing for lay audiences on the misuse of science.

Other co-authors disclosed support from Wellcome, MRC, NIHR, UKRI, British Council, GSK, British Heart Foundation, Diabetes UK, and GSK.

Primary Source

The BMJ

Source Reference: Forbes H, et al "Association between living with children and outcomes from covid-19: OpenSAFELY cohort study of 12 million adults in England" BMJ 2021; DOI: 10.1136/bmj.n628.

https://www.medpagetoday.com/infectiousdisease/covid19/91703

Rheumatic/Musculoskeletal Diseases And COVID Vaccines

 The American College of Rheumatology (ACR) has issued a guidance document about COVID-19 vaccinations for patients with rheumatic and musculoskeletal diseases (RMDs). Included is information on general concerns and foundational principles, timing of vaccination, and adaptations to therapy.

ACR cautioned, however, that the recommendations are still conditional and are based on indirect evidence derived from experience with other vaccines.

The document differs from ACR's formal guidelines, which typically take a year or more to develop, explained Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and colleagues.

"The ACR develops 'guidance' documents when the components needed to develop a formal guideline are not present, e.g., if the need to provide guidance is more urgent than a longer guidelines timeline would allow, there is not enough peer-reviewed evidence available to conduct a formal literature review, or when there is very limited expertise and experience ... to help inform the development of recommendations," the authors wrote online in Arthritis & Rheumatology.

To create the document, a task force consisting of nine rheumatologists, two infectious disease specialists, and two public health physicians was established to provide accelerated guidance to both clinicians and patients. The information will be updated as the pandemic situation evolves, and should be considered a "living document," Curtis and co-authors said.

General Considerations

This first guidance statement asserted that rheumatologists are responsible for discussing COVID-19 vaccination with their patients in a shared decision-making process.

In addition, decisions should be individualized, reflecting the variability among patients with regard to disease severity, comorbidities, and treatments. Given the limited vaccine availability and competing concerns for individual and societal needs, "simplicity should be the touchstone: to avoid confusion, improve implementation, and maintain scientific credibility," the authors advised.

Additional general considerations were that patients with autoimmune and inflammatory rheumatic diseases are at increased risk for viral infections in general, have a greater likelihood to require hospitalization with COVID-19, and generally have worse outcomes than the general population. Therefore, patients with these underlying diseases should be prioritized for vaccination, the authors advised.

However, the panel emphasized the wide range of disease severity, noting that a patient with rheumatoid arthritis whose disease is controlled with hydroxychloroquine is likely to be at far less risk than someone with severe vasculitis being treated with intravenous cyclophosphamide or rituximab (Rituxan).

Accordingly, vaccination should take place when the underlying disease is well controlled, if possible, but there is a theoretical risk for disease flare or worsening after vaccination.

Another concern was the uncertain future landscape of COVID-19 regarding long-term vaccine safety and efficacy and emerging viral strains.

Finally, the task force acknowledged that much of the evidence for the safety and efficacy of the COVID vaccine was extrapolated from studies of other vaccines, and that the response for patients receiving immunomodulatory drugs "was likely to be blunted, albeit with uncertain diminution in either the magnitude or duration of response compared to the general population."

Medication Concerns

Although recognizing that there was little evidence to guide the timing of vaccination, the panel recommended that vaccination not be deferred because of disease severity or activity, with the exception of patients experiencing life-threatening illness requiring treatment in the intensive care unit.

The panel stated that there was no preference for one vaccine over another, and that patients should receive whatever was most easily available.

Strong consensus (i.e., agreement by all panel members) was seen for the statement that there was no need to delay vaccination for patients receiving hydroxychloroquine, sulfasalazine, leflunomide, apremilast (Otezla), or intravenous immune globulin.

A similar, though moderate consensus, existed for the majority of other immunomodulators, with the exception of rituximab. Patients receiving rituximab should schedule their vaccination to be initiated 4 weeks before their next scheduled rituximab dose. This recommendation derived from a study showing differences in response to influenza vaccination depending on timing of the rituximab dose, the authors explained.

As to the timing of immunomodulatory treatment in relation to vaccination, the panel recommended that methotrexate be withheld for a week after each dose of the vaccine -- a recommendation that was based on studies of pneumococcal and influenza vaccines. A similar recommendation was made for JAK inhibitors, "based on concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response," the authors explained.

hey also recommended that abatacept (Orencia) be withheld for a week before and after the first dose of the vaccine only. This recommendation was based on data suggesting a possible negative effect of this drug on the immunogenicity of the vaccine, and also because "the first vaccine dose primes naive T cells, naive T cell priming is inhibited by CTLA4, and abatacept is a CTLA4-Ig construct," the panelists explained.

For intravenous cyclophosphamide, which is generally given at intervals of 2 or 4 weeks, the recommendation was to arrange for the cyclophosphamide dosing to be given a week after the vaccine doses, if possible.

Rituximab administration was recommended to take place 2 to 4 weeks after the second vaccine dose if feasible, but only if the disease is sufficiently controlled to permit such a delay. However, this recommendation was based on immune responses to other vaccines, which may not be fully generalizable to the COVID vaccine "especially since the degree to which efficacy is attributable to induction of host T cell vs B cell (antibody-based) immunity is uncertain at this time," Curtis and co-authors cautioned.

Research Agenda

They also set forth a series of goals to be addressed as additional experience and data accrue -- for example, calling for more information about the risks of flare and vaccine reactogenicity among RMD patients, and for data on long-term safety and durability, particularly in the context of immunomodulatory therapy and the emergence of new viral strains.

The team also recommended that a biorepository be established to coordinate vaccine-related research, "considering the future potential to identify lab-based correlates of protection relevant for individual patients."

The document also suggested that serologic tests be developed that could detect inadequate responses to the vaccine among patients who might benefit from additional booster doses, and that vaccine hesitancy be addressed for at-risk RMD patients, particularly those belonging to vulnerable and underserved populations.

Disclosures

The authors reported financial relationships with the National Institutes of Health, the U.S. Department of Defense, AbbVie, Amgen, Janssen, Bristol Myers Squibb, Genentech, Gilead, GlaxoSmithKline, Eli Lilly, Myriad, Pfizer, Sanofi, Bayer, Boehringer Ingelheim, Corbus, Horizon, the Alliance for Academic Internal Medicine, the Rheumatology Research Foundation, the Arthritis Foundation, the Lupus Foundation of America, and the Permanente Medical Group.

Primary Source

Arthritis & Rheumatology

Source Reference: Curtis J, et al "American College of Rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases -- version 1" Arthritis Rheum 2021; doi:10.1002/art.41734.

https://www.medpagetoday.com/rheumatology/generalrheumatology/91721

FDA official: US AstraZeneca stockpile not in danger of expiring

 The U.S. stockpile of tens of millions of unused AstraZeneca vaccines is not in danger of expiring, a top administration health official said Wednesday.

"I do not believe we are at risk of throwing this out at any time in the near future,” Peter Marks, the director of the Food and Drug Administration's vaccine center, told a House panel.

The vaccine has been authorized for emergency use in the European Union and many countries around the world, but the company has not yet applied for authorization in the U.S.

The federal government preordered 300 million doses of the vaccine under the Trump administration, but issues with clinical trials have held up its authorization and the FDA is still waiting on additional data.

Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, told the House Energy and Commerce oversight subcommittee that AstraZeneca's U.S. clinical trial will be available “within a reasonable period,” likely early next month.

Still, the U.S. has tens of millions of unused doses of the vaccine in storage. Officials have said the stockpile is intended to make it easier to quickly distribute the vaccine across the country if the company receives FDA clearance in the coming weeks.

Other countries, including Mexico, have pressed the Biden administration to share doses, as has AstraZeneca.

But the White House said the U.S. has rejected all requests from other countries to share doses of its vaccines, and won't consider sharing until everyone in the country has been vaccinated.

Experts and global health advocates think the U.S. has the ability to donate vaccines to other countries without significantly impacting their availability to Americans, but has been unwilling to make such a plan.

In the U.S., demand for vaccines still outpaces supply, but that is expected to change in the coming weeks. States are opening up eligibility, and President Biden said he expects there will be enough supply for every American who wants a vaccine by the end of May.

https://thehill.com/policy/healthcare/543661-fda-official-us-astrazeneca-stockpile-not-in-danger-of-expiring

Lilly Covid-19 drug no longer distributed in 3 states due to variant

 The US government is no longer distributing Eli Lilly’s bamlanivimab into California, Arizona and Nevada because of the prevalence of a viral variant that is not susceptible to the monoclonal antibody, FDA acting commissioner Janet Woodcock told physicians taking part in a webinar with the American Medical Association on Wednesday.

Woodcock did not elaborate further on the variant or the decision to halt the distribution, but overall, the FDA remains uniquely positioned to screen the monoclonals against the different variants, Woodcock added, and that’s been predictive of how and where the treatments will work.

A Lilly spokesperson told Endpoints News in a statement: “We recognize the U.S. government has made the decision to no longer allow direct ordering of bamlanivimab alone in California, Arizona and Nevada due to concerns about the prevalence of the ‘California’ variant, with the specific L452R substitution found in B.1.429/B.1.427 lineages (a.k.a. 20C/CAL.20C). Importantly, preclinical data from our labs demonstrate that the combination of bamlanivimab and etesevimab maintains its neutralizing effect against this variant, specifically.”

Overall, Woodcock acknowledged that the initial rollout of the monoclonal antibodies “wasn’t the greatest” because it was centered on a distribution model for Gilead’s antiviral remdesivir, and “hospitals were in no position to give out monoclonals.”

“We’re getting there but it’s taken quite a long time,” Woodcock said in reference to the monoclonal antibodies in the US. “Mass vaccination is hard enough but mass infusion is a real challenge for our health care system.”

John Farley, director of the FDA’s office of infectious diseases, said that the FDA expects to soon broaden the definition of who falls into the “high risk” category that determines who can receive the monoclonal antibodies.

“We know from the field that we would benefit by broadening this a bit and we’re expecting to do that soon,” he said.

He also said that the three authorized monoclonal antibodies remain active against the variant originating in the UK, but there are “other, more worrisome variants” and physicians should expect to soon see more information on those.

As far as the wider therapeutic landscape for Covid-19, Woodcock again noted the fact that just 5% of clinical trials for Covid-19 treatments were adequately powered and randomized to provide actionable data.

“Low accrual rates and inadequate power mean that safety and efficacy data will be uninterpretable,” she said. She also criticized the slow rollout of the NIH-run trials for Covid-19 therapeutics.

Overall, she explained some of the major challenges that she saw as head of therapeutics at Operation Warp Speed, and moving forward, she discussed what a robust ecosystem for clinical trials in the US would look like.

https://endpts.com/lillys-covid-19-drug-bamlanivimab-is-no-longer-distributed-in-3-states-because-of-a-variant/

Cancer Patients Respond Poorly to First COVID mRNA Vax Dose

 Barely one-quarter of patients with cancer obtained protection against COVID-19 after one dose of the Pfizer/BioNTech vaccine, a prospective study showed.

The data found a "strikingly low" 28% immune efficacy rate in patients with cancer, including 13% in patients with blood cancers. In contrast, first-dose seroconversion occurred in 97% of a healthy control group, Adrian Hayday, PhD, of King's College London, and co-authors concluded in a report posted to the preprint server medRxiv.

A second dose at day 21, however, brought adequate immunity to nearly all the cancer patients, they said.

"These data support prioritization of cancer patients for an early (21-day) second dose of the BNT162b2 vaccine," Hayday and colleagues wrote in the preprint. "Given the globally poor responses to vaccination in patients with hematological cancers, post-vaccination serological testing, creation of herd immunity around these patients using a strategy of 'ring vaccination,' and careful follow-up should be prioritized."

"Delayed boosting potentially leaves most solid and hematological cancer patients wholly or partially unprotected, with implications for their own health, their environment, and the evolution of variant-of-concern strains," the researchers added. "Prompt boosting of solid cancer patients quickly overcomes the poor efficacy of the primary inoculum in solid cancer patients."

In general, patients with cancer have been excluded from clinical trials of COVID-19 vaccines, following evidence of sustained immune dysregulation, inefficient seroconversion, and prolonged viral shedding after COVID-19 infection. The exclusion has raised questions about the vaccines' safety and efficacy in patients with cancer, Hayday and co-authors noted.

Moreover, British health officials changed the interval between the first and second dose to 12 weeks to maximize population coverage. Whether that interval is appropriate for patients with cancer, however, particularly those on systemic anti-cancer therapy, remains unclear, the authors continued.

To examine the issue, they prospectively studied 151 patients with cancer (solid tumors and hematologic malignancies) and 54 healthy individuals (mostly healthcare workers) who received an initial dose of the Pfizer/BioNTech vaccine against COVID-19. Blood samples were obtained from all study participants at baseline and at 3 and 5 weeks after vaccination.

In keeping with the British policies for COVID vaccination, participants vaccinated from Dec. 8 to 29 received two doses of vaccine, 30 days apart. Participants vaccinated after that received the initial dose and remained in follow-up to the planned booster dose 12 weeks later.

The primary endpoint was humoral and cellular immune response in the patients following the first vaccine injection. Immune efficacy was defined by antiviral IgG titers 21 days after the initial (priming) vaccine dose. The secondary endpoint was vaccine safety.

The patients with cancer had a median age of 73, and two thirds had one or more comorbid conditions. Solid malignancies accounted for 63% of the patient population and hematologic malignancies for 37%.

Most of the patients with solid tumors had late-stage disease associated with a cancer diagnosis exceeding 24 months. The healthy control group consisted of vaccine-eligible individuals who were not age-matched to the patients.

Among evaluable cancer patients, 31 received both vaccine doses and 118 received only the first dose. In the control group, 16 participants received both vaccine doses and the rest received only the priming dose.

To account for possible immune stimulation by past or concurrent infection, the researchers asked the patients with cancer to provide nose and throat swabs every 10 days. Because of the emergence of the B.1.1.7 variant and the national lockdown that started Jan. 4, only 79 patients were able to participate in screening for the entire study period, and only 12 had more than one swab test.

During the first 21 days after the priming dose, six patients developed COVID-19, including two patients who developed severe disease and died. No patient tested positive for the coronavirus after 21 days.

At 21 days post-priming dose, immune efficacy was poor, as antibody seroconversion had occurred in 39% of patients with solid tumors and 13% of those with hematologic malignancies.

"In sum, a priming inoculum ... induced seroconversion in the great majority of healthy controls but failed to achieve this in most solid and hematological cancer patients, with efficacy in the hematological cancer cohort being significantly worse than in solid cancer patients," the investigators wrote. "Moreover, not all seroconverted cancer patients showed virus neutralization."

Nonresponse correlated with reduced numbers of B cells in patients with solid or hematologic malignancies, the team added.

In a subgroup of patients with immune results after the priming and booster vaccine doses, all 12 patients in the control group achieved immune response after the booster dose, as did 18 of 19 patients with solid tumors, including eight patients who did not seroconvert after the priming dose. In contrast, nine of 21 patients without a booster dose had seroconverted.

Too few patients with hematologic malignancies were eligible for a booster dose to draw conclusions about the effects of the second dose.

With regard to safety, more than half the patients with cancer reported no toxicity after the first vaccine dose, as compared with 37.5% of the control group, the researchers reported. Among study participants evaluable after the booster dose, 71% of cancer patients and 31.25% of the control group reported no toxic effects. Additionally, 6.8% of the patients versus 50% of the control group reported both local and systemic effects after the booster dose.

Disclosures

Funding for the study came from multiple governmental, academic, and nonprofit organizations.

The authors reported having no relevant relationships with industry.

Primary Source

medRxiv

Source Reference: Monin-Aldama L, et al "Interim results of the safety and immune efficacy of one versus two doses of COVID-19 vaccine BNT162b2 for cancer patients in the context of the UK vaccine priority guidelines" medRxiv 2021; DOI: 10.1101/2021.03.17.21253131.

https://www.medpagetoday.com/infectiousdisease/covid19/91726

New theories on whether AstraZeneca shot linked to blood clots probed

 Scientists are exploring several possibilities that might explain at least 18 reports of extremely rare blood clots in the brain that occurred in individuals in the days and weeks after receiving the AstraZeneca COVID-19 vaccine.

European investigators have put forward one theory that the vaccine triggers an unusual antibody in some rare cases; others are trying to understand whether the cases are linked with birth control pills.

But many scientists say there is no definitive evidence and it is not clear whether or why AstraZeneca’s vaccine would cause an issue not shared by other vaccines that target a similar part of the coronavirus.

Most of the rare blood clots have been seen in women and most cases have been reported in Europe. Two cases have been reported in India.

The European Medicines Agency said a preliminary review suggests the vaccine is not associated with an increase in the overall risk of blood clots. But it did not rule out an association with rare cases of blood clots in vessels draining the blood from the brain known as cerebral venous sinus thrombosis (CVST).

Researchers in Germany and Norway, where some of the cases have been reported, this week hypothesized that the vaccine could be triggering an immune response in which the body produces antibodies that could result in blood clots.

Professor Paal Andre Holme of Norway’s Oslo University Hospital, which treated three healthcare workers with severe blood clots after they received the AstraZeneca vaccine, told a news conference on Thursday that “we’ve made discoveries” that could “explain the clinical progression of our patients.”

Holme warned that the findings were preliminary. “This is only the beginning of all the research that is being done,” he said. He did not release any data supporting his hypothesis.

A team of German researchers at Greifswald University Clinic on Friday said they came to a similar conclusion. If proven correct, there may be a way to treat the condition, the scientists said.

EMA researchers on Thursday said they are undertaking several investigations to determine whether the rare blood clots might be linked with the vaccine, or occurring by chance. They noted that many of the events occurred in younger women.

CVST, though rare, has been associated with pregnancy and the use of oral contraceptives. “That’s one of the things that we will be further investigating in the near future,” said Sabine Straus, chair of EMA’s safety committee.

EMA also intends to investigate whether those who developed the condition had been infected previously or at the time of the vaccine with COVID-19, which can cause blood clots.

Several U.S. vaccine experts remain cautious about the antibody hypothesis and said the high level of publicity of the events could be causing more clinicians to report the condition than normal, which would make it appear that the events are related to the vaccine.

AstraZeneca’s vaccine has received emergency use authorization in 70 countries, but it has not yet been approved in the United States.

The U.S. experts also question why such events would occur only at increased rates with the AstraZeneca vaccine and not the vaccines by Pfizer Inc and BioNTech SE, Moderna Inc, Johnson & Johnson and Russia’s Sputnik V vaccine - all of which are intended to produce antibodies aimed at the “spike” portion of the coronavirus that it uses to enter cells.

Like the J&J and the Sputnik vaccine, AstraZeneca’s uses a non-replicating cold virus known as an adenovirus to deliver spike proteins into cells and produce an immune response.

“We’ll have to see when (German and Norwegian scientists) submit a peer-reviewed publication and the scientific community can review it,” said Dr. Peter Hotez, a vaccine researcher at Baylor College of Medicine in Houston. “There’s no reason why the AstraZeneca vaccine would do this whereas the others, including the adenovirus-based COVID-19 vaccines, wouldn’t.”

https://www.reuters.com/article/us-health-coronavirus-vaccine/scientists-probe-new-theories-on-whether-astrazeneca-shot-linked-to-blood-clots-idUSKBN2BC01M

Progesterone therapy may improve COVID-19 outcomes for men

 COVID-19 disproportionately affects men compared with women, raising the possibility that a hormone like progesterone may improve clinical outcomes for certain hospitalized men with the disease. New research from Cedars-Sinai published online in the journal Chest supports this hypothesis.

The pilot clinical trial, involving 40 men, is believed to be the first published study to use progesterone to treat male COVID-19 patients whose lung functions have been compromised by the coronavirus. While the findings are promising, larger clinical trials are needed to establish the potential of this experimental therapy, the investigators said.

The study was prompted by multiple reports that men are at higher risk of mortality and severe illness from COVID-19 than are women, according to Sara Ghandehari, MD, director of Pulmonary Rehabilitation in the Women's Guild Lung Institute at Cedars-Sinai and principal investigator for the trial.

"As an ICU doctor, I was struck by the gender disparity among COVID-19 patients who were very sick, remained in the hospital and needed ventilators," she said. In addition, some published research had indicated that premenopausal women, who generally have higher progesterone levels, had less severe COVID-19 disease than did postmenopausal women, who have lower progesterone levels. While the bodies of both men and women naturally produce progesterone, women produce much more of the hormone during their reproductive years.

Protective effect from female hormones

Ghandehari hypothesized that the gender differences in disease outcomes might be due, in part, to a protective effect from female hormones. In particular, preclinical studies elsewhere had pointed to progesterone as having certain anti-inflammatory properties. This finding suggested progesterone might be useful in dampening a sometimes-fatal immune response, known as a "cytokine storm," that can worsen lung damage and attack other organs in COVID-19 patients.

For the Cedars-Sinai clinical trial, conducted from April through August 2020, 40 male patients who were hospitalized with moderate to severe COVID-19 were randomly assigned to one of two groups. Patients in the control group received the standard medical care at the time for the disease. Patients in the experimental group received standard care plus twice-daily injections of 100 milligrams of progesterone for five days while they were hospitalized. Both groups were assessed daily for 15 days or until they were discharged from the hospital.

The study showed that, compared with the control group, patients in the group treated with progesterone scored a median 1.5 points higher on a standard seven-point scale of clinical status after seven days. The scale ranged from a high of 7 ("not hospitalized, no limitations on activities") to 1 ("death"). Although the progesterone group overall also had fewer days of hospitalization and a lower need for supplemental oxygen and mechanical ventilation, the differences between the two groups in those specific categories were not statistically significant.

There were no serious adverse events, including life-threatening events, attributable to progesterone administration. There were two deaths, one in each group, during the15-day study period, neither of which was attributable to progesterone.

"While our findings are encouraging for the potential of using progesterone to treat men with COVID-19, our study had significant limitations," Ghandehari said.

She noted the sample size was relatively small and involved mainly white, Hispanic and obese patients with a moderate burden of comorbidities, which increase the risk for worse outcomes. Further, although the clinical trial was randomized and controlled, it was unblinded—meaning that the investigators, the patients and the treating physicians knew who received the experimental treatment.

"Further research is necessary in larger, more heterogeneous populations, including postmenopausal women and at other treatment centers, to establish the degree of clinical efficacy and to assess any other potential safety concerns of this treatment approach," said Ghandehari, who also is assistant director of the Lung Transplant Program at Cedars-Sinai.

Progesterone is approved by the U.S. Food and Drug Administration (FDA) for use in fertility-related conditions in women but not for the modulation of immunologic-based, inflammatory responses. The FDA allowed this special use for the purpose of the Cedars-Sinai clinical trial under an investigational new drug application.

In addition to multiple Cedars-Sinai investigators, this study involved Donald Stein, Ph.D., from Emory University in Atlanta, and Heli Ghandehari, an independent biostatistical consultant from San Diego.

More information: Sara Ghandehari et al, Progesterone in Addition to Standard of Care Versus Standard of Care Alone in the Treatment of Men Hospitalized with Moderate to Severe COVID-19: A Randomized, Controlled Pilot Trial, Chest (2021). DOI: 10.1016/j.chest.2021.02.024

https://medicalxpress.com/news/2021-03-progesterone-therapy-covid-outcomes-men.html