News Scan for Oct 19, 2020

Pre-exposure hydroxychloroquine fail
COVID-19 in nursing homes
Gender differences in COVID-19 reactions

Trial finds no significant COVID effect of pre-exposure hydroxychloroquine

A randomized, controlled clinical trial involving high-risk healthcare workers found that pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce COVID-19 compared with placebo, researchers reported late last week in Clinical Infectious Diseases.

The randomized, double-blind trial, led by researchers with the University of Minnesota, enrolled 1,483 healthcare workers in the United States and Manitoba from Apr 6 to May 26. Participants were assigned in a 2:2:1:1 ratio to receive 400 milligrams of hydroxychloroquine once weekly or twice weekly for 12 weeks or placebo prescribed in a matched fashion. High-risk healthcare workers were defined as working in an emergency department or intensive care unit, on a dedicated COVID-19 ward, or as a first responder. Overall, 79% of the healthcare workers reported performing aerosol-generating procedures.

The primary outcome was COVID-19–free survival time by laboratory-confirmed or probable compatible illness. A prespecified subgroup analysis was conducted to investigate whether hydroxychloroquine drug concentrations correlated with COVID-19 protection.

Overall, confirmed or probable COVID-19–compatible illness occurred in 29 participants (5.9%) receiving once-weekly hydroxychloroquine, 29 (5.9%) receiving twice-weekly hydroxychloroquine, and 39 (7.9%) receiving placebo. The corresponding incidence of COVID-19 or compatible illness was 0.27 and 0.28 events per person-year for those taking hydroxychloroquine once or twice weekly, compared with 0.38 events per person-year for those who received placebo. Compared to placebo, the hazard ratios were for COVID-19 or compatible illness were 0.72 (95% confidence interval [CI]; 0.44 to 1.16; P = 0.18) with once-weekly and 0.74 (95% CI, 0.46 to 1.19; P = 0.22) with twice-weekly hydroxychloroquine, respectively.

Hydroxychloroquine blood concentrations did not differ between participants who developed COVID-19–compatible illness and those who did not.

The authors note that enrollment in the study ended prematurely, after a severe decline that followed several studies that highlighted hydroxychloroquine safety concerns, and a subsequent warning from the Food and Drug Administration. As a result, the study was underpowered. In addition, the doses of hydroxychloroquine may have been insufficient, they said.

"There was no statistically significant reduction in the incidence of COVID-19 in our study," the authors wrote. "However, investigation into more frequent dosing may be warranted."
Oct 17 Clin Infect Dis abstract


Study finds high rates of asymptomatic infection in nursing facilities

A large, multistate study of SARS-CoV-2 infection in skilled nursing facilities (SNFs) in JAMA Internal Medicine today finds high asymptomatic and presymptomatic infection, underscoring the importance of universal testing to identify and isolate cases. The study also identified more asymptomatic and presymptomatic cases in areas with high rates of local community infection, pointing to SNF location as a predictor of outbreaks.  

Previous studies in the general population suggest that an estimated 40% to 45% of COVID-19 infections are asymptomatic at the time of testing. There is little data on prevalence in nursing facility settings, but some reports point to higher asymptomatic rates in SNFs.

The study authors used electronic medical record data and daily infection logs from a multistate long-term care provider with around 350 SNFs to identify polymerase chain reaction–confirmed cases from Mar 16 to Jul 15. Residents were considered symptomatic if they displayed COVID-19–related symptoms at the time of testing or in the 5 days prior, presymptomatic if they developed symptoms in the 14 days following testing, and asymptomatic if they developed no symptoms in the 14 days after a positive test.

The authors analyzed cumulative case counts for SNFs that underwent one or more testing surveys, either facility-wide (all residents tested) or unit-based (all residents on specific units tested), and compared case counts in counties with varying levels of countywide COVID-19.

The researchers identified 5,403 cases in SNFs overall, with 40.6% classified as asymptomatic, 19.1% presymptomatic, and 40.3% symptomatic at the time of testing. Facilities that underwent at least one facility-wide survey had slightly higher rates of asymptomatic and presymptomatic infection (40.9% and 19.3%, respectively) than those that performed unit-based surveys only (37.0% and 16.3%, respectively).

SNFs in counties with higher SARS-CoV-2 prevalence had higher counts of asymptomatic and presymptomatic cases than those in counties with lower prevalence, adding to evidence that SNF location and community prevalence are predictive of facility outbreaks.
Oct 19 JAMA Intern Med study


Higher perception of COVID-19 risk, greater compliance in women

A study in the Proceedings of the National Academy of Sciences last week found that women are more likely to see COVID-19 as a serious health problem and more likely to agree and comply with containment measures, highlighting the importance of gender-based public health messaging.

Scientists have documented higher COVID-19 mortality in men worldwide, with a number of factors speculated to play a role, such as differences in biology, preexisting conditions, occupation, and likelihood of seeking health care. Gender differences in public policy compliance behaviors have not been fully examined but may help explain observed mortality differences, the authors said.

The study conducted a two-wave survey of 21,649 participants in eight countries with high per-capita income and advanced health systems in March and April. Participants were asked to rate the seriousness of expected COVID-19 health consequences in their country, and their agreement and level of compliance with public policy measures.

Women were more likely to consider COVID-19 a very serious health problem (59.0% vs 48.7% in March; 39.6% vs 33.0% in April). Overall agreement with restraining measures decreased for both men and women over time, but women remained more likely to agree (54.1% vs 47.7% in March; 42.6% vs 37.4% in April).

Notably, compliance with public policy rules was markedly higher in women, and gender differences persisted despite overall decreases in compliance from March to April (88.1% vs 83.2% in March; 77.6% vs 71.8% in April). The study authors found smaller differences among cohabiting married couples and among individuals most directly exposed to the pandemic, suggesting that gender differences in beliefs and behavior may decrease with exposure to similar information and first-hand experience.

The authors suggest that higher compliance in women may reduce the likelihood of contracting and spreading the disease, pointing to the role of gender-related behavioral differences in disease transmission. In a news release from Bocconi University in Milan, lead author Vincenzo Galasso, PhD, said, "Policy makers who promote a new normality made of reduced mobility, face masks and other behavioral changes should, therefore, design a gender-differentiated communication if they want to increase the compliance of men."
Oct 15 Proc Natl Acad Sci study
Oct 16 Bocconi University news release

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