Sex‐specific disparities in COVID‐19 outcomes

Abstract

Abstract Objectives Sex‐specific disparities in morbidity and mortality of COVID‐19 illness are not well understood. Neutralizing antibodies (Ab) may protect against severe COVID‐19 illness. We investigated the association of sex with disease progression and SARS‐CoV‐2 Ab response. Methods In this exploratory analysis of the phase 3, multicenter, randomized, placebo‐controlled Convalescent Plasma in Outpatients (C3PO) trial, we examined whether sex was associated with progression to severe illness, defined as a composite of all‐cause hospitalization, emergency/urgent care visit, or death within 15 days from study enrollment. Patients had a positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) test, symptom onset within 7 days, stable condition for emergency department discharge, and were either ≥50 years old or had at least one high‐risk feature for disease progression. Patients received blinded convalescent plasma or placebo in a 1:1 fashion and were evaluated on days 15 and 30 after infusion. Blood samples were collected on day 0 (pre‐/post‐infusion), 15, and 30 to measure Ab levels with the Broad Institute using the Plaque Reduction Neutralization Test assay. Results Of 511 patients enrolled (median age 54 [Iinterquartile range 41–62] years, 46% male, 66% white, 20% black, 3.5% Asian), disease progression occurred in 36.7% of males and 25.9% of females (unadjusted risk difference 10.8%, 95% confidence interval [CI], 2.8–18.8%). Sex‐disparities did not persist when adjusted for treatment group, age, viremic status, symptom onset, and tobacco use (adjusted risk difference 5.6%, 95% confidence interval [CI], −2.2% to 13.4%), but were present in the subgroup presenting 3 or more days after symptom onset (adjusted risk difference 12.6%, 95% CI, 3.4% to 21.9%). Mean baseline Ab levels (log scale) available for 367 patients were similar between sexes (difference 0.19 log units, 95% CI, −0.08 to 0.46). The log‐scale mean increase from baseline to day 15 after adjusting for treatment assignment and baseline levels was larger in males than females (3.26 vs. 2.67). A similar difference was noted when the groups were subdivided by outcome. Conclusions Progression of COVID‐19 was similar in males and females when adjusted for age, tobacco use, and viremia status in this study. However, in the cohort presenting 3 or more days after symptom onset, COVID‐19 outcomes were worse in males than females. Neutralizing Ab levels increased more in males but did not correlate with sex differences in outcomes.

Keywords

• C3PO
• Covid‐19
• outcomes
• sex disparity