Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: Insights from the MGH COVID-19 patient registry.

Emily S Lau,Andrea S Foulkes,Caitlin A Selvaggi,Jennifer E Ho,Steven A Lubitz,Ingrid V Bassett,Samantha M Paniagua,Jessica K Wang,Elizabeth E Liu,Jenna N Mcneill,Aleksandar R Zivkovic

doi:10.1371/journal.pone.0250774

Abstract

BackgroundMen are at higher risk for serious complications related to COVID-19 infection than women. More robust immune activation in women has been proposed to contribute to decreased disease severity, although systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known.Study design and methodsWe examined sex differences in inflammatory markers among 453 men (mean age 61) and 328 women (mean age 62) hospitalized with COVID-19 infection at the Massachusetts General Hospital from March 8 to April 27, 2020. Multivariable linear regression models were used to examine the association of sex with initial and peak inflammatory markers. Exploratory analyses examined the association of sex and inflammatory markers with 28-day clinical outcomes using multivariable logistic regression.ResultsInitial and peak CRP were higher in men compared with women after adjustment for baseline differences (initial CRP: ß 0.29, SE 0.07, p = 0.0001; peak CRP: ß 0.31, SE 0.07, p<0.0001) with similar findings for IL-6, PCT, and ferritin (p<0.05 for all). Men had greater than 1.5-greater odds of dying compared with women (OR 1.71, 95% CI 1.04–2.80, p = 0.03). Sex modified the association of peak CRP with both death and ICU admission, with stronger associations observed in men compared with women (death: OR 9.19, 95% CI 4.29–19.7, p <0.0001 in men vs OR 2.81, 95% CI 1.52–5.18, p = 0.009 in women, Pinteraction = 0.02).ConclusionsIn a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection.

Highlights

Emerging data suggest that men are at higher risk for severe coronavirus disease 2019 (COVID-19) infection compared with women despite similar rates of infection [1]
Initial and peak C-reactive protein (CRP) were higher in men compared with women after adjustment for baseline differences with similar findings for IL-6, PCT, and ferritin (p
In a sample of 781 men and women hospitalized with COVID-19 infection, men exhibited more robust inflammatory activation as evidenced by higher initial and peak inflammatory markers, as well as worse clinical outcomes

Summary

Introduction

Emerging data suggest that men are at higher risk for severe coronavirus disease 2019 (COVID-19) infection compared with women despite similar rates of infection [1]. Despite a growing body of evidence supporting sex differences in immune response, how inflammation contributes to COVID-19 disease severity in men vs women is not known. In light of reports implicating systemic inflammation as a potential driver of severity of COVID-19 disease, it is notable that stronger immune responses in women have been postulated to contribute to decreased mortality in women [10]. More robust immune activation in women has been proposed to contribute to decreased disease severity, systemic inflammation has been associated with worse outcomes in COVID-19 infection. Whether systemic inflammation contributes to sex differences in COVID-19 infection is not known

Methods

Results

Conclusion