Sex Differences in Inflammatory Markers in Patients Hospitalized with COVID-19 Infection: Insights from the MGH COVID-19 Patient Registry

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2021 Apr 28

PMID 33909684

Citations 32

Authors

Emily S Lau

Jenna N McNeill

Samantha M Paniagua

Elizabeth E Liu

Jessica K Wang

Ingrid V Bassett

Caitlin A Selvaggi

Steven A Lubitz

Andrea S Foulkes

Jennifer E Ho

Affiliations

Soon will be listed here.

Abstract

Background: Men 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 Methods: We 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.

Results: Initial 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).

Conclusions: 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. Better understanding of sex differences in immune responses to COVID-19 infection may shed light on the pathophysiology of COVID-19 infection.

Citing Articles

Biochemical differences based on sex and clusters of biomarkers in patients with COVID-19: analysis from the CARDIO COVID 19-20 registry.

Canon-Estrada F, Munoz-Ordonez J, Escalante-Forero M, Rodas Y, Arteaga-Tobar A, Azcarate-Rodriguez V BMC Cardiovasc Disord. 2025; 25(1):147.

PMID: 40045210 PMC: 11881352. DOI: 10.1186/s12872-025-04565-3.

Plasma ferritin, C-reactive protein, and adenosine deaminase levels in tuberculous lymphadenitis and pleuritis and their role in monitoring treatment response.

Nisa Z, Zeshan B, Ambreen A, Mustafa T BMC Infect Dis. 2024; 24(1):1375.

PMID: 39623309 PMC: 11613811. DOI: 10.1186/s12879-024-10228-z.

Delineating sex-specific circulating host response signatures associated with COVID-19 severity and mortality.

Keur N, Flikweert A, Ricano-Ponce I, Muller Kobold A, van der Sar-van der Brugge S, Rodenhuis-Zybert I iScience. 2024; 27(11):111150.

PMID: 39507250 PMC: 11539596. DOI: 10.1016/j.isci.2024.111150.

A Retrospective Study: Evaluating the Impact of the COVID-19 Pandemic on Inflammatory Markers in Hospitalized Patients.

Elnagi E, Al-Maqati T, Maawadh R, AlBahrani S, Al Khalaf F, Alzahrani F Infect Dis Rep. 2024; 16(4):735-749.

PMID: 39195007 PMC: 11353753. DOI: 10.3390/idr16040056.

Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications.

G Q Barros-Aragao F, Pinto T, Carregari V, Rezende N, Pinheiro T, Reis-de-Oliveira G Brain Behav Immun Health. 2024; 39:100805.

PMID: 39022627 PMC: 11253226. DOI: 10.1016/j.bbih.2024.100805.

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