Sex differences in inflammatory markers in patients hospitalized with COVID-19 infection: Insights from the MGH COVID-19 patient registry
Open accessAbstract
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, P interaction = 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.
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Proinflammatory cytokines and cardiac biomarkers are elevated in men with COVID-19 compared with women, including ferritin, CRP, IL-6, IL-8, and IL-18.
“Proinflammatory cytokines and cardiac biomarkers have been reported to be elevated in men with COVID-19 compared with women including ferritin, CRP (C-reactive protein), IL-6, IL-8, and IL-18. 13,121-123”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [123]
The Results report higher CRP, ferritin, and IL-6 in men hospitalized with COVID-19, and the Discussion reports prior findings of higher IL-18 in men. The paper does not report higher IL-8 or cardiac biomarkers in men; its findings are limited to hospitalized patients. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMen have more neutrophils and monocytes, whereas women have more T cells, similar to autoimmune myocarditis.
“And men have more neutrophils and monocytes, whereas women have more T cells, 13,121-123 similar to autoimmune myocarditis. 124,125”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [123]
The Results report sex differences in inflammatory markers, not neutrophil, monocyte, or T-cell counts. The Discussion mentions a prior study finding lower overall lymphocyte counts in men, but that does not establish the claimed T-cell difference. Searches for the named cell types found no passage addressing the claim. (LLM, conf=0.75)
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- Authors
- Lau, E. S., McNeill, J. N., Paniagua, S. M., Liu, E. E., Wang, J. K., Bassett, I. V., Selvaggi, C. A., Lubitz, S. A., Foulkes, A. S., & Ho, J. E.
- Affiliations
- Massachusetts General Hospital (US)
- Corresponding author
- Ho, Jennifer E.
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2021-04-28
- Volume
- 16
- Issue
- 4
- Pages
- e0250774
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC8081177
- OpenAlex
- W3159952420
- Cited by
- 65
- References
- 18
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 11 · 2023: 18 · 2022: 20 · 2021: 9
- FWCI
- 4.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- MGH Division of Clinical Research
- Weissman Family MGH Research Scholar Award
- NIH (5T32HL094301-07, K24 AI141036, AI058736-16S1, AI141036, 1R01HL139731, R01 GM127862, R01 HL134893, R01 HL140224, K24 HL153669)
- American Heart Association (18SFRN34250007)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- COVID-19 pandemic, sex differences, inflammatory markers, C-reactive protein, interleukin-6, procalcitonin, ferritin, systemic inflammation, mortality, intensive care unit admission, hospitalized patients, immune response
- MeSH terms
- COVID-19, SARS-CoV-2, Adult, Aged, Female, Hospitalization, Humans, Inflammation, Male, Massachusetts, Middle Aged, Registries, Severity of Illness Index, Sex Factors, Biomarkers
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