Greater COVID-19 Severity in Men May Be Due to Greater Inflammatory Response
Key findings
- This retrospective analysis of the Massachusetts General Hospital COVID-19 Registry compared sex differences in inflammatory markers between 453 men and 328 women admitted with COVID-19 infection from March 8 to April 27, 2020
- Levels of both initial and peak inflammatory markers were significantly higher in men than women
- Men had significantly increased odds of dying compared with women (OR, 1.71; P=0.03)
- Associations between peak C-reactive protein levels and death or ICU admission were more pronounced in men than women
- A better understanding of the sex differences in the immune response to COVID-19 may be key to the development of targeted therapies
In nearly all 38 countries that have publicly reported sex-specific COVID-19 data, rates of severe disease and death from COVID-19 infection are substantially higher in men compared with women. Systemic inflammation has been associated with worse outcomes in COVID-19 infection, but whether systemic inflammation contributes to sex differences among patients hospitalized with COVID-19 infection is not known.
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Now, a study at Massachusetts General Hospital has provided support for a role of systemic inflammation in mediating COVID-19 disease severity and mortality, particularly in men. Emily Lau, MD, cardiologist and investigator in the Division of Cardiology at the Corrigan Minehan Heart Center of Massachusetts General Hospital, Jenna N. McNeill, MD, pulmonologist and investigator in the Division of Pulmonary and Critical Care Medicine, and Jennifer Ho, MD, heart failure cardiologist and investigator at the Cardiovascular Research Center, and colleagues report the results in PLoS One.
Study Methods
The researchers reviewed data from the Mass General COVID-19 Registry on 781 patients who were hospitalized with PCR-confirmed COVID-19 between March 8 and April 27, 2020. Biologic sex was defined as the sex assigned at birth: 453 patients (58%) were male and 328 (42%) were female.
Sex and Inflammatory Markers
In multivariable analyses:
- Initial levels of C-reactive protein (CRP), ferritin and interleukin-6 (IL-6) were significantly greater in men than women (P<0.05 for all)
- Peak levels of CRP, ferritin, IL-6 and procalcitonin were significantly greater in men than women (P<0.05 for all)
- The initial erythrocyte sedimentation rate (ESR) was significantly lower in men than women, but there was no difference between men and women in peak ESR
Sex and Outcomes
- Death: Increased risk in men even after multivariable adjustment (OR, 1.71; 95% CI, 1.04–2.80; P=0.03)
- ICU admission: No significant difference between sexes
- Composite of death and ICU admission: No significant difference between sexes
Sex, Inflammatory Markers and Outcomes
In exploratory analyses, the association between peak CRP levels and death or ICU admission was more pronounced in men compared with women. For each standard deviation of increase in peak CRP level:
- Death: OR, 9.19 in men vs. 2.81 in women (P for interaction = 0.02)
- ICU admission: OR, 7.26 in men vs. 2.78 in women (P for interaction = 0.009)
A better understanding of the sex differences in the immune response to COVID-19 may be key in the development of targeted therapies.
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