Journal Article Epublish 2 citations
PubMed: 40721715 DOI: 10.1038/s41598-025-11470-4
Sex differences in inflammation and markers of gut integrity in long COVID.
Sci Rep 15(1):27374
Authors: Jared C Durieux, Ziad Koberssy, Joviane Daher, Jhony Baissary, Marc Abboud, Ornina Atieh, Christopher Woolverton, Grace A McComsey
Affiliations
- Clinical Research Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
- College of Public Health, Kent State University, Kent, OH, USA.
- School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
- Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.
- College of Public Health, Kent State University, Kent, OH, USA.
- School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
- Clinical Research Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Abstract
Endothelial damage represents an essential pathogenic mechanism of respiratory and multiorgan dysfunction as seen in the post-acute phase of COVID-19. Biological differences between male and female sex, inflammation, and gut integrity may have an integral role in endothelial damage and explain the residual effects of COVID-19 infection in long COVID, yet evidence is limited. Confirmed COVID-19 negative participants were 1:1 propensity-score matched to COVID-19 positive participants. Symptoms occurring at least one-month following COVID-infection and lasting more than three-months was defined as long COVID. Measures of endothelial function included reactive hyperemic index (RHI ≥ 1.67 = normal endothelial function) and augmentation index (higher AIx = worse arterial elasticity). A total of 89 COVID-19 negative participants was matched to 89 COVID-19 positive participants. Among the COVID-19 survivors, the median age was 42.92 years, 46.07% were female sex, and 57 (64%) had long COVID. Higher levels of inflammation (TNF-RI and oxLDL) and gut integrity (zonulin and BDG) was associated (P < 0.05) with a two-fold increase in the odds of long COVID. Female sex, independent of COVID-19 status, was 4x more likely to have worse AIx (P < 0.0001) compared to male sex. Among female sex with long COVID, higher levels of inflammation (IL-6, VCAM, hsCRP) and gut integrity (zonulin) was independently associated (P < 0.05) with higher AIx. Female sex with long COVID symptoms had the worse inflammation, gut integrity, and arterial stiffness among COVID-19 survivors. This reinforces the importance of continued, long-term follow-up care following COVID-19 infection, with special attention needed for female sex who may be at a higher cardiovascular disease risk.
MeSH
Sex Characteristics, Sex, Natural Science Disciplines, Infections, Post-Acute Covid-19 Syndrome, Sex Differences