Trial Report Sex Modifies the Effect of COVID-19 on Arterial Elasticity, 2024, Durieux et al.

[SNT Gatchaman]

Sex Modifies the Effect of COVID-19 on Arterial Elasticity
Durieux, Jared C.; Zisis, Sokratis N.; Mouchati, Christian; Labbato, Danielle; Abboud, Marc; McComsey, Grace A.

There is limited long-term evidence on the effects of COVID-19 on vascular injury between male and female sex. An adult cohort of COVID-19 survivors (COVID+) and confirmed SARS-CoV-2 antibody-negative participants (COVID-) were prospectively enrolled. COVID+ participants who have documented the presence of persistent symptoms four weeks following infection were considered to have post-acute sequelae of COVID-19 (PASC).

Non-invasive, FDA-approved EndoPAT (Endo-PAT2000) was used for endothelial assessment. COVID-(n = 94) were 1:1 propensity score matched to COVID+ (n = 151) on baseline covariates including sex.

Among COVID+, 66.2% (n = 100) had PASC. Higher levels of coagulation marker, D-dimer (p = 0.001), and gut permeability marker, zonulin (p = 0.001), were associated with female sex. Estimated differences in augmentation index (AI) between COVID− (0.9 ± 17.2) and COVID+ (8.4 ± 15.7; p = 0.001) and between female and male sex (12.9 ± 1.9; p < .0001) were observed. Among COVID+ with PASC, the average AI (10.5 ± 1.6) was 9.7 units higher than COVID− (p < .0001) and 6.2 units higher compared to COVID+ with no PASC (p = 0.03). COVID+ PASC+ female sex had the highest AI (14.3 ± 1.9).

The effects of SARS-CoV-2 infection on vascular function varies across strata of sex and female sex in the post-acute phase of COVID-19 have the worse arterial elasticity (highest AI).

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[SNT Gatchaman]

In our study, we demonstrated that the effects of SARS-CoV-2 infection on augmentation index vary across strata of sex and that female sex in the post-acute phase of COVID-19 have the worse arterial elasticity (highest Al). Additionally, we provided evidence that SARS-CoV-2 infection, PASC, and sex were independently associated with Al and that higher levels of Al, as well as coagulation marker D-dimer, and gut permeability marker zonulin were associated with female sex. This extends our previous findings that showed the association of arterial elasticity, inflammation, and gut permeability with PASC.

The mechanisms underlying the sex‑specific disparity in PASC are not fully understood, but interactions between sex hormones and the gut microbiome may contribute. It is known that there is a mutual interaction between sex steroids and the gut microbiota, interactions that play a prominent role in the development of metabolic diseases. Estrogens produced in the body can be metabolized by gut microbes, with the resultant metabolites influencing the host. Additionally, sex hormones directly modulate the metabolism of bacteria through steroid receptors. The observed sex differences in gut microbiota composition have led to multiple studies highlighting the interaction between steroid hormones and the gut microbiota, as well as its influence on diseases like obesity and diabetes. Our finding of sex‑related differences in the gut permeability marker zonulin among COVID‑survivors with PASC is novel and deserves further investigation.