Hormone Replacement Therapy and COVID-19 Outcomes in Kidney Transplant Recipients Compared With the General Population

ABSTRACT

Background: In the non-immunosuppressed (non-IS) population, female sex is protective against adverse COVID-19 (C19) outcomes, possibly due to estrogenrelated immunity. Sex-based risk is attenuated in IS kidney transplant recipients (KTRs). Exogenous estrogen is associated with reduced C19 mortality in non-IS postmenopausal females. Here, we aimed to study the impact of estrogen or testosterone hormone replacement therapy (HRT) on C19 outcomes in KTRs compared to the general population. Method(s) We studied adult (>45 yrs) KTRs from across the US with C19 from 05-01-20 to 05-12-22, using EHR data from the National COVID Cohort Collaborative. Female and male patients were classified as no HRT, or HRT use in the last 6 months (exogenous systemic estrogens for females;testosterone for males). Using MV cox proportional hazards models and logistic regression, we determined the risk of developing a major adverse renal or cardiac event (MARCE), mortality, and other 90-day post-C19 outcomes. We repeated this analysis in a non-IS control group for comparison. Result(s) Over the study period, 11,498 KTRs and >1.9M non-IS patients were diagnosed with C19. In non-IS, relative to no HRT use, HRT use in the last 6 months was associated with significantly lower risk of MARCE (Hazard Ratio [HR] 0.54, 95% Confidence Interval [CI] 0.51-0.59, for females;0.63, 0.56-0.70, for males), mortality (HR 0.45, CI 0.40-0.51, for females;0.55, 0.45-0.66, for males), and all secondary events for males and females (Figure 1). In KTRs, HRT was not associated with any post-C19 outcome in either males or females;there was a trend towards lower risk in males on HRT vs not on HRT, for most outcomes. Conclusion(s) HRT was protective against adverse C19 outcomes in older non-IS males and females, but not in KTRs. The modifying effects of IS on the benefits of HRT requires further investigation.