Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a disproportionately severe effect on men, suggesting that the androgen pathway plays a role in the disease. Studies on the effect of castration and androgen receptor blockade have been mixed, while 5a-reductase inhibitor (5ARI) use in men with COVID-19 (2019 novel coronavirus) have shown potential benefits. We assessed the association of 5ARI use on risk of community acquired SARS-CoV-2 infection. Materials and Methods: A total of 60,474 males in a prospective registry of people tested for SARS-CoV-2 between March 8, 2020 and February 15, 2021 were included. Using a matched cohort design, men using 5ARIs were matched 1:1 to non5ARI users. Independent analysis using unconditional multivariable logistic regression on the entire unmatched data set was completed for validation. Primary outcome measures were the association of 5ARI use on rates of SARS-Cov-2 positivity and disease severity. Results: Of the men 1,079 (1.8%) reported 5ARI use and 55,100 were available for matching. The final matched cohorts included 944 men each. Mean duration of use was 60.4 months (IQR 17e84 months). Absolute risk for infection was significantly lower in 5ARI users compared to nonusers, 42.3% (399/944) vs 47.2% (446/944), respectively (absolute risk reduction [ARR] 4.9%, OR 0.81, 95% CI 0.67e0.97, p[0.026). Unconditional multivariable logistic regression analysis of the entire study cohort of 55,100 men confirmed the protective association of 5ARI use (ARR 5.3%, OR[0.877, 95% CI 0.774e0.995, p[0.042). Use of 5ARIs was not associated with disease severity. Conclusions: Use of 5ARIs in men without prostate cancer was associated with a reduction in community acquired SARS-CoV-2 infection.

IntroductionWound related complications (WRC) are a significant source of morbidity in kidney transplant recipients, and may be mitigated by surgical approach. We hypothesize that the anterior rectus sheath approach (ARS) may decrease WRC and inpatient opiate use compared to the Gibson Approach (GA).MethodsThis double‐blinded randomized controlled trial allocated kidney transplant recipients aged 18 or older, exclusive of other procedures, 1:1 to ARS or GA at a single hospital. The ARS involves a muscle‐splitting paramedian approach to the iliopsoas fossa, compared to the muscle‐cutting GA. Patients and data analysts were blinded to randomization.ResultsSeventy five patients were randomized to each group between August 27, 2019 and September 18, 2020 with a minimum 12 month follow‐up. There was no difference in WRC between groups (p = .23). Nine (12%) and three patients (4%) experienced any WRC in the ARS and GA groups, respectively. Three and one Clavien IIIb complications occurred in the ARS and GA groups, respectively. In a multiple linear regression model, ARS was associated with decreased inpatient opioid use (β = –58, 95% CI: –105 to –12, p = .016).ConclusionsThe ARS did not provide a WRC benefit in kidney transplant recipients, but may be associated with decreased inpatient opioid use.

This timely observational analysis examines whether there is an association between 5ARIs and SARS-CoV-2 infection. Although this report identified a 4.9% ARR, significant challenges remain as to whether 5ARIs represent an important addition tool in preventing SARS-CoV-2 infection.First, observational studies are subject to selection bias. Infection, particularly early in the pandemic, disproportionally affected under-resourced populations. The observed lower association between 5ARI use and infection may be a reflection of this phenomenon. With the exception of race, the analysis does not account for socioeconomic factors including income, insurance status, or area deprivation index.Second, concerns remain for the risk of inflation bias in biomedical studies, 1 and this risk increases with the number of statistical tests, outcomes and variables used in modeling. Using approaches to correct for multiple comparisons is one way to account for this problem. In such cases, a p value of 0.05 may not be appropriate as a cut-off for significance. Another strategy to minimize inflation bias is to publish a detailed analysis plan prior to execution of any statistical tests. Neither approach appears to have been utilized in this study.