key: cord-0865209-w90s952l
authors: Meng, Jialin; Ge, Qintao; Li, Jiawei; Lu, Xiaofan; Chen, Yonghao; Wang, Haitao; Zhang, Meng; Du, Juan; Zhang, Li; Hao, Zongyao; Liang, Chaozhao
title: Protective trend of anti-androgen therapy during the COVID-19 pandemic: a meta-analysis
date: 2022-03-24
journal: J Infect
DOI: 10.1016/j.jinf.2022.03.020
sha: cd9f9a98f7e97140677c8f7b6dcf2152441b2a6b
doc_id: 865209
cord_uid: w90s952l

nan

Dear Editor, Androgen rereport (AR) is an important transcription factor; thus, androgen and AR-associated pathways play pivotal roles in the progression of several diseases, including prostate cancer (PCa), benign prostatic hyperplasia (BPH), breast cancer, acne, and alopecia [1, 2] . Anti-androgen therapy is widely used for the clinical treatment of prostatic disease, including androgen deprivation therapy (ADT) via surgical castration, pharmacological castration, or androgen receptor blocked therapy for PCa, and 5 alpha-reductase inhibitor (5ARI) for BPH.

Influenced by the COVID-19 pandemic, the impact of SARS-CoV-2 on patients receiving anti-androgen therapy has raised increased attention. Montopoli et al. [3] first reported the potential impact of anti-androgen therapy on SARS-CoV-2 infection, where ADT may provide partial protection of PCa patients from SARS-CoV-2 infection. Lyon et al. [4] also demonstrated a reduction in communityacquired SARS-CoV-2 infection with long-term 5ARI administration. However, inconsistent voices were also acknowledged. Notably, several clinical trials (e.g., NCT04446429, NCT04530500, NCT04475601, NCT04354701) also tested the potential protective function of anti-androgen therapy.

In this study, we comprehensively searched publications up to March 15, 2022, in PubMed, Google Scholar, Embase, Cochrane Library and ClinicalTrials, with the following keywords: "androgen", "anti-androgen therapy", "androgen deprivation therapy", "ADT", "5 alpha-reductase inhibitor", "5ARI", "COVID-19", "2019-nCoV", "SARS-CoV-2", "2019 novel coronavirus", and "coronavirus disease 2019". We also searched the reference lists of relevant reviews and studies to avoid any missing articles within the topic. The inclusion criteria were preset: (1) case control study with anti-androgen therapy group and non-therapy group; (2) infection of SARS-CoV-2 detected by reverse transcriptase-polymerase chain reaction test; (3) available data for each group and the accurate number of events; (4) study populations being at least fifteen cases. Case reports, repeated articles, review papers and preprints were eliminated. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Detailed information on the enrolled studies is listed in Tables S1-S2.

The "metafor" R package was employed to perform the meta-analysis. The odds ratio (OR) with 95% confidence interval (CI) generated from the total number and event number was used to evaluate the impact of anti-androgen therapy and was further integrated into the overall OR. The I 2 and Tau 2 values were calculated to quantify the heterogeneity of each subset. Cumulative meta-analysis was used to display the cumulative impact of anti-androgen therapy on events; specifically, we accumulated the studies in the order of fewer to more patients in the control group. Potential publication bias was evaluated by a funnel plot. Figure 1A) . To further understand the impact of antiandrogen therapy to avoid SARS-CoV-2 infection, cumulative analysis was further conducted. The studies were accumulated in the order of fewer to more patients in control groups to avoid sparse data bias. We observed that the ORs remained less than one in each step after sample accumulation, which strongly supported the findings that anti-androgen therapy may prevent SARS-CoV-2 infection (Figure 2A) . With the pandemic of the SARS-CoV-2 omicron variant and the clinical trials that have been widely applied to human beings with anti-androgen therapy, it is fortunate that the anti-androgen therapy has not caused greater harm from SARS-CoV-2 to patients. Although Welén et al. [8] reported disappointing results among enzalutamide failure to prevent SARS-CoV-2, we still hold a favorable expectation of anti-androgen therapy with the protective trend from the metaanalysis and the biological findings; further studies that enable uncovering the association between anti-androgen therapy and COVID-19 are highly warranted. Light gray at the beginning, dark gray at the end.

Androgen receptor-related diseases: what do we know?

Antiandrogen Therapies for Androgenetic Alopecia and Acne Vulgaris

Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532)

Reductase Inhibitors Are Associated with Reduced Risk of SARS-CoV-2 Infection: A Matched-Pair, Registry-Based Analysis

Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2

The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19. iScience

A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data

We would like to acknowledge Dr. Vaibhav Patel from Mount Sinai University for his great attention to preparing supporting data for their study.

The authors have no conflicts of interest to declare.