BACKGROUND: To explore the potential mechanisms of SARS-CoV-2 in targeting the prostate gland, leading to exacerbation of benign prostatic hyperplasia (BPH) symptoms and greater risks of BPH complications such as acute urinary retention. METHODS: A categorized and comprehensive search in the literature has been conducted by 10 April 2021 using international databases including PubMed, Embase, Web of Science, Scopus, and Cochrane Library in line with the PRISMA guidelines recommendations. PICO strategy was used to formulate the research question. The following terms were used: urology, COVID-19, coronavirus, BPH, inflammation, androgen receptors, LUTS, IPSS, PSA, and SARS-CoV-2 or a combination of them. Studies with irrelevant purposes and duplicates were excluded. The selected studies were performed on humans and published in English. RESULTS: The research revealed 89 articles. After title screening and considering exclusion criteria, 52 papers were included for the systematic review. BPH is a common condition affecting older men. SARS-CoV-2 infects the host cell by binding to angiotensin converting enzyme 2 (ACE2). A hyperactivated RAS system during infection with SARS-CoV-2 may lead to activation of pro-inflammatory pathways and increased cytokine release. Thus, this virus can lead to exacerbation of lower urinary tract symptoms (LUTS) and trigger inflammatory processes in the prostate gland. Since androgen receptors (AR) play an important role in the BPH pathophysiology and infection with SARS-CoV-2 may be androgen-mediated, BPH progression and its related symptoms can be a complication of COVID-19 through AR involvement and metabolic disturbances. CONCLUSIONS: Based on the current findings, SARS-CoV-2 can possibly damage the prostate and worsen BPH and its related LUTS through ACE2 signaling, AR-related mechanisms, inflammation, and metabolic derangement. We encourage future studies to investigate the possible role of COVID-19 in the progression of BPH-related LUTS and examine the prostatic status in susceptible patients with relevant available questionnaires (e.g., IPSS) and serum biomarkers (e.g., PSA).