Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomized clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness. Graphical Abstract ga1
【저자키워드】 COVID-19, Drug repurposing, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, Sex, ACE2, angiotensin-converting enzyme 2, Pregnancy, health equity, RBD, receptor binding domain, JAK, Janus kinase, ARDS, acute respiratory distress syndrome, IL, interleukin, CI, Confidence interval, CDC, Centers for Disease Control and Prevention, ICU, Intensive care unit, TNF-α, tumor necrosis factor alpha, DOAC, direct oral anticoagulant, VTE, venous thromboembolism, HR, hazard ratio, TMPRSS2, Transmembrane Protease Serine 2, NIH, National Institutes of Health, MERS, middle-East respiratory syndrome, MAbs, monoclonal antibodies, EMA, European Medicines Agency, AF, atrial fibrillation, HCV, hepatitis C virus, TCM, traditional Chinese medicine, RAAS, renin-angiotensin-aldosterone system, mTOR, Mammalian target of rapamycin, PF4, platelet factor 4, TCZ, tocilizumab, CYP, cytochrome P, ACE-Is, ACE inhibitors, AIFA, Italian Medicines Agency, AnxA1/FPR2, Annexin A1/formyl-peptide receptor 2, ARBs, Angiotensin-II receptor blockers, AT1R, Angiotensin receptor type-1, BLAZE-1, Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies, DHT, Dihydrotestosterone, DMARDs, Disease-modifying anti-rheumatic drugs, E2, 17β-estradiol, E4, Estetrol, ER, Estrogen receptor, FAERS, FDA Adverse Events Reporting Monitoring System, FcRn, Neonatal Fc receptor, FDA, Food & Drug Administration, GC, Glucocorticoids, GM-CSF, Granulocyte macrophage-colony stimulating factor, H2S, Hydrogen sulfide, IgG1, Immunoglobulin subclass 1, IL-6R, IL-6 receptor, JAKi, JAK inhibitors, LMWH, Low-molecular-weight heparin, PEG, Polyethylene glycol, PG, Progesterone, SERMs, Selective estrogen receptor modulators, SETH, Spanish Society of Liver Transplantation, T, Testosterone, Th1, T helper 1 cells, TIV, Trivalent influenza vaccination, Gender pharmacology,