Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity. (November 2021)

• Record Type: Journal Article
• Authors: Spini, Andrea; Giudice, Valentina; Brancaleone, Vincenzo; Morgese, Maria Grazia; De Francia, Silvia; Filippelli, Amelia; Ruggieri, Anna; Ziche, Marina; Ortona, Elena; Cignarella, Andrea; Trabace, Luigia
• Is Part Of: Pharmacological research. Volume 173(2021)
• Publication Date: 2021-11
• Subjects: ACE2 Angiotensin-converting enzyme 2 -- ACE-Is ACE inhibitors -- AF Atrial fibrillation -- AIFA Italian Medicines Agency -- AnxA1/FPR2 Annexin A1/formyl-peptide receptor 2 -- ARBs Angiotensin-II receptor blockers -- ARDS Acute respiratory distress syndrome -- AT1R Angiotensin receptor type-1 -- BLAZE-1 Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies -- CDC Centers for Disease Control and Prevention -- CI Confidence Interval -- COVID-19 Coronavirus Disease 2019 -- CYP Cytochrome P -- DHT Dihydrotestosterone -- DMARDs Disease-modifying anti-rheumatic drugs -- DOAC Direct oral anticoagulant -- E2 17β-estradiol -- E4 Estetrol -- EMA European Medicines Agency -- 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 -- HCV Hepatitis C virus -- HR Hazard ratio -- ICU Intensive care unit -- IgG1 Immunoglobulin subclass 1 -- IL Interleukin -- IL-6R IL-6 receptor -- JAK Janus Kinase -- JAKi JAK inhibitors -- LMWH Low-molecular-weight heparin -- mAbs Monoclonal antibodies -- MERS Middle-East Respiratory Syndrome -- mTOR Mammalian target of rapamycin -- NIH National Institutes of Health -- PEG Polyethylene glycol -- PF4 Platelet factor 4 -- PG Progesterone -- RAAS Renin-angiotensin-aldosterone system -- RBD Receptor binding domain -- SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 -- SERMs Selective estrogen receptor modulators -- SETH Spanish Society of Liver Transplantation -- T Testosterone -- TCM Traditional Chinese Medicine -- TCZ Tocilizumab -- Th1 T helper 1 cells -- TIV Trivalent influenza vaccination -- TMPRSS2 Transmembrane protease serine 2 -- TNF-α Tumor Necrosis Factor alpha -- VTE Venous thromboembolism; Gender pharmacology -- Sex -- Drug repurposing -- COVID-19 -- Pregnancy -- Health equity; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105848
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: 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