Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity

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 randomised 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 3,000 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.

Outcomes of COVID-19 Critically Ill Extremely Elderly Patients: Analysis of a Large, National, Observational Cohort

“…There have been publications addressing the different immune profiles of males and females, which could impact the clinical response to a variety of molecules, including corticosteroids [ 43 ]. In our cohort, no interaction effect was found between gender and corticosteroids administration and mortality.…”

Hormones and Sex-Specific Medicine in Human Physiopathology

“…In conclusion, sex hormones' influence on COVID-19 is indisputable but not yet fully understood. Awareness of how they impact the course of the disease may implement novel treatment strategies as underlined by the increased interest in sex differences in possible target treatment recently shown by researchers involved in drug development in COVID-19 [94].…”

Sex-Related Factors in Cardiovascular Complications Associated to COVID-19

“…The influence of sex hormones is not limited to the susceptibility to infection or to the extent of the viral load, but it also determines the severity of symptoms and the correlated complications, thus impacting the sex-related outcomes of COVID-19 disease. By virtue of the protective role of female sex hormones, the lethality rate for COVID-19 is reduced in women of fertile age and it is noticeably lower than in men, but it gradually increases to over 20% during the post-menopausal age [ 39 ]. Premenopausal women had lower rates and short duration of hospitalization along with less requirement for respiratory support compared to post-menopausal women [ 39 ].…”

“…By virtue of the protective role of female sex hormones, the lethality rate for COVID-19 is reduced in women of fertile age and it is noticeably lower than in men, but it gradually increases to over 20% during the post-menopausal age [ 39 ]. Premenopausal women had lower rates and short duration of hospitalization along with less requirement for respiratory support compared to post-menopausal women [ 39 ]. Moreover, a direct correlation between COVID-19 and menopausal condition and an inverse association with combined oral contraceptive pill use have been reported [ 40 ].…”

“…Concerning cardiovascular complications secondary to COVID-19 therapies, there is limited information about sex differences, mainly due to the prevalent inclusion of men in randomized clinical trials and to the lack of sex-targeted treatment strategies [ 39 ]. Tentative considerations could be made about antiviral therapies, due to the previous knowledge of differential efficacy and safety of antiviral drugs between sexes, with increased adverse effects in females, likely due to differences in the pharmacokinetics and pharmacodynamics profiles and to the influence of sex hormones [ 124 ].…”