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Editorial- December

A recent study published online on 9th December in Nature Communications by Peckham et al. (2020) shows gender based development of severity of COVID-19 subjected to ITU (intensive therapy unit). The study is based on meta-analysis of reports from 47 countries including 3,111,714 cases. However, study considers the equivalent risks of infection in both males and females, still it shows higher odds for males. The requirement of ITU and death is respectively observed 2.84 times higher and 1.39 times higher in males.

Study highlights the differences between male and females for both innate and adaptive immune system. Earlier findings from number of animals including mammals have revealed the genetic and hormonal guidance behind the better immunity in females than male. Higher expression of TLR7 (toll-like receptor 7) gene in females are reported than male. TLR7 gene is responsible for pathogen recognition through molecular pattern development and, accordingly develops immunity responses. TLR7 is able to recognize single stranded RNA of viruses. TLR expression causes translocation of transcription factors as nuclear factor kappa-light-chain-enhancer of activation of B cells. It results in anti-viral responses through production of cytokines.

Estradiol (E2) is major female sex hormone involved in estrous and menstrual cycle. A study shows the enhancement of production of pro-inflammatory cytokines at low doses. It also increases the expression of PRR (pattern recognition receptors). Even progesterone, released by corpus luteum promote the production of different types of cytokines following various pathways. A separate study shows the inhibitory effects of androgens and testosterone, prominent in males.

Marked association between morbidity/mortality is noted in advanced age as authors points out the age-related decline in B cells in males. Even hypertension and diabetes are also linked with COVID-19. Individual studies have presented prevalence of them in males compared to females. Still, a greater number of researches are needed to understand the mechanism of differences in odds of COVID-19 related to gender.