Sex‐related differences in COVID‐19 lethality

Abstract

Many countries have been affected by the worldwide outbreak of COVID‐19. Among Western countries, Italy has been particularly hit at the beginning of the pandemic, immediately after China. In Italy and elsewhere, women seem to be less affected than men by severe/fatal COVID‐19 infection, regardless of their age. Although women and men are affected differently by this infection, very few studies consider different therapeutic approaches for the two sexes. Understanding the mechanisms underlying these differences may help to find appropriate and sex specific therapies. Here, we consider that other mechanisms are involved to explain this difference, in addition to the protection attributable to oestrogens. Several X‐linked genes (such as ACE2) and Y‐linked genes (SRY and SOX9) may explain sex differences. Cardiovascular comorbidities are among the major enhancers of virus lethality. In addition, the number of sex‐independent, non‐genetic factors that can change susceptibility and mortality is enormous, and many other factors should be considered, including gender and cultural habits in different countries.

Clinical Characteristics, Risk Factors and Predictive Value of COVID-19 Pneumonia: A Retrospective Study of 173 Patients in Wuhan, China

“…In addition to estrogen protection and different lifestyle, angiotensin-converting enzyme (ACE) 2 may explain sex differences. ACE2 is a receptor for SARS-CoV-2 entry into cells, and its higher expression in male lungs may correlate with high prevalence, severe illness rate and mortality in males [12][13][14]. However, our data did not con rm sex differences in COVID-19 pneumonia.…”

An overview of Betacoronaviruses-associated severe respiratory syndromes, focusing on sex-type-specific immune responses

“…By receiving this vaccine, body produce copies of the spike protein, which does not cause disease, but triggers the immune system to learn to react defensively, producing an immune response against SARS-CoV-2 [79] . Despite the diversity of medical interventions, the fact that incidence of COVID-19, its mortality rate, and the effects of medical interventions vary between males and females, has not substantially affected the scientific investigations and very few studies consider various therapeutic approaches for the two sexes [80] . Variations in weight, body mass index, and hormonal changes (during puberty, menstrual cycles, and menopause) can be factors that lead to sexual differences in adverse reactions to antiviral drugs [81] Hence, an appropriate treatment for patients is the use of hormone therapy.…”

“…Variations in weight, body mass index, and hormonal changes (during puberty, menstrual cycles, and menopause) can be factors that lead to sexual differences in adverse reactions to antiviral drugs [81] Hence, an appropriate treatment for patients is the use of hormone therapy. Sex hormones such as testosterone, progesterone, and estradiol can be considered in these therapeutic processes ( Table 1 ) [80] , [82] , [83] .…”

Predicting Potential SARS-COV-2 Drugs—In Depth Drug Database Screening Using Deep Neural Network Framework SSnet, Classical Virtual Screening and Docking

“…These results may add utility to our workflow as a robust means to quickly identify ligand scaffolds as well as pre-existing drugs with high binding probabilities. Currently, the sex-dependent difference in CoVID-19 pathology and therapeutic effects of estrogen are being associated with different ACE2/TMPRSS2 expression, [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ], or immune system modulation [ 51 , 55 , 56 , 60 , 61 , 62 , 63 ]. To the best of our knowledge direct binding of sex hormones to ACE2 has not been observed.…”