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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.

SUBMITTER: Penna C

PROVIDER: S-EPMC7405496 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Sex-related differences in COVID-19 lethality.

Penna Claudia C Mercurio Valentina V Tocchetti Carlo G CG Pagliaro Pasquale P

British journal of pharmacology 20200805 19

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 t ...[more]

PMID: 32698249

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Project description:BackgroundMales and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration.MethodsWe performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence.ResultsWe found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3-3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients.ConclusionsMales had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.

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Sex-related differences in COVID-19 lethality.

Publications

Sex-related differences in COVID-19 lethality.

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