Sex differences in immune responses to SARS-CoV-2 in patients with COVID-19

Abstract

Millions of people infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been diagnosed with coronavirus infectious disease 2019 (COVID-19). The prevalence and severity of COVID-19 differ between sexes. To explain these differences, we analyzed clinical features and laboratory values in male and female COVID-19 patients. The present study included a cohort of 111 people, i.e. 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia (CAP) patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels in the peripheral blood were analyzed. Higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, monocyte counts, and CRP and ALT levels were found in male COVID-19 patients. Decreased lymphocyte subset counts and proportions were observed in COVID-19 patients, except for the CD3+ and CD8+ T cell proportions. The lower CD4+ T cell proportions and higher CD8+ T cell proportions were observed in male and severe COVID-19 patients and the differences were independent of estrogen level. The CD4+ T cell proportion was negatively associated with the CD8+ T cell proportion in male COVID-19 patients; this correlation was non-significant in females. Our work demonstrates differences between sexes in circulating monocyte counts and CD4+ T cell and CD8+ T cell proportions in COVID-19 patients, independent of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.

Sex Differences in Immunity to Viral Infections

“…During SARS-CoV-2 infection, it has been reported that males present higher pro-inflammatory cytokine expression, including IL-6, than females (90,91). While COVID-19 is known to cause lymphopenia in both sexes, T cell frequencies and activation remains greater in females than males during SARS-CoV-2 infection, even at older ages (91,92). In contrast, male sex is associated with greater anti SARS-CoV-2 antibody production in convalescent patients (91,93,94) as well as fewer breakthrough SARS-CoV-2 infections following vaccination (95).…”

Can commercial automated immunoassays be utilized to predict neutralizing antibodies after SARS-CoV-2 infection? A comparative study between three different assays

“…Also, the selected samples were obtained from various time points (7-35 days) after the positive RT-PCR test to account for variability and delay of elicited immune response among different individuals. Further, other studies have shown that male individuals produce weaker immune responses, particularly nAbs, than females [54,55]. Hence, identifying the thresholds of protective immunity in male individuals is essential to avoid false-negative results and accurately estimate herd immunity.…”

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

“…A meta-analysis of the mean difference in lymphocyte counts at admission between patients with good and with poor COVID-19 outcomes has shown that lymphopenia was significantly associated with severe COVID-19 and this association was affected by age but not by sex (Zhao Q. et al, 2020). However, some studies have suggested that the male sex is inversely associated with lymphocyte count, especially in patients with comorbidity , although not always confirmed (Zhao G. et al, 2021). In the peripheral blood of SARS-CoV-2-infected patients, both CD4+ and CD8+ T cell blood counts are dramatically decreased compared to healthy controls, with the highest evidence observed in severe cases (de Candia et al, 2021).…”

“…In the peripheral blood of SARS-CoV-2-infected patients, both CD4+ and CD8+ T cell blood counts are dramatically decreased compared to healthy controls, with the highest evidence observed in severe cases ( de Candia et al, 2021 ). Nevertheless, male COVID-19 patients have shown lower CD4+ T cell and higher CD8+ T cell proportions than female patients, indicating a possible more severe immune dysregulation ( Zhao G. et al, 2021 ; Table 4 ).…”