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

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. This study included a cohort of 111 people, i.e., 36 COVID-19 patients, 54 sex- and age-matched common viral community-acquired pneumonia patients, and 21 healthy controls. Monocyte counts, lymphocyte subset counts, and alanine aminotransferase (AST), aspartate aminotransferase (ALT), 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 independently 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, independently of estrogen levels, are associated with the clinical manifestations in COVID-19 patients with high specificity.