Abstract
To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.
Highlights
Sex-disaggregated data from the ongoing coronavirus disease 2019 (COVID-19) pandemic indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes disproportionate mortality in males
We assigned adult COVID-19 patients into four groups according to sex and age and simultaneously determined the features of sexand age-specific clinical and immunological responses to SARS-CoV-2 infection
The present findings emphasize that COVID-19 pathogenesis and treatment should be tailored according to sex and age
Summary
Sex-disaggregated data from the ongoing coronavirus disease 2019 (COVID-19) pandemic indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes disproportionate mortality in males. Reports from 37 of the 38 countries that have provided sex-disaggregated data demonstrate that COVID-19 fatality rates are higher in males than in females [1,2,3,4]. In explaining the sexual dimorphism in the clinical and immunological features of COVID-19, both biological sex and age factors should be addressed simultaneously. This is because the differences in immune profiles and disease susceptibility patterns throughout life are attributable to variation in sex steroid concentrations, which affects both innate and adaptive immune responses at different ages [6,7]. In this study, sex- and age-specific differences in the clinical and immunological characteristics of SARS-CoV-2 infection were simultaneously highlighted
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