Sex- and age-specific clinical and immunological features of coronavirus disease 2019

PLoS Pathog. 2021 Mar 26;17(3):e1009420. doi: 10.1371/journal.ppat.1009420. eCollection 2021 Mar.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aging / immunology*
  • Aging / pathology
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Female
  • Humans
  • Lymphocyte Count
  • Lymphocytes / immunology*
  • Lymphocytes / pathology
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • Sex Characteristics*
  • Sex Factors

Grants and funding

This work was supported by the National Natural Science Foundation of China 82070855 (to ML). the National Natural Science Foundation of China 81670336 (to ML), the Wenzhou Grant for Scientific Talents, Wenzhou Science and Technology Bureau RX2016003 (to ML), the Key Research and Development Program of Zhejiang Province 2019C03011 (to SJ and TL), the Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China 2020ZX09201002 (to TL) and the Wenzhou Science and Technology Key problem program ZY2020001 (to TL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.