Persistent attenuation of lymphocyte subsets after mass SARS-CoV-2 infection

Growing evidence suggests that lymphocyte subsets are declined in COVID-19 patients, but it is unclear if these alterations persist after widespread exposure to SARS-CoV-2 or how long they last.

We analyzed lymphocyte subset data from 40,537 patients across three phases: pre-COVID, mass infection, and post-COVID. The counts of lymphocyte subsets and CD4⁺/CD8⁺ ratios were compared using Mann-Whitney U test or Kruskal-Wallis H test. Monthly post-exposure data were compared with pre-exposure data to assess the persistence of impact on lymphocyte subsets by SARS-CoV-2, and subgroup analyses were performed in patients with cardiovascular disease.

During mass infection, T cells, CD4⁺T cells, CD8⁺T cells, NK cells, and B cells dropped significantly. Even 20 months post-infection, CD8⁺ T cells remained 9.9% below baseline. Baseline lymphocyte subsets differed significantly by sex and age. Immune recovery varied by age and sex, with older adults and males showing prolonged lymphopenia. In cardiovascular disease patients, T lymphocytes remained 72.9% below baseline for 20 months post-infection.

Our findings redefine SARS-CoV-2 infection as a condition of long-lasting immune compromise. The sustained subnormal lymphocytes-particularly in cardiovascular disease cohorts-highlight a key immunologic feature of long COVID and underscore the need for personalized care.