sharon sanders
Editor-in-Chief & President
Research ArticleVolume 16310828
7February 2026
Open access
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Persistent attenuation of lymphocyte subsets after mass SARS-CoV-2 infection
Zhengqi Jiang[SUP]1,#[/SUP] ∙ Tichao Shan[SUP]2,#[/SUP] ∙ Yucan Li[SUP]1[/SUP] ∙ … ∙ Heyu Ni[SUP]6,7[/SUP] ∙ Jun Peng[SUP]1[/SUP] ∙ Miao Xu[SUP]1[/SUP] miao.xu@sdu.edu.cn … Show more
Affiliations & NotesArticle Info
Highlights
•
SARS-CoV-2 causes lasting immune dysregulation for over 20 months.
•
The impact of SARS-CoV-2 on lymphocytes was especially severe in patients with CVD.
•
Lymphocyte deficiency is related to long COVID pathogenesis.
•
Long-term immune dysregulation of long COVID demands tailored treatment.
Abstract
Objectives
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.
Methods
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[SUP]+[/SUP]/CD8[SUP]+[/SUP] 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.
Results
During mass infection, T cells, CD4[SUP]+[/SUP]T cells, CD8[SUP]+[/SUP]T cells, NK cells, and B cells dropped significantly. Even 20 months post-infection, CD8[SUP]+[/SUP] 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.
Conclusion
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.
https://www.ijidonline.com/article/S1201-9712(25)00509-0/fulltext
7February 2026
Open access
Download Full Issue
Persistent attenuation of lymphocyte subsets after mass SARS-CoV-2 infection
Zhengqi Jiang[SUP]1,#[/SUP] ∙ Tichao Shan[SUP]2,#[/SUP] ∙ Yucan Li[SUP]1[/SUP] ∙ … ∙ Heyu Ni[SUP]6,7[/SUP] ∙ Jun Peng[SUP]1[/SUP] ∙ Miao Xu[SUP]1[/SUP] miao.xu@sdu.edu.cn … Show more
Affiliations & NotesArticle Info
Highlights
•
SARS-CoV-2 causes lasting immune dysregulation for over 20 months.
•
The impact of SARS-CoV-2 on lymphocytes was especially severe in patients with CVD.
•
Lymphocyte deficiency is related to long COVID pathogenesis.
•
Long-term immune dysregulation of long COVID demands tailored treatment.
Abstract
Objectives
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.
Methods
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[SUP]+[/SUP]/CD8[SUP]+[/SUP] 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.
Results
During mass infection, T cells, CD4[SUP]+[/SUP]T cells, CD8[SUP]+[/SUP]T cells, NK cells, and B cells dropped significantly. Even 20 months post-infection, CD8[SUP]+[/SUP] 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.
Conclusion
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.
https://www.ijidonline.com/article/S1201-9712(25)00509-0/fulltext