How Does COVID-19 Disrupt Immune Homeostasis and Its Association with Multiple System Diseases?

Background: The immunopathological events and immune residues induced by COVID-19, particularly lymphocyte damage, play a central role in the pathogenesis of Long COVID. Identifying easy-to-detect biomarkers is crucial for understanding the persistence of symptoms.

Objective: To elucidate the immune mechanisms underlying Long COVID, focusing on lymphocyte damage and immune retention, and to evaluate the lymphocyte ratio (LYM%) >40 as a potential biomarker for immune status.

Methods: A retrospective analysis was conducted on 16,256 radiological workers (2015–2017 pre-pandemic vs. 2021–2025 pandemic periods). Peripheral blood parameters, including white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and LYM%, were analyzed. A control group of 1,949 non-medical workers was included.

Results: From 2021 to 2025, a continuous decrease in NLR and a significant increase in average LYM% were observed. The detection rate of LYM% >40 increased markedly, peaking at 52.39% in 2025 (P < 0.01). Neutrophil counts decreased while lymphocyte counts increased.

Conclusion: The average LYM% and the detection rate of LYM% >40 are strongly associated with post-COVID immune status. Repairing the immune system damaged by SARS-CoV-2 is a critical strategy to control Long COVID and prevent ongoing outbreaks.

Gang Liu graduated from Lanzhou University in 1997 with a PhD in preventive medicine and works at the Gansu Provincial Center for Disease Control and Prevention. In 2019, after becoming a registered health physicist, he served as the technical lead for an exploratory study of low-dose dose-effect relationships. The technology of biological dose estimation is at the leading level in China and has reached the international advanced level. He is mainly engaged in the fields of radiobiology, immunology, tumor screening and radiation protection in radiation therapy. Revision of the 2011 IAEA Manual based on the findings of the radiological sensitivity and dose rate survey, published online in the FASEB Journal, the leading international (top) journal for Contributions to radiological sensitivity and dose rate research findings; Chromosomal aberration analysis: Novel noninvasive techniques for early-stage cancer screening, et al.