Dr Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, United States
Introduction: SARS-CoV-2 infection can lead to asymptomatic or severe symptoms, and the memory immune response is crucial for preventing reinfection and reducing disease severity. This study aims to investigate the long-term durability and functionality of humoral and T-cell immunity in recovered patients three years after initial infection, as the understanding of immune responses to SARS-CoV-2 in the long term remains uncertain.
Methods: The study included 86 patients categorized into groups: 30 in the mild illness recovery group, 33 in the severe illness group caused by the Omicron variant, and 23 survivors of critical illness from the original COVID-19 strain. Flow cytometry was used to analyze immune cell subsets (T cells, B cells, and NK cells) in specific and nonspecific immunity using whole blood samples. Cell stimulation with PMA and ionomycin was conducted for 4 hours to assess IFN-γ production in CD4+ T cells, CD8+ T cells, and NK cells. IgM and IgG antibodies against SARS-CoV-2 nucleoprotein, along with neutralizing antibody titers (NAbs), were measured using the paramagnetic particle chemiluminescent immunoassay (CLIA) technique. Serum levels of IL2, IL4, IL6, IL10, TNF-α, and IFN-γ were quantified using flow cytometry. Additionally, blood cells were stimulated with COVID-19 antigen peptides for 18 hours, and intracellular cytokines were measured using flow cytometry on the collected blood cells.
Results: Survivors of critical illness displayed higher counts and elevated expression of certain immune cell subsets compared to mild recovery cases and severe patients. Conversely, other immune cell populations were lower in critical illness survivors. B cell subsets were reduced during severe infection, while NCP-IgG and NAbs were higher in critical illness survivors. NK cell numbers increased after recovery, while several cytokine levels decreased. Stimulation with SARS-CoV-2 antigens led to increased pro-inflammatory cytokines and stable or decreased anti-inflammatory cytokines.
Conclusions: The findings suggest that severe COVID-19 survivors may experience prolonged immune dysregulation for an extended period, possibly lasting three years or more.
