Immune system changes during COVID-19 recovery play key role in determining disease severity

Coronavirus disease 2019 (COVID-19), an acute respiratory infection, is largely associated with dysregulation and impairment of the immune system. This study investigated how the immune system changes were related to disease severity in COVID-19 patients. The frequencies of different immune cells and levels of pro- and anti-inflammatory cytokines in whole blood of participants were determined by flow cytometry and enzyme-linked immunosorbent assay, respectively. The values of other inflammatory agents were also studied. In the late recovery stage, unlike CD56^high CD16^+/- NK cells and monocytes, CD56^low CD16⁺ NK cell numbers were increased (P < 0.0001-0.05). Th1, Th2, and Th17 cell percentages were significantly lower in patients than healthy control (P < 0.0001-0.05), while their frequencies were increased following disease recovery (P < 0.0001-0.05). The numbers of Tregs, activated CD4+ T cells, and exhausted CD8+ T cells were significantly decreased during a recovery (P < 0.0001-0.05). No significant change was observed in exhausted CD4+ T cell number during a recovery (P > 0.05). B cell showed an increased percentage in patients compared to healthy subjects (P < 0.0001-0.05), whereas its number was reduced following recovery (P < 0.0001-0.05). IL-1α, IL-1β, IL-6, TNF-α, and IL-10 levels were significantly decreased in the late recovery stage (P < 0.0001-0.05). However, TGF-β1 level was not significantly changed during the recovery (P > 0.05). Lymphocyte numbers in patients were significantly decreased (P < 0.001), unlike ESR value (P < 0.001). Lymphocyte number was negatively correlated to ESR value and Th2 number (P < 0.05), while its association with monocyte was significantly positive at the first day of recovery (P < 0.05). The immune system changes during the disease recovery to improve and regulate immune responses and thereby may associate with the reduction in disease severity.