Dynamic Changes in the Immune Response Correlate with Disease Severity and Outcomes During Infection with SARS-CoV-2

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout China and worldwide. Little is known about the dynamic changes in the patient immune responses to SARS-CoV-2 and how different responses are correlated with disease severity and outcomes.

Seventy-four patients with confirmed COVID-19 were enrolled in this prospective research. The demographic information, medical history, symptoms, signs and laboratory results were analyzed and compared between severe and non-severe patients. The leukocytes, lymphocyte subsets and inflammatory cytokines were longitudinally collected.

Of the 74 patients included, 17 suffered from severe disease. The severe patients tended be older (65.29 ± 12.33 years vs. 45.37 ± 18.66 years) and had a greater degree of underlying disease (41.18% vs. 24.56%), lower baseline lymphocyte counts [0.64 (0.46-0.95) × 10⁹ vs. 1.27 (0.95-1.70) × 10⁹], higher neutrophil-lymphocyte ratios [NLRs; 3.76 (3.15-5.51) vs. 2.07 (1.48-2.93)] and lower baseline eosinophil counts [0 (0-0.01) × 10⁹ vs. 0.03 (0.01-0.06) × 10⁹] than those in non-severe patients. The baseline helper T (Th) cells (335.47 vs. 666.46/μl), suppressor T(Ts) cells (158 vs. 334/μl), B cells (95 vs. 210/μl) and natural killer (NK) cells (52 vs. 122/μl) were significantly decreased in severe cases compared to that in non-severe cases. In addition, the baseline neutrophils were positively correlated with the severity of COVID-19, and the baseline lymphocytes were negatively correlated with the severity of COVID-19. The dynamic change of T cells, Th cells and IFN-γ in the severe cases were parallel to the amelioration of the disease.

Collectively, our study provides novel information on the kinetics of the immune responses in a cohort of COVID-19 patients with different disease severities. Furthermore, our study indicates that both innate and adaptive immune responses correlate with better clinical outcomes.