Associations of clinical features and dynamic immune response with the duration of viral RNA shedding in patients with COVID-19

Background: Clinical features and the dynamic changes of the immune response in coronavirus disease-2019 (COVID-19) patients play essential roles in the disease courses. We hypothesized that clinical features and longitudinal dynamic immune response of COVID-19 patients might be associated with viral shedding duration. Methods: In this retrospective study, we documented 413 adult patients with laboratory-confirmed COVID-19 from Wuhan Huoshenshan Hospital. Demographic, clinical, and laboratory data were extracted from electronic medical records. Risk factors associated with viral shedding duration were examined using odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariable logistic regression models. Results: The median duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding was 48 days (interquartile range, 40-58 days) among all patients. Fever symptom (OR, 2.23; 95% CI, 1.46-3.44), delayed admission after symptom onset (OR, 15.33; 95% CI, 9.14-26.65), CD8⁺ T cells (OR, 1.93; 95% CI, 1.10-3.44) were associated with prolonged viral shedding. In contrast, shorter viral shedding was associated with CD4⁺ T cells (OR, 0.38; 95% CI, 0.16-0.88), the ratios of CD4⁺ T cells to CD8⁺ T cells (OR, 0.79; 95% CI, 0.63-0.98). Longitudinal dynamic analyses demonstrate that sustained monocyte level was associated with shorter viral shedding (OR, 0.41; 95% CI, 0.22-0.76). More importantly, the associations of CD4⁺ T cells, CD8⁺ T cells, the ratio of CD4⁺ T cells to CD8⁺ T cells, and sustained monocyte level were confined to male patients. Conclusions: Higher CD4⁺ T cells, sustained monocyte level, and lower CD8⁺ T cells might shorten the disease course. The male-specific associations supported the contribution of sex-dependent immune responses to the disease courses.