Disease‐duration based comparison of subsets of immune cells in SARS CoV‐2 infected patients presenting with mild or severe symptoms identifies prognostic markers for severity

Abstract

Introduction: Infection with SARS-CoV-2 leads to a spectrum of symptoms. Understanding the basis for severity remains crucial for better management and therapy development. So far, older age, associated-comorbidities, and IL-6 have been associated with severity/mortality. Materials and methodology: As a primary step, we analyzed the frequency and functional profile of innate immune cells (NK cells/dendritic cells/monocytes) and adaptive immunity-driving lymphocytes (B cells/T cells/follicular T helper cells) by flow cytometry. Sixty cases of SARS CoV-2 infection (25 severe, 35 mild) and ten healthy subjects without SARS CoV-2 IgG were included. Disease-duration based analysis of immune profile was explored for early events differentiating the two disease forms. Neutralizing antibody titers were determined by PRNT. Results and conclusion: Disease severity was found to be associated with impaired maturation of mDCs and hyperactivation of NK, follicular T helper cells, and CD8 T cells. Lower IL-21 receptor expression on memory B cells indicated an imbalance in IL-21/IL-21 R ratio. Lower BCMA positive plasmablast cells in severe cases did suggest a probable absence of long-term humoral immunity. Multivariate analysis revealed a progressive association of PD-1+CD4 T cells with PRNT50 titers. Thus, in addition to identifying probable prognostic markers for severity, our study emphasizes the definite need for in-depth viral antigen-specific functional analyses in a larger patient cohort and with multiple sampling.