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

Immun Inflamm Dis. 2021 Jun;9(2):419-434. doi: 10.1002/iid3.402. Epub 2021 Jan 16.


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.

Keywords: PRNT50; SARS CoV-2; adaptive immune cells; disease severity; innate immune cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antigen Presentation
  • COVID-19 / blood
  • COVID-19 / immunology*
  • Comorbidity
  • Cytokines / blood
  • Dendritic Cells / immunology*
  • Female
  • Flow Cytometry
  • Follow-Up Studies
  • Humans
  • India
  • Lymphocyte Activation
  • Lymphocyte Subsets / immunology*
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Prognosis
  • SARS-CoV-2* / immunology
  • Severity of Illness Index
  • Time Factors


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines