Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection

J Clin Invest. 2021 Jan 4;131(1):e140491. doi: 10.1172/JCI140491.


SARS-CoV-2 causes a wide spectrum of clinical manifestations and significant mortality. Studies investigating underlying immune characteristics are needed to understand disease pathogenesis and inform vaccine design. In this study, we examined immune cell subsets in hospitalized and nonhospitalized individuals. In hospitalized patients, many adaptive and innate immune cells were decreased in frequency compared with those of healthy and convalescent individuals, with the exception of an increase in B lymphocytes. Our findings show increased frequencies of T cell activation markers (CD69, OX40, HLA-DR, and CD154) in hospitalized patients, with other T cell activation/exhaustion markers (PD-L1 and TIGIT) remaining elevated in hospitalized and nonhospitalized individuals. B cells had a similar pattern of activation/exhaustion, with increased frequency of CD69 and CD95 during hospitalization followed by an increase in PD1 frequencies in nonhospitalized individuals. Interestingly, many of these changes were found to increase over time in nonhospitalized longitudinal samples, suggesting a prolonged period of immune dysregulation after SARS-CoV-2 infection. Changes in T cell activation/exhaustion in nonhospitalized patients were found to positively correlate with age. Severely infected individuals had increased expression of activation and exhaustion markers. These data suggest a prolonged period of immune dysregulation after SARS-CoV-2 infection, highlighting the need for additional studies investigating immune dysregulation in convalescent individuals.

Keywords: COVID-19; Cellular immune response; Immunology.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Differentiation / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • COVID-19 / immunology*
  • COVID-19 / pathology
  • Female
  • Humans
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology


  • Antigens, Differentiation