Transcriptomic characteristics and impaired immune function of patients who retest positive for SARS-CoV-2 RNA

J Mol Cell Biol. 2021 Dec 30;13(10):748-759. doi: 10.1093/jmcb/mjab067.

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global public health crisis. Some patients who have recovered from COVID-19 subsequently test positive again for SARS-CoV-2 RNA after discharge from hospital. How such retest-positive (RTP) patients become infected again is not known. In this study, 30 RTP patients, 20 convalescent patients, and 20 healthy controls were enrolled for the analysis of immunological characteristics of their peripheral blood mononuclear cells. We found that absolute numbers of CD4+ T cells, CD8+ T cells, and natural killer cells were not substantially decreased in RTP patients, but the expression of activation markers on these cells was significantly reduced. The percentage of granzyme B-producing T cells was also lower in RTP patients than in convalescent patients. Through transcriptome sequencing, we demonstrated that high expression of inhibitor of differentiation 1 (ID1) and low expression of interferon-induced transmembrane protein 10 (IFITM10) were associated with insufficient activation of immune cells and the occurrence of RTP. These findings provide insight into the impaired immune function associated with COVID-19 and the pathogenesis of RTP, which may contribute to a better understanding of the mechanisms underlying RTP.

Keywords: CD8+; COVID-19; NK cells; RTP patients; T cells; immune function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • COVID-19 / virology
  • COVID-19 Nucleic Acid Testing
  • Case-Control Studies
  • Convalescence*
  • Female
  • Healthy Volunteers
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Inhibitor of Differentiation Protein 1 / genetics
  • Inhibitor of Differentiation Protein 1 / immunology
  • Lymphocyte Activation Gene 3 Protein
  • Male
  • Middle Aged
  • Patient Readmission
  • RNA, Viral / isolation & purification
  • Reinfection / genetics
  • Reinfection / immunology*
  • Reinfection / virology
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / isolation & purification
  • Transcriptome / immunology*
  • Young Adult

Substances

  • Antigens, CD
  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • RNA, Viral
  • Lymphocyte Activation Gene 3 Protein