Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease

Immunity. 2020 Aug 18;53(2):442-455.e4. doi: 10.1016/j.immuni.2020.06.024. Epub 2020 Jun 30.


We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR and TCR) sequences from the blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires were associated with interferon type I and III responses, early CD4+ and CD8+ T cell activation, and counterregulation by the co-receptors BTLA, Tim-3, PD-1, TIGIT, and CD73. Tfh, Th17-like, and nonconventional (but not classical antiviral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.

Keywords: B cell repertoire; COVID-19; SARS-CoV-2-specific antibody; T cell compartments; T cell receptor clusters; T cell repertoire; cytokine profile; immunoglobulin heavy chain; interferon.

Publication types

  • Comment

MeSH terms

  • Betacoronavirus
  • COVID-19
  • Coronavirus Infections*
  • Cytokines*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Pandemics*
  • Pneumonia, Viral*
  • Receptors, Antigen, B-Cell / genetics
  • SARS-CoV-2
  • Severity of Illness Index


  • Cytokines
  • Receptors, Antigen, B-Cell