Living Repository of Millions of T and B Cell Receptor Sequences from Patients with COVID-19

Abstract

We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a living repository of currently >14 million B and T cell receptor (BCR/TCR) sequences from 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 was associated with interferon type I and III responses, early CD4+/CD8+ activation and counterregulation by BTLA, Tim-3, PD-1, TIGIT and CD73. Tfh, Th17-like and nonconventional (but not classical anti-viral) Th1 polarizations were induced. COVID-19 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 cohort – especially the subset with effective viral clearance – reveals fundamental insight into adaptive immunity to SARS-CoV-2 with the living repository providing a bottleneck resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.

Conflict of Interest: The authors declare no competing interests.

Ethical Approval: Blood collection was performed under institutional review board approvals number 2020-039 and 11/17.

Keywords: COVID-19, SARS-CoV-2, TCR, BCR, T cell cluster, B cell cluster, cytokine, immune checkpoint, immune repertoire, next-generation sequencing