Diagnosis and Tracking of SARS-CoV-2 Infection By T-Cell Receptor Sequencing
By
Rachel M Gittelman,
Enrico Lavezzo,
Thomas M. Snyder,
H Jabran Zahid,
Rebecca Elyanow,
Sudeb Dalai,
Ilan Kirsch,
Lance Baldo,
Laura Manuto,
Elisa Franchin,
Claudia Del Vecchio,
Monia Pacenti,
Caterina Boldrin,
Margherita Cattai,
Francesca Saluzzo,
A Padoan,
Mario Plebani,
Fabio Simeoni,
Jessica Bordini,
Nicola I. Lorè,
Dejan Lazarevic,
Daniela Maria Cirillo,
Paolo Ghia,
Stefano Toppo,
Jonathan M. Carlson,
Harlan S Robins,
Giovanni Tonon,
Andrea Crisanti
Posted 12 Nov 2020
medRxiv DOI: 10.1101/2020.11.09.20228023
In viral diseases T cells exert a prominent role in orchestrating the adaptive immune response and yet a comprehensive assessment of the T-cell repertoire, compared and contrasted with antibody response, after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently lacking. A prior population-scale study of the municipality of Vo', Italy, conducted after the initial SARS-CoV-2 outbreak uncovered a high frequency of asymptomatic infected individuals and their role in transmission in this town. Two months later, we sampled the same population's T-cell receptor repertoire structure in terms of both diversity (breadth) and frequency (depth) to SARS-CoV-2 antigens to identify associations with both humoral response and protection. For this purpose, we analyzed T-cell receptor and antibody signatures from over 2,200 individuals, including 76 PCR-confirmed SARS-CoV-2 cases (25 asymptomatic, 42 symptomatic, 9 hospitalized). We found that 97.4% (74/76) of PCR confirmed cases had elevated levels of T-cell receptors specific for SARS-CoV-2 antigens. The depth and breadth of the T-cell receptor repertoire were both positively associated with neutralizing antibody titers; helper CD4+ T cells directed towards viral antigens from spike protein were a primary factor in this correlation. Higher clonal depth of the T-cell response to the virus was also significantly associated with more severe disease course. A total of 40 additional suspected infections were identified based on T-cell response from the subjects without confirmatory PCR tests, mostly among those reporting symptoms or having household exposure to a PCR-confirmed infection. Taken together, these results establish that T cells are a sensitive, reliable and persistent measure of past SARS-CoV-2 infection that are differentially activated depending on disease morbidity.
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