AUTHOR=Snyder Thomas M. , Gittelman Rachel M. , Klinger Mark , May Damon H. , Osborne Edward J. , Taniguchi Ruth , Jabran Zahid H. , Kaplan Ian M. , Dines Jennifer N. , Noakes Matthew T. , Pandya Ravi , Chen Xiaoyu , Elasady Summer , Svejnoha Emily , Ebert Peter , Pesesky Mitchell W. , De Almeida Patricia , O’Donnell Hope , DeGottardi Quinn , Keitany Gladys , Lu Jennifer , Vong Allen , Elyanow Rebecca , Fields Paul , Al-Asadi Hussein , Greissl Julia , Baldo Lance , Semprini Simona , Cerchione Claudio , Nicolini Fabio , Mazza Massimiliano , Delmonte Ottavia M. , Dobbs Kerry , Laguna-Goya Rocio , Carreño-Tarragona Gonzalo , Barrio Santiago , Imberti Luisa , Sottini Alessandra , Quiros-Roldan Eugenia , Rossi Camillo , Biondi Andrea , Bettini Laura Rachele , D’Angio Mariella , Bonfanti Paolo , Tompkins Miranda F. , Alba Camille , Dalgard Clifton , Sambri Vittorio , Martinelli Giovanni , Goldman Jason D. , Heath James R. , Su Helen C. , Notarangelo Luigi D. , Paz-Artal Estela , Martinez-Lopez Joaquin , Howie Bryan , Carlson Jonathan M. , Robins Harlan S. 

TITLE=Magnitude and dynamics of the T-cell response to SARS-CoV-2 infection at both individual and population levels

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1488860

DOI=10.3389/fimmu.2024.1488860

ISSN=1664-3224

ABSTRACT=IntroductionT cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.MethodsHere, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared “public” T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.ResultsCollectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3–7 = 85.1% [95% CI = 79.9–89.7]; Day 8–14 = 94.8% [90.7–98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1–98.3]).DiscussionThe approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.