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. 2022 Dec 19;75(12):2079-2087.
doi: 10.1093/cid/ciac353.

Clinical Validation of a Novel T-Cell Receptor Sequencing Assay for Identification of Recent or Prior Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Sudeb C Dalai  1   2 , Jennifer N Dines  1 , Thomas M Snyder  3 , Rachel M Gittelman  3 , Tera Eerkes  4 , Pashmi Vaney  4 , Sally Howard  4 , Kipp Akers  5 , Lynell Skewis  5 , Anthony Monteforte  5 , Pamela R Witte  5 , Cristina Wolf  5 , Hans Nesse  5 , Megan Herndon  5 , Jia Qadeer  1 , Sarah Duffy  1 , Emily Svejnoha  1 , Caroline Taromino  1 , Ian M Kaplan  6 , John Alsobrook  7 , Thomas Manley  1 , Lance Baldo  1
Affiliations

Clinical Validation of a Novel T-Cell Receptor Sequencing Assay for Identification of Recent or Prior Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Sudeb C Dalai et al. Clin Infect Dis. .

Abstract

Background: While diagnostic, therapeutic, and vaccine development in the coronavirus disease 2019 (COVID-19) pandemic has proceeded at unprecedented speed, critical gaps in our understanding of the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unaddressed by current diagnostic strategies.

Methods: A statistical classifier for identifying prior SARS-CoV-2 infection was trained using >4000 SARS-CoV-2-associated T-cell receptor (TCR) β sequences identified by comparing 784 cases and 2447 controls from 5 independent cohorts. The T-Detect COVID (Adaptive Biotechnologies) assay applies this classifier to TCR repertoires sequenced from blood samples to yield a binary assessment of past infection. Assay performance was assessed in 2 retrospective (n = 346; n = 69) and 1 prospective cohort (n = 87) to determine positive percent agreement (PPA) and negative percent agreement (NPA). PPA was compared with 2 commercial serology assays, and pathogen cross-reactivity was evaluated.

Results: T-Detect COVID demonstrated high PPA in individuals with prior reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection (97.1% 15+ days from diagnosis; 94.5% 15+ days from symptom onset), high NPA (∼100%) in presumed or confirmed SARS-CoV-2 negative cases, equivalent or higher PPA than 2 commercial serology tests, and no evidence of pathogen cross-reactivity.

Conclusions: T-Detect COVID is a novel T-cell immunosequencing assay demonstrating high clinical performance for identification of recent or prior SARS-CoV-2 infection from blood samples, with implications for clinical management, risk stratification, surveillance, and understanding of protective immunity and long-term sequelae.

Keywords: COVID-19; SARS-CoV-2; T-cell receptor; diagnostic; next-generation sequencing.

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Conflict of interest statement

Potential conflicts of interest . S. C. D. declares employment and equity ownership with Adaptive Biotechnologies and employment with Stanford University School of Medicine at the time of this study. T. M. and L. B. declare leadership, employment, and equity ownership with Adaptive Biotechnologies at the time of this study. All other authors declare employment and equity ownership with Adaptive Biotechnologies at the time of this study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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