Clinical Validation of a Novel T-Cell Receptor Sequencing Assay for Identification of Recent or Prior Severe Acute Respiratory Syndrome Coronavirus 2 Infection
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
- Evaluated articles (Rapid Reviews Infectious Diseases)
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.
Article activity feed
-
-
Carolina Scagnolari
Review 1: "Clinical Validation of a Novel T-cell Receptor Sequencing Assay for Identification of Recent or Prior SARS-CoV-2 Infection"
-
Carolina Scagnolari
Review of "Clinical Validation of a Novel T-cell Receptor Sequencing Assay for Identification of Recent or Prior SARS-CoV-2 Infection"
Reviewer: Carolina Scagnolari (Sapienza University of Rome) | 📗📗📗📗◻️
-
SciScore for 10.1101/2021.01.06.21249345: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics: All samples were collected pursuant to an Institutional Review Board (IRB)-approved clinical study protocol.
Consent: For residual samples collected under prospective study protocols, informed consent was obtained from participants.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the …SciScore for 10.1101/2021.01.06.21249345: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Ethics: All samples were collected pursuant to an Institutional Review Board (IRB)-approved clinical study protocol.
Consent: For residual samples collected under prospective study protocols, informed consent was obtained from participants.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, the limitations of serologic testing, including high variability in test performance across platforms and antibody isotypes tested18, waning or loss of antibody signal over time11,13,14, and absence of detectable antibodies in up to 10% of individuals including those with immunocompromising conditions25,26, expose unmet clinical and public health needs for immunologic testing strategies for SARS-CoV-2 that are consistent, durable, and more informative. Using TCR gene sequencing from whole blood samples, we describe a sequence-based assay to identify recent or prior SARS-CoV-2 infection which demonstrates high PPA (>97% beyond 15 days following diagnosis), high NPA in presumed or confirmed negative SARS-CoV-2 infection (∼100%), equivalent or higher PPA compared to commercially available EUA serology tests, and lack of cross reactivity with a number of viral and/or respiratory tract pathogens. This performance was consistent across several retrospective and prospective cohorts and longitudinal sampling timeframes. Utilizing this approach in a real-world setting, we have shown previously that robust T-cell signals are persistent at least 6 months after primary SARS-CoV-2 infection42, consistent with other reports44. In the SARS-CoV-1 pandemic, detectable virus-specific T-cell responses were observed in recovered individuals up to 17 years later21. In direct real-world comparisons with serologic testing, we have observed up to a 20% lower sensitivity of commercially avai...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04583982 Completed ImmuneSense™ COVID-19 Study NCT04494893 Recruiting ImmuneRACE - Immune Response Action to COVID-19 Events Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
-
