TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID-19 patients.
J Leukoc Biol
; 111(1): 283-289, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1178997
ABSTRACT
The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T lymphocyte response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 781 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 158 SARS-CoV-2 specific TRB sequences belonging to 134 clusters in our COVID-19 patients. Next, we investigated 113 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences toward the nonstructural proteins (NSPs) encoded within ORF1a/b of the SARS-CoV-2 genome was observed in clusters associated with critical disease course when compared to COVID-19 clusters associated with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from NSPs of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Proteins
/
Severity of Illness Index
/
Receptors, Antigen, T-Cell, alpha-beta
/
COVID-19
/
Hospitalization
Type of study:
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Aged
/
Humans
Language:
English
Journal:
J Leukoc Biol
Year:
2022
Document Type:
Article
Affiliation country:
JLB.6COVCRA1120-762R
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