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Proc Natl Acad Sci U S A ; 119(34): e2201541119, 2022 08 23.
Article in English | MEDLINE | ID: covidwho-1984598


Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) ß and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRß and TCRδ loci, including some TCRß sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.

Adaptive Immunity , COVID-19 , Immunoglobulin Heavy Chains , Receptors, Antigen, T-Cell, alpha-beta , Receptors, Antigen, T-Cell , SARS-CoV-2 , Adaptive Immunity/genetics , Aged , B-Lymphocytes/immunology , COVID-19/genetics , COVID-19/immunology , Genetic Loci , Humans , Immunoglobulin Heavy Chains/genetics , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , SARS-CoV-2/immunology , Seroconversion , T-Lymphocytes/immunology
Nat Med ; 26(10): 1623-1635, 2020 10.
Article in English | MEDLINE | ID: covidwho-717130


Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.

Antibodies, Viral/immunology , B-Lymphocytes/immunology , Coronavirus Infections/immunology , Cytokines/immunology , Dendritic Cells/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Aged , B-Lymphocyte Subsets/immunology , Basophils/immunology , Betacoronavirus , COVID-19 , Case-Control Studies , Cell Cycle , Chemokine CXCL10/immunology , Chemokines/immunology , Cohort Studies , Coronavirus Infections/blood , Disease Progression , Female , Flow Cytometry , Hospitalization , Humans , Immunologic Memory , Immunophenotyping , Interleukin-10/immunology , Interleukin-6/immunology , Leukocyte Count , Lymphocyte Activation/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Prognosis , SARS-CoV-2 , Severity of Illness Index , T-Lymphocyte Subsets/immunology , Up-Regulation