Longitudinal Analysis of T and B Cell Receptor Repertoire Transcripts Reveal Dynamic Immune Response in COVID-19 Patients

Abstract

Severe COVID-19 is associated with profound lymphopenia and an elevated neutrophil to lymphocyte ratio. We applied a novel dimer avoidance multiplexed polymerase chain reaction next-generation sequencing assay to analyze T (TCR) and B cell receptor (BCR) repertoires. Surprisingly, TCR repertoires were markedly diminished during the early onset of severe disease but recovered during the convalescent stage. Monitoring TCR repertoires could serve as an indicative biomarker to predict disease progression and recovery. Panoramic concurrent assessment of BCR repertoires demonstrated isotype switching and a transient but dramatic early IgA expansion. Dominant B cell clonal expansion with decreased diversity occurred following recovery from infection. Profound changes in T cell homeostasis raise critical questions about the early events in COVID-19 infection and demonstrate that immune repertoire analysis is a promising method for evaluating emergent host immunity to SARS-CoV-2 viral infection, with great implications for assessing vaccination and other immunological therapies.

The Future of Blood Testing Is the Immunome

“…For example, in patients who have had influenza or received an influenza vaccine, AIRR-seq has demonstrated an increase in influenza-specific antibody and TR genes in the blood and in tissues (15)(16)(17)(18)(19)(20). Similar results have been demonstrated in viral infections as diverse as dengue and SARS-CoV-2 (21)(22)(23)(24)(25)(26)(27)(28). Noteworthy in this regard is the current effort to discern a T cell fingerprint for SARS-CoV-2 exposure, immune status and possibly even immunopathology in the ImmuneCODE project, a collaboration between Adaptive Biotechnologies and Microsoft, which leverages a rapidly growing and publicly accessible dataset of over 1,400 TR immunomes from individuals who were exposed to SARS-CoV-2 (28,29).…”

Profiling of T Cell Repertoire in SARS-CoV-2-Infected COVID-19 Patients Between Mild Disease and Pneumonia

“…Second, the time point of sampling for patients with mild disease (15–18 days) and pneumonia (17–53 days) was different. Such factors might affect the profiling of TCR repertoire in different patients, since SAS-CoV-2-specific TCR clonotypes are dynamic throughout the course of viral infection [ 38 , 39 ]. Nevertheless, TCR repertoire status of COVID-19 patients in our study should still predominantly reflect a stable SARS-CoV-2-responding T cell immunity as they were in the convalescent stage at the time of sample collection.…”

Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity

“…Pathways identified using this epigenetic approach suggest alternative regulation of the adaptive immune response between MS and PS subjects. Differential regulation of pathways related to the transition from innate immunity, marked by the implication of dectin-1 and the toll-like receptor cascade, to adaptive immunity, suggested by activation of T and B cell receptor signaling, were observed in these sub-populations (28–30) . These observations confirm that chromatin accessibility remodeling corresponds to symptom severity, as first indicated by differential transcription factor activity.…”