Immune Repertoire Sequencing Reveals an Abnormal Adaptive Immune System in COVID-19 Survivors.

Accumulating evidence suggests that SARS-CoV-2 impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of COVID-19. Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a six-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large TCR/BCR clones, decreased diversity, abnormal class switch recombination and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19 + CD138 + B cells were found in COVID-19 survivors. The proportion of CD4 + T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3 + CD4 - T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3 + CD4 - T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage. This article is protected by copyright. All rights reserved.