Immune repertoire sequencing reveals an abnormal adaptive immune system in COVID‐19 survivors

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (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 Coronavirus Disease 2019 (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 6‐month follow‐up after hospital discharge. Immune repertoire sequencing revealed abnormal T‐ and B‐cell expression and function with large T cell receptor/B cell receptor 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.