Post‐hospitalization rehabilitation alleviates long‐term immune repertoire alteration in COVID‐19 convalescent patients

The global pandemic of Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an once‐in‐a‐lifetime public health crisis. Among hundreds of millions of people who have contracted with or are being infected with COVID‐19, the question of whether COVID‐19 infection may cause long‐term health concern, even being completely recovered from the disease clinically, especially immune system damage, needs to be addressed. Here, we performed seven‐chain adaptome immune repertoire analyses on convalescent COVID‐19 patients who have been discharged from hospitals for at least 6 months. Surprisingly, we discovered lymphopenia, reduced number of unique CDR3s, and reduced diversity of the TCR/BCR immune repertoire in convalescent COVID‐19 patients. In addition, the BCR repertoire appears to be activated, which is consistent with the protective antibody titres, but serological experiments reveal significantly lower IL‐4 and IL‐7 levels in convalescent patients compared to those in healthy controls. Finally, in comparison with convalescent patients who did not receive post‐hospitalization rehabilitation, the convalescent patients who received post‐hospitalization rehabilitation had attenuated immune repertoire abnormality, almost back to the level of healthy control, despite no detectable clinic demographic difference. Overall, we report the potential long‐term immunological impairment for COVID‐19 infection, and correction of this impairment via post‐hospitalization rehabilitation may offer a new prospect for COVID‐19 recovery strategy.