The Unreversible Reduced but Persistent Activated NK and CD8 + T cell in Severe/Critical COVID-19 during Omicron Pandemic in China.

As a hallmark of COVID-19 progression, lymphopenia alongside with its subtle immune disturbance has been widely reported, although yet to be thoroughly elucidated. Aiming at exploring clinical immune biomarkers with accessibility in the current and acute Omicron epidemic abrupted in China post-control era, we design a real-world prospective observation cohort in Peking Union Medical College Hospital to describe immunological, hematological profiles inducing lymphocyte subsets related to SARS-CoV-2 infection. In this COVID-19 cohort, we enrolled 17 mild/moderate (M/M), 24 severe (S) and 25 critical (C) patients. The dynamics of lymphocytes of COVID-19 demonstrated that the sharp decline of NK, CD8 and CD4 T cell counts was main contributor to lymphopenia in S/C group, compared to M/M group. Expressions of activation marker CD38 and proliferation marker Ki-67 both in CD8 T and NK cell were significantly higher in all COVID-19 patients than that in healthy donors, independent of disease severity. The subsequent analysis showed in contrast to M/M group, NK and CD8 T cell counts remained low-level after therapy in S/C group. CD38 and Ki-67 expression in NK and CD8 T cell still stay at a high level, despite of active treatment. Targeting at relatively elderly patients with SARS-CoV-2 infection, severe COVID-19 features the unreversible reduction of NK and CD8 T cell with persistent activation and proliferation, which assist clinician in early recognizing and saving severe or critical COVID-19 patients. Given that immunophenotype, the new immunotherapy improving NK and CD8T lymphocyte antiviral efficiency should be considered.