Immunophenotype In Severe And Critical COVID-19

BackgroundSince December 2019,the COVID-19 pandemic has caused widespread infections and fatalities worldwide.In the spite of dramatic changes in viral protein sequence and epidemiological patterns,the sudden surge of infections in China has posed a significant challenge for local healthcare systems.Therefore,it is imperative to clarify the immunophenotypic characteristics of severe and critical COVID-19 patients,identifying early warning indicators of poor prognosis to guide subsequent treatment and prevention.MethodsWe established a single-center,prospective,observational cohort based on COVID-19 patients admitted to Peking Union Medical College Hospital from December 1,2022,to April 30,2023.During a screening period of approximately three days after admission,all patients were evaluated to determine clinical severity.COVID-19 associated clinical information was collected including demographics,vaccination and treatment histories,comorbidities,and routine laboratory test.All patients were followed up on the first day,seventh day,28th day,and third month post enrollment.During these visits,extra peripheral blood samples were collected and analyzed for peripheral lymphocyte subpopulations.At the latter two follow-up visits,telephone or face-to-face follow-up were conducted to evaluate COVID-19-related sequelae using questionnaire.Based on the longterm dynamic lymphocyte subpopulation data,we outlined the characteristic immunophenotype of severe and critical COVID-19.We further identified early warning immunological indicators associated with mortality.ResultsIn this study,a total of 74 hospitalized COVID-19 patients in the acute phase were enrolled,including 17 mild or moderate patients,31 severe patients,and 26 critical patients.We found that all COVID-19 patients had lymphopenia that primarily affecting T and NK cells,compared to healthy controls.Almost all patients showed a significant increase in activation and proliferation proportion of T and NK cells.Especially,severe and critical patients had significantly reduced T lymphocyte counts and decreased percentage of PD1+CD8+T cells than mild or moderate patients.Further follow-up assessments revealed that all patients exhibited significant COVID-19-related sequelae at the 28th day and third month post infection,although the number of symptoms decreased over time.Moreover,the immunophenotypic profiles of majority of patients had not fully recovered back to normal.The recovery of T and NK cells was relatively delayed in severe and critical patients compared to mild or moderate patients,with persistent activation and proliferation.There was a total of 13 deaths in this cohort,including 11 critical patients,with a death rate of 42.3%in critical group.Using LASSO regression and logistic models,we identified white blood cell count as a significant risk factor for death.And lymphocyte percentage,PD-1+CD8+T cell percentage,and CD28+CD4+T cell count were significant protective factors for death.ConclusionIn summary,our findings highlight the profound insight of immunophenotype in severe and critical COVID-19,which is unreversible reduction but persistent activated T and NK cells.Specifically,severe and critical patients displayed significantly decreased proportion of PD-1+CD8+T cell.At the 3 months post infection,the aftermath of immune dysfunction was still evident in all patients.The pattern of delayed recovery of CD8+T and NK cells and prolonged abnormal activation was identified as characteristic immunophenotypic dynamic in severe and critical patients.Decreased PD-1+CD8+T cells and CD28+CD4+T cells at the acute phase were significantly associated with death.In light of these findings,the timeliness,high quality,and appropriateness of immune responses are deemed significant determinants of COVID-19 prognosis.