Manuscript title: Loss in the expansion of SARS-CoV-2 specific immunity is a key risk factor in fatal patients with COVID-19

Knowledge of the dynamic immunological characteristics of patients with coronavirus disease 2019 (COVID-19) is essential for clinicians to understand the progression of the disease. Our data showed that the immune system and function gradually remodeled and declined with age, starting from age 16 until age 91 in 25,239 healthy controls. An analysis of the relationship between the number of lymphocytes and age revealed that the lymphocyte and subset counts tended to decline with age significantly. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity declined with age and was associated with survival time in fatal cases. Loss in the expansion of SARS-CoV-2-specific immunity could be expanded in vitro . The concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and prolonged SARS-CoV-2 exposure predicted fatal outcomes. Our findings provide a basis for further analysis of SARS-CoV-2-specific immunity and understanding of the pathogenesis of fatal COVID-19 cases. Highlights ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement National Natural Science Foundation of China (Grant No. 81830052 and 81530053). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This case series was approved by the institutional ethics board All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes We have all data in the experiment.