In December 2022, China ceased the zero-COVID-19 policy, resulting in an increase in hospitalizations and deaths due to COVID-19, particularly among the elderly population. We applied 4D-DIA mass spectrometry for serum proteome analysis and provided a comprehensive characterization of disease features of elderly patients among Chinese population. Our study elucidated that immune senescence, lung damage and cardiovascular disorders are predominant causes of death in elderly patients among Chinese population. Comparing to clinical indices, proteomic analysis is more sensitive in tracing these disorders. We also provided a prediction panel for survival outcome of these elderly patients with CXCL10, CXCL16 and IL1RA level, which was validated by ELISA. These biomarkers, in conjunction with clinical indices and severity evaluations, hold promise for predicting elderly patient survival outcomes, a significant advancement towards reducing the mortality rate—the priority of COVID-19 control.