Immunological characteristics in elderly COVID-19 patients: a post-COVID era analysis

<bold>Background:</bold> Advanced age is a primary risk factor for adverse COVID-19 outcomes, potentially attributed to immunosenescence and dysregulated inflammatory responses. In the post-pandemic era, with containment measures lifted, the elderly remain particularly susceptible, highlighting the need for intensified focus on immune health management. <bold>Methods:</bold> A total of 281 elderly patients were enrolled in this study and categorized based on their clinical status at the time of admission into three groups: non-severe (n = 212), severe survivors (n = 49), and severe non-survivors (n = 20). Binary logistic regression analysis was employed to identify independent risk factors associated with disease severity and in-hospital outcomes. The diagnostic performance of risk factors was assessed using the receiver operating characteristic (ROC) curves. Kaplan-Meier survival analysis and log-rank test were utilized to compare the 30-day survival rates. Furthermore, the transcriptomic data of CD4(+) T cells were extracted from Gene Expression Omnibus (GEO) database. Gene Set Enrichment Analysis (GSEA) was applied to reveal biological processes and pathways involved. <bold>Results:</bold> In the comparison between severe and non-severe COVID-19 cases, significant elevations were observed in the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and Serum Amyloid A (SAA) levels, concurrent with a notable reduction in CD8(+) T cells, CD4(+) T cells, natural killer (NK) cells, and monocytes (all p < 0.05). CD4(+) T cells (OR: 0.997 [0.995-1.000], p<0.05) and NLR (OR: 1.03 [1.001-1.060], p<0.05) were independent risk factors affecting disease severity. The diagnostic accuracy for COVID-19 severity, as measured by the area under the curve (AUC) for CD4(+) T cells and NLR, was 0.715 (95% CI: 0.645-0.784) and 0.741 (95% CI: 0.675-0.807), respectively. Moreover, patients with elevated NLR or IL-6 levels at admission exhibited significantly shorter survival times. Gene Set Enrichment Analysis (GSEA) revealed several biological pathways that are implicated in the regulation of immune responses and metabolic processes. <bold>Conclusions:</bold> Lymphocytopenia and the cytokine storm onset are significant predictors of an unfavorable prognosis in elderly patients. The decrease in CD4(+) T cells among elderly patients is detrimental to disease recovery, and the biological pathways regulated by these cells could potentially heighten vulnerability to SARS-CoV-2 infection, thereby exacerbating the development of associated complications.