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

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.

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.

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.

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.