Comparative cohort analysis shows lymphopenia and neutrophil-to-lymphocyte ratio identify mild COVID-19 in frail elderly, indicating potential for early treatment insights.
Background: Systemic inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with severe COVID-19, but their role in mild disease among frail older adults remains unclear. Early Israeli admission policies enabled hematologic profiling of asymptomatic and mild cases. Methods: Retrospective cohort of adults ≥65 years admitted to a geriatric center (March 2020–March 2021). Patients with Mild/asymptomatic COVID-19 cases were compared with patients hospitalized for other infections (pneumonia, urinary tract infection, cellulitis). Admission indices such as NLR, derived neutrophil-to-lymphocyte ratio (dNLR), PLR, hemoglobin-to-lymphocyte ratio (HLR), red cell distribution width (RDW), and C-reactive protein (CRP) were analyzed using receiver operating characteristic (ROC) curves. Sensitivity analyses compared COVID-19 with bacterial pneumonia and assessed one-week changes. Results: Among 450 patients (177 COVID-19 and 273 non-COVID; median age 85–86), COVID-19 cases showed lower white blood cell counts (WBC), neutrophils, and CRP but more marked lymphopenia. The most discriminative indices were dNLR, PLR, HLR, and RDW, which differed most (all p < 0.001), while NLR and systemic immune-inflammation index (SII) showed limited discrimination. The best AUC was 0.69. dNLR, PLR, and HLR remained elevated after one week. Conclusion: In frail older adults with early or mild COVID-19, modest but consistent hematologic patterns, including lymphopenia with elevated dNLR, PLR, and HLR, and lower RDW, were distinguished COVID-19 from other infections, although single-marker accuracy was limited. These routine indices may assist early differentiation when virologic testing is delayed or unavailable.
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