Comparative effectiveness of anti-inflammatory and antiviral therapies on NLR and survival outcomes in severe COVID-19: multicenter retrospective study

Abstract

Background. The COVID-19 pandemic has highlighted the critical role of immune dysregulation and systemic inflammation in disease severity, particularly in patients with severe respiratory illness. Elevated levels of pro-inflammatory cytokines, such as IL-6, and biomarkers like the neutrophil-to-lymphocyte ratio (NLR) have been associated with worse outcomes. This study enrolled laboratory-confirmed SARS-CoV-2 patients with acute respiratory illness requiring intestive care unit (ICU) admission, including mechanical ventilation, to evaluate the effect of different treatments on NLR, neutrophil count (NC), and lymphocyte count (LC). Methods. A retrospective, multicenter, observational cohort study was conducted across 15 tertiary hospitals in Saudi Arabia, involving 1,490 ICU-admitted COVID-19 patients between March 1, 2020, and October 30, 2020. Data on patient demographics, comorbidities, laboratory results, and treatment outcomes were collected using the Research Electronic Data Capture (REDCap) system. The study evaluated the effect of different treatments on NLR, neutrophil count (NC), and lymphocyte count (LC). Results. This study utilized 1,490 patients in the study of whom 73.6% were male and 26.1% were female. The average age of patients was 56.2 years, with a mean NLR of 8.77 ± 8.64, showing significant systemic inflammation. Tocilizumab (p = 0.031), oseltamivir (p = 0.004), and linezolid (0.029) showed statistically significant effects on NLR. Tocilizumab demonstrated the highest mean survival time with 60.813 days, compared to linezolid (49.359 days) and ostilomavir (40.635 days). However, patients not getting linezolid or ostilomavir had longer mean survival times, suggesting potential limitations in their efficacy. Tocilizumab also showed a weak positive correlation with NC (r = 0.086, p = 0.001), further supporting its role in modulating inflammation and improving the immune system. Conclusion. Among the evaluated therapies, tocilizumab and oseltamivir showed a consistent trend of lower NLR values in both survivors and non-survivors, compared to those not receiving these treatments. These findings suggest that tocilizumab and oseltamivir may offer some efficacy in modulating immune response (as measured by NLR) and potentially improving outcomes. However, due to observed weak correlations no single therapy alone appears sufficient to predict or reduce mortality, emphasizing the need for multimodal treatment strategies and further investigation into combined biomarker models.