Sex-Dependent Performance of the Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte and Mean Platelet Volume-to-Platelet Ratios in Discriminating COVID-19 Severity

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and mean platelet volume-to-platelet ratio (MPR) are combined hematology tests that predict COVID-19 severity, although with different cut-off values. Because sex significantly impacts immune responses and the course of COVID-19, the ratios could be biased by sex. PURPOSE: This study aims to evaluate sex-dependent differences in the contribution of NLR, PLR, MLR, and MPR to COVID-19 severity and mortality upon hospital admission using a sample of pneumonia patients with SARS-CoV-2 infection. METHODS: This single-center observational cross-sectional study included 3,280 confirmed COVID-19 cases (CDC 2019-Novel Coronavirus real-time RT-PCR Diagnostic) from Quito (Ecuador). The receiver operating characteristic (ROC) curve analysis was conducted to identify optimal cut-offs of the above parameters when discriminating severe COVID-19 pneumonia and mortality risks after segregation by sex. Severe COVID-19 pneumonia was defined as having PaO(2) < 60 mmHg and SpO(2) < 94%, whereas non-severe COVID-19 pneumonia was defined as having PaO(2) ≥ 60 mmHg and SpO(2) ≥ 94%. RESULTS: The mortality rate of COVID-19 among men was double that in women. Severe COVID-19 pneumonia and non-surviving patients had a higher level of NLR, MLR, PLR, and MPR. The medians of NLR, MLR, and MPR in men were significantly higher, but PLR was not different between men and women. In men, these ratios had lower cut-offs than in women (NLR: 2.42 vs. 3.31, MLR: 0.24 vs. 0.35, and PLR: 83.9 vs. 151.9). The sensitivity of NLR, MLR, and PLR to predict pneumonia severity was better in men (69–77%), whereas their specificity was enhanced in women compared to men (70–76% vs. 23–48%). CONCLUSION: These ratios may represent widely available biomarkers in COVID-19 since they were significant predictors for disease severity and mortality although with different performances in men and women.