(1) Introduction: In the present study, we investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) as a marker of severity and mortality in COVID-19 infection. (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate to severe coronavirus 19 (COVID-19), all of whom were hospitalized after being admitted to the emergency department (ED). (3) Results: A total of 1035 patients were included in our study. Neither lymphocytes, platelets or PLR were associated with disease severity. Lymphocyte count was significantly lower and PLR values were significantly higher in the group of patients who died, and both were associated with mortality in the univariate analysis (OR: 0.524, 95% CI: (0.336–0.815), p = 0.004) and (OR: 1.001, 95% CI: (1.000–1.001), p = 0.042), respectively. However, the only biological parameter significantly associated with mortality in the multivariate analysis was platelet count (OR: 0.996, 95% CI: (0.996–1.000), p = 0.027). The best PLR value for predicting mortality in COVID-19 was 356.6 (OR: 3.793, 95% CI: (1.946–7.394), p < 0.001). (4) Conclusion: A high PLR value is however associated with excess mortality.

(1) Introduction: Multiple studies have demonstrated that lymphocyte count monitoring is a valuable prognostic tool for clinicians during inflammation. The aim of our study was to determine the prognostic value of delta lymphocyte H24 from admission from the emergency department for mortality and severity of SARS-CoV-2 infection. (2) Methods: We have made a retrospective and multicentric study in six major hospitals of northeastern France. The patients were hospitalized and had a confirmed diagnosis of SARS-CoV-2 infection. (3): Results: A total of 1035 patients were included in this study. Factors associated with infection severity were CRP > 100 mg/L (OR: 2.51, CI 95%: (1.40–3.71), p < 0.001) and lymphopenia < 800/mm3 (OR: 2.15, CI 95%: (1.42–3.27), p < 0.001). In multivariate analysis, delta lymphocytes H24 (i.e., the difference between lymphocytes values at H24 and upon admission to the ED) < 135 was one of the most significant biochemical factors associated with mortality (OR: 2.23, CI 95%: (1.23–4.05), p = 0.009). The most accurate threshold for delta lymphocytes H24 was 75 to predict severity and 135 for mortality. (4) Conclusion: Delta lymphocytes H24 could be a helpful early screening prognostic biomarker to predict severity and mortality associated with COVID-19.