Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: A meta-analysis

Abstract

Background: The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, was suggested to be predictive of severity and mortality in COVID-19 patients. Here, we investigated whether NLR levels on admission could predict the severity and mortality of COVID-19 patients.

Methods: A literature search was conducted on 23 July 2020 to retrieve all published articles, including grey literature and preprints, investigating the association between on-admission NLR values and severity or mortality in COVID-19 patients. A meta-analysis was performed to determine the overall standardized mean difference (SMD) in NLR values and the pooled risk ratio (RR) for severity and mortality with the 95% Confidence Interval (95%CI).

Results: A total of 38 articles, including 5699 patients with severity outcomes and 6033 patients with mortality outcomes, were included. The meta-analysis showed that severe and non-survivors of COVID-19 had higher on-admission NLR levels than non-severe and survivors (SMD 0.88; 95%CI 0.72-1.04; I² = 75.52% and 1.87; 95%CI 1.25-2.49; I² = 97.81%, respectively). Regardless of the different NLR cut-off values, the pooled mortality RR in patients with elevated vs. normal NLR levels was 2.74 (95%CI 0.98-7.66).

Conclusion: High NLR levels on admission were associated with severe COVID-19 and mortality. Further studies need to focus on determining the optimal cut-off value for NLR before clinical use.

Keywords: COVID-19; Meta-analysis; Mortality; Neutrophil-to-lymphocyte ratio; Severity.

Fig. 1

Prisma diagram for study selection. A systematic literature search was done on 23 July 2020 to identify peer-reviewed papers, preprints, and grey literature.

Fig. 2

Neutrophil-to-lymphocyte ratio (NLR) value on admission in severe vs. non-severe COVID-19 patients. A) Forest Plot for all included studies using the DerSimonian-Laird random-effect models showing elevated NLR values on admission in severe compared to non-severe COVID-19. B) Publication bias analysis of all included studies using the Funnel Plot indicating a potential publication bias.

Fig. 3

Bubble plot for meta-regression. The association between NLR values on admission and severity of COVID-19 (A) and COVID-19 mortality (B) was not affected by age (p = 0.236; p = 0.595, respectively).

Fig. 4

Neutrophil-to-lymphocyte ratio (NLR) value on admission in non-survivor vs. survivor of COVID-19 patients. A) Forest Plot for all included studies using the DerSimonian-Laird random-effects model showing elevated NLR values on admission in non-survivors compared to survivors of COVID-19. B) Publication bias analysis of all included studies using the Funnel Plot indicating a potential publication bias. C) Forest Plot using the DerSimonian-Laird random-effects model showing the association between NLR value on admission and all-cause mortality risk.