The diagnostic and prognostic role of neutrophil-to-lymphocyte ratio in COVID-19: a systematic review and meta-analysis

Abstract

Background: The world urgently requires surrogate markers to diagnose COVID-19 and predict its progression. The severity is not easily predicted via currently used biomarkers. Critical COVID-19 patients need to be screened for hyperinflammation to improve mortality but expensive cytokine measurement is not routinely conducted in most laboratories. The neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker in patients with various diseases. We evaluated the diagnostic and prognostic accuracy of the NLR in COVID-19 patients.Methods: We searched for relevant articles in seven databases. The quantitative analysis was conducted if at least two studies were evaluating the NLR role in COVID-19.Results: We included 8,120 individuals, including 7,482 COVID-19 patients, from 32 articles. Patients with COVID-19 had significantly higher levels of NLR compared to negative individuals. Advanced COVID-19 stages had significantly higher levels of NLR than earlier stages.Expert Opinion: We found significantly higher levels of NLR in advanced stages compared to earlier stages of COVID-19 with good accuracy to diagnose and predict the disease outcome, especially mortality prediction. A close evaluation of critical SARS-CoV-2 patients and efficient early management are essential measures to decrease mortality. NLR could help in assessing the resource allocation in severe COVID-19 patients even in restricted settings.

Keywords: Neutrophil-to-lymphocyte ratio – covid-19 – coronavirus – diagnosis – prognosis – systematic review – meta-analysis.

Figure 1.

The PRISMA chart showing the flow of publications via the review process. Out of 291 articles, a total of 32 articles with 8,120 individuals, including 7,482 COVID-19 patients, were included.

Figure 2.

The prognostic accuracy of NLR for prediction of severity of COVID-19. (a) forest plot showing the sensitivity and specificity with its 95% confidence intervals, (b) forest plot showing the positive and negative LR with its 95% confidence intervals, (c) uni-variable meta-regression to explore heterogeneity between studies assessing the prognostic accuracy of NLR, (d) Deeks’ funnel plot asymmetry test for detecting the publication bias. Each circle indicates an individual study in the meta-analysis. The figures show that the accuracy measures for predicting severity were a sensitivity of 75% [69, 81%], a specificity of 79% [72, 84%] and DOR of 11.45 [7.74, 16.93]) and the P-values for heterogeneity and publication bias were <0.001.

Figure 3.

The SROC and the AUC with each circle indicates an individual study in the meta-analysis. The curve is the regression that summarizes the overall test accuracy. The AUC = 0.83.

Figure 4.

A meta-analysis of the association between the NLR and COVID-19 severity. Forest plot showing the pooled MD with its 95% CI using a random-effects model. The black diamond represents the pooled effect size. The figure shows that moderate and severe COVID-19 infected patients had significantly higher levels of NLR than mild and non-severely infected patients.