Does Neutrophil-to-lymphocyte Ratio at Admission Predict Severity and Mortality in COVID-19 Patients? A Systematic Review and Meta-analysis

Abstract

Background: Coronavirus disease-2019 (COVID-2019) pandemic continues to be a significant public health problem. Severe COVID-19 cases have a poor prognosis and extremely high mortality. Prognostic factor evidence can help healthcare providers understand the likely prognosis and identify subgroups likely to develop severe disease with increased mortality risk so that timely treatments can be initiated. This meta-analysis has been performed to evaluate the neutrophil-to-lymphocyte ratio (NLR) at admission as a prognostic factor to predict severe coronavirus disease and mortality.

Materials and methods: A literature search was conducted through April 30, 2021, to retrieve all published studies, including gray literature and preprints, investigating the association between NLR and severity or mortality in COVID-19 patients. Screening of studies and data extraction have been done by two authors independently. The methodological quality of the included studies was assessed by the Quality in Prognosis Studies (QUIPS) tool.

Results: Twenty-four studies involving 4,080 patients reported the prognostic value of NLR for severe COVID-19. The pooled sensitivity (SEN), specificity (SPE), and area under the curve were 0.75 (95% CI 0.69-0.80), 0.74 (95% CI 0.70-0.78), and 0.81 (95% CI 0.77-0.84). Fifteen studies involving 4,071 patients reported the prognostic value of NLR for mortality in COVID-19. The pooled sensitivity (SEN), specificity (SPE), and area under curve were 0.80 (95% CI 0.72-0.86), 0.78 (95% CI 0.69-0.85), and 0.86 (95% CI 0.83-0.89).

Conclusion: The prognostic value of NLR at admission for severity and mortality in patients with COVID-19 is good. Evaluating the NLR at admission can assist treating clinicians to identify early the cases likely to worsen. This would help to conduct early triage, identify potentially high-risk cases, and start optimal monitoring and management, thus reducing the overall mortality of COVID-19.

Trial registry: This meta-analysis was prospectively registered on PROSPERO database (Registration Number: CRD42021247801).

How to cite this article: Sarkar PG, Pant P, Kumar J, Kumar A. Does Neutrophil-to-lymphocyte Ratio at Admission Predict Severity and Mortality in COVID-19 Patients? A Systematic Review and Meta-analysis. Indian J Crit Care Med 2022;26(3):361-375.

Keywords: COVID-19 ARDS; COVID-19 mortality; Neutrophil-to-lymphocyte ratio; Prognosis.

Flowchart 1

Flow diagram for the identification of eligible studies

Fig. 1

Risk of bias assessment using QUIPS tool

Figs 2A and B

Funnel plots reporting publication bias. (A) Studies reporting NLR for severity; (B) Studies reporting NLR for mortality

Figs 3A and B

(A) Forest plot of the sensitivity and specificity of NLR to predict severity in COVID-19 patients. The pooled sensitivity (SEN) and specificity (SPE) were 0.75 (95% CI 0.69–0.80) and 0.74 (95% CI 0.70–0.78); (B) Summary receiver operating characteristic graph of the included studies. The AUC of NLR to predict severity was 0.81 (95% CI 0.77–0.84)

Figs 4A and B

(A) Forest plot of the sensitivity and specificity of NLR to predict mortality in COVID-19 patients. The pooled sensitivity (SEN) and specificity (SPE) were 0.80 (95% CI 0.72–0.85) and 0.78 (95% CI 0.70–0.85); (B) Summary receiver operating characteristic graph of the included studies. The AUC of NLR to predict mortality was 0.86 (95% CI 0.82–0.88)

Figs 5A and B

Meta-regression analysis: no statistically significant covariate effects of sex, diabetes, hypertension, COPD, CAD, heart failure, age, and NLR cutoff on the pooled sensitivity and pooled specificity for predicting: (A) Severity in COVID-19; and (B) Mortality in COVID-19