Predictive value of neutrophil-to-lymphocyte ratio and other inf lammatory indicators in estimating clinical severity of coronavirus disease

Guang-qing Yu, Qing Zhang, Run-chang Wang, Shi-qin Jiang

1 Department of Microbiological Laboratory, Bao’an District Center for Disease Control and Prevention, Shenzhen 518101, China

2 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan 430030, China

3 Department of Clinical Pharmacy, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen 518104, China

Corresponding Author: Shi-qin Jiang, Email: jiangsq5262@163.com

Dear editor,

The recent outbreak of coronavirus disease (COVID-19)has become a major public health issue caused by 2019 novel coronavirus (2019-nCoV).[1]Severe COVID-19 patients may reveal a dysregulated immune response that allows the development of v iral hyperinf lammation.[2]In the fight against COVID-19, inflammatory parameters towards illness severity should be identified to improve the prognosis of patients. In this study, we aimed to assess the discriminative ability of several inf lammation indicators in severe COVID-19 infection.

We conducted a comprehensive search through electronic databases until May 26, 2020: PubMed, the Cochrane Library, EMBASE, and Web of Science.Keywords included COVID-19, nCoV-2019, 2019-nCoV,severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), neutrophil-to-lymphocyte ratio (NLR), plateletto-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). To be included, studies must provide mean and standard deviation (SD) values or median and interquartile range or adjusted odds ratio (OR) with corresponding 95% conf idence interval (CI). The pooled weighted mean difference (WMD) and pooledORwere worked out by STATA 12.0.

After the application of selection criteria, there were 13 studies[2-14]with 2,140 patients included that provided data describing NLR, PLR, and MLR on COVID-19 cases and in-hospital mortality. The meta-analysis for the continuous outcome variables included ten studies,[2-11]and for the binary variables included six studies.[5,8,10,12-14]There were two studies reporting clear data on in-hospital mortality.[12,14]

Overall, more severe COVID-19 infection was associated with higher NLR (WMD=3.55, 95%CI2.47-4.64,P＜0.001) and higher MLR (WMD=0.39, 95%CI0.19-0.59,P＜0.001). There was no signif icant difference in PLR (WMD=81.48, 95%CI-93.44 to 256.40,P=0.361) between the severe group and the non-severe group. For COVID-19 patients, NLR with the pooledORvalue could predict the severe infection (OR=1.40,95%CI1.02-1.93,P=0.038) and in-h ospital mortality(OR=1.08, 95%CI1.02-1.15,P=0.009).

As for blood parameters in severe COVID-19, seven studies described counts of white blood cell (WBC),neutrophil, and lymphocyte in the non-severe and severe groups. Patients with severe COVID-19 had higher WBC counts (WMD=1.48×109/L, 95%CI0.90-2.05,P＜0.001),higher neutrophil counts (WMD=1.80×109/L, 95%CI1.25-2.35,P＜0.001), and fewer lymphocyte counts (WMD=-0.35×109/L, 95%CI-0.48 to -0.22,P＜0.001) than those in the non-severe group. Four studies compared platelet counts between the two groups, and severe cases demonstrated lower platelet counts (WMD= -26.39×109/L, 95%CI-46.50 to -6.27,P＜0.010) compared with the non-severe group.Three studies reported the monocyte counts. However, no statistical difference was found between the two groups(WMD=0.00×109/L, 95%CI-0.02 to 0.03,P=0.731).Seven studies depicted C-reactive protein (CRP)levels, and severe cases also had higher CRP levels(WMD=41.23 mg/L, 95%CI28.86-53.60,P＜0.001).The pooledWMDfor blood parameters of the included studies are presented in Table 1.

Table 1. Pooled outcomes of blood parameters in severe COVID-19

Meta-regression analysis showed that the increased NLR in severe COVID-19 patients was associated with WBC (P=0.007) and neutrophil (P=0.011) but not lymphocyte, CRP, age, or the study size of COVID-19.There was no evidence of publication bias according to theWMDof NLR. Sensitivity analysis showed no significant differences produced by excluding every single study.

In conclusion, during severe COVID-19 infection,NLR, MLR, WBC, neutrophil, and CRP were significantly increased, while lymphocyte and platelet were signif icantly decreased. Patients with a higher level of NLR experienced a higher risk of in-hospital mo rtality. The assessments of NLR and other inf lammatory indicators may help physicians to identify severe patients with COVID-19 and predict the prognosis of this infection.

Funding:None.

Ethical approval:Not needed.

Conflicts of interest:The authors have no conflict of interest to declare.

Contributors:GQY and QZ contributed equally to this work.GQY, QZ, RCW searched the database, collected the data and performed the meta-analysis. GQY and SQJ reviewed and revised the manuscript. All authors approved the f inal version.