World Journal of Emergency Medicine, 2021, 12(1): 79-80 doi: 10.5847/wjem.j.1920-8642.2021.01.014

Letter to the Editor

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

Guang-qing Yu1, Qing Zhang2, Run-chang Wang2, Shi-qin Jiang,3

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

Received: 2020-06-15   Accepted: 2020-09-10   Online: 2021-03-15

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Guang-qing Yu, Qing Zhang, Run-chang Wang, Shi-qin Jiang. Predictive value of neutrophil-to-lymphocyte ratio and other inflammatory indicators in estimating clinical severity of coronavirus disease. World Journal of Emergency Medicine, 2021, 12(1): 79-80 doi:10.5847/wjem.j.1920-8642.2021.01.014

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 viral hyperinflammation.[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 inflammation 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 (SARS-CoV-2), neutrophil-to-lymphocyte ratio (NLR), platelet-to-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% confidence interval (CI). The pooled weighted mean difference (WMD) and pooled OR were worked out by STATA 12.0.

After the application of selection criteria, there were 13 studies[2,3,4,5,6,7,8,9,10,11,12,13,14] 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,[2,3,4,5,6,7,8,9,10,11] 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% CI 2.47-4.64, P<0.001) and higher MLR (WMD=0.39, 95% CI 0.19-0.59, P<0.001). There was no significant 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 pooled OR value could predict the severe infection (OR=1.40, 95% CI 1.02-1.93, P=0.038) and in-hospital mortality (OR=1.08, 95% CI 1.02-1.15, 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% CI 0.90-2.05, P<0.001), higher neutrophil counts (WMD=1.80×109/L, 95% CI 1.25-2.35, 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% CI 28.86-53.60, P<0.001). The pooled WMD for blood parameters of the included studies are presented in Table 1.

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

IndicatorsNumber of studies
reporting variables
Number of
patients analyzed
Pooled WMD with 95% CII2P-value
WBC[2-4,6-9]71,5141.48×109/L (0.90-2.05)65.1%<0.001
Neutrophil[2-4,6-9]71,5141.80×109/L (1.25-2.35)61.4%<0.001
Lymphocyte[2-4,6-9]71,514-0.35×109/L (-0.48 to -0.22)81.7%<0.001
Monocyte[2,4,6]36610.00×109/L (-0.02 to 0.03)0.0%0.731
Platelet[3,6,8,9]4894-26.39×109/L (-46.50 to -6.27)66.1%<0.010
CRP[2,4,5,7-10]71,53941.23 mg/L (28.86-53.60)72.2%<0.001

WBC: white blood cell; CRP: C-reactive protein; WMD: weighted mean difference; CI: confidence interval.

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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 the WMD of 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 significantly decreased. Patients with a higher level of NLR experienced a higher risk of in-hospital mortality. The assessments of NLR and other inflammatory 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 final version.

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BACKGROUND: Several studies have described the clinical characteristics of patients with novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19), indicating severe patients tended to have higher neutrophil to lymphocyte ratio (NLR). Whether baseline NLR could be an independent predictor of in-hospital death in Chinese COVID-19 patients remains to be investigated. METHODS: A cohort of patients with COVID-19 admitted to the Zhongnan Hospital of Wuhan University from January 1 to February 29 was retrospectively analyzed. The baseline data of laboratory examinations, including NLR, were collected. Univariate and multivariate logistic regression models were developed to assess the independent relationship between the baseline NLR and in-hospital all-cause death. A sensitivity analysis was performed by converting NLR from a continuous variable to a categorical variable according to tertile. Interaction and stratified analyses were conducted as well. RESULTS: 245 COVID-19 patients were included in the final analyses, and the in-hospital mortality was 13.47%. Multivariate analysis demonstrated that there was 8% higher risk of in-hospital mortality for each unit increase in NLR (Odds ratio [OR]=1.08; 95% confidence interval [95% CI], 1.01 to 1.14; P=0.0147). Compared with patients in the lowest tertile, the NLR of patients in the highest tertile had a 15.04-fold higher risk of death (OR=16.04; 95% CI, 1.14 to 224.95; P=0.0395) after adjustment for potential confounders. Notably, the fully adjusted OR for mortality was 1.10 in males for each unit increase of NLR (OR=1.10; 95% CI, 1.02 to 1.19; P=0.016). CONCLUSIONS: NLR is an independent risk factor of the in-hospital mortality for COVID-19 patients especially for male. Assessment of NLR may help identify high risk individuals with COVID-19.

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BACKGROUND: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. METHODS: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. FINDINGS: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0.6 (0.6-0.8)] but increases in neutrophil counts [4.7 (3.6-5.8)] than 27 mild cases [1.1 (0.8-1.4); 2.0 (1.5-2.9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8(+) T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-gamma levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0.93) and neutrophil-to-CD8(+) T cell ratio (N8R) (AUC =0.94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19. INTERPRETATION: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases. FUNDING: The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.

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The characteristics and death risk factors of 132 COVID-19 pneumonia patients with comorbidities: a retrospective single center analysis in Wuhan, China

Diabetes Res Clin Pract. 2020; 166:108299.

DOI:10.1016/j.diabres.2020.108299      URL     PMID:32623030      [Cited within: 3]

AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of 11 mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.2%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of >/=1.5 mug/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of >/=10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11 mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.

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