key: cord-1045713-bph0ro5v authors: Yan, Xisheng; Li, Fen; Wang, Xiao; Yan, Jie; Zhu, Fen; Tang, Shifan; Deng, Yingzhong; Wang, Hua; Chen, Rui; Yu, Zhili; Li, Yaping; Shang, Jingzhou; Zeng, Lingjun; Zhao, Jie; Guan, Chaokun; Liu, Qiaomei; Chen, Haifeng; Gong, Wei; Huang, Xin; Zhang, Yu‐Jiao; Liu, Jianguang; Dong, Xiaoyan; Zheng, Wen; Nie, Shaoping; Li, Dongsheng title: Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: A retrospective cross‐sectional study date: 2020-06-09 journal: J Med Virol DOI: 10.1002/jmv.26061 sha: 9f5f3a14f584bdcd33ea19eb4bd08db7e9435795 doc_id: 1045713 cord_uid: bph0ro5v This retrospective study was designed to explore whether neutrophil to lymphocyte ratio (NLR) is a prognostic factor in patients with coronavirus disease 2019 (COVID‐19). A cohort of patients with COVID‐19 admitted to the Tongren Hospital of Wuhan University from 11 January 2020 to 3 March 2020 was retrospectively analyzed. Patients with hematologic malignancy were excluded. The NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR values were measured at the time of admission. The primary outcome was all‐cause in‐hospital mortality. A multivariate logistic analysis was performed. A total of 1004 patients with COVID‐19 were included in this study. The mortality rate was 4.0% (40 cases). The median age of nonsurvivors (68 years) was significantly older than survivors (62 years). Male sex was more predominant in nonsurvival group (27; 67.5%) than in the survival group (466; 48.3%). NLR value of nonsurvival group (median: 49.06; interquartile range [IQR]: 25.71‐69.70) was higher than that of survival group (median: 4.11; IQR: 2.44‐8.12; P < .001). In multivariate logistic regression analysis, after adjusting for confounding factors, NLR more than 11.75 was significantly correlated with all‐cause in‐hospital mortality (odds ratio = 44.351; 95% confidence interval = 4.627‐425.088). These results suggest that the NLR at hospital admission is associated with in‐hospital mortality among patients with COVID‐19. Therefore, the NLR appears to be a significant prognostic biomarker of outcomes in critically ill patients with COVID‐19. However, further investigation is needed to validate this relationship with data collected prospectively. Municipal Population and Family Planning Commission Foundation, Grant/Award Number: WX16C03 confidence interval = 4.627-425.088). These results suggest that the NLR at hospital admission is associated with in-hospital mortality among patients with COVID-19. Therefore, the NLR appears to be a significant prognostic biomarker of outcomes in critically ill patients with COVID-19. However, further investigation is needed to validate this relationship with data collected prospectively. Wuhan and was confirmed as the cause of the NCIP. 5 Studies have shown that the disease caused by SARS-CoV-2, recently named as coronavirus disease 2019 (COVID- 19) by World Health Organization (WHO), could induce symptoms including fever, dry cough, dyspnea, fatigue, and lymphopenia in infected patients. In more severe cases, infections causing viral pneumonia may lead to severe acute respiratory syndrome (SARS) and even death. 2, 3, 6 Most of the initial cases of COVID-19, the disease caused by SARS-CoV-2, were all related to Huanan Seafood Wholesale Market, which sells aquatic products, live poultries, and wild animals. 2 The first batch of cases identified later showed no exposure or even no relation to Huanan Wholesale Market, and the human-to-human transmission was confirmed; moreover, nosocomial infections were reported in some health care workers. 3, 7 The number of fatalities due to COVID-19 is escalating. However, at this time, there are no specific vaccines or treatments for COVID-19. Most therapy consists of empirical antibiotics, antiviral therapy (oseltamivir), and systemic corticosteroids, which may have a limited effect on a fatal outcome. Evidence is now accumulating that the condition of some patients with COVID-19 deteriorates rapidly. As of 20 May 2020, WHO's online COVID-19 situation dashboard reveals there have been 4 801 202 confirmed cases of COVID-19, including 318 935 deaths. Thus, identifying the prognostic predictors of mortality in patients with COVID-19 might be useful for assessing the disease severity and making optimal treatment decisions. The neutrophil to lymphocyte ratio (NLR) has been suggested as a simple marker of the systemic inflammatory response in critical care patients. 8, 9 It has also been reported as an independent prognostic factor for noninfectious diseases, such as acute myocardial infarction, stroke, and several types of cancers. [10] [11] [12] In addition, NLR has been shown to be an independent indicator of both short-term and long-term mortality in critically ill patients. 13 Therefore, the NLR is a systemic inflammatory marker and a potential predictor of clinical risk and outcome in many diseases. To our knowledge, the utility of NLR to predict mortality in patients with COVID-19 has not been studied yet. Based on the previous studies, we hypothesized that NLR might relate to the disease severity and mortality in patients with COVID-19. In the current study, we sought to investigate whether NLR is a prognostic factor in patients with COVID-19. All adult (age >18 years old) patients who were diagnosed with COVID-19 according to WHO interim guidance were screened, and those who died or were discharged between 11 January 2020 and 3 March 2020 were included in our study. Data were collected from patients who were cured and discharged, or who died without a cure. were amplified and tested. The primers used were as follows: Target 1 (ORF1ab): forward primer, CCCTGTGGGTTTTACA-CTTAA; reverse pri-and myocardial enzymes. Chest radiographs or computed tomography scan were also done for all inpatients. 15 All patients age more than 18 years, and having neutrophil and lymphocyte counts results within 24 hours after admission, were included in this study. Patients who missed the neutrophil and lymphocyte records or with chronic hematological disorder were excluded. The electronic medical records of the patients were reviewed by a trained research team of physicians in Wuhan Third Hospital & Tongren Hospital of Wuhan University. Epidemiological, clinical, laboratory, treatment, and outcome data were analyzed. Patient data included demographics, medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, and treatment (antiviral, antibiotic, and corticosteroid therapies, and respiratory support). All data were checked by two physicians (HC and JS) and a third researcher (SN) adjudicated any difference in interpretation between the two primary reviewers. Baseline characteristics were presented as median with interquartile range (IQR) for continuous variables and as number with percentage for categorical variables. Comparisons between continuous variables were analyzed by the Student t and Mann-Whitney U test based on variable distribution, and categorical variables were analyzed by the χ 2 test. The data were tested to the Kolmogorov-Smirnov normality test for homogeneity of variance. To assess the relationship between the NLR and inhospital mortality, we did the receiver operating characteristics (ROC) curve and reported area under the ROC curve. Next, we grouped the patients based on the cut-off value of NLR during hospitalization. In addition, to adjust potential confounding with variables, we did a multivariate regression analysis. The following variables were considered for multivariable adjustment: age, gender, smoking status, laboratory data, comorbidities, and intensive care unit (ICU) length of stay. The results were reported as hazard ratio and 95% confidence interval (95% CI). All statistical processes were performed with the Statistical Package for the Social Sciences 20.0 (SPSS Inc, Chicago, IL). A two-sided P value less than .05 was considered statistically significant. Nonparametric ROC analysis showed that the cut-off value of the ROC curve as the optimal threshold for in-hospital mortality was 11 .75, that is, when NLR was more than 11.75, the model had the strongest predictive ability, with an area under the curve of 0.945% and 95% CI of 0.917 to 0.973 (Figure 1 ), sensitivity of 97.5%, specificity of 78.1%, and Yoden index of 0.756. We further divided patients into two groups using NLR greater than or less than or equal to 11.75 as the criterion to compare the clinical characteristics of patients with a high NLR and those with a low NLR (Table 2 ). After multivariate logistic regression analysis, high-NLR remained independently associated with in-hospital death. In addition, we found that higher levels of hs-CRP, NT-proBNP, and blood urea nitrogen, as well as history of hypertension, respiratory failure, digestive system diseases, and cerebrovascular diseases, were also independently associated with in-hospital mortality (Table 3 ). In this study, we found there was an association between NLR and the clinical outcomes in patients with COVID-19. 16 Based on the ROC curve analysis, the NLR showed the significant performance to predict in-hospital mortality. The cut-off level for the NLR was 11.75 ( Figure 1 ). Our study supports that a high NLR is a strong predictor for in-hospital mortality in pa- Tracking COVID-19 responsibly. Lancet Clinical features of patients infected with 2019 novel coronavirus in Wuhan Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study First case of 2019 novel coronavirus in the United States A novel coronavirus from patients with pneumonia in China Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-toperson transmission: a study of a family cluster Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill Prognostic significance of neutrophil-to-lymphocyte ratio in patients with sepsis: a prospective observational study Neutrophil to lymphocyte ratio is related to stent thrombosis and high mortality in patients with acute myocardial infarction Correlation and prognostic role of neutrophil to lymphocyte ratio and SYNTAX score in patients with acute myocardial infarction treated with percutaneous coronary intervention: a six-year experience Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: a meta-analysis Inflammation biomarkers in blood as mortality predictors in community-acquired pneumonia admitted patients: importance of comparison with neutrophil count percentage or neutrophil-lymphocyte ratio New coronavirus pneumonia prevention and control program Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Neutrophil to lymphocyte ratio is associated with in-hospital mortality in older adults admitted to the emergency department The role of neutrophil to lymphocyte count ratio in the differential diagnosis of pulmonary tuberculosis and bacterial community-acquired pneumonia: a cross-sectional study at Ayder and Mekelle Hospitals Neutrophil to lymphocyte ratio and cardiovascular diseases: a review The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer Neutrophil-lymphocyte ratio as a predictor of adverse outcomes of acute pancreatitis Dysregulation of immune response in patients with COVID-19 in Wuhan, China SARS immunity and vaccination Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study Older adults in the emergency department: a systematic review of patterns of use, adverse outcomes, and effectiveness of interventions White blood cell counts, leukocyte ratios, and eosinophils as inflammatory markers in patients with coronary artery disease Older patients in the emergency department: a review Neutrophils in development of multiple organ failure in sepsis Persistent lymphopenia after diagnosis of sepsis predicts mortality Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern Lymphocytopenia and neutrophillymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality-a cohort study Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: A retrospective cross-sectional study The authors declare that there are no conflict of interests. http://orcid.org/0000-0001-6110-9630