Neutrophil‐to‐lymphocyte ratio as a predictor of clinical outcomes in critically ill COVID‐19 patients: A retrospective observational study

Abstract Background Timely identification of patients at risk of worse clinical outcomes is vital in managing coronavirus disease 2019 (COVID‐19). The neutrophil‐to‐lymphocyte ratio (NLR) calculated from complete blood count can predict the degree of systemic inflammation and guide therapy accordingly. Hence, we did a study to investigate the role of NLR value on intensive care unit (ICU) admission in predicting clinical outcomes of critically ill COVID‐19 patients. Methods We conducted a retrospective analysis of electronic health records of COVID‐19 patients admitted to ICUs at Hazm Mebaireek General Hospital, Qatar, from March 7, 2020 to July 18, 2020. Patients with an NLR equal to or higher than the cut‐off value derived from the receiver operating characteristic curve were compared to those with an NLR value below the cut‐off. The primary outcome studied was all‐cause ICU mortality. The secondary outcomes evaluated were the requirement of mechanical ventilation and ICU length of stay (LOS). Results Five hundred and nineteen patients were admitted to ICUs with severe COVID‐19 infection during the study period. Overall, ICU mortality in the study population was 14.6% (76/519). NLR on ICU admission of ≥6.55 was obtained using Youden's index to predict ICU mortality, with a sensitivity of 81% and specificity of 41%. Mortality was significantly higher in patients with age ≥60 years (p < 0.001), chronic kidney disease (p = 0.03), malignancy (p < 0.002), and NLR ≥ 6.55 (p < 0.003). There was also a significant association between the requirement of mechanical ventilation (34.7% vs. 51.8%, p < 0.001) and increased ICU LOS (8 vs. 10 days, p < 0.01) in patients with ICU admission NLR ≥ 6.55. Conclusion Higher NLR values on ICU admission are associated with worse clinical outcomes in critically ill COVID‐19 patients.


| INTRODUCTION
Complete blood count (CBC) is a simple, low-risk, inexpensive test routinely requested in clinical practice. Despite being used for many years, new implications of CBC are still being explored, with neutrophilto-lymphocyte ratio (NLR) being one of them. NLR is calculated from the white cell differential count as a ratio of the number of neutrophils divided by the number of lymphocytes. It is an inflammatory biomarker used in the early detection of sepsis, 1 screening and diagnosis of inflammatory diseases, 2 identifying and managing surgical emergencies, 3 predicting postoperative complications, 4 and prognostication of malignancies. 5 Coronavirus disease (COVID-19) is an infectious respiratory system illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initial cases were identified in Wuhan city, China, in December 2019. Since then, the infection quickly spread and was declared a pandemic by World Health Organization (WHO) on March 11, 2020. 6 The majority of infected people experience mild to moderate symptoms and recover without specific treatment. However, older people and those with medical comorbidities are more likely to develop serious illnesses. So far, more than 599 million cases and 6.4 million deaths have been reported globally due to  There is growing evidence that a hyperinflammatory response to SARS-CoV-2 results in rapid deterioration and worse outcomes in critically ill COVID-19 patients. 8 However, a quick, easy-to-perform, and reliable test to detect pathogenic inflammation and guide management before clinical worsening occurs is still lacking. NLR can be used by itself or in combination with other criteria to identify patients at risk of disease progression and intervene promptly. However, the value of NLR associated with severe disease and adverse outcomes is not well established.
This persuaded us to conduct a retrospective study investigating the role of NLR as a marker to identify high-risk patients and predict unfavorable clinical outcomes in critically ill COVID-19 patients.

| Statistical analysis
The IBM Statistical Package for Social Sciences (SPSS version 24.0) was used to analyze the data. Numerical variables were summarized using mean ± SD or median (IQR) according to distribution, while categorical variables were summarized as frequencies or percentages.
The χ 2 test and Fisher's exact test were used to compare categorical data. As the numerical data followed a non-normal distribution, twotailed nonparametric tests, namely, Spearman's correlation and Youden's index, was 6.55 for NLR on ICU admission, with a sensitivity of 81% and specificity of 41% ( Figure 1). Several variables were evaluated for association with mortality, as presented in Khatib: Supervision; writingreview and editing.

ACKNOWLEDGMENT
The publication of this article was funded by Qatar National Library.

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The data supporting this study's findings are available from the corresponding author upon reasonable request.

ETHICS STATEMENT
The study was approved by the MRC at Hamad Medical Corporation

TRANSPARENCY STATEMENT
The lead author Husain Shabbir Ali affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.