The Role of Neutrophil-to-Lymphocyte Ratio in Risk Stratification and Prognostication of COVID-19: A Systematic Review and Meta-Analysis

Abstract

Several studies have proposed that the neutrophil–lymphocyte ratio (NLR) is one of the various biomarkers that can be useful in assessing COVID-19 disease-related outcomes. Our systematic review analyzes the relationship between on-admission NLR values and COVID-19 severity and mortality. Six different severity criteria were used. A search of the literature in various databases was conducted from 1 January 2020 to 1 May 2021. We calculated the pooled standardized mean difference (SMD) for the collected NLR values. A meta-regression analysis was performed, looking at the length of hospitalization and other probable confounders, such as age, gender, and comorbidities. A total of sixty-four studies were considered, which included a total of 15,683 patients. The meta-analysis showed an SMD of 3.12 (95% CI: 2.64–3.59) in NLR values between severe and non-severe patients. A difference of 3.93 (95% CI: 2.35–5.50) was found between survivors and non-survivors of the disease. Upon summary receiver operating characteristics analysis, NLR showed 80.2% (95% CI: 74.0–85.2%) sensitivity and 75.8% (95% CI: 71.3–79.9%) specificity for the prediction of severity and 78.8% (95% CI: 73.5–83.2%) sensitivity and 73.0% (95% CI: 68.4–77.1%) specificity for mortality, and was not influenced by age, gender, or co-morbid conditions. Conclusion: On admission, NLR predicts both severity and mortality in COVID-19 patients, and an NLR > 6.5 is associated with significantly greater the odds of mortality.

Prognostic Nutritional Index, Controlling Nutritional Status (CONUT) Score, and Inflammatory Biomarkers as Predictors of Deep Vein Thrombosis, Acute Pulmonary Embolism, and Mortality in COVID-19 Patients

“…Furthermore, the predictive role of these markers has been proven in the cases of renal pathologies [ 32 , 33 , 34 ], cardiovascular pathologies [ 35 , 36 , 37 , 38 , 39 , 40 ], oncological pathologies [ 41 , 42 , 43 , 44 ], and, most recently, for COVID-19 patients [ 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

Inflammatory Biomarkers as Prognostic Factors of Acute Deep Vein Thrombosis Following the Total Knee Arthroplasty

“…Hematological reports, based on neutrophil, monocyte, lymphocyte, and platelets total number: monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), are routine inflammatory biomarkers, easy to use, with low costs. Moreover, the predictive role of these reports has been recently demonstrated in the literature in the case of cardiovascular pathology [ 24 , 25 , 26 , 27 ], pulmonary embolism [ 28 , 29 ], chronic kidney disease [ 30 , 31 , 32 ], the case of COVID-19 patients [ 33 , 34 , 35 , 36 , 37 , 38 ], as well as in the case of peri-prosthetic infection after total joint arthroplasty [ 39 , 40 , 41 ].…”

Carotid Plaque Features and Inflammatory Biomarkers as Predictors of Restenosis and Mortality Following Carotid Endarterectomy

“…Among the systemic inflammatory biomarkers, the most accessible and easy to implement in current medical practice are hematological reports based on the total number of monocytes, neutrophils, lymphocytes, and platelets, respectively: monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic Inflammation Response Index (SIRI), and aggregate index of systemic inflammation (AISI), whose predictive role has been demonstrated in the case of cardiovascular pathologies [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ], oncological pathologies [ 24 , 25 , 26 , 27 ], chronic kidney disease [ 28 , 29 , 30 ], and, more recently, in the case of COVID-19 patients [ 31 , 32 , 33 , 34 , 35 , 36 , 37 ].…”