Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients

Abstract

Background: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). Objectives: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte (dNLR) for invasive mechanical ventilation (IMV) need and death in critically ill COVID-19 patients. Methods: Observational, retrospective, and multicentric analysis on 272 patients with severe or critical COVID-19 from two tertiary centers. Hematological indices were adjusted for confounders through multivariate analysis using Cox regression. Results: Patients comprised 186 males and 86 females with no difference across groups (p > 0.05). ΔNLR > 2 had the best independent predictive value for IMV need (HR = 5.05 (95% CI, 3.06–8.33, p < 0.0001)), followed by ΔSII > 340 (HR = 3.56, 95% CI 2.21–5.74, p < 0.0001) and ΔdNLR > 1 (HR = 2.61, 95% CI 1.7–4.01, p < 0.0001). Death was also best predicted by an NLR > 11 (HR = 2.25, 95% CI: 1.31–3.86, p = 0.003) followed by dNLR > 6.93 (HR = 1.89, 95% CI: 1.2–2.98, p = 0.005) and SII > 3700 (HR = 1.68, 95% CI: 1.13–2.49, p = 0.01). Conclusions: Dynamic changes of NLR, SII, and dNLR independently predict IMV need and death in critically ill COVID-19 patients.

Development and Internal Validation of a New Prognostic Model Powered to Predict 28-Day All-Cause Mortality in ICU COVID-19 Patients—The COVID-SOFA Score

“…In our cohort, demographic characteristics were similar to those of other study cohorts, non-survivors being older and having more comorbidities [ 17 , 18 ]. Regarding hematological changes induced by SARS-CoV-2, these were similar with previously reported data, with lymphopenia, neutrophilia and higher D-dimer values being associated with poor outcome [ 19 , 20 ]. The SOFA score values in COVID-19 patients admitted to ICU have important variations between studies [ 19 ], depending on: (i) the selected patients, (ii) the moment of measurement (e.g., ICU admission, before endotracheal intubation, repeated measurements), and (iii) missing data and how points were assigned [ 21 , 22 , 23 , 24 , 25 ].…”

“…In order to build the predictive model, after stepwise multivariate Cox PH regression was performed, the SOFA score independently predicted death together with age and NLR. Both age and NLR are considered to have independent predictive value for death [ 17 , 18 , 19 ], progression to severe or critical disease [ 19 , 30 ] and need for invasive mechanical ventilation [ 19 ] in COVID-19 patients. Moreover, given the fact that age and NLR have independent prognostic value in bacterial sepsis [ 31 , 32 ], we can speculate that this new score is reproducible in patients with COVID-19 and bacterial co-infection.…”

“…Based on the published data [ 20 , 33 , 34 , 35 ], quantitative and qualitative alterations of lymphocytes can be considered as a separate organ dysfunction in viral sepsis secondary to SARS-CoV-2 infection. Lastly, NLR values are highly correlated with C-reactive protein and D-dimer values [ 19 ].…”

Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases

“…Its predictive value for progression of severe disease [ 37 ] and mortality [ 38 ] was largely confirmed by several studies [ 39 , 40 ]. In a study carried out in an ICU [ 41 ], non-survivors had significantly lower lymphocyte values (0.99 × 10 3 /mL (±0.87) vs. 0.77 × 10 3 /mL (±0.4), p = 0.003) and higher dNLR (7.13 (±3.9) vs. 8.77 (±4.58), p = 0.002) and NLR (12.34 (±9.54) vs. 15.4 (±9.43), p = 0.001) values. Moreover, NLR and dNLR showed the best independent predictive values for invasive mechanical ventilation need and death [ 41 ].…”

“…In a study carried out in an ICU [ 41 ], non-survivors had significantly lower lymphocyte values (0.99 × 10 3 /mL (±0.87) vs. 0.77 × 10 3 /mL (±0.4), p = 0.003) and higher dNLR (7.13 (±3.9) vs. 8.77 (±4.58), p = 0.002) and NLR (12.34 (±9.54) vs. 15.4 (±9.43), p = 0.001) values. Moreover, NLR and dNLR showed the best independent predictive values for invasive mechanical ventilation need and death [ 41 ]. Data from our group [ 42 ] showed that in-hospital mortality in COVID-19 patients is predicted by a NLR > 11.38 (AUC = 0.771, p = < 0.0001, sensitivity = 77.5%, specificity = 65.9%).…”