Biomarkers Predictive of Extubation and Survival of COVID-19 Patients

Abstract

Purpose Many patients with COVID-19 who develop acute respiratory distress syndrome (ARDS) require prolonged periods of mechanical ventilation. Mechanical ventilation may amplify ventilator-associated complications and extend resource utilization. A better understanding of prognostic indicators could help in the planning and distribution of resources, particularly in resource-limited areas. We analyzed laboratory studies of intubated COVID-19 patients with the goal of identifying biomarkers that may predict extubation success and survival to discharge. Methods A retrospective chart review was performed on all COVID-19 patients requiring mechanical ventilation between January 3, 2020, and January 7, 2020, in a single academic tertiary care center in Northeastern New York State. The electronic medical record was used to collect 14 laboratory variables at three time points: admission, intubation, and extubation (including terminal extubation) for all intubated intensive care unit (ICU) patients treated for COVID-19. Mean laboratory values were analyzed with the Mann-Whitney U test. Categorical variables were analyzed with the two-sample Wilcoxon rank-sum test. Results Seventy-two patients met the inclusion criteria. Forty-three patients were male. The mean age was 61 years. The overall mortality was 50%. On admission, intubated patients who survived had significantly higher platelet counts (p=0.024), and absolute lymphocyte counts (ALC; p=0.047). Notably, ferritin (p=0.018) and aspartate transaminase (AST; p=0.0045) levels were lower in survivors. At the time of intubation, survivors again had a higher platelet count (p=0.024) and ALC (p=0.037) levels. They had a lower D-dimer (p=0.0014), ferritin (p=0.0015), lactate dehydrogenase (LDH; p=0.0145), and AST (p=0.018) compared to intubated patients who died. At extubation, survivors had higher platelet count (p=0.0002), ALC (p=0.0013), and neutrophil/lymphocyte ratio (NLR; p=0.0024). Survivors had lower d-dimer (p=0.035), ferritin (p=0.0012), CRP (p=0.045), LDH (p=0.002), AST (p<0.001), and ALK (p=0.0048). Conclusions Biomarkers associated with increased risk of mortality include platelet count, ALC, lymphocyte percentage, NLR, D-dimer, ferritin, C-reactive protein (CRP), AST, alanine transaminase (ALT), and alkaline phosphatase (ALK). This study provides additional evidence that these biomarkers have prognostic value in patients with severe COVID-19. The goal is to find objective surrogate markers of disease improvement or success of extubation. When considered within the larger body of data, it is our hope that a mortality risk calculator can be generated for intubated COVID-19 patients.

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

“…In our study, this was highlighted by the change in the discriminative power (value of AUC) of these indices over time. AUC values for the derived hematological indices, even the ICU admission values, are roughly in line with the AUC reported in other studies [ 12 , 15 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], but different cut-off values were taken. For example, the cut-off value range for NLR as a predictor for disease severity or death is very wide—from 3.3 to 15.2 [ 12 , 15 , 24 , 27 , 32 ]—making it difficult to establish a final cut-off value.…”

“…NLR is the most studied hematological index in COVID-19 patients and higher values were correlated with disease severity and progression [ 12 , 13 , 23 , 24 , 25 ], death [ 13 , 14 , 22 , 24 , 26 ], and treatment response [ 27 ]. Our observations are in agreement for NLR but also for PLR, MLR, SII, and dNLR and are correlated with results from other studies [ 11 , 12 , 13 , 14 , 15 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 ].…”

“…NLR is the most studied hematological index in COVID-19 patients and higher values were correlated with disease severity and progression [ 12 , 13 , 23 , 24 , 25 ], death [ 13 , 14 , 22 , 24 , 26 ], and treatment response [ 27 ]. Our observations are in agreement for NLR but also for PLR, MLR, SII, and dNLR and are correlated with results from other studies [ 11 , 12 , 13 , 14 , 15 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 ]. In our study, dynamic changes of these hematological indices had stronger correlations and better predictive value for progression to IMV in non-intubated patients and death compared with ICU admission values.…”

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

“…In the early disease course, neuron-specific enolase (NSE) can be used to differentiate patients who are going to develop dyspnea ( 21 ). On admission, higher lymphocyte and platelet counts and lower ferritin, D-dimer, lactate dehydrogenase (LDH), and aspartate transaminase (AST) have all been associated with lower risk of mortality in COVID-19 patients who ultimately required intubation and mechanical ventilation ( 22 ). Surfactant protein-D, angiopoietin-2, triggering receptor expressed on myeloid cell (TREM)-1, and TREM-2 levels were found to be higher in mild/moderate and severe/critical COVID-19 pneumonia than in asymptomatic and uncomplicated cases.…”

Albumin as a Prognostic Indicator in Pre-Intubated Patients With SARS-CoV-2: A Retrospective, Multi-Institutional Study

“…Post-anticoagulant D-dimer was shown to predict in-hospital mortality in a cohort of 1,835 adult patients with polymerase chain reaction-confirmed SARS-CoV-2 [1]. Topp et al (2021) demonstrated that patients who survived the infection had lower D-dimer, ferritin, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) levels when they were intubated [2]. Alternatively, a multivariate model aimed at identifying the risk for poor outcomes applied on a sample cohort of 2,545 patients in New York City found that age, albumin, creatinine, C-reactive protein (CRP), and LDH were predictive variables [3].…”