Analysis of Early Biomarkers Associated with the Development of Critical Respiratory Failure in Coronavirus Disease 2019 (COVID-19)

Abstract

Certain biomarkers predict death due to acute respiratory distress syndrome in COVID-19 patients. We retrospectively analyzed biomarkers associated with time to mechanical ventilation for respiratory failure due to COVID-19 (time-to-mechanical ventilation) in 135 consecutive patients in our hospital. We analyzed biomarkers that were elevated immediately (at admission) and later (3 days after admission) using Cox proportional hazards regression analysis. Independent biomarkers of time-to-mechanical ventilation were high C-reactive protein (CRP), interleukin (IL)-6, and Krebs von den Lungen-6 (KL-6) concentrations at admission and elevated CRP, high-mobility group box-1 protein (HMGB-1), and d-dimer levels and low platelets 3 days after admission. Receiver operating characteristic analysis for detecting the association between independent biomarkers associated with time-to-event in multivariate analyses and the start of mechanical ventilation revealed that these biomarkers had area under the curve values higher than 0.700. The present study suggests that CRP was the only biomarker associated with time-to-mechanical ventilation both at admission and 3 days after admission. Moreover, IL-6 (an inflammatory cytokine), HMGB-1 (a late inflammatory mediator), and KL-6 (reflecting injury and/or remodeling of type II pneumocytes) were associated with outcomes in COVID-19 as reported previously. In conclusion, increased CRP, IL-6, KL-6, HMGB-1, and d-dimer levels and decreased platelet counts were associated with the start of mechanical ventilation due to COVID-19.

Prediction Value of KREBS Von Den Lungen-6 (KL-6) Biomarker in COVID-19 Patients: A Systematic Review and Meta-Analysis

“…These articles were re-evaluated based on full-text contents, resulting in exclusion of 8 articles. Finally, 15 studies met the inclusion criteria and were included in our meta-analysis ( Figure 1 ) [ 5 , 8 , 12 , 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. All selected studies were published between 2020 and 2022.…”

“…Greater clinical value could be found in using KL-6 at admission to predict the subsequent course of COVID-19. Twelve studies involved in our meta-analysis assessed the KL-6 level according to the disease severity [ 6 , 8 , 14 , 19 , 20 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Our analysis demonstrated that there was a significantly higher level of KL-6 in patients suffering from severe COVID-19 than mild-to-moderate.…”

“…The center of each square represents the mean differences for individual trials, and the corresponding horizontal line stands for a 95% confidence interval. The diamonds represent pooled results [ 5 , 8 , 14 , 19 , 20 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Early alveolar epithelial cell necrosis is a potential driver of COVID-19-induced acute respiratory distress syndrome

“…The release of DAMPs to extracellular spaces is a characteristic of necrosis that distinguishes it from apoptosis 58 . Several previous studies have also reported that circulating levels of DAMPs, such as HMGB-1 [59][60][61][62] , histone 62,63 , cell free-DNA 62,63 , mitochondrial DNA [64][65][66] and S100 proteins 67,68 are elevated in severe COVID-19.…”

D-dimer as a predictive and prognostic marker among COVID-19 patients

“…9,21 The PT results showed a non-significant difference, which was consistent with a previous study that reported a normal PT values. 1 The INR mean values indicated a significant decrease in COVID-19 12,13,31,37 Study limitations. A number of coagulation parameters, including factor V111, fibrinogen, thrombin time, and Von Willebrand factor, were not included due to their absence in the routine laboratory investigation for our COVID-19 patients' study group, so it is highly recommended for further studies to include all the coagulation-related parameters.…”