Inflammasome-related markers at the ICU admission are not associated with outcome in the critically ill COVID-19 patients

Abstract

PurposeDevelopment of targeted biological therapies for COVID-19 requires reliable biomarkers that could help indicate the responding patients. Hyperactivation of the inflammasome by SARS-CoV2 virus is hypothesized to contribute to severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins at the admission to the intensive care unit (ICU).Patients and methodsPlasma samples were obtained from 45 critically ill COVID-19 patients and from10 patients with severe traumatic brain injury (TBI) at the admission to the ICU. The concentration of IL-1α, IL-1β, IL-18, IL-1RA, galectin-1, ASC, LDH, ferritin, and gasdermin D were analyzed. A novel cell-free caspase-1 plasma assay was developed by inhibitor-based immunoprecipitation followed by Western Blot. Demographic and clinical characteristics were recorded.ResultsThe inflammasome-related biomarkers were in similar concentration in COVID-19 and TBI patients except for galectin-1 being lower in the former. None of the tested markers were related to the outcome, length of stay or development of secondary infections. Patients with SOFA score of >9 at admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison to low-risk patients. Weak but significant correlations were observed between: IL-1α and platelets, IL-1β and platelets, ferritin and INR. Activated caspase-1 p35 was detectable in 12/22 COVID-19 patients but in none of the TBI patients. Its presence was related with higher fibrinogen and lower D-dimers. It was also significantly higher in patients with SOFA>9.ConclusionOur results indicate that the activation of the inflammasome in critically ill COVID-19 patients is a heterogenous process and is not directly related with outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.

Severe COVID‐19 patients show a dysregulation of the NLRP3 inflammasome in circulating neutrophils

“…We first analyse our case/control (19/25 subjects) cohort with respect of previously reported COVID-19 severity markers. Increasing evidences have shown that IL-8, IL-6, MMP-9 and dsDNA are elevated in serum of severe COVID-19 patients, and that caspase-1 cleavage, suggestive of inflammasome activation, is also augmented in patients' peripheral blood cells, [31][32][33][34] and specifically in neutrophils as recently reported. 26 As expected, severe COVID-19 patients showed a marked neutrophilia (Figure 1A), increased plasma levels of IL-6 (Figure 1B), IL-8 (Figure 1C), MMP-9 (Figure 1D) and dsDNA (Figure 1 E) compared with HD.…”

“…We first analyse our case/control (19/25 subjects) cohort with respect of previously reported COVID‐19 severity markers. Increasing evidences have shown that IL‐8, IL‐6, MMP‐9 and dsDNA are elevated in serum of severe COVID‐19 patients, and that caspase‐1 cleavage, suggestive of inflammasome activation, is also augmented in patients' peripheral blood cells, 31–34 and specifically in neutrophils as recently reported 26 …”