Relationship of Circulatory Markers of NETosis with COVID-19 Severity: A Prospective Cohort Study.

BACKGROUND

NETosis is a unique form of cell death leading to the formation of neutrophil extracellular traps (NETs), which may be responsible for many of the serious complications of COVID-19, such as acute respiratory distress syndrome (ARDS), cytokine storm, thromboembolic complications, acute organ dysfunction, and multiorgan failure.

AIMS: The aim was to assess the relationship between markers of NETosis [citrullinated histones (Cit-H3), myeloperoxidase (MPO), and elastase] and COVID-19, as well as its severity.

PATIENTS AND

METHODS

Ninety-nine hospitalized adult patients aged 18 years or older with COVID-19 and 30 controls were prospectively enrolled. Serum levels of Cit-H3, MPO, and elastase were measured at the time of admission, and their levels were compared between the clinical categories of COVID-19 (non-severe, severe, and critical). The correlation between markers of NETosis and the PO2/FiO2 ratio was also determined.

RESULTS

Among the NETs markers, Cit-H3 and elastase levels significantly increased in the COVID-19 patients compared to the control. In the comparison of COVID-19 categories, only Cit-H3 significantly increased in severe categories compared to the non-severe group. Citrullinated histones showed fair diagnostic ability for the prediction of the severity, with a sensitivity and specificity of approximately 74 and 64%, respectively, at a cut-off of 34 ng/mL. Elastase was found to have a weak negative correlation, while Cit-H3 had a moderate negative correlation with the PO2/FiO2 ratio.

CONCLUSIONS

Citrullinated histones, along with C-reactive protein (CRP), are independently associated with COVID-19 severity. These findings support the relevance of NETosis-related biomarkers in disease progression and may inform future research on targeted monitoring strategies.

CLINICAL TRIAL REGISTRATION NO: Clinical trial registry of India (CTRI/2020/10/028488).

HOW TO CITE THIS ARTICLE: Kumar A, Kumar N, Banerjee A, Kumar A, Kumar A, Sinha C. Relationship of Circulatory Markers of NETosis with COVID-19 Severity: A Prospective Cohort Study. Indian J Crit Care Med 2025;29(12):1032-1039.