A brief report: absence of elevated circulating NETosis markers in long-term long COVID.

BACKGROUND: Neutrophil extracellular trap (NET) formation (NETosis) has been proposed as a contributor to the pathophysiology of Long COVID (LC). However, it remains unclear whether markers of systemic NETosis remain elevated in individuals with persistent symptoms years after the initial infection. METHODS: To assess NETosis, we quantified MPO-DNA, Histone DNA, and Citrullinated H3 levels in the plasma of 51 patients with prolonged LC (mean disease duration of three years), and compared them with 52 age- and sex-matched healthy controls. RESULTS: No significant differences were observed between participants with LC and healthy controls for any of the three NETosis markers. Hierarchical clustering reveals no specific subgroups in the patient group. Furthermore, NETosis marker levels were not associated with overall symptom burden or individual symptom domains. CONCLUSIONS: In this cohort of individuals with long-term LC, we found no evidence of persistent systemic NETosis. These findings suggest that elevated circulating NETosis markers are not a universal feature of long-term LC and may indicate that neutrophil activation observed during acute or early post-acute disease does not persist in long-term disease.