Neutrophil Extracellular Trap Markers in Post Mortem Lung Biopsies from COVID-19 Patients

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, spread rapidly across the globe in 2020, with most countries experiencing two distinct waves of infection. In Brazil, the second wave was marked by the emergence of the P.1 (Gamma) variant, which disproportionately affected younger individuals and was associated with increased mortality. This study aimed to evaluate the epidemiological profile and post mortem histopathological lung findings, correlate them with laboratory results, and compare the first and second waves of COVID-19. To investigate neutrophil extracellular traps (NETs), we performed immunohistochemistry for citrullinated histone H3 (cit-H3) and myeloperoxidase (MPO). Our cohort included patients who died in the intensive care unit (ICU) of a single center in southern Brazil. The study included 42 patients, 24 from the first wave and 18 from the second, who died between March 2020 and August 2021. Laboratory data included complete blood counts and D-dimer levels. Histopathological analyses were conducted using H&E-stained slides and reviewed independently by two blinded pathologists. MPO and cit-H3 immunohistochemistry were performed to evaluate NETs markers. All cases exhibited varying degrees of inflammation and diffuse alveolar damage (DAD), with frequent microvascular thrombi. Neutrophilic infiltration was significantly higher in the second wave. Additionally, cases with intense neutrophilic infiltration showed a stronger association with thrombosis. NETs were identified in 10 cases. No significant correlation was found between histopathological findings, NETs, and laboratory blood count results. The histopathological findings were consistent with those reported globally. The second wave of COVID-19 showed higher neutrophilic infiltrate in the lung tissue. Neutrophils play a key role in the inflammatory response and NET formation might indicate an increased risk of mortality. Further studies can consider NET-targeted therapies as potential strategies.