The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19, where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured anti-NET antibodies in 328 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of 27% and 60% of patients, respectively. There was a strong correlation between anti–NET IgG and anti–NET IgM. Both anti–NET IgG and anti–NET IgM tracked with high levels of circulating NETs, impaired oxygenation efficiency, and high circulating D-dimer. Furthermore, patients who required mechanical ventilation had a greater burden of anti-NET antibodies than did those not requiring oxygen supplementation. Levels of anti–NET IgG (and, to a lesser extent, anti–NET IgM) demonstrated an inverse correlation with the efficiency of NET degradation by COVID-19 sera. Furthermore, purified IgG from COVID-19 sera with high levels of anti-NET antibodies impaired the ability of healthy control serum to degrade NETs. In summary, many individuals hospitalized with COVID-19 have anti-NET antibodies, which likely impair NET clearance and may potentiate SARS-CoV-2–mediated thromboinflammation.
【저자키워드】 COVID-19, Neutrophils, Autoimmunity, Adaptive immunity, 【초록키워드】 Neutrophils, antibodies, IgG, IgM, Hospitalized, severe COVID-19, mechanical ventilation, antibody, Neutrophil extracellular traps, neutrophil, D-dimer, oxygen, immunopathology, serum, autoantibodies, sera, Patient, Neutrophil extracellular trap, Degradation, correlation, Thromboinflammation, patients, NETs, function, Efficiency, Oxygenation, autoantibody, IgG and IgM, healthy control, individual, healthy controls, fraction, circulating, inverse correlation, oxygen supplementation, clearance, COVID-19 sera, NET, greater, required, functional, determine, contribute, variety, demonstrated, purified, Level, inherent, impair, associations, degrade, with COVID-19, 【제목키워드】 Neutrophil extracellular trap,