Autoantibodies stabilize neutrophil extracellular traps in COVID-19.
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.
['Zuo|Yu|Y|', 'Yalavarthi|Srilakshmi|S|', 'Navaz|Sherwin A|SA|', 'Hoy|Claire K|CK|', 'Harbaugh|Alyssa|A|', 'Gockman|Kelsey|K|', 'Zuo|Melanie|M|', 'Madison|Jacqueline A|JA|', 'Shi|Hui|H|', 'Kanthi|Yogendra|Y|', 'Knight|Jason S|JS|']
D000293:Adolescent D000328:Adult D001323:Autoantibodies D000086382:COVID-19 D065206:Extracellular Traps D005260:Female D006801:Humans D007074:Immunoglobulin G D007075:Immunoglobulin M D008297:Male D008875:Middle Aged D009504:Neutrophils D000086402:SARS-CoV-2 D055815:Young Adult
Neutrophils COVID-19 Adaptive immunity Autoimmunity