LAUSR

Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications. Description Individuals with persistent interstitial lung changes following COVID-19 exhibit a systemic proinflammatory neutrophil-associated immune signature. Casting a wide NET on long COVID A substantial number of individuals who recover from COVID-19 still present with long-term sequelae. Here, George et al. followed individuals after recovery from severe COVID-19 to identify features that distinguished those that had evidence of long-term pulmonary sequelae from those who made a full recovery. They found that a neutrophil-associated inflammatory phenotype was apparent in those who had persistent pulmonary symptoms, and evidence of neutrophil extracellular traps, or NETs, was found in the blood of these individuals. These data highlight a potential role for neutrophils in pulmonary long COVID.