A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae

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. Individ-uals 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 extracel-lular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a con-comitant 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.

Automated summary

Interstitial lung disease and associated fibrosis can occur in COVID-19 patients after recovery, and this study provides insights into the mechanisms behind these pulmonary sequelae. The researchers found an up-regulated neutrophil-associated immune response and antiviral signaling in the blood and upper airway of patients with lung changes. Peripheral phosphoproteome analysis identified critical kinases involved in neutrophil inflammatory pathways. Some patients did not achieve full normalization of radiological and functional changes even after 12 months of recovery.