A persistent neutrophil-associated immune signature characterises post-COVID19 pulmonary sequelae

Abstract Persistent interstitial lung changes with associated symptoms occur in a proportion of individuals that have recovered from severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) infection through unknown mechanisms. We studied individuals with severe COVID-19 longitudinally following recovery from acute illness. Subjects with interstitial lung changes at 3-6 months post-recovery had an upregulated neutrophil-associated immune signature including increased chemokines, proteases and markers of neutrophil extracellular traps detectable systemically. Similar pathways were enriched in the upper airway with a concomitant augmentation of antiviral type-I interferon signalling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Repeat sampling indicated that full normalisation of radiological and functional changes has not yet been reached in many individuals by 12 months post-recovery. These data provide functional insight into mechanisms driving pulmonary sequelae of COVID-19 and provide a rational basis for development of future targeted approaches to prevent long-term complications.