A persistent neutrophil-associated immune signature characterizes post–COVID-19 pulmonary sequelae
Peter M. George, Anna Reed, Sujal R. Desai, Anand Devaraj, Tasnim Shahridan Faiez, S. G. Laverty, Amama Kanwal, Camille Esneau, Michael K. P. Liu, Faisal Kamal, William D‐C Man, Sundeep Kaul, Suveer Singh, Georgia Lamb, Fatima K. Faizi, Michael Schuliga, Jane Read, Thomas Burgoyne, Andreia Pinto, Jake Micallef, Émilie Bauwens, Julie Candiracci, Mhammed Bougoussa, Mariëlle Herzog, Lavanya Raman, Blerina Ahmetaj‐Shala, Stuart Turville, Anupriya Aggarwal, Hugo Farne, Alessia Dalla Pria, Andrew Aswani, Francesca Patella, Weronika E. Borek, Jane A. Mitchell, Nathan W. Bartlett, Arran Dokal, Xiao‐Ning Xu, Peter Kelleher, Anand Shah, Aran Singanayagam
Abstract
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.