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Sci Transl Med
. 2022 Nov 16;14(671):eabo5795.
doi: 10.1126/scitranslmed.abo5795. Epub 2022 Nov 16.
A persistent neutrophil-associated immune signature characterizes post-COVID-19 pulmonary sequelae
Peter M George 1 2 , Anna Reed 1 2 , Sujal R Desai 1 2 , Anand Devaraj 1 2 , Tasnim Shahridan Faiez 3 , Sarah Laverty 4 , Amama Kanwal 5 , Camille Esneau 5 , Michael K C Liu 4 , Faisal Kamal 6 , William D-C Man 1 2 7 , Sundeep Kaul 1 , Suveer Singh 1 , Georgia Lamb 1 , Fatima K Faizi 3 , Michael Schuliga 5 , Jane Read 5 , Thomas Burgoyne 1 8 , Andreia L Pinto 1 , Jake Micallef 9 , Emilie Bauwens 9 , Julie Candiracci 9 , Mhammed Bougoussa 9 , Marielle Herzog 9 , Lavanya Raman 2 , Blerina Ahmetaj-Shala 2 , Stuart Turville 10 , Anupriya Aggarwal 10 , Hugo A Farne 2 10 11 , Alessia Dalla Pria 4 12 , Andrew D Aswani 13 14 , Francesca Patella 15 , Weronika E Borek 15 , Jane A Mitchell 2 , Nathan W Bartlett 5 , Arran Dokal 15 , Xiao-Ning Xu 4 , Peter Kelleher 1 12 16 17 , Anand Shah 1 18 , Aran Singanayagam 3
Affiliations
- PMID: 36383686
- DOI: 10.1126/scitranslmed.abo5795
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.