TY - JOUR T1 - Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02226-2022 SP - 2202226 AU - Nicholas A. Scott AU - Laurence Pearmain AU - Sean B. Knight AU - Oliver Brand AU - David J. Morgan AU - Christopher Jagger AU - Sarah Harbach AU - Saba Khan AU - Halima A. Shuwa AU - Miriam Franklin AU - Verena Kästele AU - Thomas Williams AU - Ian Prise AU - Flora A. McClure AU - Pamela Hackney AU - Lara Smith AU - Madhvi Menon AU - Joanne E. Konkel AU - Criag Lawless AU - James Wilson AU - Aleaxander G. Mathioudakis AU - Stefan C. Stanel AU - Andrew Ustianowski AU - Gabriella Lindergard AU - Seema Brij AU - Nawar Diar Bakerly AU - Paul Dark AU - Christopher Brightling AU - Pilar Rivera-Ortega AU - Graham M. Lord AU - Alex Horsley AU - CIRCO AU - Karen Piper Hanley AU - Timothy Felton AU - Angela Simpson AU - John R. Grainger AU - Tracy Hussell AU - Elizabeth R. Mann Y1 - 2023/01/01 UR - http://erj.ersjournals.com/content/early/2023/02/23/13993003.02226-2022.abstract N2 - Background COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID).Methods We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalization and up to 9 months of convalescence following COVID-19, respiratory syncytial virus (RSV) or influenza A (flu). Progressive fibrosing interstitial lung disease (PFILD) patients were included a positive control for severe, ongoing lung injury.Results Monocyte alterations in acute COVID-19 patients included aberrant expression of leucocyte migration molecules, continuing into convalescence (n=142) and corresponding to specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of chemokine receptor CXCR6 (p<0.0001) and adhesion molecule PSGL-1 (p<0.01), alongside preferential migration of monocytes towards CXCR6 ligand CXCL16 (p<0.05) which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in PFILD patients (p<0.001) confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited sustained reduction of the prostaglandin-generating enzyme COX-2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in RSV or flu convalescence.Conclusions Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: GL is Co-founder and Scientific Advisory Board Member of Gritstone Bio Inc., which is a public company that develops therapeutic vaccines for the treatment of cancer and infectious diseases including COVID-19.Conflict of interest: The other authors declare that they have no competing interests. ER -