TY - JOUR
T1 - Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID
AU - CIRCO
AU - Scott, Nicholas A
AU - Pearmain, Laurence
AU - Knight, Sean B
AU - Brand, Oliver
AU - Morgan, David J
AU - Jagger, Christopher
AU - Harbach, Sarah
AU - Khan, Saba
AU - Shuwa, Halima A
AU - Franklin, Miriam
AU - Kästele, Verena
AU - Williams, Thomas
AU - Prise, Ian
AU - McClure, Flora A
AU - Hackney, Pamela
AU - Smith, Lara
AU - Menon, Madhvi
AU - Konkel, Joanne E
AU - Lawless, Criag
AU - Wilson, James
AU - Mathioudakis, Aleaxander G
AU - Stanel, Stefan C
AU - Ustianowski, Andrew
AU - Lindergard, Gabriella
AU - Brij, Seema
AU - Diar Bakerly, Nawar
AU - Dark, Paul
AU - Brightling, Christopher
AU - Rivera-Ortega, Pilar
AU - Lord, Graham M
AU - Horsley, Alex
AU - Piper Hanley, Karen
AU - Felton, Timothy
AU - Simpson, Angela
AU - Grainger, John R
AU - Hussell, Tracy
AU - Mann, Elizabeth R
N1 - Copyright ©The authors 2023. For reproduction rights and permissions contact permissions@ersnet.org.
PY - 2023/5/11
Y1 - 2023/5/11
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.
AB - 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.
KW - COVID-19
KW - Chemokine CXCL16
KW - Chemokines, CXC/metabolism
KW - Convalescence
KW - Humans
KW - Influenza, Human
KW - Ligands
KW - Lung Injury
KW - Monocytes/metabolism
KW - Patient Acuity
KW - Post-Acute COVID-19 Syndrome
KW - Receptors, CXCR6
KW - Receptors, Chemokine/metabolism
KW - Receptors, Scavenger/metabolism
KW - Receptors, Virus/metabolism
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UR - http://www.scopus.com/inward/record.url?scp=85159741403&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/7110c468-b603-37e1-b2e8-d64d21be68d8/
U2 - 10.1183/13993003.02226-2022
DO - 10.1183/13993003.02226-2022
M3 - Article
C2 - 36922030
SN - 0903-1936
VL - 61
JO - The European respiratory journal
JF - The European respiratory journal
IS - 5
M1 - 2202226
ER -