Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID

CIRCO, Nicholas A Scott, Laurence Pearmain, Sean B Knight, Oliver Brand, David J Morgan, Christopher Jagger, Sarah Harbach, Saba Khan, Halima A Shuwa, Miriam Franklin, Verena Kästele, Thomas Williams, Ian Prise, Flora A McClure, Pamela Hackney, Lara Smith, Madhvi Menon, Joanne E Konkel, Criag LawlessJames Wilson, Aleaxander G Mathioudakis, Stefan C Stanel, Andrew Ustianowski, Gabriella Lindergard, Seema Brij, Nawar Diar Bakerly, Paul Dark, Christopher Brightling, Pilar Rivera-Ortega, Graham M Lord, Alex Horsley, Karen Piper Hanley, Timothy Felton, Angela Simpson, John R Grainger, Tracy Hussell, Elizabeth R Mann

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number2202226
Number of pages20
JournalThe European respiratory journal
Issue number5
Early online date11 May 2023
Publication statusE-pub ahead of print - 11 May 2023


  • COVID-19
  • Chemokine CXCL16
  • Chemokines, CXC/metabolism
  • Convalescence
  • Humans
  • Influenza, Human
  • Ligands
  • Lung Injury
  • Monocytes/metabolism
  • Patient Acuity
  • Post-Acute COVID-19 Syndrome
  • Receptors, CXCR6
  • Receptors, Chemokine/metabolism
  • Receptors, Scavenger/metabolism
  • Receptors, Virus/metabolism


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