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

Autor:	Scott NA; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Equal contribution., Pearmain L; North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.; Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.; Equal contribution., Knight SB; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Department of Respiratory Medicine, Salford Royal NHS Foundation Trust, Manchester, UK., Brand O; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Morgan DJ; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Jagger C; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Harbach S; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Khan S; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Shuwa HA; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Franklin M; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Kästele V; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Williams T; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Prise I; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., McClure FA; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Hackney P; Research Innovation, Manchester University NHS Foundation Trust, Manchester, UK., Smith L; Research Innovation, Manchester University NHS Foundation Trust, Manchester, UK., Menon M; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Konkel JE; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Lawless C; Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK., Wilson J; Regional Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK.; Department of Microbiology, Salford Royal NHS Foundation Trust, Manchester, UK., Mathioudakis AG; North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.; Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Stanel SC; North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK.; Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Ustianowski A; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Regional Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK., Lindergard G; Regional Infectious Diseases Unit, North Manchester General Hospital, Manchester, UK., Brij S; Department of Respiratory Medicine, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK., Diar Bakerly N; Department of Respiratory Medicine, Salford Royal NHS Foundation Trust, Manchester, UK., Dark P; Department of Respiratory Medicine, Salford Royal NHS Foundation Trust, Manchester, UK., Brightling C; Department of Respiratory Sciences, Leicester NIHR BRC, University of Leicester, Leicester, UK., Rivera-Ortega P; North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK., Lord GM; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Horsley A; Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Piper Hanley K; Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK., Felton T; Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Simpson A; Division of Infection, Immunity and Respiratory Medicine, Manchester NIHR BRC, Education and Research Centre, Wythenshawe Hospital, Manchester, UK., Grainger JR; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Joint senior authors., Hussell T; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.; Joint senior authors., Mann ER; Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK elizabeth.mann@manchester.ac.uk.; Maternal and Fetal Health Centre, Division of Developmental Biology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Joint senior authors.
Jazyk:	angličtina
Zdroj:	The European respiratory journal [Eur Respir J] 2023 May 11; Vol. 61 (5). Date of Electronic Publication: 2023 May 11 (Print Publication: 2023).
DOI:	10.1183/13993003.02226-2022
Abstrakt:	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 hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. Results: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with 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 C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (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 a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A 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. Competing Interests: Conflict of interest: G. Lindergard 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. The other authors declare that they have no competing interests. (Copyright ©The authors 2023.)
Databáze:	MEDLINE
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