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COVID-19 and RA share an SPP1 myeloid pathway that drives PD-L1+ neutrophils and CD14+ monocytes.
MacDonald, Lucy; Alivernini, Stefano; Tolusso, Barbara; Elmesmari, Aziza; Somma, Domenico; Perniola, Simone; Paglionico, Annamaria; Petricca, Luca; Bosello, Silvia L; Carfì, Angelo; Sali, Michela; Stigliano, Egidio; Cingolani, Antonella; Murri, Rita; Arena, Vincenzo; Fantoni, Massimo; Antonelli, Massimo; Landi, Francesco; Franceschi, Francesco; Sanguinetti, Maurizio; McInnes, Iain B; McSharry, Charles; Gasbarrini, Antonio; Otto, Thomas D; Kurowska-Stolarska, Mariola; Gremese, Elisa.
  • MacDonald L; Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, United Kingdom.
  • Alivernini S; Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, United Kingdom.
  • Tolusso B; Division of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Elmesmari A; Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Somma D; Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, United Kingdom.
  • Perniola S; Division of Rheumatology, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Paglionico A; Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, United Kingdom.
  • Petricca L; Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, United Kingdom.
  • Bosello SL; Division of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Carfì A; Division of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Sali M; Division of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Stigliano E; Division of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Cingolani A; Institute of Internal Medicine and Geriatrics and.
  • Murri R; Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Arena V; Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie - Sezione di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Fantoni M; Department of Woman and Child Health and Public Health, Area of Pathology, and U.O.S.D. Coordinamento attività di Settorato, and.
  • Antonelli M; Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Landi F; Dipartimento di Sicurezza e Bioetica, Sez. Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Franceschi F; Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Sanguinetti M; Dipartimento di Sicurezza e Bioetica, Sez. Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.
  • McInnes IB; Department of Woman and Child Health and Public Health, Area of Pathology, and U.O.S.D. Coordinamento attività di Settorato, and.
  • McSharry C; Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Gasbarrini A; Dipartimento di Sicurezza e Bioetica, Sez. Malattie Infettive, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Otto TD; Emergency Medicine, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
  • Kurowska-Stolarska M; Emergency Medicine, Università Cattolica del Sacro Cuore, Rome, Italy.
  • Gremese E; Institute of Internal Medicine and Geriatrics and.
JCI Insight ; 6(13)2021 06 18.
Article in English | MEDLINE | ID: covidwho-1346128
ABSTRACT
We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Arthritis, Rheumatoid / Monocytes / Osteopontin / COVID-19 / Neutrophils Type of study: Prognostic study Topics: Long Covid Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Jci.insight.147413

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Arthritis, Rheumatoid / Monocytes / Osteopontin / COVID-19 / Neutrophils Type of study: Prognostic study Topics: Long Covid Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Jci.insight.147413