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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaJCI insight
Stato di pubblicazionePubblicato - 2021


  • Arthritis, Rheumatoid
  • Autoimmune diseases
  • B7-H1 Antigen
  • Bronchoalveolar Lavage Fluid
  • CD48 Antigen
  • COVID-19
  • Fatty Acid-Binding Proteins
  • Humans
  • Infectious disease
  • Inflammation
  • Lectins
  • Lipopolysaccharide Receptors
  • Lung
  • Macrophages
  • Membrane Glycoproteins
  • Monocytes
  • Neutrophils
  • Osteopontin
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Immunologic
  • S100A12 Protein
  • Synovial Membrane
  • Tomography, X-Ray Computed


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