TY - JOUR
AU - MacDonald, Lucy
AU - Alivernini, Stefano
AU - Tolusso, Barbara
AU - Elmesmari, Aziza
AU - Somma, Domenico
AU - Perniola, Simone
AU - Paglionico, Annamaria
AU - Petricca, Luca
AU - Bosello, Silvia L.
AU - Carfì, Angelo
AU - Sali, Michela
AU - Stigliano, Egidio
AU - Cingolani, Antonella
AU - Murri, Rita
AU - Arena, Vincenzo
AU - Fantoni, Massimo
AU - Antonelli, Massimo
AU - Landi, Francesco
AU - Franceschi, Francesco
AU - Sanguinetti, Maurizio
AU - McInnes, Iain B.
AU - McSharry, Charles
AU - Gasbarrini, Antonio
AU - Otto, Thomas D.
AU - Kurowska-Stolarska, Mariola
AU - Gremese, Elisa
PY - 2021
DA - July
TI - COVID-19 and RA share SPP1 myeloid pathway that drives PD-L1pos neutrophils and CD14pos monocytes
JO - JCI Insight
VL - 6
IS - 13
DO - https://doi.org/10.1172/jci.insight.147413
AB - 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 BALF macrophage clusters FCN1pos and FCN1posSPP1pos predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48highS100A12pos and CD48posSPP1pos that drive Rheumatoid Arthritis (RA) synovitis. BALF macrophage cluster FABP4pos predominant in healthy lung was transcriptionally related to STM cluster TREM2pos 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 remained high in post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared to other causes of severe pneumonia, and immunohistochemistry localized SPP1pos macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives pro-inflammatory activation of CD14pos monocytes and development of PD-L1pos 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 monitoring.
PB - American Society for Clinical Investigation
UR - http://eprints.gla.ac.uk/245406/
KW - Coronavirus (COVID-19)
ER