tetano
Editor, Senior Moderator
Nat Microbiol
. 2025 Aug 22.
doi: 10.1038/s41564-025-02090-9. Online ahead of print. SARS-CoV-2 infection induces pro-fibrotic and pro-thrombotic foam cell formation
Diana M Battaglia[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Claire E Post[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Wenbo Yao[SUP] #[/SUP][SUP] 2 3 4 5 [/SUP], Angela Wahl[SUP] #[/SUP][SUP] 6 7 8 9 [/SUP], Lisa E Gralinski[SUP] 10 11 [/SUP], Hongwei Liu[SUP] 12 13 [/SUP], Hong Dang[SUP] 14 [/SUP], Victoria J Madden[SUP] 15 [/SUP], Kristen K White[SUP] 15 [/SUP], Sarah R Leist[SUP] 10 [/SUP], Kenneth H Dinnion 3rd[SUP] 10 11 [/SUP], Gabriela De la Cruz[SUP] 16 [/SUP], Bentley R Midkiff[SUP] 16 [/SUP], Heather M Froggatt[SUP] 10 [/SUP], Kendra Gully[SUP] 10 [/SUP], Mark Zweigart[SUP] 10 [/SUP], J Rachel Reader[SUP] 17 [/SUP], Katherine J Olstad[SUP] 17 [/SUP], Jeffrey I Everitt[SUP] 18 [/SUP], Koen K A Van Rompay[SUP] 17 [/SUP], Kristina De Paris[SUP] 4 11 [/SUP], Eniko Sajti[SUP] 19 [/SUP], Raymond J Pickles[SUP] 11 14 [/SUP], Edward P Browne[SUP] 3 4 11 20 [/SUP], Corbin D Jones[SUP] 12 13 [/SUP], Richard C Boucher Jr[SUP] 14 [/SUP], Ralph S Baric[SUP] 10 11 21 [/SUP], J Victor Garcia[SUP] 22 23 24 25 [/SUP]
Affiliations
COVID-19 and long COVID are characterized by a dysregulated immune response. However, the role of macrophages during viral infection is poorly defined. Here we demonstrate that SARS-CoV-2 infection results in increased macrophage numbers and extensive formation of enlarged lipid-laden macrophages or foam cells using humanized mice, rhesus macaques and post-mortem human lung tissue. Notably, infection by other coronaviruses tested, SARS-CoV-1, MERS-CoV and two bat coronaviruses (SHC014-CoV or WIV1-CoV), did not result in macrophage proliferation or foam cell formation. Foam cells in SARS-CoV-2-infected human lung tissue display a pro-fibrotic and pro-thrombotic phenotype as they are enriched for genes associated with platelet activation and aggregation, as well as extracellular matrix organization and collagen synthesis. After viral clearance, macrophage numbers remain elevated, and lung fibrosis and thrombi persist. Importantly, we show that pre-exposure prophylaxis or early treatment with a SARS-CoV-2 antiviral, EIDD-2801, prevents increases in macrophage cell numbers and foam cell formation, and reduces fibrosis markers. These observations highlight the contribution of macrophages to lung inflammation and tissue injury leading to the pulmonary fibrosis observed in COVID-19 patients.
. 2025 Aug 22.
doi: 10.1038/s41564-025-02090-9. Online ahead of print. SARS-CoV-2 infection induces pro-fibrotic and pro-thrombotic foam cell formation
Diana M Battaglia[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Claire E Post[SUP] #[/SUP][SUP] 2 3 4 [/SUP], Wenbo Yao[SUP] #[/SUP][SUP] 2 3 4 5 [/SUP], Angela Wahl[SUP] #[/SUP][SUP] 6 7 8 9 [/SUP], Lisa E Gralinski[SUP] 10 11 [/SUP], Hongwei Liu[SUP] 12 13 [/SUP], Hong Dang[SUP] 14 [/SUP], Victoria J Madden[SUP] 15 [/SUP], Kristen K White[SUP] 15 [/SUP], Sarah R Leist[SUP] 10 [/SUP], Kenneth H Dinnion 3rd[SUP] 10 11 [/SUP], Gabriela De la Cruz[SUP] 16 [/SUP], Bentley R Midkiff[SUP] 16 [/SUP], Heather M Froggatt[SUP] 10 [/SUP], Kendra Gully[SUP] 10 [/SUP], Mark Zweigart[SUP] 10 [/SUP], J Rachel Reader[SUP] 17 [/SUP], Katherine J Olstad[SUP] 17 [/SUP], Jeffrey I Everitt[SUP] 18 [/SUP], Koen K A Van Rompay[SUP] 17 [/SUP], Kristina De Paris[SUP] 4 11 [/SUP], Eniko Sajti[SUP] 19 [/SUP], Raymond J Pickles[SUP] 11 14 [/SUP], Edward P Browne[SUP] 3 4 11 20 [/SUP], Corbin D Jones[SUP] 12 13 [/SUP], Richard C Boucher Jr[SUP] 14 [/SUP], Ralph S Baric[SUP] 10 11 21 [/SUP], J Victor Garcia[SUP] 22 23 24 25 [/SUP]
Affiliations
- PMID: 40846999
- DOI: 10.1038/s41564-025-02090-9
COVID-19 and long COVID are characterized by a dysregulated immune response. However, the role of macrophages during viral infection is poorly defined. Here we demonstrate that SARS-CoV-2 infection results in increased macrophage numbers and extensive formation of enlarged lipid-laden macrophages or foam cells using humanized mice, rhesus macaques and post-mortem human lung tissue. Notably, infection by other coronaviruses tested, SARS-CoV-1, MERS-CoV and two bat coronaviruses (SHC014-CoV or WIV1-CoV), did not result in macrophage proliferation or foam cell formation. Foam cells in SARS-CoV-2-infected human lung tissue display a pro-fibrotic and pro-thrombotic phenotype as they are enriched for genes associated with platelet activation and aggregation, as well as extracellular matrix organization and collagen synthesis. After viral clearance, macrophage numbers remain elevated, and lung fibrosis and thrombi persist. Importantly, we show that pre-exposure prophylaxis or early treatment with a SARS-CoV-2 antiviral, EIDD-2801, prevents increases in macrophage cell numbers and foam cell formation, and reduces fibrosis markers. These observations highlight the contribution of macrophages to lung inflammation and tissue injury leading to the pulmonary fibrosis observed in COVID-19 patients.