SARS-CoV-2 Infection Induces Pro-Fibrotic and Pro-Thrombotic Lipid-Laden Macrophage Expansion in Lungs
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ABSTRACT:
PROVIDER: PRJNA1049038 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27106323_1.fastq.gz | Fastqsanger.gz | |||
| SRR27106323_2.fastq.gz | Fastqsanger.gz | |||
| SRR27106324_1.fastq.gz | Fastqsanger.gz | |||
| SRR27106324_2.fastq.gz | Fastqsanger.gz | |||
| SRR27106325_1.fastq.gz | Fastqsanger.gz |
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Project description:SARS-CoV-2 Infection Induces Pro-Fibrotic and Pro-Thrombotic Lipid-Laden Foam Cell Formation
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Project description:SARS-CoV-2 is the causative agent of COVID-19 and long COVID, two illnesses characterized by a dysregulated immune response. Macrophages have long been considered a key component of the dysregulated immune response occurring during severe cases of COVID-19 and long COVID. Using humanized mice implanted with human lung tissue, we demonstrate that macrophage replication is induced by SARS-CoV-2 infection which also promotes macrophage enlargement and the formation of lipid laden cells. Notably, we show that enlarged macrophages display a pro-fibrotic and pro-thrombotic phenotype. Even after immune-mediated clearance of replication competent virus, macrophage numbers remained elevated, and lung fibrosis and thrombi formation were still present. Importantly, we also showed that pre-exposure prophylaxis or early treatment with a SARS-CoV-2 antiviral, EIDD-2801, was able to reduce macrophage expansion and prevent COVID-19 mediated lung pathology such as fibrosis by reducing collagen deposition and decreasing smooth muscle actin, a biomarker of fibrosis. Elevated macrophage numbers were observed in a mouse-adapted SARS-CoV-2 model, and enlarged macrophage were elevated in a non-human primate model of SARS-CoV-2 infection, and in cadaveric human lung samples from SARS-CoV-2 infected individuals. We postulate that SARS-CoV-2 infection induces the production of foam cells which in turn contribute to pathology associated with COVID-19 including thrombi formation.
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