COVID-19 and non-alcoholic fatty liver disease: Biological insights from multi-omics data
Corresponding Author
Carlos J. Pirola
Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Correspondence
Carlos J. Pirola, Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Silvia Sookoian, Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Silvia Sookoian
Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Correspondence
Carlos J. Pirola, Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Silvia Sookoian, Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Carlos J. Pirola
Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Correspondence
Carlos J. Pirola, Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Silvia Sookoian, Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Silvia Sookoian
Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Correspondence
Carlos J. Pirola, Systems Biology of Complex Diseases, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Silvia Sookoian, Clinical and Molecular Hepatology, Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS), Universidad Abierta Interamericana, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Av. Montes de Oca 745, 2 piso, (1270AAH) CABA, Buenos Aires, Argentina.
Email: [email protected]
Search for more papers by this authorCarlos J. Pirola and Silvia Sookoian should be considered joint senior authors.
Handling Editor: Luca Valenti
Abstract
We explored the shared pathophysiological mechanisms between COVID-19 and non-alcoholic fatty liver disease (NAFLD) by integrating multi-omics data. We studied common genetic risk factors and underlying biological processes using functional enrichment analysis. To understand the sex-specific pathways involved in the clinical course of SARS-CoV-2 infection, we processed sex-stratified data from COVID-19 genome-wide association datasets. We further explored the transcriptional signature of the liver cells in healthy and COVID-19 tissue specimens. We also integrated genetic and metabolomic information. We found that COVID-19 and NAFLD share biological disease mechanisms, including pathways that regulate the inflammatory and lipopolysaccharide response. Single-cell transcriptomics revealed enrichment of complement-related pathways in Kupffer cells, syndecan-mediated signalling in plasma cells, and epithelial-to-mesenchymal transition in hepatic stellate cells. The strategy of pathway-level analysis of genomic and metabolomic data uncovered l-lactic acid, Krebs cycle intermediate compounds, arachidonic acid and cortisol among the most prominent shared metabolites.
CONFLICT OF INTEREST
The authors do not have any disclosures to report.
Supporting Information
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