Enhanced production of eicosanoids in plasma and activation of DNA damage pathways in PBMCs are correlated with the severity of ancestral COVID-19 infection.

DNA damage RNAseq SARS-coV-2 eicosanoids fatty acid lipidomics

Journal

medRxiv : the preprint server for health sciences
Titre abrégé: medRxiv
Pays: United States
ID NLM: 101767986

Informations de publication

Date de publication:
15 Sep 2023
Historique:
pubmed: 25 9 2023
medline: 25 9 2023
entrez: 25 9 2023
Statut: epublish

Résumé

Many questions remain unanswered regarding the implication of lipid metabolites in severe SARS-CoV-2 infections. By re-analyzed sequencing data from the nasopharynx of a previously published cohort, we found that We performed a total fatty acid panel on plasma and bulk RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) collected from 10 infected and 10 uninfected patients. Univariate comparison of lipid metabolites revealed that lipid metabolites were increased in SARS-CoV-2 patients including the lipid mediators Arachidonic Acid (AA) and Eicosapentaenoic Acid (EPA). AA, EPA and the fatty acids Docosahexaenoic acid (DHA) and Docosapentaenoic acid (DPA), were positively correlated to WHO disease severity score. Transcriptomic analysis demonstrated that COVID-19 patients can be segregated based on WHO scores. Ontology, KEGG and Reactome analysis identified pathways enriched for genes related to innate immunity, interactions between lymphoid and nonlymphoid cells, interleukin signaling and, cell cycling pathways. Our study offers an association between nasopharynx mucosa eicosanoid genes expression, specific serum inflammatory lipids and, subsequent DNA damage pathways activation in PBMCs to severity of COVID-19 infection.

Sections du résumé

Background UNASSIGNED
Many questions remain unanswered regarding the implication of lipid metabolites in severe SARS-CoV-2 infections. By re-analyzed sequencing data from the nasopharynx of a previously published cohort, we found that
Methods and findings UNASSIGNED
We performed a total fatty acid panel on plasma and bulk RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) collected from 10 infected and 10 uninfected patients. Univariate comparison of lipid metabolites revealed that lipid metabolites were increased in SARS-CoV-2 patients including the lipid mediators Arachidonic Acid (AA) and Eicosapentaenoic Acid (EPA). AA, EPA and the fatty acids Docosahexaenoic acid (DHA) and Docosapentaenoic acid (DPA), were positively correlated to WHO disease severity score. Transcriptomic analysis demonstrated that COVID-19 patients can be segregated based on WHO scores. Ontology, KEGG and Reactome analysis identified pathways enriched for genes related to innate immunity, interactions between lymphoid and nonlymphoid cells, interleukin signaling and, cell cycling pathways.
Conclusions UNASSIGNED
Our study offers an association between nasopharynx mucosa eicosanoid genes expression, specific serum inflammatory lipids and, subsequent DNA damage pathways activation in PBMCs to severity of COVID-19 infection.

Identifiants

DOI: 10.1101/2023.09.14.23295549 PMID: 37745424 PMC: PMC10516085
pubmed: 37745424
doi: 10.1101/2023.09.14.23295549
pmc: PMC10516085
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIGMS NIH HHS
ID : P20 GM104357
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE031928
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM149404
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121334
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM115428
Pays : United States

Auteurs

Jeffrey A Tomalka (JA)

Dept. of Pathology and Laboratory Medicine. Emory University School of Medicine. Atlanta, GA, USA.

Anna Owings (A)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Michelle Galeas-Pena (M)

Department of Medicine, Section of Gastroenterology and Hepatology, Tulane University School of Medicine. New Orleans, LA, USA.

Carly G K Ziegler (CGK)

Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA.
Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.

Tanya O Robinson (TO)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Thomas G Wichman (TG)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Hannah Laird (H)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Haley B Williams (HB)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Neha S Dhaliwal (NS)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Steven Everman (S)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Yousaf Zafar (Y)

Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.

Alex K Shalek (AK)

Program in Health Sciences & Technology, Harvard Medical School & MIT, Boston, MA, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA.
Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Program in Immunology, Harvard Medical School, Boston, MA, USA.
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Harvard Stem Cell Institute, Cambridge, MA, USA.

Bruce H Horwitz (BH)

Program in Immunology, Harvard Medical School, Boston, MA, USA.
Division of Emergency Medicine, Boston Children's Hospital, Boston, MA, USA.
Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.

Jose Ordovas-Montanes (J)

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Program in Immunology, Harvard Medical School, Boston, MA, USA.
Harvard Stem Cell Institute, Cambridge, MA, USA.
Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA.

Sarah C Glover (SC)

Department of Medicine, Section of Gastroenterology and Hepatology, Tulane University School of Medicine. New Orleans, LA, USA.
Dept. of Cell and Molecular Biology; Cancer Center and Research Institute. University of Mississippi Medical Center. Jackson, MS, USA.

Yann Gibert (Y)

Dept. of Cell and Molecular Biology; Cancer Center and Research Institute. University of Mississippi Medical Center. Jackson, MS, USA.

Classifications MeSH