Cardiometabolic Traits, Sepsis, and Severe COVID-19: A Mendelian Randomization Investigation

Mark J Ponsford^{1

2}, Apostolos Gkatzionis³, Venexia M Walker^{4

5}, Andrew J Grant³, Robyn E Wootton, Luke S P Moore^{6

7

8}, Segun Fatumo⁹, Amy M Mason^{10

11}, Verena Zuber^{3

12}, Cristen Willer¹³, Humaira Rasheed^{4

14}, Ben Brumpton^{4

14

15}, Kristian Hveem^{14

16}, Jan Kristian Damås^{17

18}, Neil Davies^{4

14}, Bjørn Olav Åsvold^{14

19}, Erik Solligård^{20

21}, Simon Jones², Stephen Burgess^{3

10}, Tormod Rogne²⁰, Dipender Gill^{12

22

23

24}

Affiliations

¹ Immunodeficiency Centre of Wales, University Hospital Wales, Heath Park, Cardiff, United Kingdom (M.J.P.).
² Division of Immunology, Infection, and Inflammation, Tenovus Institute, Cardiff University, United Kingdom (M.J.P., S.J.).
³ Medical Research Council Biostatistics Unit, School of Clinical Medicine, University of Cambridge, United Kingdom (A.G., A.J.G., V.Z., S.B.).
⁴ MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, United Kingdom (V.M.W., R.E.W., H.R., B.B., N.D.).
⁵ Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia (V.M.W.).
⁶ National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (L.S.P.M.), Imperial College London, United Kingdom.
⁷ Chelsea and Westminster National Health Service Foundation Trust, London, United Kingdom (L.S.P.M.).
⁸ Imperial Biomedical Research Centre, Imperial College London and Imperial College National Health Service Healthcare Trust, United Kingdom (L.S.P.M.).
⁹ Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom (S.F.).
¹⁰ Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (A.M.M., S.B.).
¹¹ National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, United Kingdom (A.M.M.).
¹² Department of Epidemiology and Biostatistics, School of Public Health (V.Z., D.G.), Imperial College London, United Kingdom.
¹³ Departments of Internal Medicine, Human Genetics and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (C.W.).
¹⁴ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing (H.R., B.B., K.H., N.D., B.O.Å.), Norwegian University of Science and Technology, Trondheim.
¹⁵ Department of Thoracic Medicine (B.B.), St Olavs Hospital, Trondheim University Hospital, Norway.
¹⁶ Department of Research, Innovation and Education (K.H.), St Olavs Hospital, Trondheim University Hospital, Norway.
¹⁷ Department of Infectious Diseases (J.K.D.), St Olavs Hospital, Trondheim University Hospital, Norway.
¹⁸ Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim (J.K.D.).
¹⁹ Department of Endocrinology (B.O.Å.), St Olavs Hospital, Trondheim University Hospital, Norway.
²⁰ Gemini Center for Sepsis Research, Department of Circulation and Medical Imaging (E.S., T.R., E.S.), Norwegian University of Science and Technology, Trondheim.
²¹ Clinic of Anesthesia and Intensive Care (E.S.), St Olavs Hospital, Trondheim University Hospital, Norway.
²² Novo Nordisk Research Centre Oxford, Old Road Campus, United Kingdom (D.G.).
²³ Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London, United Kingdom (D.G.).
²⁴ Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (D.G.).

PMID: 32966752
PMCID: PMC7594537
DOI: 10.1161/CIRCULATIONAHA.120.050753

Cardiometabolic Traits, Sepsis, and Severe COVID-19: A Mendelian Randomization Investigation

Mark J Ponsford et al. Circulation. 2020.

. 2020 Nov 3;142(18):1791-1793.

doi: 10.1161/CIRCULATIONAHA.120.050753. Epub 2020 Sep 23.

Authors

Affiliations

¹ Immunodeficiency Centre of Wales, University Hospital Wales, Heath Park, Cardiff, United Kingdom (M.J.P.).
² Division of Immunology, Infection, and Inflammation, Tenovus Institute, Cardiff University, United Kingdom (M.J.P., S.J.).
³ Medical Research Council Biostatistics Unit, School of Clinical Medicine, University of Cambridge, United Kingdom (A.G., A.J.G., V.Z., S.B.).
⁴ MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, United Kingdom (V.M.W., R.E.W., H.R., B.B., N.D.).
⁵ Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia (V.M.W.).
⁶ National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance (L.S.P.M.), Imperial College London, United Kingdom.
⁷ Chelsea and Westminster National Health Service Foundation Trust, London, United Kingdom (L.S.P.M.).
⁸ Imperial Biomedical Research Centre, Imperial College London and Imperial College National Health Service Healthcare Trust, United Kingdom (L.S.P.M.).
⁹ Department of Non-Communicable Diseases Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom (S.F.).
¹⁰ Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, United Kingdom (A.M.M., S.B.).
¹¹ National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, United Kingdom (A.M.M.).
¹² Department of Epidemiology and Biostatistics, School of Public Health (V.Z., D.G.), Imperial College London, United Kingdom.
¹³ Departments of Internal Medicine, Human Genetics and Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor (C.W.).
¹⁴ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing (H.R., B.B., K.H., N.D., B.O.Å.), Norwegian University of Science and Technology, Trondheim.
¹⁵ Department of Thoracic Medicine (B.B.), St Olavs Hospital, Trondheim University Hospital, Norway.
¹⁶ Department of Research, Innovation and Education (K.H.), St Olavs Hospital, Trondheim University Hospital, Norway.
¹⁷ Department of Infectious Diseases (J.K.D.), St Olavs Hospital, Trondheim University Hospital, Norway.
¹⁸ Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim (J.K.D.).
¹⁹ Department of Endocrinology (B.O.Å.), St Olavs Hospital, Trondheim University Hospital, Norway.
²⁰ Gemini Center for Sepsis Research, Department of Circulation and Medical Imaging (E.S., T.R., E.S.), Norwegian University of Science and Technology, Trondheim.
²¹ Clinic of Anesthesia and Intensive Care (E.S.), St Olavs Hospital, Trondheim University Hospital, Norway.
²² Novo Nordisk Research Centre Oxford, Old Road Campus, United Kingdom (D.G.).
²³ Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London, United Kingdom (D.G.).
²⁴ Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George's University Hospitals National Health Service Foundation Trust, London, United Kingdom (D.G.).

PMID: 32966752
PMCID: PMC7594537
DOI: 10.1161/CIRCULATIONAHA.120.050753

No abstract available

Keywords: Mendelian randomization analysis; coronavirus; risk factors; sepsis.

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Conflict of interest statement

Dr Moore has consulted for DNAelectronics (2015–2018), Dairy Crest (2017–2018), bioMerieux (2013–2020), Pfizer (2018–2020), and Umovis Laboratory (2020); received speaker fees from Profile Pharma (2018); received research grants from the National Institute for Health Research (2013–2020), CW+ Charity (2018–2019), and Leo Pharma (2016); and received educational grants from Eumedica (2016–2018). Dr Gill is employed part-time by Novo Nordisk. The other authors report no conflicts.

Figures

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References

1. Ponsford MJ, Gkatzionis A, Walker V, Grant A, Wootton RE, Moore LSP, Fatumo S, Mason A, Zuber V, Willer C, et al. Cardiometabolic traits, sepsis and severe covid-19 with respiratory failure: a Mendelian randomization investigation [published online June 20, 2020]. medRxiv. doi: 10.1101/2020.06.18.20134676. https://www.medrxiv.org/content/10.1101/2020.06.18.20134676v1. - DOI - PMC - PubMed
1. Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, Fernández J, Prati D, Baselli G, Asselta R, et al. Genome-wide association study of severe Covid-19 with respiratory failure [published online June 17, 2020]. N Engl J Med. doi:10.1056/NEJMoa2020283 - PMC - PubMed
1. COVID-Host Genetics Initiative The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur J Hum Genet. 2020;28:715–718. doi: 10.1038/s41431-020-0636-6 - PMC - PubMed
1. Slob EAW, Burgess S. A comparison of robust Mendelian randomization methods using summary data. Genet Epidemiol. 2020;44:313–329. doi: 10.1002/gepi.22295 - PMC - PubMed
1. Sattar N, McInnes IB, McMurray JJV. Obesity is a risk factor for severe COVID-19 infection: multiple potential mechanisms. Circulation. 2020;142:4–6. doi: 10.1161/CIRCULATIONAHA.120.047659 - PubMed

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Cardiometabolic Traits, Sepsis, and Severe COVID-19: A Mendelian Randomization Investigation

Affiliations

Cardiometabolic Traits, Sepsis, and Severe COVID-19: A Mendelian Randomization Investigation

Authors

Affiliations

Conflict of interest statement

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References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical