{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:28:20Z","timestamp":1790504900171,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Pre-existing comorbidities such as obesity or metabolic diseases can adversely affect the clinical outcome of COVID-19. Chronic metabolic disorders are globally on the rise and often a consequence of an unhealthy diet, referred to as a Western Diet. For the first time in the Syrian hamster model, we demonstrate the detrimental impact of a continuous high-fat high-sugar diet on COVID-19 outcome. We observed increased weight loss and lung pathology, such as exudate, vasculitis, hemorrhage, fibrin, and edema, delayed viral clearance and functional lung recovery, and prolonged viral shedding. This was accompanied by an altered, but not significantly different, systemic IL-10 and IL-6 profile, as well as a dysregulated serum lipid response dominated by polyunsaturated fatty acid-containing phosphatidylethanolamine, partially recapitulating cytokine and lipid responses associated with severe human COVID-19. Our data support the hamster model for testing restrictive or targeted diets and immunomodulatory therapies to mediate the adverse effects of metabolic disease on COVID-19.<\/jats:p>","DOI":"10.3390\/v13122506","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T22:06:10Z","timestamp":1639519570000},"page":"2506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["High-Fat High-Sugar Diet-Induced Changes in the Lipid Metabolism Are Associated with Mildly Increased COVID-19 Severity and Delayed Recovery in the Syrian Hamster"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0489-6591","authenticated-orcid":false,"given":"Julia R.","family":"Port","sequence":"first","affiliation":[{"name":"Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle R.","family":"Adney","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5894-953X","authenticated-orcid":false,"given":"Benjamin","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan E.","family":"Schulz","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Sturdevant","sequence":"additional","affiliation":[{"name":"Genomics Unit, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7091-3046","authenticated-orcid":false,"given":"Brian J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria A.","family":"Avanzato","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"},{"name":"Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2376-2633","authenticated-orcid":false,"given":"Myndi G.","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothi N.","family":"Purushotham","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"},{"name":"The Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin A.","family":"Stromberg","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Leighton","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharine M.","family":"Bosio","sequence":"additional","affiliation":[{"name":"Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8907-8821","authenticated-orcid":false,"given":"Carl","family":"Shaia","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2288-3196","authenticated-orcid":false,"given":"Vincent J.","family":"Munster","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105951","DOI":"10.1016\/j.rmed.2020.105951","article-title":"Coronavirus Disease 2019-related dyspnea cases difficult to interpret using chest computed tomography","volume":"167","author":"Nie","year":"2020","journal-title":"Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109147","DOI":"10.1016\/j.ejrad.2020.109147","article-title":"Spectrum of chest computed tomographic (CT) findings in coronavirus disease-19 (COVID-19) patients in India","volume":"129","author":"Parry","year":"2020","journal-title":"Eur. J. Radiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbi.2020.04.040","article-title":"The impact of nutrition on COVID-19 susceptibility and long-term consequences","volume":"87","author":"Butler","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_4","first-page":"449","article-title":"Insulin resistance in insulin-resistant and diabetic hamsters (Mesocricetus auratus) is associated with abnormal hepatic expression of genes involved in lipid and glucose metabolism","volume":"59","author":"Li","year":"2009","journal-title":"Comp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3892\/mmr.2020.11127","article-title":"Obesity\u2014A risk factor for increased COVID-19 prevalence, severity and lethality (Review)","volume":"22","author":"Petrakis","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/oby.22831","article-title":"High Prevalence of Obesity in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Requiring Invasive Mechanical Ventilation","volume":"28","author":"Simonnet","year":"2020","journal-title":"Obesity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/S0140-6736(11)60813-1","article-title":"The global obesity pandemic: Shaped by global drivers and local environments","volume":"378","author":"Swinburn","year":"2011","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1089\/met.2018.0105","article-title":"Prevalence of Optimal Metabolic Health in American Adults: National Health and Nutrition Examination Survey 2009\u20132016","volume":"17","author":"Cai","year":"2019","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The Global Epidemic of the Metabolic Syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1093\/ajcn.81.2.341","article-title":"Origins and evolution of the Western diet: Health implications for the 21st century","volume":"81","author":"Cordain","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2017.03.008","article-title":"Obesity altered T cell metabolism and the response to infection","volume":"46","author":"Green","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S406","DOI":"10.1513\/AnnalsATS.201706-447AW","article-title":"Obesity Impairs the Adaptive Immune Response to Influenza Virus","volume":"14","author":"Green","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rogero, M.M., and Calder, P.C. (2018). Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Nutrients, 10.","DOI":"10.3390\/nu10040432"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.cmet.2021.02.006","article-title":"COVID-19 and metabolic diseases: A heightened awareness of health inequities and a renewed focus for research priorities","volume":"33","author":"Cefalu","year":"2021","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dalb\u00f8ge, L.S., Pedersen, P.J., Hansen, G., Fabricius, K., Hansen, H.B., Jelsing, J., and Vrang, N. (2015). A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135634"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S0022-2143(96)90013-X","article-title":"Effects of dietary carbohydrates on glucose and lipid metabolism in golden Syrian hamsters","volume":"128","author":"Vriend","year":"1996","journal-title":"J. Lab. Clin. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1093\/cid\/ciaa644","article-title":"Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility","volume":"71","author":"Chan","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/s41586-020-2342-5","article-title":"Pathogenesis and transmission of SARS-CoV-2 in golden hamsters","volume":"583","author":"Sia","year":"2020","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1080\/22221751.2020.1858177","article-title":"Defining the Syrian hamster as a highly susceptible preclinical model for SARS-CoV-2 infection","volume":"9","author":"Rosenke","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.4269\/ajtmh.21-0229","article-title":"Inactivation of SARS-CoV-2 Laboratory Specimens","volume":"104","author":"Haddock","year":"2021","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0014-2999(01)01249-3","article-title":"High fat fed hamster, a unique animal model for treatment of diabetic dyslipidemia with peroxisome proliferator activated receptor alpha selective agonists","volume":"427","author":"Wang","year":"2001","journal-title":"Eur. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_25","first-page":"e50172","article-title":"Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique","volume":"75","author":"McGovern","year":"2013","journal-title":"JoVE"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2000045","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045","article-title":"Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR","volume":"25","author":"Corman","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.antiviral.2017.03.025","article-title":"Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets","volume":"143","author":"Falzarano","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_28","first-page":"e1009195","article-title":"K18-hACE2 mice develop respiratory disease resembling severe COVID-19","volume":"17","author":"Yinda","year":"2021","journal-title":"bioRxiv"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.2337\/dc12-0246","article-title":"Patterns of insulin concentration during the OGTT predict the risk of type 2 diabetes in Japanese Americans","volume":"36","author":"Hayashi","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Washington, I.M., and Van Hoosier, G. (2012). Clinical Biochemistry and Hematology. The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents, Elsevier.","DOI":"10.1016\/B978-0-12-380920-9.00003-1"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.orcp.2020.07.002","article-title":"Obesity and mortality of COVID-19. Meta-analysis","volume":"14","author":"Hussain","year":"2020","journal-title":"Obes. Res. Clin. Pract."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E105","DOI":"10.1152\/ajpendo.00198.2020","article-title":"Obesity and COVID-19: Immune and metabolic derangement as a possible link to adverse clinical outcomes","volume":"319","author":"Korakas","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41575-019-0144-8","article-title":"Past, present and future perspectives in nonalcoholic fatty liver disease","volume":"16","author":"Sanyal","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bramante, C., Tignanelli, C.J., Dutta, N., Jones, E., Tamariz, L., Clark, J.M., Usher, M., Metlon-Meaux, G., and Ikramuddin, S. (2020). Non-alcoholic fatty liver disease (NAFLD) and risk of hospitalization for Covid-19. medRxiv.","DOI":"10.1101\/2020.09.01.20185850"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rathnasinghe, R., Jangra, S., Cupic, A., Martinez-Romero, C., Mulder, L.C.F., Kehrer, T., Yildiz, S., Choi, A., Mena, I., and De Vrieze, J. (2021). The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera. medRxiv.","DOI":"10.1101\/2021.01.19.21249592"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Osterrieder, N., Bertzbach, L.D., Dietert, K., Abdelgawad, A., Vladimirova, D., Kunec, D., Hoffmann, D., Beer, M., Gruber, A.D., and Trimpert, J. (2020). Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters. Viruses, 12.","DOI":"10.1101\/2020.06.10.144188"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/s41590-020-0778-2","article-title":"SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function","volume":"21","author":"Winkler","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.it.2020.10.012","article-title":"A Potential Role of Interleukin 10 in COVID-19 Pathogenesis","volume":"42","author":"Lu","year":"2021","journal-title":"Trends Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Invest."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/JLB.3COVR0520-272R","article-title":"Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts","volume":"108","author":"Wang","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_41","first-page":"e06155","article-title":"IL-6 and IL-10 as predictors of disease severity in COVID 19 patients: Results from Meta-analysis and Regression","volume":"7","author":"Dhar","year":"2020","journal-title":"medRxiv"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4049\/jimmunol.2001025","article-title":"Cutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators","volume":"206","author":"Schwarz","year":"2021","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/bmjebm-2020-111451","article-title":"COVID-19 and metabolic syndrome: Could diet be the key?","volume":"26","author":"Demasi","year":"2021","journal-title":"BMJ Evid. Based Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1016\/S2665-9913(20)30120-X","article-title":"The immunology of COVID-19: Is immune modulation an option for treatment?","volume":"2","author":"Zhong","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e13338","DOI":"10.1111\/eci.13338","article-title":"COVID-19 and non-alcoholic fatty liver disease: Two intersecting pandemics","volume":"50","author":"Portincasa","year":"2020","journal-title":"Eur. J. Clin. Investig."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/12\/2506\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:47:25Z","timestamp":1760168845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/12\/2506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,14]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["v13122506"],"URL":"https:\/\/doi.org\/10.3390\/v13122506","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,14]]}}}