Obesity Is a Risk Factor for Severe COVID-19 Infection

Abstract

HomeCirculationVol. 142, No. 1Obesity Is a Risk Factor for Severe COVID-19 Infection Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBObesity Is a Risk Factor for Severe COVID-19 InfectionMultiple Potential Mechanisms Naveed Sattar, Iain B. McInnes and John J.V. McMurray Naveed SattarNaveed Sattar Naveed Sattar, MD, Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom. Email E-mail Address: [email protected] https://orcid.org/0000-0002-1604-2593 Institute of Cardiovascular and Medical Sciences (N.S., J.J.V.M.), University of Glasgow, United Kingdom. , Iain B. McInnesIain B. McInnes Institute of Infection, Immunity and Inflammation (I.B.M.), University of Glasgow, United Kingdom. and John J.V. McMurrayJohn J.V. McMurray Institute of Cardiovascular and Medical Sciences (N.S., J.J.V.M.), University of Glasgow, United Kingdom. Originally published22 Apr 2020https://doi.org/10.1161/CIRCULATIONAHA.120.047659Circulation. 2020;142:4–6Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: April 22, 2020: Ahead of Print The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide research efforts to identify people at greatest risk of developing critical illness and dying. Initial data pointed toward older individuals being particularly vulnerable, as well as those with diabetes mellitus or cardiovascular (including hypertension), respiratory, or kidney disease. These problems are often concentrated in certain racial groups (eg, African Americans and Asians), which also appear to be more prone to worse COVID-19 outcomes.1 Increasing numbers of reports have linked obesity to more severe COVID-19 illness and death.1–3 In a French study, the risk for invasive mechanical ventilation in patients with COVID-19 infection admitted to the intensive treatment unit was more than 7-fold higher for those with body mass index (BMI) >35 compared with BMI <25 kg/m2.2 Among individuals with COVID-19 who were <60 years of age in New York City, those with a BMI between 30 to 34 kg/m2 and >35 kg/m2 were 1.8 times and 3.6 times more likely to be admitted to critical care, respectively, than individuals with a BMI <30 kg/m2.3We suggest obesity or excess ectopic fat deposition may be a unifying risk factor for severe COVID-19 infection, reducing protective cardiorespiratory reserve as well as potentiating the immune dysregulation that appears, at least in part, to mediate the progression to critical illness and organ failure in a proportion of patients with COVID-19 (Figure). Whether obesity is an independent risk factor for susceptibility to infection requires further research.Download figureDownload PowerPointFigure. Pathways potentially linking obesity or excess ectopic fat to more severe coronavirus disease 2019 (COVID-19) illness. There are multiple pathways by which obesity (or excess ectopic fat) may increase the effect of COVID-19 infection. These include underlying impairments in cardiovascular, respiratory, metabolic, and thrombotic pathways in relation to obesity, all of which reduce reserve and ability to cope with COVID-19 infection and the secondary immune reaction to it. At the same time, there are several reasons why obese individuals may have amplified or dysregulated immune response, linked both to greater viral exposure, as well as the possibility that excess adipose tissue potentiates the immune response. BP indicates blood pressure; COVID-19, coronavirus disease 2019; CV, cardiovascular; FEV1, forced expiratory volume; FVC, forced vital capacity; and SES, socioeconomic status.From a cardiovascular perspective, trial and genetic evidence conclusively show that obesity (and excess fat mass) are causally related to hypertension, diabetes mellitus, coronary heart disease, stroke, atrial fibrillation, renal disease, and heart failure. Obesity potentiates multiple cardiovascular risk factors, the premature development of cardiovascular disease, and adverse cardiorenal outcomes. There is also a metabolic concern. In individuals with diabetes mellitus, or at high risk of diabetes mellitus, obesity and excess ectopic fat lead to impairment of insulin resistance and reduced β-cell function. Both the latter limit ability to evoke an appropriate metabolic response on immunologic challenge, leading some patients with diabetes mellitus to require substantial amounts of insulin during severe infections. Overall, the integrated regulation of metabolism required for the complex cellular interactions, and for effective host defense, is lost, leading to functional immunologic deficit. COVID-19 may also directly disrupt pancreatic β-cell function through an interaction with angiotensin-converting enzyme 2. Furthermore, obesity enhances thrombosis, which is relevant given the association between severe COVID-19 and prothrombotic disseminated intravascular coagulation and high rates of venous thromboembolism.Beyond cardiometabolic and thrombotic consequences, obesity has detrimental effects on lung function, diminishing forced expiratory volume and forced vital capacity (Figure). Higher relative fat mass is also linked to such adverse changes, perhaps relevant to emerging reports of greater critical illness from COVID-19 in certain ethnicities, eg, Asians.1 Asians often display lower cardiorespiratory fitness and carry proportionally more fat tissue at lower BMIs. With extreme obesity (eg, BMI >40 kg/m2), care for individuals admitted to intensive therapy units is often impeded as these patients are more difficult to image, ventilate, nurse, and rehabilitate.With respect to the immune response, there is a clear association between obesity and basal inflammatory status characterized by higher circulating interleukin 6 and C-reactive protein levels. Adipose tissue in obesity is "proinflammatory," with increased expression of cytokines and particularly adipokines. There is also dysregulated tissue leukocyte expression, and inflammatory macrophage (and innate lymphoid) subsets replace tissue regulatory (M2) phenotypic cells. Obesity per se is an independent and causal risk factor for the development of immune-mediated disease, eg, psoriasis,4 suggesting that such adipose state may have systemic immune consequence on additional environmental provocation. In terms of host defense, obesity impairs adaptive immune responses to influenza virus5 and conceivably could do so in COVID-19. Obese individuals may exhibit greater viral shedding, suggesting potential for great viral exposure, especially if several family members are overweight. This may be aggravated in overcrowded multigenerational households, which are more common in the socioeconomically deprived communities in which obesity is prevalent. All these observations point toward a potential for obesity to give rise to a more adverse virus versus host immune response relationship in COVID-19. Poorer nutritional status and hyperglycemia may further aggravate the situation in some obese individuals.Much of the focus of COVID-19 has been on older people. However, it is important to remember that weight and muscle mass start to decline at advanced age but relative fat mass increases, particularly in those with comorbid diseases such as cardiovascular and respiratory conditions. Older age is also associated with more hypertension and diabetes mellitus because of stiffer vessels and impaired metabolic efficiency, respectively. People who are older (eg, >70 years of age), similar to younger obese individuals, have less cardiorespiratory reserve to cope with COVID-19 infection. Immune senescence is well recognized, as is the concept of inflammaging, and both may influence virus–host dynamics in the elderly and infection outcomes.What are the implications of these emerging observations for future research and public health messaging? With respect to research, predictive instruments for those most at risk of severe outcomes should consider BMI. Mechanistic understanding of the relationship between obesity and COVID-19 may suggest therapeutic interventions (eg, proven weight loss drugs, low-calorie diets) to potentially reduce the risk of developing severe COVID-19 illness. With respect to public health, it is important to communicate risks without causing anxiety. People worldwide should be encouraged to improve their lifestyle to lessen risk both in the current and subsequent waves of COVID-19. In addition to increasing activity levels, there should be improved messaging on better diet, focusing on simpler advice to help people adopt sustainable changes. This is particularly challenging with current stay-at-home rules limiting activity levels—the lockdown cost of weight gain. Even more worrying is that the resultant economic downturn may worsen obesity, especially in the most vulnerable individuals, a risk that governments need to address after the current pandemic. Indeed, this pandemic has highlighted that more—not less—must be done to tackle and prevent obesity in societies for the prevention of chronic disease and greater adverse reactions to viral pandemics.AcknowledgmentsThe authors thank Liz Coyle from the University of Glasgow for her excellent technical assistance in the preparation of this article.Sources of FundingThe work in this study is supported by the British Heart Foundation Center of Research Excellence Grant RE/18/6/34217.DisclosuresDr Sattar reports personal fees from Amgen, AstraZeneca, Eli Lilly, Novo Nordisk, Pfizer, and Sanofi and personal fees and research grants from Boehringer Ingelheim outside the submitted work. Drs McInnes and McMurray report no conflicts.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.https://www.ahajournals.org/journal/circNaveed Sattar, MD, Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom. Email [e-mail]1. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O'Donnell LF, Chernyak Y, Tobin K, Cerfolio RJ, Francois F, Horwitz LI. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study.BMJ2020; 369:m1966. doi: 10.1136/bmj.m1966CrossrefMedlineGoogle Scholar2. Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, Labreuche J, Mathieu D, Pattou F, Jourdain M, Lille Intensive Care COVID-19 and Obesity Study Group. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation [published online April 9, 2020].Obesity (Silver Spring). doi: 10.1002/oby.22831. https://onlinelibrary.wiley.com/doi/10.1002/oby.22831Google Scholar3. Lighter J, Phillips M, Hochman S, Sterling S, Johnson D, Francois F, Stachel A. Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission [published online April 9, 2020].Clin Infect Dis. 2020. doi:10.1093/cid/ciaa415. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa415/5818333CrossrefGoogle Scholar4. Budu-Aggrey A, Brumpton B, Tyrrell J, Watkins S, Modalsli EH, Celis-Morales C, Ferguson LD, Vie GÅ, Palmer T, Fritsche LG, et al. Evidence of a causal relationship between body mass index and psoriasis: a mendelian randomization study.PLoS Med. 2019; 16:e1002739. doi: 10.1371/journal.pmed.1002739CrossrefMedlineGoogle Scholar5. Green WD, Beck MA. Obesity impairs the adaptive immune response to influenza virus.Ann Am Thorac Soc. 2017; 14(suppl 5):S406–S409. doi: 10.1513/AnnalsATS.201706-447AWCrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. 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Ramos T and Adhikary D (2024) Genome Designing for Nutritional Quality in Amaranthus Compendium of Crop Genome Designing for Nutraceuticals, 10.1007/978-981-19-3627-2_56-2, (1-33), . Aktiz Bıçak E and Oğlak S (2023) Clinical characterisation and management outcome of obstetric patients following intensive care unit admission for COVID-19 pneumonia, Journal of Obstetrics and Gynaecology, 10.1080/01443615.2023.2218915, 43:2, Online publication date: 8-Dec-2023. Nganabashaka J, Niyibizi J, Umwali G, Rulisa S, M. Bavuma C, Byiringiro J, Ntawuyirushintege S, Niyomugabo P, Izerimana L, Tumusiime D and Keetile M (2023) The effects of COVID-19 mitigation measures on physical activity (PA) participation among adults in Rwanda: An online cross-sectional survey, PLOS ONE, 10.1371/journal.pone.0293231, 18:11, (e0293231) Moll-Bernardes R, Ferreira J, Sousa A, Tortelly M, Pimentel A, Figueiredo A, Schaustz E, Secco J, Sales A, Terzi F, Xavier de Brito A, Sarmento R, Noya-Rabelo M, Fortier S, Matos e Silva F, Vera N, Conde L, Cabral-Castro M, Albuquerque D, Rosado de-Castro P, Camargo G, Pinheiro M, Souza O, Bozza F, Luiz R and Medei E (2023) Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity, International Journal of Obesity, 10.1038/s41366-023-01407-0 Onyango T, Zhou F, Bredholt G, Brokstad K, Lartey S, Mohn K, Özgümüs T, Kittang B, Linchausen D, Shafiani S, Elyanow R, Blomberg B, Langeland N and Cox R (2023) SARS-CoV-2 specific immune responses in overweight and obese COVID-19 patients, Frontiers in Immunology, 10.3389/fimmu.2023.1287388, 14 Chenchula S, Sharma S, Tripathi M, Chavan M, Misra A and Rangari G (2023) Prevalence of overweight and obesity and their effect on COVID‐19 severity and hospitalization among younger than 50 years versus older than 50 years population: A systematic review and meta‐analysis, Obesity Reviews, 10.1111/obr.13616, 24:11, Online publication date: 1-Nov-2023. Boutari C, Kokkorakis M, Stefanakis K, Valenzuela-Vallejo L, Axarloglou E, Volčanšek Š, Chakhtoura M and Mantzoros C (2023) Recent research advances in metabolism, clinical and experimental, Metabolism, 10.1016/j.metabol.2023.155722, (155722), Online publication date: 1-Nov-2023. Woodward-Lopez G, Esaryk E, Rauzon S, Hewawitharana S, Thompson H, Cordon I and Whetstone L (2023) Associations between Changes in Food Acquisition Behaviors, Dietary Intake, and Bodyweight during the COVID-19 Pandemic among Low-Income Parents in California, Nutrients, 10.3390/nu15214618, 15:21, (4618) Zhang Y, Li J, Feng L, Luo Y, Pang W, Qiu K, Mao M, Song Y, Cheng D, Rao Y, Wang X, Hu Y, Ying Z, Pu X, Lin S, Huang S, Liu G, Zhang W, Xu W, Zhao Y and Ren J (2023) A Population-Based Outcome-Wide Association Study of the Comorbidities and Sequelae Following COVID-19 Infection, Journal of Epidemiology and Global Health, 10.1007/s44197-023-00161-w Jeong S, Yun S, Park S and Mun S (2023) Understanding cross-data dynamics of individual and social/environmental factors through a public health lens: explainable machine learning approaches, Frontiers in Public Health, 10.3389/fpubh.2023.1257861, 11 Cosentino F, Verma S, Ambery P, Treppendahl M, van Eickels M, Anker S, Cecchini M, Fioretto P, Groop P, Hess D, Khunti K, Lam C, Richard-Lordereau I, Lund L, McGreavy P, Newsome P, Sattar N, Solomon S, Weidinger F, Zannad F and Zeiher A (2023) Cardiometabolic risk management: insights from a European Society of Cardiology Cardiovascular Round Table, European Heart Journal, 10.1093/eurheartj/ehad445, 44:39, (4141-4156), Online publication date: 14-Oct-2023. ATUK KAHRAMAN T and YILMAZ M (2023) Comparison of The Nutritional Habits of Individuals With and Without a COVID-19 Diagnosis: An Online Cross-Sectional Study From TürkiyeCOVID-19 Tanısı Alan ve Almayan Bireylerin Beslenme Alışkanlıklarının Karşılaştırılması: Türkiye'den Çevrimiçi Kesitsel Bir Çalışma, İzmir Katip Çelebi Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, 10.61399/ikcusbfd.1244702, 8:3, (1009-1017) Sprockel Díaz J, Coral Zuñiga V, Angarita Gonzalez E, Tabares Rodríguez S, Carrillo Ayerbe M, Acuña Cortes I, Montoya Rumpf R, Martínez Arias L, Parra J and Diaztagle Fernández J (2023) Obesity and the obesity paradox in patients with severe COVID-19, Medicina Intensiva (English Edition), 10.1016/j.medine.2023.03.009, 47:10, (565-574), Online publication date: 1-Oct-2023. Sprockel Díaz J, Coral Zuñiga V, Angarita Gonzalez E, Tabares Rodríguez S, Carrillo Ayerbe M, Acuña Cortes I, Montoya Rumpf R, Martínez Arias L, Parra J and Diaztagle Fernández J (2023) Obesity and the obesity paradox in patients with severe COVID-19, Medicina Intensiva, 47:10, (565-574), Online publication date: 1-Oct-2023. T, C and S (2023) The COVID-19, Cardiovascular and a Online publication date: 1-Oct-2023. B, K, C, Lin W, Y, T, Lin M and (2023) in the of COVID-19, International Journal of Sciences, van J, J, S, L, van M, M, S, R, van A, A, M, Y, A and (2023) of with SARS-CoV-2 after of H, M, H, M, A, M, M, M, S, W, A, M, I, M, M and (2023) as a Factor in A Infection and E, R, S and related to an Journal of Online publication date: de M, C, D, Silva C, J, T, F, M, I, D, J, T, E, da L, R, F and (2023) The T regulatory with infection and outcome in COVID-19 patients mechanical Scientific A, P, E, G and K (2023) the Risk for Clinical in with A A, M, T, J, S, J, S, Li G, J, N, J, R, G and S (2023) of COVID-19 on Care Online publication date: L, Z, T, A, M, D, M, D and A (2023) as a of COVID-19 of the prospective study, Online publication date: T, K, S, K, H, K, N and J (2023) Impact of body on after infection, PLOS ONE, K, A, T, T, K, M, T, A, and J (2023) Association between obesity and in COVID-19 patients requiring invasive mechanical a study, Scientific M, S, S, A, M, R, and S (2023) Association of body mass index with COVID-19 outcome in a hospital in de Online publication date: P, A, R, R and A Impact of pandemic on development and in and International Journal of Online publication date: C, Y, R, M, R and S status of in a COVID-19 and R (2023) Obesity and of Online publication date: W, E, L, D, M, K, J, J, Figueiredo J, J, A, S, A and M (2023) and Risk of Disease The American Journal of Online publication date: A, V, I, Y, A and A (2023) and immune response coronavirus infection on the of obesity and Obesity and metabolism, A, F, N, A, S, R, M and N (2023) C and inflammatory factors related to COVID-19 consequences, K, O, J, A and (2023) SARS-CoV-2 Infection to and in N, G, H, C, E, G, J, and T (2023) inflammatory syndrome in cohort study of risk factors, S, S and T (2023) The associated with lifestyle risk factors and nutritional status for COVID-19 patients in the Journal of Public in V, N, N, I, M, I, V, T, M, M, A, D and M (2023) and as of in COVID-19 Ko Y, Z, R and S (2023) Association among and Risk Factors with SARS-CoV-2 Infection, and Online publication date: B, T, S and L of a complex to reduce metabolic syndrome in with Online publication date: Y, N, Yang J, C, Zhang A, B, E and C A in the of Online publication date: I, O, I, M, A, R and (2023) is the of adipose tissue in metabolic and future in the Online publication date: G, F, A, R, M, F, Johansen M, F, G, G, N, P, T, I, A, P, G, C and S (2023) and of COVID-19 associated therapeutic Journal of Li C, J, Huang J and (2023) the coronavirus disease New and New Online publication date: A, S, B, Z, A and C (2023) COVID-19 Medical Tsao C, Aday A, Almarzooq Z, Anderson C, Arora P, Avery C, Baker-Smith C, Beaton A, Boehme A, A, Commodore-Mensah Y, Elkind M, Evenson K, C, S, Generoso G, Heard D, Hiremath S, J, Kalani R, Kazi D, Ko D, D, Liu J, J, Magnani J, Michos E, Mussolino M, Navaneethan S, Parikh N, Poudel R, Rezk-Hanna M, Roth G, Shah N, St-Onge M, Thacker E, S, Voeks J, Wang N, Wong N, Wong S, Yaffe K and S (2023) Heart Disease and Stroke A Report From the American Heart Association, Circulation, Online publication date: R, S, A and D of obesity among from and lifestyle perspective, British Food Journal, Online publication date: M, X, H, and J (2023) The of obesity and thrombotic and Frontiers in Cardiovascular A, A, A, S, I, E, N, N, A, H, A, A, R, R, A, M, A, M, M, E, S, S and S (2023) The Impact of and Obesity on the of and Obesity, G, J, A, V, P, K, C, A, F, D, F, M and I (2023) SARS-CoV-2 infection adipose tissue in D, H, M, and M in older the of of the Online publication date: D, B, E, X, M, J, and J (2023) of COVID-19 infection in people with diabetes mellitus or obesity in the care in A cohort study of the Care Online publication date: S, M, M, M, Z, A, A and K (2023) The of and A A, F, A, M, G, X, E, S and G (2023) of D for and H, T, Y, T, M, M, S, K and M (2023) Clinical and the risk of hospitalization of patients with coronavirus disease 2019 in a