Factors Associated with Increased Morbidity and Mortality of Obese and Overweight COVID-19 Patients

Amany Magdy Beshbishy, Helal F Hetta, Diaa E Hussein, Abdullah A Saati, Christian C Uba, Nallely Rivero-Perez, Adrian Zaragoza-Bastida, Muhammad Ajmal Shah, Tapan Behl, Gaber El-Saber Batiha, Amany Magdy Beshbishy, Helal F Hetta, Diaa E Hussein, Abdullah A Saati, Christian C Uba, Nallely Rivero-Perez, Adrian Zaragoza-Bastida, Muhammad Ajmal Shah, Tapan Behl, Gaber El-Saber Batiha

Abstract

Overweight and obesity are defined as an unnecessary accumulation of fat, which poses a risk to health. It is a well-identified risk factor for increased mortality due to heightened rates of heart disease, certain cancers, musculoskeletal disorders, and bacterial, protozoan and viral infections. The increasing prevalence of obesity is of concern, as conventional pathogenesis may indeed be increased in obese hosts rather than healthy hosts, especially during this COVID-19 pandemic. COVID-19 is a new disease and we do not have the luxury of cumulative data. Obesity activates the development of gene induced hypoxia and adipogenesis in obese animals. Several factors can influence obesity, for example, stress can increase the body weight by allowing people to consume high amounts of food with a higher propensity to consume palatable food. Obesity is a risk factor for the development of immune-mediated and some inflammatory-mediated diseases, including atherosclerosis and psoriasis, leading to a dampened immune response to infectious agents, leading to weaker post-infection impacts. Moreover, the obese host creates a special microenvironment for disease pathogenesis, marked by persistent low-grade inflammation. Therefore, it is advisable to sustain healthy eating habits by increasing the consumption of various plant-based and low-fat foods to protect our bodies and decrease the risk of infectious diseases, especially COVID-19.

Keywords: COVID-19; coronaviruses; influenza; obesity; thrombosis.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The coronavirus disease (COVID-19) transmission.
Figure 2
Figure 2
Mechanism of COVID-19 in the host [40].
Figure 3
Figure 3
COVID-19 and obesity.

References

    1. World Health Organization . Obesity and Overweight. Key Facts. WHO; Geneva, Switzerland: 2018.
    1. Aguilar M., Bhuket T., Torres S., Liu B., Wong R.J. Prevalence of the metabolic syndrome in the United States, 2003–2012. JAMA. 2015;313:1973–1974. doi: 10.1001/jama.2015.4260.
    1. Abbas A.M., Fathy S.K., Fawzy A.T., Salem A.S., Shawky M.S. The mutual effects of COVID-19 and obesity. Obes. Med. 2020:100250. doi: 10.1016/j.obmed.2020.100250.
    1. Schmidt F.M., Weschenfelder J., Sander C., Minkwitz J., Thormann J., Chittka T., Mergl R., Kirkby K.C., Faßhauer M., Stumvoll M. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS ONE. 2015;10:e0121971. doi: 10.1371/journal.pone.0121971.
    1. Caër C., Rouault C., Le Roy T., Poitou C., Aron-Wisnewsky J., Torcivia A., Bichet J.-C., Clément K., Guerre-Millo M., André S. Immune cell-derived cytokines contribute to obesity-related inflammation, fibrogenesis and metabolic deregulation in human adipose tissue. Sci. Rep. 2017;7:1–11. doi: 10.1038/s41598-017-02660-w.
    1. Honce R., Schultz-Cherry S. Impact of obesity on influenza A virus pathogenesis, immune response, and evolution. Front. Immunol. 2019;10:1071. doi: 10.3389/fimmu.2019.01071.
    1. Wang Z., Nakayama T. Inflammation, a link between obesity and cardiovascular disease. Med. Inflamm. 2010;2010 doi: 10.1155/2010/535918.
    1. Richard C., Wadowski M., Goruk S., Cameron L., Sharma A.M., Field C.J. Individuals with obesity and type 2 diabetes have additional immune dysfunction compared with obese individuals who are metabolically healthy. BMJ Open Diabetes Res. Care. 2017;5 doi: 10.1136/bmjdrc-2016-000379.
    1. Lee Y.S., Kim J.-W., Osborne O., Sasik R., Schenk S., Chen A., Chung H., Murphy A., Watkins S.M., Quehenberger O. Increased adipocyte O2 consumption triggers HIF-1α, causing inflammation and insulin resistance in obesity. Cell. 2014;157:1339–1352. doi: 10.1016/j.cell.2014.05.012.
    1. Huh J.Y., Park Y.J., Ham M., Kim J.B. Crosstalk between adipocytes and immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. Mol. Cells. 2014;37:365. doi: 10.14348/molcells.2014.0074.
    1. Andersen C.J., Murphy K.E., Fernandez M.L. Impact of obesity and metabolic syndrome on immunity. Adv. Nutr. 2016;7:66–75. doi: 10.3945/an.115.010207.
    1. Luzi L., Radaelli M.G. Influenza and obesity: Its odd relationship and the lessons for COVID-19 pandemic. Acta Diabetol. 2020 doi: 10.1007/s00592-020-01522-8.
    1. Afolabi H.A., bin Zakariya Z., Shokri A.B.A., Hasim M.N.B.M., Vinayak R., Afolabi-Owolabi O.T., Elesho R.F. The relationship between obesity and other medical comorbidities. Obes. Med. 2020;17:100164. doi: 10.1016/j.obmed.2019.100164.
    1. Sattar N., McInnes I.B., McMurray J.J. Obesity a risk factor for severe COVID-19 infection: Multiple potential mechanisms. Circulation. 2020 doi: 10.1161/CIRCULATIONAHA.120.047659.
    1. Hâncu A., Mihălţan F. Two Pandemics Coalition: Covid-19 and Obesity. Intern. Med. 2020;17:37–45. doi: 10.2478/inmed-2020-0109.
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239–1242. doi: 10.1001/jama.2020.2648.
    1. Ouchi N., Parker J.L., Lugus J.J., Walsh K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 2011;11:85–97. doi: 10.1038/nri2921.
    1. Ahn S.-Y., Sohn S.-H., Lee S.-Y., Park H.-L., Park Y.-W., Kim H., Nam J.-H. The effect of lipopolysaccharide-induced obesity and its chronic inflammation on influenza virus-related pathology. Environ. Toxicol. Pharmacol. 2015;40:924–930. doi: 10.1016/j.etap.2015.09.020.
    1. Karlsson E.A., Hertz T., Johnson C., Mehle A., Krammer F., Schultz-Cherry S. Obesity outweighs protection conferred by adjuvanted influenza vaccination. mBio. 2016;7 doi: 10.1128/mBio.01144-16.
    1. Xue K.S., Stevens-Ayers T., Campbell A.P., Englund J.A., Pergam S.A., Boeckh M., Bloom J.D. Parallel evolution of influenza across multiple spatiotemporal scales. eLife. 2017;6:e26875. doi: 10.7554/eLife.26875.
    1. Zhang A.J., To K.K., Li C., Lau C.C., Poon V.K., Chan C.C., Zheng B.-J., Hung I.F., Lam K.S., Xu A. Leptin mediates the pathogenesis of severe 2009 pandemic influenza A (H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. J. Infect. Dis. 2013;207:1270–1280. doi: 10.1093/infdis/jit031.
    1. Park S., Jeon J.-H., Min B.-K., Ha C.-M., Thoudam T., Park B.-Y., Lee I.-K. Role of the pyruvate dehydrogenase complex in metabolic remodeling: Differential pyruvate dehydrogenase complex functions in metabolism. Diabetes Metabol. J. 2018;42:270–281. doi: 10.4093/dmj.2018.0101.
    1. Zheng Q., Cui G., Chen J., Gao H., Wei Y., Uede T., Chen Z., Diao H. Regular exercise enhances the immune response against microbial antigens through up-regulation of toll-like receptor signaling pathways. Cell. Physiol. Biochem. 2015;37:735–746. doi: 10.1159/000430391.
    1. Reidy P.T., Yonemura N.M., Madsen J.H., McKenzie A.I., Mahmassani Z.S., Rondina M.T., Lin Y.K., Kaput K., Drummond M.J. An accumulation of muscle macrophages is accompanied by altered insulin sensitivity after reduced activity and recovery. Acta Physiol. 2019;226:e13251. doi: 10.1111/apha.13251.
    1. Na H.-N., Nam J.-H. Adenovirus 36 as an obesity agent maintains the obesity state by increasing MCP-1 and inducing inflammation. J. Infect. Dis. 2012;205:914–922. doi: 10.1093/infdis/jir864.
    1. Kim J., Na H., Kim J.-A., Nam J.-H. What we know and what we need to know about adenovirus 36-induced obesity. Int. J. Obes. 2020 doi: 10.1038/s41366-020-0536-4.
    1. Trayhurn P. Hypoxia and adipose tissue function and dysfunction in obesity. Physiol. Rev. 2013;93:1–21. doi: 10.1152/physrev.00017.2012.
    1. Jang M.-K., Son Y., Jung M.H. ATF3 plays a role in adipocyte hypoxia-mediated mitochondria dysfunction in obesity. Biochem. Biophys. Res. Commun. 2013;431:421–427. doi: 10.1016/j.bbrc.2012.12.154.
    1. Na H., Kim H., Nam J. Novel genes and cellular pathways related to infection with adenovirus-36 as an obesity agent in human mesenchymal stem cells. Int. J. Obes. 2012;36:195–200. doi: 10.1038/ijo.2011.89.
    1. Na H., Kim J., Lee H., Shim K., Kimm H., Jee S., Jo I., Nam J. Association of human adenovirus-36 in overweight Korean adults. Int. J. Obes. 2012;36:281–285. doi: 10.1038/ijo.2011.102.
    1. Mizumoto K., Kagaya K., Zarebski A., Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Eurosurveillance. 2020;25:2000180. doi: 10.2807/1560-7917.ES.2020.25.10.2000180.
    1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020 doi: 10.1056/NEJMoa2001017.
    1. Guan W.-J., Ni Z.-Y., Hu Y., Liang W.-H., Ou C.-Q., He J.-X., Liu L., Shan H., Lei C.-L., Hui D.S. Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032.
    1. WHO Characterizes COVID-19 as a Pandemic (11 March 2020) [(accessed on 23 August 2020)]; Available online: .
    1. Zhang Y., Chen C., Zhu S., Shu C., Wang D., Song J., Song Y., Zhen W., Feng Z., Wu G. Isolation of 2019-nCoV from a stool specimen of a laboratory-confirmed case of the coronavirus disease 2019 (COVID-19) China CDC Wkly. 2020;2:123–124. doi: 10.46234/ccdcw2020.033.
    1. Guo Y.-R., Cao Q.-D., Hong Z.-S., Tan Y.-Y., Chen S.-D., Jin H.-J., Tan K.-S., Wang D.-Y., Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Milit. Med. Res. 2020;7:1–10. doi: 10.1186/s40779-020-00240-0.
    1. Batiha G.E., Tayebwa D.S., Beshbishy A.M., N’Da D.D., Yokoyama N., Igarashi I. Inhibitory effects of novel ciprofloxacin derivatives on the growth of four Babesia species and Theileria equi. Parasitol. Res. 2020;119:3061–3073. doi: 10.1007/s00436-020-06796-z.
    1. Shereen M.A., Khan S., Kazmi A., Bashir N., Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J. Adv. Res. 2020 doi: 10.1016/j.jare.2020.03.005.
    1. Perrier A., Bonnin A., Desmarets L., Danneels A., Goffard A., Rouillé Y., Dubuisson J., Belouzard S. The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal. J. Biol. Chem. 2019;294:14406–14421. doi: 10.1074/jbc.RA119.008964.
    1. Alanagreh L.A., Alzoughool F., Atoum M. The human coronavirus disease COVID-19: Its origin, characteristics, and insights into potential drugs and its mechanisms. Pathogens. 2020;9:331. doi: 10.3390/pathogens9050331.
    1. Magdy Beshbishy A., Alghamdi S., Onyiche T.E., Zahoor M., Rivero-Perez N., Zaragoza-Bastida A., Ghorab M.A., Meshaal A.K., El-Esawi M.A., Hetta H.F., et al. Biogenesis, biologic function and clinical potential of exosomes in different diseases. Appl. Sci. 2020;10:4428. doi: 10.3390/app10134428.
    1. Ogden C.L., Fakhouri T.H., Carroll M.D., Hales C.M., Fryar C.D., Li X., Freedman D.S. Prevalence of obesity among adults, by household income and education—United States, 2011–2014. MMWR. Morb. Mortal. Wkl. Rep. 2017;66:1369. doi: 10.15585/mmwr.mm6650a1.
    1. Onder G., Rezza G., Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020;323:1775–1776. doi: 10.1001/jama.2020.4683.
    1. 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. Clin. Infect. Dis. 2020 doi: 10.1093/cid/ciaa415.
    1. Caspard H., Jabbour S., Hammar N., Fenici P., Sheehan J.J., Kosiborod M. Recent trends in the prevalence of type 2 diabetes and the association with abdominal obesity lead to growing health disparities in the USA: An analysis of the NHANES surveys from 1999 to 2014. Diabetes Obes. Metabol. 2018;20:667–671. doi: 10.1111/dom.13143.
    1. Simonnet A., Chetboun M., Poissy J., Raverdy V., Noulette J., Duhamel A., Labreuche J., Mathieu D., Pattou F., Jourdain M. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity. 2020 doi: 10.1002/oby.22831.
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 2020 doi: 10.1016/S0140-6736(20)30566-3.
    1. Cai Q., Chen F., Wang T., Luo F., Liu X., Wu Q., He Q., Wang Z., Liu Y., Liu L. Obesity and COVID-19 severity in a designated hospital in Shenzhen, China. Diabetes Care. 2020 doi: 10.2337/dc20-0576.
    1. Mehra M.R., Desai S.S., Ruschitzka F., Patel A.N. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis. Lancet. 2020 doi: 10.1016/S0140-6736(20)31180-6.
    1. Petrilli C.M., Jones S.A., Yang J., Rajagopalan H., O’Donnell L.F., Chernyak Y., Tobin K., Cerfolio R.J., Francois F., Horwitz L.I. Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City. MedRxiv. 2020 doi: 10.1101/2020.04.08.20057794.
    1. Dietz W., Santos-Burgoa C. Obesity and its Implications for COVID-19 Mortality. Obesity. 2020;28:1005. doi: 10.1002/oby.22818.
    1. Petersen A., Bressem K., Albrecht J., Thiess H.-M., Vahldiek J., Hamm B., Makowski M., Niehues A., Niehues S., Adams L.C. Obesity and COVID-19: The role of visceral adipose tissue. medRxiv. 2020 doi: 10.1101/2020.05.14.20101998.
    1. Bornstein S.R., Dalan R., Hopkins D., Mingrone G., Boehm B.O. Endocrine and metabolic link to coronavirus infection. Nat. Rev. Endocrinol. 2020;16:297–298. doi: 10.1038/s41574-020-0353-9.
    1. Bourgeois C., Gorwood J., Barrail-Tran A., Lagathu C., Capeau J., Desjardins D., Le Grand R., Damouche A., Béréziat V., Lambotte O. Specific biological features of adipose tissue, and their impact on HIV persistence. Front. Microbiol. 2019;10 doi: 10.3389/fmicb.2019.02837.
    1. Rao S., Lau A., So H.-C. Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of SARS-CoV-2: A Mendelian Randomization analysis highlights tentative relevance of diabetes-related traits. Diabetes Care. 2020 doi: 10.2337/dc20-0643.
    1. Zheng K.I., Gao F., Wang X.-B., Sun Q.-F., Pan K.-H., Wang T.-Y., Ma H.-L., Liu W.-Y., George J., Zheng M.-H. Obesity as a risk factor for greater severity of COVID-19 in patients with metabolic associated fatty liver disease. Metabolism. 2020:154244. doi: 10.1016/j.metabol.2020.154244.
    1. Hall K. A review of the carbohydrate–insulin model of obesity. Eur. J. Clin. Nutr. 2017;71:323–326. doi: 10.1038/ejcn.2016.260.
    1. Schulte E.M., Avena N.M., Gearhardt A.N. Which foods may be addictive? The roles of processing, fat content, and glycemic load. PLoS ONE. 2015;10:e0117959. doi: 10.1371/journal.pone.0117959.
    1. Petrakis D., Margină D., Tsarouhas K., Tekos F., Stan M., Nikitovic D., Kouretas D., Spandidos D.A., Tsatsakis A. Obesity—A risk factor for increased COVID-19 prevalence, severity and lethality (Review) Mol. Med. Rep. 2020;22:9–19. doi: 10.3892/mmr.2020.11127.
    1. Driggin E., Madhavan M.V., Bikdeli B., Chuich T., Laracy J., Biondi-Zoccai G., Brown T.S., Der Nigoghossian C., Zidar D.A., Haythe J. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J. Am. Coll. Cardiol. 2020;75:2352–2371. doi: 10.1016/j.jacc.2020.03.031.
    1. Rodríguez M.Á., Crespo I., Olmedillas H. Exercising in times of COVID-19: What do experts recommend doing within four walls? Rev. Espanola Cardiol. (Engl. Ed.) 2020 doi: 10.1016/j.rec.2020.04.001.
    1. Isasi C.R., Parrinello C.M., Jung M.M., Carnethon M.R., Birnbaum-Weitzman O., Espinoza R.A., Penedo F.J., Perreira K.M., Schneiderman N., Sotres-Alvarez D. Psychosocial stress is associated with obesity and diet quality in Hispanic/Latino adults. Ann. Epidemiol. 2015;25:84–89. doi: 10.1016/j.annepidem.2014.11.002.
    1. Liang T. Handbook of COVID-19 prevention and treatment. [(accessed on 23 August 2020)];First Affil. Hosp. Zhejiang Univ. Sch. Med. Compil. Accord. Clin. Exp. 2020 :1–59. Available online:
    1. Castaner O., Goday A., Park Y.-M., Lee S.-H., Magkos F., Shiow S.-A.T.E., Schröder H. The gut microbiome profile in obesity: A systematic review. Int. J. Endocrinol. 2018;2018 doi: 10.1155/2018/4095789.
    1. Bäckhed F., Ding H., Wang T., Hooper L.V., Koh G.Y., Nagy A., Semenkovich C.F., Gordon J.I. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA. 2004;101:15718–15723. doi: 10.1073/pnas.0407076101.
    1. Turnbaugh P.J., Ley R.E., Mahowald M.A., Magrini V., Mardis E.R., Gordon J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027. doi: 10.1038/nature05414.
    1. Koliada A., Syzenko G., Moseiko V., Budovska L., Puchkov K., Perederiy V., Gavalko Y., Dorofeyev A., Romanenko M., Tkach S. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol. 2017;17:1–6. doi: 10.1186/s12866-017-1027-1.
    1. Gómez-Hernández A., Beneit N., Díaz-Castroverde S., Escribano Ó. Differential role of adipose tissues in obesity and related metabolic and vascular complications. Int. J. Endocrinol. 2016;2016 doi: 10.1155/2016/1216783.
    1. Winer D.A., Luck H., Tsai S., Winer S. The intestinal immune system in obesity and insulin resistance. Cell Metab. 2016;23:413–426. doi: 10.1016/j.cmet.2016.01.003.
    1. Boucard-Jourdin M., Kugler D., Ahanda M.-L.E., This S., De Calisto J., Zhang A., Mora J.R., Stuart L.M., Savill J., Lacy-Hulbert A. β8 integrin expression and activation of TGF-β by intestinal dendritic cells are determined by both tissue microenvironment and cell lineage. J. Immunol. 2016;197:1968–1978. doi: 10.4049/jimmunol.1600244.
    1. Wang T., Chen R., Liu C., Liang W., Guan W., Tang R., Tang C., Zhang N., Zhong N., Li S. Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19. Lancet Haematol. 2020;7:e362–e363. doi: 10.1016/S2352-3026(20)30109-5.
    1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020;18:844–847. doi: 10.1111/jth.14768.
    1. Lorenzet R., Napoleone E., Cutrone A., Donati M.B. Thrombosis and obesity: Cellular bases. Thromb. Res. 2012;129:285–289. doi: 10.1016/j.thromres.2011.10.021.
    1. Campello E., Zabeo E., Radu C.M., Spiezia L., Gavasso S., Fadin M., Woodhams B., Vettor R., Simioni P. Hypercoagulability in overweight and obese subjects who are asymptomatic for thrombotic events. Thromb. Haemost. 2015;113:85–96.
    1. Samad F., Ruf W. Inflammation, obesity, and thrombosis. Blood J. Am. Soc. Hematol. 2013;122:3415–3422. doi: 10.1182/blood-2013-05-427708.
    1. Sanchis-Gomar F., Lavie C.J., Mehra M.R., Henry B.M., Lippi G. Obesity and outcomes in COVID-19: When an epidemic and pandemic collide. Mayo Clin. Proc. 2020;95:1445–1453. doi: 10.1016/j.mayocp.2020.05.006.
    1. Milner J.J., Beck M.A. The impact of obesity on the immune response to infection. Proc. Nutr. Soc. 2012;71:298–306. doi: 10.1017/S0029665112000158.
    1. Trim W., Turner J.E., Thompson D. Parallels in immunometabolic adipose tissue dysfunction with ageing and obesity. Front. Immunol. 2018;9:169. doi: 10.3389/fimmu.2018.00169.
    1. Laddu D.R., Lavie C.J., Phillips S.A., Arena R. Physical activity for immunity protection: Inoculating populations with healthy living medicine in preparation for the next pandemic. Prog. Cardiovasc. Dis. 2020 doi: 10.1016/j.pcad.2020.04.006.
    1. Tanaka S.I., Isoda F., Ishihara Y., Kimura M., Yamakawa T. T lymphopaenia in relation to body mass index and TNF-α in human obesity: Adequate weight reduction can be corrective. Clin. Endocrinol. 2001;54:347–354. doi: 10.1046/j.1365-2265.2001.1139cn2155.x.
    1. Meliopoulos V., Livingston B., Van de Velde L.-A., Honce R., Schultz-Cherry S. Absence of β6 integrin reduces influenza disease severity in highly susceptible obese mice. J. Virol. 2019;93 doi: 10.1128/JVI.01646-18.
    1. El-Saber Batiha G., Magdy Beshbishy A., Stephen Adeyemi O., Nadwa E., Rashwan E., Yokoyama N., Igarashi I. Safety and efficacy of hydroxyurea and eflornithine against most blood parasites Babesia and Theileria. PLoS ONE. 2020;15:e0228996. doi: 10.1371/journal.pone.0228996.
    1. Kass D.A., Duggal P., Cingolani O. Obesity could shift severe COVID-19 disease to younger ages. Lancet (Lond. Engl.) 2020 doi: 10.1016/S0140-6736(20)31024-2.
    1. Maier H.E., Lopez R., Sanchez N., Ng S., Gresh L., Ojeda S., Burger-Calderon R., Kuan G., Harris E., Balmaseda A. Obesity increases the duration of influenza A virus shedding in adults. J. Infect. Dis. 2018;218:1378–1382. doi: 10.1093/infdis/jiy370.
    1. Smith A.G., Sheridan P.A., Harp J.B., Beck M.A. Diet-induced obese mice have increased mortality and altered immune responses when infected with influenza virus. J. Nutr. 2007;137:1236–1243. doi: 10.1093/jn/137.5.1236.
    1. Karlsson E.A., Sheridan P.A., Beck M.A. Diet-induced obesity impairs the T cell memory response to influenza virus infection. J. Immunol. 2010;184:3127–3133. doi: 10.4049/jimmunol.0903220.
    1. Honce R., Karlsson E.A., Wohlgemuth N., Estrada L.D., Meliopoulos V.A., Yao J., Schultz-Cherry S. Obesity-related microenvironment promotes emergence of virulent influenza virus strains. mBio. 2020;11 doi: 10.1128/mBio.03341-19.
    1. Easterbrook J.D., Dunfee R.L., Schwartzman L.M., Jagger B.W., Sandouk A., Kash J.C., Memoli M.J., Taubenberger J.K. Obese mice have increased morbidity and mortality compared to non-obese mice during infection with the 2009 pandemic H1N1 influenza virus. Influenza Other Respir. Viruses. 2011;5:418–425. doi: 10.1111/j.1750-2659.2011.00254.x.
    1. Karlsson E.A., Meliopoulos V.A., van de Velde N.C., van de Velde L.-A., Mann B., Gao G., Rosch J., Tuomanen E., McCullers J., Vogel P. A perfect storm: Increased colonization and failure of vaccination leads to severe secondary bacterial infection in influenza virus-infected obese mice. mBio. 2017;8 doi: 10.1128/mBio.00889-17.
    1. Paich H.A., Sheridan P.A., Handy J., Karlsson E.A., Schultz-Cherry S., Hudgens M.G., Noah T.L., Weir S.S., Beck M.A. Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus. Obesity. 2013;21:2377–2386. doi: 10.1002/oby.20383.
    1. O’Shea D., Corrigan M., Dunne M.R., Jackson R., Woods C., Gaoatswe G., Moynagh P.N., O’Connell J., Hogan A. Changes in human dendritic cell number and function in severe obesity may contribute to increased susceptibility to viral infection. Int. J. Obes. 2013;37:1510–1513. doi: 10.1038/ijo.2013.16.
    1. Radigan K.A., Morales-Nebreda L., Soberanes S., Nicholson T., Nigdelioglu R., Cho T., Chi M., Hamanaka R.B., Misharin A.V., Perlman H. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages. PLoS ONE. 2014;9:e108138. doi: 10.1371/journal.pone.0108138.
    1. Rebeles J., Green W.D., Alwarawrah Y., Nichols A.G., Eisner W., Danzaki K., MacIver N.J., Beck M.A. Obesity-induced changes in T-cell metabolism are associated with impaired memory T-cell response to influenza and are not reversed with weight loss. J. Infect. Dis. 2019;219:1652–1661. doi: 10.1093/infdis/jiy700.
    1. Rocha V.Z., Libby P. Obesity, inflammation, and atherosclerosis. Nat. Rev. Cardiol. 2009;6:399–409. doi: 10.1038/nrcardio.2009.55.
    1. Batiha G.E., Beshbishy A.M., Tayebwa D.S., Adeyemi O.S., Yokoyama N., Igarashi I. Anti-piroplasmic potential of the methanolic Peganum harmala seeds and ethanolic Artemisia absinthium leaf extracts. J. Protoz. Res. 2019;29:8–25.
    1. Shoelson S.E., Herrero L., Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132:2169–2180. doi: 10.1053/j.gastro.2007.03.059.
    1. Lee H., Lee I.S., Choue R. Obesity, inflammation and diet. Pediatr. Gastroenterol. Hepatol. Nutr. 2013;16:143–152. doi: 10.5223/pghn.2013.16.3.143.
    1. Setty A.R., Curhan G., Choi H.K. Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses’ Health Study II. Arch. Intern. Med. 2007;167:1670–1675. doi: 10.1001/archinte.167.15.1670.
    1. Manzel A., Muller D.N., Hafler D.A., Erdman S.E., Linker R.A., Kleinewietfeld M. Role of “Western diet” in inflammatory autoimmune diseases. Curr. Allergy Asthma Rep. 2014;14:404. doi: 10.1007/s11882-013-0404-6.
    1. Nakamizo S., Honda T., Adachi A., Nagatake T., Kunisawa J., Kitoh A., Otsuka A., Dainichi T., Nomura T., Ginhoux F. High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing γδ T cells. Sci. Rep. 2017;7:1–13. doi: 10.1038/s41598-017-14292-1.
    1. Neimann A.L., Shin D.B., Wang X., Margolis D.J., Troxel A.B., Gelfand J.M. Prevalence of cardiovascular risk factors in patients with psoriasis. J. Am. Acad. Dermatol. 2006;55:829–835. doi: 10.1016/j.jaad.2006.08.040.
    1. Cohen A., Sherf M., Vidavsky L., Vardy D., Shapiro J., Meyerovitch J. Association between psoriasis and the metabolic syndrome. Dermatology. 2008;216:152–155. doi: 10.1159/000111512.
    1. Paules C.I., Sullivan S.G., Subbarao K., Fauci A.S. Chasing seasonal influenza—The need for a universal influenza vaccine. N. Engl. J. Med. 2018;378:7–9. doi: 10.1056/NEJMp1714916.
    1. Smit M.A., Wang H.-L., Kim E., Barragan N., Aldrovandi G.M., El Amin A.N., Mascola L., Pannaraj P.S. Influenza vaccine is protective against laboratory-confirmed influenza in obese children. Pediatr. Infect. Dis. J. 2016;35:440–445. doi: 10.1097/INF.0000000000001029.
    1. Sheridan P.A., Paich H.A., Handy J., Karlsson E.A., Hudgens M.G., Sammon A.B., Holland L.A., Weir S., Noah T.L., Beck M.A. Obesity is associated with impaired immune response to influenza vaccination in humans. Int. J. Obes. 2012;36:1072–1077. doi: 10.1038/ijo.2011.208.
    1. Moser J.A.S., Galindo-Fraga A., Ortiz-Hernández A.A., Gu W., Hunsberger S., Galán-Herrera J.F., Guerrero M.L., Ruiz-Palacios G.M., Beigel J.H., Group L.R.I.S. Underweight, overweight, and obesity as independent risk factors for hospitalization in adults and children from influenza and other respiratory viruses. Influenza Other Respir. Viruses. 2019;13:3–9. doi: 10.1111/irv.12618.
    1. Torres L., Martins V.D., Faria A.M.C., Maioli T.U. The intriguing relationship between obesity and infection. J. Infectiol. 2018;1:5. doi: 10.29245/2689-9981/2018/1.1104.
    1. Dhurandhar N., Bailey D., Thomas D. Interaction of obesity and infections. Obes. Rev. 2015;16:1017–1029. doi: 10.1111/obr.12320.
    1. Louie J.K., Acosta M., Samuel M.C., Schechter R., Vugia D.J., Harriman K., Matyas B.T. A novel risk factor for a novel virus: Obesity and 2009 pandemic influenza A (H1N1) Clin. Infect. Dis. 2011;52:301–312. doi: 10.1093/cid/ciq152.
    1. Zulkipli M.S., Dahlui M., Peramalah D., Wai V.H.C., Bulgiba A., Rampal S. The association between obesity and dengue severity among pediatric patients: A systematic review and meta-analysis. PLoS Negl. Trop. Dis. 2018;12:e0006263. doi: 10.1371/journal.pntd.0006263.
    1. El-Saber Batiha G., Alqahtani A., Ilesanmi O.B., Saati A.A., El-Mleeh A., Hetta H.F., Magdy Beshbishy A. Avermectin derivatives, pharmacokinetics, therapeutic and toxic dosages, mechanism of action, and their biological effects. Pharmaceuticals. 2020;13:196. doi: 10.3390/ph13080196.
    1. Birnbaum H.G., Morley M., Greenberg P.E., Colice G.L. Economic burden of respiratory infections in an employed population. Chest. 2002;122:603–611. doi: 10.1378/chest.122.2.603.
    1. Harpsøe M.C., Nielsen N.M., Friis-Møller N., Andersson M., Wohlfahrt J., Linneberg A., Nohr E.A., Jess T. Body mass index and risk of infections among women in the Danish National Birth Cohort. Am. J. Epidemiol. 2016;183:1008–1017. doi: 10.1093/aje/kwv300.
    1. Han Y.-Y., Forno E., Gogna M., Celedón J.C. Obesity and rhinitis in a nationwide study of children and adults in the United States. J. Allergy Clin. Immunol. 2016;137:1460–1465. doi: 10.1016/j.jaci.2015.12.1307.
    1. Cocoros N.M., Lash T.L., DeMaria A., Jr., Klompas M. Obesity as a risk factor for severe influenza-like illness. Influenza Other Respir. Viruses. 2014;8:25–32. doi: 10.1111/irv.12156.
    1. Maccioni L., Weber S., Elgizouli M., Stoehlker A.-S., Geist I., Peter H.-H., Vach W., Nieters A. Obesity and risk of respiratory tract infections: Results of an infection-diary based cohort study. BMC Public Health. 2018;18:271. doi: 10.1186/s12889-018-5172-8.
    1. Lee Y.L., Chen Y.C., Chen Y.A. Obesity and the occurrence of bronchitis in adolescents. Obesity. 2013;21:E149–E153. doi: 10.1002/oby.20262.
    1. Short K.R., Kedzierska K., van de Sandt C.E. Back to the future: Lessons learned from the 1918 influenza pandemic. Front. Cell. Infect. Microbiol. 2018;8:343. doi: 10.3389/fcimb.2018.00343.
    1. Martin E.T., Archer C., McRoberts J., Kulik J., Thurston T., Lephart P., Kaye K.S. Epidemiology of severe influenza outcomes among adult patients with obesity in Detroit, Michigan, 2011. Influenza Other Respir. Viruses. 2013;7:1004–1007. doi: 10.1111/irv.12115.
    1. He J., Liu Z.-W., Lu Y.-P., Li T.-Y., Liang X.-J., Arck P.C., Huang S.-M., Hocher B., Chen Y.-P. A systematic review and meta-analysis of influenza a virus infection during pregnancy associated with an increased risk for stillbirth and low birth weight. Kidney Blood Press. Res. 2017;42:232–243. doi: 10.1159/000477221.
    1. Nakajima N., Hata S., Sato Y., Tobiume M., Katano H., Kaneko K., Nagata N., Kataoka M., Ainai A., Hasegawa H. The first autopsy case of pandemic influenza (A/H1N1pdm) virus infection in Japan: Detection of a high copy number of the virus in type II alveolar epithelial cells by pathological and virological examination. Jpn. J. Infect. Dis. 2010;63:67–71.
    1. Al-Tawfiq J.A., Auwaerter P.G. Healthcare-associated infections: The hallmark of Middle East respiratory syndrome coronavirus with review of the literature. J. Hosp. Infect. 2019;101:20–29. doi: 10.1016/j.jhin.2018.05.021.
    1. Alserehi H., Wali G., Alshukairi A., Alraddadi B. Impact of Middle East Respiratory Syndrome coronavirus (MERS-CoV) on pregnancy and perinatal outcome. BMC Infect. Dis. 2016;16:1–4. doi: 10.1186/s12879-016-1437-y.
    1. Montes-Galindo D.A., Espiritu-Mojarro A.C., Melnikov V., Moy-López N.A., Soriano-Hernandez A.D., Galvan-Salazar H.R., Guzman-Muñiz J., Guzman-Esquivel J., Martinez-Fierro M.L., Rodriguez-Sanchez I.P. Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: A study on hamsters. Arch. Virol. 2019;164:775–786. doi: 10.1007/s00705-018-04132-6.
    1. Pasarica M., Loiler S., Dhurandhar N.V. Acute effect of infection by adipogenic human adenovirus Ad36. Arch. Virol. 2008;153:2097. doi: 10.1007/s00705-008-0219-2.
    1. Pasarica M., Shin A.C., Yu M., Yang H.M.O., Rathod M., Jen K.L.C., Kumar S.M., MohanKumar P.S., Markward N., Dhurandhar N.V. Human adenovirus 36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats. Obesity. 2006;14:1905–1913. doi: 10.1038/oby.2006.222.
    1. Atkinson R., Dhurandhar N., Allison D., Bowen R., Israel B., Albu J., Augustus A. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int. J. Obes. 2005;29:281–286. doi: 10.1038/sj.ijo.0802830.
    1. Vangipuram S., Yu M., Tian J., Stanhope K., Pasarica M., Havel P.J., Heydari A., Dhurandhar N. Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells. Int. J. Obes. 2007;31:87–96. doi: 10.1038/sj.ijo.0803366.
    1. Vangipuram S.D., Sheele J., Atkinson R.L., Holland T.C., Dhurandhar N.V. A human adenovirus enhances preadipocyte differentiation. Obes. Res. 2004;12:770–777. doi: 10.1038/oby.2004.93.
    1. Sang Y., Shields L.E., Sang E.R., Si H., Pigg A., Blecha F. Ileal transcriptome analysis in obese rats induced by high-fat diets and an adenoviral infection. Int. J. Obes. 2019;43:2134–2142. doi: 10.1038/s41366-019-0323-2.
    1. Morgan O.W., Bramley A., Fowlkes A., Freedman D.S., Taylor T.H., Gargiullo P., Belay B., Jain S., Cox C., Kamimoto L. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A (H1N1) disease. PLoS ONE. 2010;5:e9694. doi: 10.1371/journal.pone.0009694.
    1. Venkata C., Sampathkumar P., Afessa B. Hospitalized patients with 2009 H1N1 influenza infection: The Mayo Clinic experience. Mayo Clin. Proc. 2010;85:798–805. doi: 10.4065/mcp.2010.0166.
    1. Martín V., Castilla J., Godoy P., Delgado-Rodríguez M., Soldevila N., Fernández-Villa T., Molina A.J., Astray J., Castro A., González-Candelas F. High Body Mass Index as a Risk Factor for Hospitalization Due to Influenza: A Case–Control Study. Arch. Bronconeumol. (Engl. Ed.) 2016;52:299–307. doi: 10.1016/j.arbr.2015.11.011.
    1. Taubenberger J.K., Morens D.M. The pathology of influenza virus infections. Annu. Rev. Pathol. Mech. Dis. 2008;3:499–522. doi: 10.1146/annurev.pathmechdis.3.121806.154316.
    1. Russell A.B., Trapnell C., Bloom J.D. Extreme heterogeneity of influenza virus infection in single cells. eLife. 2018;7:e32303. doi: 10.7554/eLife.32303.
    1. O’Brien K.B., Vogel P., Duan S., Govorkova E.A., Webby R.J., McCullers J.A., Schultz-Cherry S. Impaired wound healing predisposes obese mice to severe influenza virus infection. J. Infect. Dis. 2012;205:252–261. doi: 10.1093/infdis/jir729.
    1. Klinkhammer J., Schnepf D., Ye L., Schwaderlapp M., Gad H.H., Hartmann R., Garcin D., Mahlakõiv T., Staeheli P. IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission. eLife. 2018;7:e33354. doi: 10.7554/eLife.33354.
    1. Yamane K., Indalao I.L., Chida J., Yamamoto Y., Hanawa M., Kido H. Diisopropylamine dichloroacetate, a novel pyruvate dehydrogenase kinase 4 inhibitor, as a potential therapeutic agent for metabolic disorders and multiorgan failure in severe influenza. PLoS ONE. 2014;9:e98032. doi: 10.1371/journal.pone.0098032.
    1. Kim Y.-H., Kim J.-K., Kim D.-J., Nam J.-H., Shim S.-M., Choi Y.-K., Lee C.-H., Poo H. Diet-induced obesity dramatically reduces the efficacy of a 2009 pandemic H1N1 vaccine in a mouse model. J. Infect. Dis. 2012;205:244–251. doi: 10.1093/infdis/jir731.
    1. Ritter J.B., Wahl A.S., Freund S., Genzel Y., Reichl U. Metabolic effects of influenza virus infection in cultured animal cells: Intra-and extracellular metabolite profiling. BMC Syst. Biol. 2010;4:61. doi: 10.1186/1752-0509-4-61.
    1. Wang B., Russell M.L., Fonseca K., Earn D.J., Horsman G., Van Caeseele P., Chokani K., Vooght M., Babiuk L., Walter S.D. Predictors of influenza a molecular viral shedding in Hutterite communities. Influenza Other Respir. Viruses. 2017;11:254–262. doi: 10.1111/irv.12448.
    1. Yan J., Grantham M., Pantelic J., De Mesquita P.J.B., Albert B., Liu F., Ehrman S., Milton D.K., Consortium E. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. Proc. Natl. Acad. Sci. USA. 2018;115:1081–1086. doi: 10.1073/pnas.1716561115.
    1. Carrat F., Vergu E., Ferguson N.M., Lemaitre M., Cauchemez S., Leach S., Valleron A.-J. Time lines of infection and disease in human influenza: A review of volunteer challenge studies. Am. J. Epidemiol. 2008;167:775–785. doi: 10.1093/aje/kwm375.
    1. Rahmati-Ahmadabad S., Hosseini F. Exercise against SARS-CoV-2 (COVID-19): Does workout intensity matter?(A mini review of some indirect evidence related to obesity) Obes. Med. 2020:100245. doi: 10.1016/j.obmed.2020.100245.
    1. Grant W.B., Lahore H., McDonnell S.L., Baggerly C.A., French C.B., Aliano J.L., Bhattoa H.P. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients. 2020;12:988. doi: 10.3390/nu12040988.
    1. Nutrition and Your Health: 2015–2020 Dietary Guidelines for Americans. 8th ed. US Government Printing Office; Washington, DC, USA: 2015.
    1. World Health Organization . Diet, Nutrition, and the Prevention of Chronic Diseases: Report of a Joint WHO/FAO Expert Consultation. World Health Organization; Geneva, Switzerland: 2003.
    1. Blanck H.M., Collins J. CDC’s Winnable Battles: Improved Nutrition, Physical Activity, and Decreased Obesity. Mary Ann Liebert, Inc.; New Rochelle, NY, USA: 2013.
    1. Fogli-Cawley J.J., Dwyer J.T., Saltzman E., McCullough M.L., Troy L.M., Meigs J.B., Jacques P.F. The 2005 dietary guidelines for Americans and insulin resistance in the Framingham offspring cohort. Diabetes Care. 2007;30:817–822. doi: 10.2337/dc06-1927.
    1. Klein S., Sheard N.F., Pi-Sunyer X., Daly A., Wylie-Rosett J., Kulkarni K., Clark N.G. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: Rationale and strategies. A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Am. J. Clin. Nutr. 2004;80:257–263.
    1. Qatanani M., Lazar M.A. Mechanisms of obesity-associated insulin resistance: Many choices on the menu. Genes Dev. 2007;21:1443–1455. doi: 10.1101/gad.1550907.
    1. Choon Lim Wong G., Narang V., Lu Y., Camous X., Nyunt M.S.Z., Carre C., Tan C., Xian C.H., Chong J., Chua M. Hallmarks of improved immunological responses in the vaccination of more physically active elderly females. Exerc. Immunol. Rev. 2019;25:20–33.
    1. Warren K.J., Olson M.M., Thompson N.J., Cahill M.L., Wyatt T.A., Yoon K.J., Loiacono C.M., Kohut M.L. Exercise improves host response to influenza viral infection in obese and non-obese mice through different mechanisms. PLoS ONE. 2015;10:e0129713. doi: 10.1371/journal.pone.0129713.
    1. Codella R., Luzi L., Inverardi L., Ricordi C. The anti-inflammatory effects of exercise in the syndromic thread of diabetes and autoimmunity. Eur. Rev. Med. Pharmacol. Sci. 2015;19:3709–3722.
    1. Hagman E., Besor O., Hershkop K., Santoro N., Pierpont B., Mata M., Caprio S., Weiss R. Relation of the degree of obesity in childhood to adipose tissue insulin resistance. Acta Diabetol. 2019;56:219–226. doi: 10.1007/s00592-018-01285-3.

Source: PubMed

3
S'abonner