Skip to main content

Advertisement

Log in

The interplay of aging, adipose tissue, and COVID-19: a potent alliance with implications for health

  • REVIEW
  • Published:
GeroScience Aims and scope Submit manuscript

Abstract

Obesity has emerged as a significant public health challenge. With the ongoing increase in life expectancy, the prevalence of obesity is steadily growing, particularly among older age demographics. The extension of life expectancy frequently results in additional years of vulnerability to chronic health issues associated with obesity in the elderly.

The concept of SARS-CoV-2 directly infecting adipose tissue stems from the fact that both adipocytes and stromal vascular fraction cells express ACE2, the primary receptor facilitating SARS-CoV-2 entry. It is noteworthy that adipose tissue demonstrates ACE2 expression levels similar to those found in the lungs within the same individual. Additionally, ACE2 expression in the adipose tissue of obese individuals surpasses that in non-obese counterparts. Viral attachment to ACE2 has the potential to disturb the equilibrium of renin-angiotensin system homeostasis, leading to an exacerbated inflammatory response.

Consequently, adipose tissue has been investigated as a potential site for active SARS-CoV-2 infection, suggesting its plausible role in virus persistence and contribution to both acute and long-term consequences associated with COVID-19.

This review is dedicated to presenting current evidence concerning the presence of SARS-CoV-2 in the adipose tissue of elderly individuals infected with the virus. Both obesity and aging are circumstances that contribute to severe health challenges, heightening the risk of disease and mortality. We will particularly focus on examining the mechanisms implicated in the long-term consequences, with the intention of providing insights into potential strategies for mitigating the aftermath of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Gholi Z, Vahdat Shariatpanahi Z, Yadegarynia D, Eini-Zinab H. Associations of body mass index with severe outcomes of COVID-19 among critically ill elderly patients: a prospective study. Front Nutr. 2023;10:993292. https://doi.org/10.3389/fnut.2023.993292.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rodriguez A, Martin-Loeches I, Moreno G, Diaz E, Ferre C, Salgado M, et al. Association of obesity on the outcome of critically ill patients affected by COVID-19. Med Intensiva (Engl Ed). 2023. https://doi.org/10.1016/j.medine.2023.08.003.

    Article  PubMed  Google Scholar 

  3. Yoon SS, Lim Y, Jeong S, Han HW. Association of weight changes with SARS-CoV-2 infection and severe COVID-19 outcomes: a nationwide retrospective cohort study. J Infect Public Health. 2023;16(12):1918–24. https://doi.org/10.1016/j.jiph.2023.10.002.

    Article  PubMed  Google Scholar 

  4. TadayonNajafabadi B, Rayner DG, Shokraee K, Shokraie K, Panahi P, Rastgou P, et al. Obesity as an independent risk factor for COVID-19 severity and mortality. Cochrane Database Syst Rev. 2023;5(5):CD015201. https://doi.org/10.1002/14651858.CD015201.

    Article  Google Scholar 

  5. Candelli M, Pignataro G, Saviano A, Ojetti V, Gabrielli M, Piccioni A, et al. Is BMI associated with COVID-19 severity? A retrospective observational study. Curr Med Chem. 2023;30(39):4466–78. https://doi.org/10.2174/0929867330666230206095923.

    Article  CAS  PubMed  Google Scholar 

  6. Arutyunov AG, Tarlovskaya EI, Galstyan GR, Batluk TI, Bashkinov RA, Arutyunov GG, et al. The impact of BMI on the course of the acute SARS-COV-2 infection and the risks that emerge during the first year after the hospital discharge. Subanalysis evidence of the AKTIV and AKTIV 2 registries. Probl Endokrinol (Mosk). 2023;69(1):36–49. https://doi.org/10.14341/probl13175.

  7. Vasheghani M, Hessami Z, Rekabi M, Abedini A, Qanavati A. Evaluating possible mechanisms linking obesity to COVID-19: a narrative review. Obes Surg. 2022;32(5):1689–700. https://doi.org/10.1007/s11695-022-05933-0.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Vegiopoulos A, Rohm M, Herzig S. Adipose tissue: between the extremes. The EMBO J. 2017;36(14):1999–2017. https://doi.org/10.15252/embj.201696206.

    Article  CAS  PubMed  Google Scholar 

  9. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56. https://doi.org/10.1210/jc.2004-0395.

    Article  CAS  PubMed  Google Scholar 

  10. Frasca D. Obesity accelerates age defects in human B cells and induces autoimmunity. Immunometabolism. 2022;4(2):e220010. https://doi.org/10.20900/immunometab20220010.

  11. Jura M, Kozak LP. Obesity and related consequences to ageing. Age. 2016;38(1):23. https://doi.org/10.1007/s11357-016-9884-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Amorim JA, Coppotelli G, Rolo AP, Palmeira CM, Ross JM, Sinclair DA. Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat Rev Endocrinol. 2022;18(4):243–58. https://doi.org/10.1038/s41574-021-00626-7.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Siervo M, Lara J, Celis-Morales C, Vacca M, Oggioni C, Battezzati A, et al. Age-related changes in basal substrate oxidation and visceral adiposity and their association with metabolic syndrome. Eur J Nutr. 2016;55(4):1755–67. https://doi.org/10.1007/s00394-015-0993-z.

    Article  CAS  PubMed  Google Scholar 

  14. Meier HCS, Mitchell C, Karadimas T, Faul JD. Systemic inflammation and biological aging in the health and retirement study. GeroScience. 2023;45(6):3257–65. https://doi.org/10.1007/s11357-023-00880-9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kalathookunnel Antony A, Lian Z, Wu H. T Cells in adipose tissue in aging. Front Immunol. 2018;9:2945. https://doi.org/10.3389/fimmu.2018.02945.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Schleh MW, Caslin HL, Garcia JN, Mashayekhi M, Srivastava G, Bradley AB, et al. Metaflammation in obesity and its therapeutic targeting. Sci Trans Med. 2023;15(723):9382. https://doi.org/10.1126/scitranslmed.adf9382.

    Article  CAS  Google Scholar 

  17. Shin J, Shimomura I. COVID-19, Obesity, and GRP78: unraveling the pathological link. J Obesity Metabol Synd. 2023;32(3):183–96. https://doi.org/10.7570/jomes23053.

    Article  Google Scholar 

  18. Calim A, Yanic U, Halefoglu AM, Damar A, Ersoy C, Topcu H, et al. Is there a relationship between epicardial adipose tissue, inflammatory markers, and the severity of COVID-19 pneumonia? Sisli Etfal Hastan Tip Bul. 2023;57(3):387–96. https://doi.org/10.14744/SEMB.2023.99582.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Basty N, Sorokin EP, Thanaj M, Srinivasan R, Whitcher B, Bell JD, et al. Abdominal imaging associates body composition with COVID-19 severity. PLoS ONE. 2023;18(4):e0283506. https://doi.org/10.1371/journal.pone.0283506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Maurya R, Sebastian P, Namdeo M, Devender M, Gertler A. COVID-19 Severity in obesity: leptin and inflammatory cytokine interplay in the link between high morbidity and mortality. Front Immunol. 2021;12:649359. https://doi.org/10.3389/fimmu.2021.649359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. AbdelMassih A, Yacoub E, Husseiny RJ, Kamel A, Hozaien R, El Shershaby M, et al. Hypoxia-inducible factor (HIF): the link between obesity and COVID-19. Obes Med. 2021;22:100317. https://doi.org/10.1016/j.obmed.2020.100317.

    Article  PubMed  Google Scholar 

  22. Steenblock C, Bechmann N, Beuschlein F, Wolfrum C, Bornstein SR. Do adipocytes serve as a reservoir for severe acute respiratory symptom coronavirus-2? The Journal of endocrinology. 2023;258(2). https://doi.org/10.1530/JOE-23-0027.

  23. Hunter GR, Gower BA, Kane BL. Age related shift in visceral fat. Int J Body Compos Res. 2010;8(3):103–8.

    PubMed  PubMed Central  Google Scholar 

  24. Dixon AE, Peters U. The effect of obesity on lung function. Expert Rev Respir Med. 2018;12(9):755–67. https://doi.org/10.1080/17476348.2018.1506331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yilmaz EM, Sehmen E, Arslan HN, Bolat MS, Yigit Y. The effect of the visceral adiposity index on the severity of COVID-19 disease: results of a cross-sectional study. Europ Rev Med PharmacolSsci. 2023;27(19):9446–53. https://doi.org/10.26355/eurrev_202310_33973.

    Article  CAS  Google Scholar 

  26. Sanchez-Aguillon F, Alarcon-Valdes P, Rojano-Rodriguez M, Ibarra-Arce A, Olivo-Diaz A, Santillan-Benitez JG, et al. Presence of human adenovirus 36 in visceral fat tissue, viral load, and analysis of its genetic variability. J Med Virol. 2023;95(8):e29015. https://doi.org/10.1002/jmv.29015.

    Article  CAS  PubMed  Google Scholar 

  27. Pallikkuth S, Mohan M. Adipose tissue: sanctuary for HIV/SIV persistence and replication. Trends Microbiol. 2015;23(12):748–50. https://doi.org/10.1016/j.tim.2015.11.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Maffia-Bizzozero S, Cevallos C, Lenicov FR, Freiberger RN, Lopez CAM, Guano Toaquiza A, et al. Viable SARS-CoV-2 omicron sub-variants isolated from autopsy tissues. Front Microbiol. 2023;14:1192832. https://doi.org/10.3389/fmicb.2023.1192832.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hirata Y, Makino Y, Iida S, Katano H, Nagasawa S, Rokutan H, et al. COVID-19 analysis in tissue samples acquired by minimally invasive autopsy in out-of-hospital deaths with postmortem degeneration. Jpn J Infect Dis. 2023;76(5):302–9. https://doi.org/10.7883/yoken.JJID.2023.140.

    Article  PubMed  Google Scholar 

  30. Pepe-Mooney BJ, Smith CJ, Sherman MS, North TE, Padera RF, Jr., Goessling W. SARS-CoV-2 viral liver aggregates and scarce parenchymal infection implicate systemic disease as a driver of abnormal liver function. Hepatology Communications. 2023;7(11):e0290. https://doi.org/10.1097/HC9.0000000000000290.

  31. Hartard C, Chaqroun A, Settembre N, Gauchotte G, Lefevre B, Marchand E, et al. Multiorgan and vascular tropism of SARS-CoV-2. Viruses. 2022;14(3):515. https://doi.org/10.3390/v14030515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Massoth LR, Desai N, Szabolcs A, Harris CK, Neyaz A, Crotty R, et al. Comparison of RNA in situ hybridization and immunohistochemistry techniques for the detection and localization of SARS-CoV-2 in human tissues. Am J Surg Pathol. 2021;45(1):14–24. https://doi.org/10.1097/PAS.0000000000001563.

    Article  PubMed  Google Scholar 

  33. Basolo A, Poma AM, Bonuccelli D, Proietti A, Macerola E, Ugolini C, et al. Adipose tissue in COVID-19: detection of SARS-CoV-2 in adipocytes and activation of the interferon-alpha response. J Endocrinol Invest. 2022;45(5):1021–9. https://doi.org/10.1007/s40618-022-01742-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Poma AM, Basolo A, Ali G, Bonuccelli D, Di Stefano I, Conti M, et al. SARS-CoV-2 spread to endocrine organs is associated with obesity: an autopsy study of COVID-19 cases. Endocrine. 2023. https://doi.org/10.1007/s12020-023-03518-0.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hornung F, Schulz L, Kose-Vogel N, Hader A, Griesshammer J, Wittschieber D, et al. Thoracic adipose tissue contributes to severe virus infection of the lung. Int J Obes. 2023;47(11):1088–99. https://doi.org/10.1038/s41366-023-01362-w.

    Article  CAS  Google Scholar 

  36. Colleluori G, Graciotti L, Pesaresi M, Di Vincenzo A, Perugini J, Di Mercurio E, et al. Visceral fat inflammation and fat embolism are associated with lung’s lipidic hyaline membranes in subjects with COVID-19. Int J Obes. 2022;46(5):1009–17. https://doi.org/10.1038/s41366-022-01071-w.

    Article  CAS  Google Scholar 

  37. Zickler M, Stanelle-Bertram S, Ehret S, Heinrich F, Lange P, Schaumburg B, et al. Replication of SARS-CoV-2 in adipose tissue determines organ and systemic lipid metabolism in hamsters and humans. Cell Metab. 2022;34(1):1–2. https://doi.org/10.1016/j.cmet.2021.12.002.

    Article  CAS  PubMed  Google Scholar 

  38. Saccon TD, Mousovich-Neto F, Ludwig RG, Carregari VC, Dos Anjos Souza AB, Dos Passos ASC, et al. SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner. Nat Commun. 2022;13(1):5722. https://doi.org/10.1038/s41467-022-33218-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Santiago-Olivares C, Martinez-Alvarado E, Rivera-Toledo E. Persistence of RNA viruses in the respiratory tract: an overview. Viral Immunol. 2023;36(1):3–12. https://doi.org/10.1089/vim.2022.0135.

    Article  CAS  PubMed  Google Scholar 

  40. Chen B, Julg B, Mohandas S, Bradfute SB, Force RMPT. Viral persistence, reactivation, and mechanisms of long COVID. eLife. 2023;12:e86015. https://doi.org/10.7554/eLife.86015.

  41. Arner P, Spalding KL. Fat cell turnover in humans. Biochem Biophys Res Commun. 2010;396(1):101–4. https://doi.org/10.1016/j.bbrc.2010.02.165.

    Article  CAS  PubMed  Google Scholar 

  42. Li Y, Schneider AM, Mehta A, Sade-Feldman M, Kays KR, Gentili M, et al. SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes. J Clin Invest. 2021;131(13):e148635. https://doi.org/10.1172/JCI148635.

  43. Jarhult JD, Hultstrom M, Bergqvist A, Frithiof R, Lipcsey M. The impact of viremia on organ failure, biomarkers and mortality in a Swedish cohort of critically ill COVID-19 patients. Sci Rep. 2021;11(1):7163. https://doi.org/10.1038/s41598-021-86500-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Myhre PL, Prebensen C, Jonassen CM, Berdal JE, Omland T. SARS-CoV-2 viremia is associated with inflammatory, but not cardiovascular biomarkers, in patients hospitalized for COVID-19. J Am Heart Assoc. 2021;10(9):e019756. https://doi.org/10.1161/JAHA.120.019756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tepasse PR, Hafezi W, Lutz M, Kuhn J, Wilms C, Wiewrodt R, et al. Persisting SARS-CoV-2 viraemia after rituximab therapy: two cases with fatal outcome and a review of the literature. Br J Haematol. 2020;190(2):185–8. https://doi.org/10.1111/bjh.16896.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Janardhan V, Janardhan V, Kalousek V. COVID-19 as a blood clotting disorder masquerading as a respiratory illness: a cerebrovascular perspective and therapeutic implications for stroke thrombectomy. J Neuroimaging. 2020;30(5):555–61. https://doi.org/10.1111/jon.12770.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Studle C, Nishihara H, Wischnewski S, Kulsvehagen L, Perriot S, Ishikawa H, et al. SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier. Fluids and barriers of the CNS. 2023;20(1):76. https://doi.org/10.1186/s12987-023-00479-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li Y, Schneider AM, Mehta A, Sade-Feldman M, Kays KR, Gentili M, et al. SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes. J Clin Invest. 2021: 131(13): e148635. https://doi.org/10.1172/JCI148635.

  49. Willows JW, Blaszkiewicz M, Townsend KL. The sympathetic innervation of adipose tissues: regulation, functions, and plasticity. Compr Physiol. 2023;13(3):4985–5021. https://doi.org/10.1002/cphy.c220030.

    Article  PubMed  Google Scholar 

  50. Remmelink M, De Mendonca R, D’Haene N, De Clercq S, Verocq C, Lebrun L, et al. Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. Crit Care. 2020;24(1):495. https://doi.org/10.1186/s13054-020-03218-5.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Sekulic M, Harper H, Nezami BG, Shen DL, Sekulic SP, Koeth AT, et al. Molecular detection of SARS-CoV-2 infection in FFPE samples and histopathologic findings in fatal SARS-CoV-2 cases. Am J Clin Pathol. 2020;154(2):190–200. https://doi.org/10.1093/ajcp/aqaa091.

    Article  CAS  PubMed  Google Scholar 

  52. Rao A, Bhat SA, Shibata T, Giani JF, Rader F, Bernstein KE, et al. Diverse biological functions of the renin-angiotensin system. Med Res Rev. 2023. https://doi.org/10.1002/med.21996.

    Article  PubMed  Google Scholar 

  53. Simoes e Silva AC, Silveira KD, Ferreira AJ, Teixeira MM. ACE2, angiotensin-(1–7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol. 2013;169(3):477–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yvan-Charvet L, Quignard-Boulange A. Role of adipose tissue renin-angiotensin system in metabolic and inflammatory diseases associated with obesity. Kidney Int. 2011;79(2):162–8. https://doi.org/10.1038/ki.2010.391.

    Article  CAS  PubMed  Google Scholar 

  55. Mehrabadi ME, Hemmati R, Tashakor A, Homaei A, Yousefzadeh M, Hemati K, et al. Induced dysregulation of ACE2 by SARS-CoV-2 plays a key role in COVID-19 severity. Biomed Pharmacoth Biomed Pharmacoth. 2021;137:111363. https://doi.org/10.1016/j.biopha.2021.111363.

    Article  CAS  Google Scholar 

  56. Thomas MC, Pickering RJ, Tsorotes D, Koitka A, Sheehy K, Bernardi S, et al. Genetic Ace2 deficiency accentuates vascular inflammation and atherosclerosis in the ApoE knockout mouse. Circ Res. 2010;107(7):888–97. https://doi.org/10.1161/CIRCRESAHA.110.219279.

    Article  CAS  PubMed  Google Scholar 

  57. Sattar N, Valabhji J. Obesity as a risk factor for severe COVID-19: summary of the best evidence and implications for health care. Curr Obes Rep. 2021;10(3):282–9. https://doi.org/10.1007/s13679-021-00448-8.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Kuehn BM. More severe obesity leads to more severe COVID-19 in study. JAMA. 2021;325(16):1603. https://doi.org/10.1001/jama.2021.4853.

    Article  PubMed  Google Scholar 

  59. Lopez-Ortega O, Moreno-Corona NC, Cruz-Holguin VJ, Garcia-Gonzalez LD, Helguera-Repetto AC, Romero-Valdovinos M, et al. The immune response in adipocytes and their susceptibility to infection: a possible relationship with infectobesity. Int J Mol Sci. 2022;23(11):6154. https://doi.org/10.3390/ijms23116154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rose-John S, Jenkins BJ, Garbers C, Moll JM, Scheller J. Targeting IL-6 trans-signalling: past, present and future prospects. Nat Rev Immunol. 2023;23(10):666–81. https://doi.org/10.1038/s41577-023-00856-y.

    Article  CAS  PubMed  Google Scholar 

  61. Utrero-Rico A, Ruiz-Hornillos J, Gonzalez-Cuadrado C, Rita CG, Almoguera B, Minguez P, et al. IL-6-based mortality prediction model for COVID-19: validation and update in multicenter and second wave cohorts. J Allergy Clin Immunol. 2021;147(5):1652-6161 e1. https://doi.org/10.1016/j.jaci.2021.02.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kang S, Kishimoto T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp Mol Med. 2021;53(7):1116–23. https://doi.org/10.1038/s12276-021-00649-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Rando MM, Biscetti F, Masciocchi C, Capocchiano ND, Nicolazzi MA, Nardella E, et al. Identification of early predictors of clinical outcomes of COVID-19 outbreak in an Italian single center using a machine-learning approach. Europ Rev Med Pharmacol Sci. 2023;27(19):9454–69. https://doi.org/10.26355/eurrev_202310_33974.

    Article  CAS  Google Scholar 

  64. Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity is a positive modulator of IL-6R and IL-6 expression in the subcutaneous adipose tissue: significance for metabolic inflammation. PLoS ONE. 2015;10(7): e0133494. https://doi.org/10.1371/journal.pone.0133494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ahmed B, Si H. The aging of adipocytes increases expression of pro-inflammatory cytokines chronologically. Metabolites. 2021;11(5):292. https://doi.org/10.3390/metabo11050292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ou MY, Zhang H, Tan PC, Zhou SB, Li QF. Adipose tissue aging: mechanisms and therapeutic implications. Cell Death Dis. 2022;13(4):300. https://doi.org/10.1038/s41419-022-04752-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lu WH, Guyonnet S, Martinez LO, Lucas A, Parini A, Vellas B, et al. Association between aging-related biomarkers and longitudinal trajectories of intrinsic capacity in older adults. GeroScience. 2023;45(6):3409–18. https://doi.org/10.1007/s11357-023-00906-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Haugstoyl ME, Cornillet M, Strand K, Stiglund N, Sun D, Lawrence-Archer L, et al. Phenotypic diversity of human adipose tissue-resident NK cells in obesity. Front Immunol. 2023;14:1130370. https://doi.org/10.3389/fimmu.2023.1130370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Campiotti L, Gariboldi MB, Mortara L, Noonan DM, Gallo D, Nigro O, et al. Negative impact of high body mass index on cetuximab-mediated cellular cytotoxicity against human colon carcinoma cells. J Chemother. 2021;33(2):132–5. https://doi.org/10.1080/1120009X.2020.1777722.

    Article  CAS  PubMed  Google Scholar 

  70. El-Sayed Moustafa JS, Jackson AU, Brotman SM, Guan L, Villicana S, Roberts AL, et al. ACE2 expression in adipose tissue is associated with cardio-metabolic risk factors and cell type composition-implications for COVID-19. Int J Obes. 2022;46(8):1478–86. https://doi.org/10.1038/s41366-022-01136-w.

    Article  CAS  Google Scholar 

  71. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7. https://doi.org/10.1002/path.1570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 2020;9(1):45. https://doi.org/10.1186/s40249-020-00662-x.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Al Heialy S, Hachim MY, Senok A, Gaudet M, Abou Tayoun A, Hamoudi R, et al. Regulation of angiotensin- converting enzyme 2 in obesity: implications for COVID-19. Front Physiol. 2020;11:555039. https://doi.org/10.3389/fphys.2020.555039.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Martinez-Colon GJ, Ratnasiri K, Chen H, Jiang S, Zanley E, Rustagi A, et al. SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages. Sci Translational Med. 2022;14(674):eabm9151. https://doi.org/10.1126/scitranslmed.abm9151.

    Article  CAS  Google Scholar 

  75. Yuan S, Yan B, Cao J, Ye ZW, Liang R, Tang K, et al. SARS-CoV-2 exploits host DGAT and ADRP for efficient replication. Cell Discov. 2021;7(1):100. https://doi.org/10.1038/s41421-021-00338-2.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Dias SSG, Soares VC, Ferreira AC, Sacramento CQ, Fintelman-Rodrigues N, Temerozo JR, et al. Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators. PLoS Pathog. 2020;16(12):e1009127. https://doi.org/10.1371/journal.ppat.1009127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Reiterer M, Rajan M, Gomez-Banoy N, Lau JD, Gomez-Escobar LG, Ma L, et al. Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2. Cell Metab. 2021;33(12):2484. https://doi.org/10.1016/j.cmet.2021.10.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mayi BS, Leibowitz JA, Woods AT, Ammon KA, Liu AE, Raja A. The role of neuropilin-1 in COVID-19. PLoS Pathog. 2021;17(1):e1009153. https://doi.org/10.1371/journal.ppat.1009153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Behl T, Kaur I, Aleya L, Sehgal A, Singh S, Sharma N, et al. CD147-spike protein interaction in COVID-19: get the ball rolling with a novel receptor and therapeutic target. Sci Total Environ. 2022;808:152072. https://doi.org/10.1016/j.scitotenv.2021.152072.

    Article  CAS  PubMed  Google Scholar 

  80. Gao Q, Zhang W, Li T, Yang G, Zhu W, Chen N, et al. Interrelationship between 2019-nCov receptor DPP4 and diabetes mellitus targets based on protein interaction network. Sci Rep. 2022;12(1):188. https://doi.org/10.1038/s41598-021-03912-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Essalmani R, Jain J, Susan-Resiga D, Andreo U, Evagelidis A, Derbali RM, et al. Distinctive roles of furin and TMPRSS2 in SARS-CoV-2 infectivity. J Virol. 2022;96(8):e0012822. https://doi.org/10.1128/jvi.00128-22.

    Article  CAS  PubMed  Google Scholar 

  82. Balistreri G, Yamauchi Y, Teesalu T. A widespread viral entry mechanism: the C-end Rule motif-neuropilin receptor interaction. Proceedings of the National Academy of Sciences of the United States of America. 2021;118(49):e2112457118. https://doi.org/10.1073/pnas.2112457118.

  83. Soll D, Beer F, Spranger L, Li L, Spranger J, Mai K. Effects of weight loss on adipose and muscular neuropilin 1 mRNA expression in obesity: potential implication in SARS-CoV-2 infections? Obes Facts. 2022;15(1):90–8. https://doi.org/10.1159/000520419.

    Article  CAS  PubMed  Google Scholar 

  84. Yu L, Yan K, Liu P, Li N, Liu Z, Zhu W, et al. Pattern recognition receptor-initiated innate antiviral response in mouse adipose cells. Immunol Cell Biol. 2014;92(2):105–15. https://doi.org/10.1038/icb.2013.66.

    Article  CAS  PubMed  Google Scholar 

  85. Yu L, Xu Y, Wang F, Yang C, Liu G, Song X. Functional roles of pattern recognition receptors that recognize virus nucleic acids in human adipose-derived mesenchymal stem cells. Biomed Res Int. 2016;2016:9872138. https://doi.org/10.1155/2016/9872138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Dalskov L, Narita R, Andersen LL, Jensen N, Assil S, Kristensen KH, et al. Characterization of distinct molecular interactions responsible for IRF3 and IRF7 phosphorylation and subsequent dimerization. Nucleic Acids Res. 2020;48(20):11421–33. https://doi.org/10.1093/nar/gkaa873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Znaidia M, Demeret C, van der Werf S, Komarova AV. Characterization of SARS-CoV-2 evasion: interferon pathway and therapeutic options. Viruses. 2022;14(6):1247. https://doi.org/10.3390/v14061247.

  88. Quarleri J, Delpino MV. Type I and III IFN-mediated antiviral actions counteracted by SARS-CoV-2 proteins and host inherited factors. Cytokine Growth Factor Rev. 2021;58:55–65. https://doi.org/10.1016/j.cytogfr.2021.01.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Shibabaw T, Molla MD, Teferi B, Ayelign B. Role of IFN and complements system: innate immunity in SARS-CoV-2. J Inflamm Res. 2020;13:507–18. https://doi.org/10.2147/JIR.S267280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Teran-Cabanillas E, Hernandez J. Role of leptin and SOCS3 in inhibiting the type I interferon response during obesity. Inflammation. 2017;40(1):58–67. https://doi.org/10.1007/s10753-016-0452-x.

    Article  CAS  PubMed  Google Scholar 

  91. Teran-Cabanillas E, Montalvo-Corral M, Caire-Juvera G, Moya-Camarena SY, Hernandez J. Decreased interferon-alpha and interferon-beta production in obesity and expression of suppressor of cytokine signaling. Nutrition. 2013;29(1):207–12. https://doi.org/10.1016/j.nut.2012.04.019.

    Article  CAS  PubMed  Google Scholar 

  92. Sawadogo W, Tsegaye M, Gizaw A, Adera T. Overweight and obesity as risk factors for COVID-19-associated hospitalisations and death: systematic review and meta-analysis. BMJ Nutr Prev Health. 2022;5(1):10–8. https://doi.org/10.1136/bmjnph-2021-000375.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Nour TY, Altintas KH. Effect of the COVID-19 pandemic on obesity and it is risk factors: a systematic review. BMC Public Health. 2023;23(1):1018. https://doi.org/10.1186/s12889-023-15833-2.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21(3):133–46. https://doi.org/10.1038/s41579-022-00846-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Achleitner M, Steenblock C, Danhardt J, Jarzebska N, Kardashi R, Kanczkowski W, et al. Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis. Mol Psychiatry. 2023;28(7):2872–7. https://doi.org/10.1038/s41380-023-02084-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Patterson BK, Francisco EB, Yogendra R, Long E, Pise A, Rodrigues H, et al. Persistence of SARS CoV-2 S1 protein in CD16+ monocytes in post-acute sequelae of COVID-19 (PASC) up to 15 months post-infection. Front Immunol. 2021;12:746021. https://doi.org/10.3389/fimmu.2021.746021.

    Article  CAS  PubMed  Google Scholar 

  97. Craddock V, Mahajan A, Spikes L, Krishnamachary B, Ram AK, Kumar A, et al. Persistent circulation of soluble and extracellular vesicle-linked Spike protein in individuals with postacute sequelae of COVID-19. J Med Virol. 2023;95(2):e28568. https://doi.org/10.1002/jmv.28568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Swank Z, Senussi Y, Manickas-Hill Z, Yu XG, Li JZ, Alter G, et al. Persistent circulating severe acute respiratory syndrome coronavirus 2 spike is associated with post-acute coronavirus disease 2019 sequelae. Clin Infectious Dis. 2023;76(3):e487–90. https://doi.org/10.1093/cid/ciac722.

    Article  Google Scholar 

  99. Zollner A, Koch R, Jukic A, Pfister A, Meyer M, Rossler A, et al. Postacute COVID-19 is characterized by gut viral antigen persistence in inflammatory bowel diseases. Gastroenterology. 2022;163(2):495-506 e8. https://doi.org/10.1053/j.gastro.2022.04.037.

    Article  CAS  PubMed  Google Scholar 

  100. Aminian A, Bena J, Pantalone KM, Burguera B. Association of obesity with postacute sequelae of COVID-19. Diabetes Obes Metab. 2021;23(9):2183–8. https://doi.org/10.1111/dom.14454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Xiang M, Wu X, Jing H, Novakovic VA, Shi J. The intersection of obesity and (long) COVID-19: hypoxia, thrombotic inflammation, and vascular endothelial injury. Front Cardiovasc Med. 2023;10:1062491. https://doi.org/10.3389/fcvm.2023.1062491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Loosen SH, Jensen BO, Tanislav C, Luedde T, Roderburg C, Kostev K. Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients. Infection. 2022;50(5):1165–70. https://doi.org/10.1007/s15010-022-01784-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lopez-Hernandez Y, Monarrez-Espino J, Lopez DAG, Zheng J, Borrego JC, Torres-Calzada C, et al. The plasma metabolome of long COVID patients two years after infection. Sci Rep. 2023;13(1):12420. https://doi.org/10.1038/s41598-023-39049-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Abumayyaleh M, Nunez Gil IJ, Viana LMC, Raposeiras Roubin S, Romero R, Alfonso-Rodriguez E, et al. Post-COVID-19 syndrome and diabetes mellitus: a propensity-matched analysis of the International HOPE-II COVID-19 Registry. Front Endocrinol. 2023;14:1167087. https://doi.org/10.3389/fendo.2023.1167087.

    Article  Google Scholar 

  105. Zhang V, Fisher M, Hou W, Zhang L, Duong TQ. Incidence of new-onset hypertension post-COVID-19: comparison with influenza. Hypertension. 2023;80(10):2135–48. https://doi.org/10.1161/HYPERTENSIONAHA.123.21174.

    Article  CAS  PubMed  Google Scholar 

  106. Matsumoto C, Shibata S, Kishi T, Morimoto S, Mogi M, Yamamoto K, et al. Long COVID and hypertension-related disorders: a report from the Japanese Society of Hypertension Project Team on COVID-19. Hypertens Res. 2023;46(3):601–19. https://doi.org/10.1038/s41440-022-01145-2.

    Article  PubMed  Google Scholar 

  107. Al-Aly Z. Diabetes after SARS-CoV-2 infection. Lancet Diabetes Endocrinol. 2023;11(1):11–3. https://doi.org/10.1016/S2213-8587(22)00324-2.

    Article  PubMed  Google Scholar 

  108. Kwan AC, Ebinger JE, Botting P, Navarrette J, Claggett B, Cheng S. Association of COVID-19 vaccination with risk for incident diabetes after COVID-19 infection. JAMA Netw Open. 2023;6(2):e2255965. https://doi.org/10.1001/jamanetworkopen.2022.55965.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Xu E, Xie Y, Al-Aly Z. Risks and burdens of incident dyslipidaemia in long COVID: a cohort study. Lancet Diabetes Endocrinol. 2023;11(2):120–8. https://doi.org/10.1016/S2213-8587(22)00355-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Esendagli D, Topcu D, Gul E, Alperen C, Sezer R, Erol C, et al. Can adipokines predict clinical prognosis and post-COVID lung sequelae? Respir Investig. 2023;61(5):618–24. https://doi.org/10.1016/j.resinv.2023.06.001.

    Article  CAS  PubMed  Google Scholar 

  111. Flikweert AW, Kobold ACM, van der Sar-van der Brugge S, Heeringa P, Rodenhuis-Zybert IA, Bijzet J, et al. Circulating adipokine levels and COVID-19 severity in hospitalized patients. International journal of obesity. 2023;47(2):126-37 https://doi.org/10.1038/s41366-022-01246-5

  112. Landecho MF, Marin-Oto M, Recalde-Zamacona B, Bilbao I, Fruhbeck G. Obesity as an adipose tissue dysfunction disease and a risk factor for infections - Covid-19 as a case study. Eur J Intern Med. 2021;91:3–9. https://doi.org/10.1016/j.ejim.2021.03.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, et al. High prevalence of obesity in severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity. 2020;28(7):1195–9. https://doi.org/10.1002/oby.22831.

    Article  CAS  PubMed  Google Scholar 

  114. Almond M, Farne HA, Jackson MM, Jha A, Katsoulis O, Pitts O, et al. Obesity dysregulates the pulmonary antiviral immune response. Nat Commun. 2023;14(1):6607. https://doi.org/10.1038/s41467-023-42432-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Hall ME, Harmancey R, Stec DE. Lean heart: role of leptin in cardiac hypertrophy and metabolism. World J Cardiol. 2015;7(9):511–24. https://doi.org/10.4330/wjc.v7.i9.511.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Lana A, Valdes-Becares A, Buno A, Rodriguez-Artalejo F, Lopez-Garcia E. Serum leptin concentration is associated with incident frailty in older adults. Aging Disease. 2017;8(2):240–9. https://doi.org/10.14336/AD.2016.0819.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Bergantini L, d’Alessandro M, Gangi S, Bianchi F, Cameli P, Perea B, et al. Predictive role of cytokine and adipokine panel in hospitalized COVID-19 patients: evaluation of disease severity, survival and lung sequelae. Int J Mol Sci. 2023;24(16):12994. https://doi.org/10.3390/ijms241612994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621. https://doi.org/10.1016/0014-4827(61)90192-6.

    Article  CAS  PubMed  Google Scholar 

  119. Han X, Lei Q, Xie J, Liu H, Li J, Zhang X, et al. Potential regulators of the senescence-associated secretory phenotype during senescence and aging. J Gerontol A Biol Sci Med Sci. 2022;77(11):2207–18. https://doi.org/10.1093/gerona/glac097.

    Article  CAS  PubMed  Google Scholar 

  120. Nerstedt A, Smith U. The impact of cellular senescence in human adipose tissue. J Cell Commun Signal. 2023;17(3):563–73. https://doi.org/10.1007/s12079-023-00769-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, et al. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Investig. 2004;114(12):1752–61. https://doi.org/10.1172/JCI21625.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Fruhbeck G, Catalan V, Rodriguez A, Gomez-Ambrosi J. Adiponectin-leptin ratio: a promising index to estimate adipose tissue dysfunction. Relation Obesity-Ass Cardiometabol Risk Adipocyte. 2018;7(1):57–62. https://doi.org/10.1080/21623945.2017.1402151.

    Article  CAS  Google Scholar 

  123. Kohli J, Veenstra I, Demaria M. The struggle of a good friend getting old: cellular senescence in viral responses and therapy. EMBO Rep. 2021;22(4):52243. https://doi.org/10.15252/embr.202052243.

    Article  CAS  Google Scholar 

  124. Ryan EL, Hollingworth R, Grand RJ. Activation of the DNA damage response by RNA viruses. Biomolecules. 2016;6(1):2. https://doi.org/10.3390/biom6010002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Gioia U, Tavella S, Martinez-Orellana P, Cicio G, Colliva A, Ceccon M, et al. SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. Nat Cell Biol. 2023;25(4):550–64. https://doi.org/10.1038/s41556-023-01096-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Basaran MM, Hazar M, Aydin M, Uzug G, Ozdogan I, Pala E, et al. Effects of COVID-19 disease on DNA damage, oxidative stress and immune responses. Toxics. 2023;11(4):386. https://doi.org/10.3390/toxics11040386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Foo J, Bellot G, Pervaiz S, Alonso S. Mitochondria-mediated oxidative stress during viral infection. Trends Microbiol. 2022;30(7):679–92. https://doi.org/10.1016/j.tim.2021.12.011.

    Article  CAS  PubMed  Google Scholar 

  128. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev. 2017;2017:8416763. https://doi.org/10.1155/2017/8416763.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Ahmed SA, Alahmadi YM, Abdou YA. The impact of serum levels of reactive oxygen and nitrogen species on the disease severity of COVID-19. Int J Molecul Sci. 2023;24(10):8973. https://doi.org/10.3390/ijms24108973.

    Article  CAS  Google Scholar 

  130. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017;168(6):960–76. https://doi.org/10.1016/j.cell.2017.02.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, et al. MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat Cell Biol. 2015;17(8):1049–61. https://doi.org/10.1038/ncb3195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Bolourian A, Mojtahedi Z. Obesity and COVID-19: the mTOR pathway as a possible culprit. Obesity Rev. 2020;21(9):e13084. https://doi.org/10.1111/obr.13084.

    Article  CAS  Google Scholar 

  133. Gong MN, Bajwa EK, Thompson BT, Christiani DC. Body mass index is associated with the development of acute respiratory distress syndrome. Thorax. 2010;65(1):44–50. https://doi.org/10.1136/thx.2009.117572.

    Article  CAS  PubMed  Google Scholar 

  134. Popkin BM, Du S, Green WD, Beck MA, Algaith T, Herbst CH, et al. Individuals with obesity and COVID-19: a global perspective on the epidemiology and biological relationships. Obesity Rev. 2020;21(11):e13128. https://doi.org/10.1111/obr.13128.

    Article  CAS  Google Scholar 

  135. Hosoya T, Oba S, Komiya Y, Kawata D, Kamiya M, Iwai H, et al. Apple-shaped obesity: a risky soil for cytokine-accelerated severity in COVID-19. Proc Natl Acad Sci USA. 2023;120(22):e2300155120. https://doi.org/10.1073/pnas.2300155120.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Behl T, Kumar S, Singh S, Bhatia S, Albarrati A, Albratty M, et al. Reviving the mutual impact of SARS-COV-2 and obesity on patients: from morbidity to mortality. Biomedicine = Pharmacotherapy Biomed Pharmacotherapie. 2022;151:113178. https://doi.org/10.1016/j.biopha.2022.113178.

    Article  CAS  Google Scholar 

  137. Ritter A, Kreis NN, Louwen F, Yuan J. Obesity and COVID-19: molecular mechanisms linking both pandemics. Int J Mol Sci. 2020;21(16):5793. https://doi.org/10.3390/ijms21165793.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Gao M, Piernas C, Astbury NM, Hippisley-Cox J, O’Rahilly S, Aveyard P, et al. Associations between body-mass index and COVID-19 severity in 6.9 million people in England: a prospective, community-based, cohort study. The lancet Diab Endocrinol. 2021;9(6):350–9. https://doi.org/10.1016/S2213-8587(21)00089-9.

    Article  CAS  Google Scholar 

  139. Yang Y, Wang L, Liu J, Fu S, Zhou L, Wang Y. Obesity or increased body mass index and the risk of severe outcomes in patients with COVID-19: a protocol for systematic review and meta-analysis. Medicine. 2022;101(1):e28499. https://doi.org/10.1097/MD.0000000000028499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Huang Y, Lu Y, Huang YM, Wang M, Ling W, Sui Y, et al. Obesity in patients with COVID-19: a systematic review and meta-analysis. Metabol Clin Experimental. 2020;113:154378. https://doi.org/10.1016/j.metabol.2020.154378.

    Article  CAS  Google Scholar 

  141. Anderson MR, Geleris J, Anderson DR, Zucker J, Nobel YR, Freedberg D, et al. Body mass index and risk for intubation or death in SARS-CoV-2 infection : a retrospective cohort study. Ann Intern Med. 2020;173(10):782–90. https://doi.org/10.7326/M20-3214.

    Article  PubMed  Google Scholar 

  142. Shyam S, Garcia-Gavilan JF, Paz-Graniel I, Gaforio JJ, Martinez-Gonzalez MA, Corella D, et al. Association of adiposity and its changes over time with COVID-19 risk in older adults with overweight/obesity and metabolic syndrome: a longitudinal evaluation in the PREDIMED-Plus cohort. BMC Med. 2023;21(1):390. https://doi.org/10.1186/s12916-023-03079-z.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Hendren NS, de Lemos JA, Ayers C, Das SR, Rao A, Carter S, et al. Association of body mass index and age with morbidity and mortality in patients hospitalized with COVID-19: results from the American Heart Association COVID-19 Cardiovascular Disease Registry. Circulation. 2021;143(2):135–44. https://doi.org/10.1161/CIRCULATIONAHA.120.051936.

    Article  CAS  PubMed  Google Scholar 

  144. Kompaniyets L, Goodman AB, Belay B, Freedman DS, Sucosky MS, Lange SJ, et al. Body mass index and risk for COVID-19-related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death - United States, March-December 2020. MMWR Morbidity Mortality Weekly Report. 2021;70(10):355–61. https://doi.org/10.15585/mmwr.mm7010e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Singh R, Rathore SS, Khan H, Karale S, Chawla Y, Iqbal K, et al. Association of obesity with COVID-19 severity and mortality: an updated systemic review, meta-analysis, and meta-regression. Front Endocrinol. 2022;13:780872. https://doi.org/10.3389/fendo.2022.780872.

    Article  Google Scholar 

  146. Fan X, Han J, Zhao E, Fang J, Wang D, Cheng Y, et al. The effects of obesity and metabolic abnormalities on severe COVID-19-related outcomes after vaccination: a population-based study. Cell Metabol. 2023;35(4):585-600 e5. https://doi.org/10.1016/j.cmet.2023.02.016.

    Article  CAS  Google Scholar 

  147. Gaborit B, Fernandes S, Loubet P, Ninove L, Dutour A, Cariou B, et al. Early humoral response to COVID-19 vaccination in patients living with obesity and diabetes in France. The COVPOP OBEDIAB study with results from the ANRS0001S COV-POPART cohort. Metabol clin Experimental. 2023;142:155412. https://doi.org/10.1016/j.metabol.2023.155412.

    Article  CAS  Google Scholar 

  148. Chauvin C, Retnakumar SV, Bayry J. Obesity negatively impacts maintenance of antibody response to COVID-19 vaccines. Cell Rep Med. 2023;4(7):101117. https://doi.org/10.1016/j.xcrm.2023.101117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Chu J, Xing C, Du Y, Duan T, Liu S, Zhang P, et al. Pharmacological inhibition of fatty acid synthesis blocks SARS-CoV-2 replication. Nat Metab. 2021;3(11):1466–75. https://doi.org/10.1038/s42255-021-00479-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Ventura-Lopez C, Cervantes-Luevano K, Aguirre-Sanchez JS, Flores-Caballero JC, Alvarez-Delgado C, Bernaldez-Sarabia J, et al. Treatment with metformin glycinate reduces SARS-CoV-2 viral load: an in vitro model and randomized, double-blind, Phase IIb clinical trial. Biomed Pharmacoth Biomed Pharmacoth. 2022;152:113223. https://doi.org/10.1016/j.biopha.2022.113223.

    Article  CAS  Google Scholar 

  151. Le Pelletier L, Mantecon M, Gorwood J, Auclair M, Foresti R, Motterlini R, et al. Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction. eLife. 2021;10:e62635. https://doi.org/10.7554/eLife.62635.

  152. Khunti K, Davies MJ, Kosiborod MN, Nauck MA. Long COVID - metabolic risk factors and novel therapeutic management. Nat Rev Endocrinol. 2021;17(7):379–80. https://doi.org/10.1038/s41574-021-00495-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Khunti K, Kosiborod M, Ray KK. Legacy benefits of blood glucose, blood pressure and lipid control in individuals with diabetes and cardiovascular disease: time to overcome multifactorial therapeutic inertia? Diabetes Obes Metab. 2018;20(6):1337–41. https://doi.org/10.1111/dom.13243.

    Article  PubMed  Google Scholar 

  154. Ikramuddin S, Korner J, Lee WJ, Thomas AJ, Connett JE, Bantle JP, et al. Lifestyle intervention and medical management with vs without Roux-en-Y gastric bypass and control of hemoglobin A1c, LDL cholesterol, and systolic blood pressure at 5 years in the diabetes surgery study. JAMA. 2018;319(3):266–78. https://doi.org/10.1001/jama.2017.20813.

    Article  PubMed  PubMed Central  Google Scholar 

  155. Schauer PR, Bhatt DL, Kashyap SR. Bariatric surgery versus intensive medical therapy for diabetes. N Engl J Med. 2014;371(7):682. https://doi.org/10.1056/NEJMc1407393.

    Article  PubMed  Google Scholar 

  156. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577–85. https://doi.org/10.1056/NEJMoa1200111.

    Article  CAS  PubMed  Google Scholar 

  157. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Nanni G, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015;386(9997):964–73. https://doi.org/10.1016/S0140-6736(15)00075-6.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Figures 1 and 2 were created with BioRender.com.

Author information

Authors and Affiliations

Authors

Contributions

JQ and MVD: Both have contributed equally to conceptualization, methodology, and writing—review and editing.

Corresponding authors

Correspondence to Jorge Quarleri or M. Victoria Delpino.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Quarleri, J., Delpino, M.V. The interplay of aging, adipose tissue, and COVID-19: a potent alliance with implications for health. GeroScience 46, 2915–2932 (2024). https://doi.org/10.1007/s11357-023-01058-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-023-01058-z

Keywords

Navigation