Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Epidemiology and Population Health

Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe

International Journal of Obesity (2024)Cite this article

Subjects

Abstract

Background

Research on Long COVID risk factors is ongoing. High body mass index (BMI) may increase Long COVID risk, yet no evidence has been established regarding sex differences in the relationship between BMI and the risk of Long COVID. Investigating the nature of this relationship was the main objective of this study.

Methods

A population-based prospective study involving a sample of respondents aged 50 years and older (n = 4004) from 27 European countries that participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe’s (SHARE) Corona Surveys and in Waves 7 and 8 of the main SHARE survey. Logistic regression models were estimated to produce unadjusted and adjusted estimates of the sex differences in the relationship between BMI and Long COVID.

Results

Linear relationship for females, with probability of Long COVID increasing with BMI (68% at BMI = 18, 93% at BMI = 45). Non-linear relationship for males, with probability of Long COVID of 27% at BMI = 18, 68% at BMI = 33, and 40% at BMI = 45. Relationships remained significant after adjusting for known Long COVID risk factors (age and COVID-19 hospitalization), presence of chronic diseases, and respondents’ place of residence.

Conclusion

Sex differences appear to play an important role in the relationship between BMI and risk of Long COVID. Overall, females were more likely to have Long COVID, regardless of their BMI. Males at the higher end of the BMI spectrum had a lower risk of Long COVID as opposed to their female counterparts. Sex-specific research is recommended for better understanding of Long COVID risk factors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Body mass index versus probability of having Long COVID.
Fig. 2: Body mass index versus probability of having Long COVID.
Fig. 3: Body mass index versus probability of having Long COVID.

Similar content being viewed by others

Data availability

Data is available from the SHARE’s website: https://share-eric.eu/.

References

  1. Higgins V, Sohaei D, Diamandis EP, Prassas I. COVID-19: from an acute to chronic disease? Potential long-term health consequences. Crit Rev Clin Lab Sci. 2021;58:297–310.

    Article  PubMed  CAS  Google Scholar 

  2. Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA. 2020;323:1775–6.

    PubMed  CAS  Google Scholar 

  3. O’Mahoney LL, Routen A, Gillies C, Ekezie W, Welford A, Zhang A, et al. The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: a systematic review and meta-analysis. EClinicalMedicine. 2023;55:101762.

    Article  PubMed  Google Scholar 

  4. Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV, Condition WHOCCDWGoP-C-. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022;22:e102–e7.

    Article  PubMed  CAS  Google Scholar 

  5. Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis. 2021;53:737–54.

    Article  CAS  Google Scholar 

  6. Silva Andrade B, Siqueira S, de Assis Soares WR, de Souza Rangel F, Santos NO, Dos Santos Freitas A, et al. Long-COVID and post-COVID health complications: an up-to-date review on clinical conditions and their possible molecular mechanisms. Viruses. 2021;13:700.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Castanares-Zapatero D, Chalon P, Kohn L, Dauvrin M, Detollenaere J, Maertens de Noordhout C, et al. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022;54:1473–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023;21:133–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global prevalence of post-Coronavirus disease 2019 (COVID-19) condition or Long COVID: a meta-analysis and systematic review. J Infect Dis. 2022;226:1593–607.

    Article  PubMed  CAS  Google Scholar 

  10. Alrasheedi AA. The prevalence of COVID-19 in Europe by the end of November 2022: a cross-sectional study. Cureus. 2023;15:e33546.

    PubMed  PubMed Central  Google Scholar 

  11. Collaboration NCDRF. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet. 2016;387:1377–96.

    Article  Google Scholar 

  12. Popkin BM, Doak CM. The obesity epidemic is a worldwide phenomenon. Nutr Rev. 1998;56:106–14.

    Article  PubMed  CAS  Google Scholar 

  13. 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. Obes Rev. 2020;21:e13128.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Stefan N, Birkenfeld AL, Schulze MB. Global pandemics interconnected—obesity, impaired metabolic health and COVID-19. Nat Rev Endocrinol. 2021;17:135–49.

    Article  PubMed  CAS  Google Scholar 

  15. Huang HK, Bukhari K, Peng CC, Hung DP, Shih MC, Chang RH, et al. The J-shaped relationship between body mass index and mortality in patients with COVID-19: a dose-response meta-analysis. Diabetes Obes Metab. 2021;23:1701–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Gardiner J, Oben J, Sutcliffe A. Obesity as a driver of international differences in COVID-19 death rates. Diabetes Obes Metab. 2021;23:1463–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Luo XM, Jiaerken YM, Shen ZM, Wang QM, Liu BP, Zhou HM, et al. Obese COVID-19 patients show more severe pneumonia lesions on CT chest imaging. Diabetes Obes Metab. 2021;23:290–3.

    Article  PubMed  CAS  Google Scholar 

  18. Menezes DC, Lima PDL, Lima IC, Uesugi JHE, Vasconcelos P, Quaresma JAS, et al. Metabolic profile of patients with long COVID: a cross-sectional study. Nutrients. 2023;15:1197.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Debski M, Tsampasian V, Haney S, Blakely K, Weston S, Ntatsaki E, et al. Post-COVID-19 syndrome risk factors and further use of health services in East England. PLOS Glob Public Health. 2022;2:e0001188.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Desgranges F, Tadini E, Munting A, Regina J, Filippidis P, Viala B, et al. Post‑COVID‑19 syndrome in outpatients: a cohort study. J Gen Intern Med. 2022;37:1943–52.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pradhan A, Olsson PE. Sex differences in severity and mortality from COVID-19: are males more vulnerable? Biol Sex Differ. 2020;11:53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27:601–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of long COVID. Nat Med. 2021;27:626–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Gibson WT, Evans DM, An J, Jones SJM. ACE 2 coding variants: a potential X-linked risk factor for COVID-19 disease. bioRxiv. 2020.

  25. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16:626–38.

    Article  PubMed  CAS  Google Scholar 

  26. Xu K, Chen Y, Yuan J, Yi P, Ding C, Wu W, et al. Factors associated with prolonged viral RNA shedding in patients with Coronavirus Disease 2019 (COVID-19). Clin Infect Dis. 2020;71:799–806.

    Article  PubMed  CAS  Google Scholar 

  27. Börsch-Supan. A Survey of Health, Ageing and Retirement in Europe (SHARE) Wave 8. COVID-19 Survey 1. Release version: 8.0.0. SHARE-ERIC. 2022.

  28. Börsch-Supan. A Survey of Health, Ageing and Retirement in Europe (SHARE) Wave 9. COVID-19 Survey 2. Release version: 8.0.0. SHARE-ERIC. 2022.

  29. Borsch-Supan A, Brandt M, Hunkler C, Kneip T, Korbmacher J, Malter F, et al. Data resource profile: the Survey of Health, Ageing and Retirement in Europe (SHARE). Int J Epidemiol. 2013;42:992–1001.

    Article  PubMed  PubMed Central  Google Scholar 

  30. SAS-Institute. SAS 9.4 Help and Documentation. Cary, NC: SAS Institute Inc.; 2002-22.

  31. V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19:155–70.

    Article  PubMed  Google Scholar 

  32. Redondo N, Zaldívar-López S, Garrido JJ, Montoya M. SARS-CoV-2 accessory proteins in viral pathogenesis: knowns and unknowns. Front Immunol. 2021;12:708264.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–80.e8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158:1831–3.e3.

    Article  PubMed  CAS  Google Scholar 

  35. Wu CT, Lidsky PV, Xiao Y, Lee IT, Cheng R, Nakayama T, et al. SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment. Cell Metab. 2021;33:1565–76.e5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Bhatnagar J, Gary J, Reagan-Steiner S, Estetter LB, Tong S, Tao Y, et al. Evidence of severe acute respiratory syndrome coronavirus 2 replication and tropism in the lungs, airways, and vascular endothelium of patients with fatal coronavirus disease 2019: an autopsy case series. J Infect Dis. 2021;223:752–64.

    Article  PubMed  CAS  Google Scholar 

  37. Borczuk AC, Yantiss RK. The pathogenesis of coronavirus-19 disease. J Biomed Sci. 2022;29:87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Bergamaschi L, Mescia F, Turner L, Hanson AL, Kotagiri P, Dunmore BJ, et al. Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease. Immunity. 2021;54:1257–75.e8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19:102537.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Adnan Mezher M, Bahjat Alrifai S, Mahmood Raoof W. Analysis of proinflammatory cytokines in COVID-19 patients in Baghdad, Iraq. Arch Razi Inst. 2023;78:305–13.

    PubMed  PubMed Central  CAS  Google Scholar 

  41. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Peters U, Suratt BT, Bates JHT, Dixon AE. Beyond BMI: obesity and lung disease. Chest. 2018;153:702–9.

    Article  PubMed  Google Scholar 

  43. Dragon-Durey MA, Chen X, Kirilovsky A, Ben Hamouda N, El Sissy C, Russick J, et al. Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity. PLoS One. 2021;16:e0252026.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Daitch V, Yelin D, Awwad M, Guaraldi G, Milic J, Mussini C, et al. Characteristics of long COVID among older adults: a cross-sectional study. Int J Infect Dis. 2022;125:287–93.

    Article  PubMed  Google Scholar 

  45. Bai F, Tomasoni D, Falcinella C, Barbanotti D, Castoldi R, Mule G, et al. Female gender is associated with long COVID syndrome: a prospective cohort study. Clin Microbiol Infect. 2022;28:611.e9–e16.

    Article  PubMed  CAS  Google Scholar 

  46. Maamar M, Artime A, Pariente E, Fierro P, Ruiz Y, Gutiérrez S, et al. Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study. Curr Med Res Opin. 2022;38:901–9.

    Article  PubMed  CAS  Google Scholar 

  47. Stewart S, Newson L, Briggs TA, Grammatopoulos D, Young L, Gill P. Long COVID risk - a signal to address sex hormones and women’s health. Lancet Reg Health Eur. 2021;11:100242.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Mattioli AV, Coppi F, Nasi M, Pinti M, Gallina S. Long COVID: a new challenge for prevention of obesity in women. Am J Lifestyle Med. 2023;17:164–8.

    Article  PubMed  Google Scholar 

  49. Regitz-Zagrosek V, Gebhard C. Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes. Nat Rev Cardiol. 2023;20:236–47.

    Article  PubMed  Google Scholar 

  50. Scully EP. Sex, gender and infectious disease. Nat Microbiol. 2022;7:359–60.

    Article  PubMed  CAS  Google Scholar 

  51. Raveendran AV, Misra A. Post COVID-19 syndrome (“Long COVID”) and diabetes: challenges in diagnosis and management. Diabetes Metab Syndr. 2021;15:102235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. Sci Rep. 2021;11:16144.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Peter RS, Nieters A, Brockmann SO, Gopel S, Kindle G, Merle U, et al. Association of BMI with general health, working capacity recovered, and post-acute sequelae of COVID-19. Obesity. 2023;31:43–8.

    Article  PubMed  Google Scholar 

  54. Milner JJ, Beck MA. The impact of obesity on the immune response to infection. Proc Nutr Soc. 2012;71:298–306.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Keramat SA, Alam K, Keating B, Ahinkorah BO, Gyan Aboagye R, Seidu AA, et al. Morbid obesity, multiple long-term conditions, and health-related quality of life among Australian adults: estimates from three waves of a longitudinal household survey. Prev Med Rep. 2022;28:101823.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Fusco K, Thompson C, Woodman R, Horwood C, Hakendorf P, Sharma Y. The impact of morbid obesity on the health outcomes of hospital inpatients: an observational study. J Clin Med. 2021;10:4382.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Chylińska J, Łazarewicz M, Rzadkiewicz M, Adamus M, Jaworski M, Haugan G, et al. The role of gender in the active attitude toward treatment and health among older patients in primary health care—self-assessed health status and sociodemographic factors as moderators. BMC Geriatr. 2017;17:284.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Yaksi N, Teker AG, Imre A. Long COVID in hospitalized COVID-19 patients: a retrospective cohort study. Iran J Public Health. 2022;51:88–95.

    PubMed  PubMed Central  Google Scholar 

  59. Hua MJ, Gonakoti S, Shariff R, Corpuz C, Acosta RAH, Chang H, et al. Prevalence and characteristics of Long COVID seven to twelve months after hospitalization among patients from an urban safety-net hospital: a pilot study. AJPM Focus.

  60. Thompson EJ, Williams DM, Walker AJ, Mitchell RE, Niedzwiedz CL, Yang TC, et al. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun. 2022;13:3528.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Westerlind E, Palstam A, Sunnerhagen KS, Persson HC. Patterns and predictors of sick leave after Covid-19 and long Covid in a national Swedish cohort. BMC Public Health. 2021;21:1023.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, et al. Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med. 2022;28:1706–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Divo MJ, Martinez CH, Mannino DM. Ageing and the epidemiology of multimorbidity. Eur Respir J. 2014;44:1055–68.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Mansell V, Hall Dykgraaf S, Kidd M, Goodyear-Smith F. Long COVID and older people. Lancet Healthy Longev. 2022;3:e849–e54.

    Article  PubMed  Google Scholar 

  65. Di Filippo L, De Lorenzo R, Cinel E, Falbo E, Ferrante M, Cilla M, et al. Weight trajectories and abdominal adiposity in COVID-19 survivors with overweight/obesity. Int J Obes. 2021;45:1986–94.

    Article  Google Scholar 

  66. Byambasuren O, Stehlik P, Clark J, Alcorn K, Glasziou P. Effect of covid-19 vaccination on long covid: systematic review. BMJ Med. 2023;2:e000385.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The SHARE data collection has been funded by the European Commission, DG RTD through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193, COMPARE: CIT5-CT-2005-028857, SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N°211909, SHARE-LEAP: GA N°227822, SHARE M4: GA N°261982, DASISH: GA N°283646) and Horizon 2020 (SHARE-DEV3: GA N°676536, SHARE-COHESION: GA N°870628, SERISS: GA N°654221, SSHOC: GA N°823782) and by DG Employment, Social Affairs & Inclusion through VS 2015/0195, VS 2016/0135, VS 2018/0285, VS 2019/0332, and VS 2020/0313.

Author information

Author notes

  1. These authors contributed equally: Piotr Wilk, Sarah Cuschieri.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

    Piotr Wilk, Saverio Stranges & Sarah Cuschieri

  2. Department of Epidemiology, Maastricht University, Maastricht, the Netherlands

    Piotr Wilk

  3. Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy

    Saverio Stranges

  4. Department of Behavioural and Cognitive Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg

    Saverio Stranges

  5. Faculty of Medicine and Surgery, University of Malta, Msida, Malta

    Sarah Cuschieri

Authors
  1. Piotr Wilk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Saverio Stranges
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sarah Cuschieri
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PW and SC designed the study. PW performed the statistical analysis. PW and SC interpreted the data analysis and drafted the first version of the manuscript. SC and SS critically revised the manuscript. SC was responsible for revising the manuscript. SS and PW reviewed and approved the final version.

Corresponding author

Correspondence to Sarah Cuschieri.

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.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wilk, P., Stranges, S. & Cuschieri, S. Does sex modify the effect of pre-pandemic body mass index on the risk of Long COVID? Evidence from the longitudinal analysis of the Survey of Health, Ageing and Retirement in Europe. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01477-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41366-024-01477-8

Search

Advanced search

Quick links