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Clinical Research

Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity

International Journal of Obesity volume 48, pages 254–262 (2024)Cite this article

Subjects

Abstract

Background

Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients.

Methods

Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group.

Results

The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1β, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells.

Conclusion

Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

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Fig. 1: Cytokine levels and correlations in patients with and without obesity.
Fig. 2: Immune cell subsets and correlations in patients with and without obesity.
Fig. 3: Cytokine levels and immune subsets according to obesity and disease severity.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. World HO. World health organization. (2020). Who corona disease (covid-19) dashboard. World health organization. Available at https://covid19.Who.Int 2022; (accessed October 25, 2022).

  2. Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular disease, drug therapy, and mortality in covid-19. New England J Med. 2020;382:e102.

    CAS  Google Scholar 

  3. Gao M, Wang Q, Piernas C, Astbury NM, Jebb SA, Holmes MV, et al. Associations between body composition, fat distribution and metabolic consequences of excess adiposity with severe covid-19 outcomes: Observational study and mendelian randomisation analysis. Int J Obesity. 2022;46:943–50.

    CAS  Google Scholar 

  4. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (covid-19). JAMA Cardiol. 2020;5:811–8.

    PubMed  Google Scholar 

  5. Liu PP, Blet A, Smyth D, Li H. The science underlying covid-19: Implications for the cardiovascular system. Circulation. 2020;142:68–78.

    PubMed  CAS  Google Scholar 

  6. 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:e13128.

    CAS  Google Scholar 

  7. Földi M, Farkas N, Kiss S, Dembrovszky F, Szakács Z, Balaskó M, et al. Visceral adiposity elevates the risk of critical condition in covid‐19: A systematic review and meta‐analysis. Obesity. 2021;29:521–8.

    PubMed  Google Scholar 

  8. Piroth L, Cottenet J, Mariet A-S, Bonniaud P, Blot M, Tubert-Bitter P, et al. Comparison of the characteristics, morbidity, and mortality of covid-19 and seasonal influenza: A nationwide, population-based retrospective cohort study. Lancet Respiratory Med. 2021;9:251–9.

    CAS  Google Scholar 

  9. Sattar N, McInnes IB, McMurray JJ. Obesity is a risk factor for severe covid-19 infection: Multiple potential mechanisms. Circulation. 2020;142:4–6.

    PubMed  CAS  Google Scholar 

  10. Blot M, Masson D, Nguyen M, Bourredjem A, Binquet C, Piroth L. Are adipokines the missing link between obesity, immune response, and outcomes in severe covid-19? Int J Obesity. 2021;45:2126–31.

    CAS  Google Scholar 

  11. Asghar A, Sheikh N. Role of immune cells in obesity induced low grade inflammation and insulin resistance. Cellular Immunol. 2017;315:18–26.

    CAS  Google Scholar 

  12. Heilbronn LK, Campbell LV. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Current Pharmaceutical Design. 2008;14:1225–30.

    PubMed  CAS  Google Scholar 

  13. Fabbrini E, Cella M, Mccartney SA, Fuchs A, Abumrad NA, Pietka TA, et al. Association between specific adipose tissue cd4+ t-cell populations and insulin resistance in obese individuals. Gastroenterology. 2013;145:366–74.

    PubMed  CAS  Google Scholar 

  14. Wieser V, Moschen AR, Tilg H. Inflammation, cytokines and insulin resistance: A clinical perspective. Arch Immunol Ther Exp. 2013;61:119–25.

    CAS  Google Scholar 

  15. Akhvlediani T, Ali SM, Angus DC, Arabi YM, Ashraf S, Baillie JK, et al. Global outbreak research: Harmony not hegemony. Lancet Infectious Dis. 2020;20:770–2.

    Google Scholar 

  16. Moll-Bernardes R, Fortier SC, Sousa AS, Lopes RD, Vera N, Conde L, et al. Nkg2a expression among cd8 cells is associated with covid-19 progression in hypertensive patients: Insights from the brace corona randomized trial. J Clin Med. 2022;11:3713.

    PubMed  PubMed Central  CAS  Google Scholar 

  17. Gupta A, Jayakumar MN, Saleh MA, Kannan M, Halwani R, Qaisar R, et al. Sars-cov-2 infection-induced growth factors play differential roles in covid-19 pathogenesis. Life Sci. 2022;304:120703.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Venkataraman T, Frieman MB. The role of epidermal growth factor receptor (egfr) signaling in sars coronavirus-induced pulmonary fibrosis. Antiviral Res. 2017;143:142–50.

    PubMed  PubMed Central  CAS  Google Scholar 

  19. Ahmad F, Kannan M, Ansari AW. Role of sars-cov-2-induced cytokines and growth factors in coagulopathy and thromboembolism. Cytokine Growth Factor Rev. 2022;63:58–68.

    PubMed  CAS  Google Scholar 

  20. Perreau M, Suffiotti M, Marques-Vidal P, Wiedemann A, Levy Y, Laouénan C, et al. The cytokines hgf and cxcl13 predict the severity and the mortality in covid-19 patients. Nat Commun. 2021;12:4888.

    PubMed  PubMed Central  CAS  Google Scholar 

  21. Dhar SK, Vishnupriyan K, Damodar S, Gujar S, Das M. Il-6 and il-10 as predictors of disease severity in covid-19 patients: Results from meta-analysis and regression. Heliyon. 2021;7:e06155.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, et al. Profiling serum cytokines in covid-19 patients reveals il-6 and il-10 are disease severity predictors. Emerging Microbes Infections. 2020;9:1123–30.

    PubMed  PubMed Central  CAS  Google Scholar 

  23. Huang F, Liu X, Sun X, Li Z. Il-10 served as an indicator in severe covid-19 patients. J Med Virol. 2020;93:1233–5.

    PubMed  PubMed Central  Google Scholar 

  24. Moll-Bernardes R, De Sousa AS, Macedo AVS, Lopes RD, Vera N, Maia LCR, et al. Il-10 and il-12 (p70) levels predict the risk of covid-19 progression in hypertensive patients: Insights from the brace-corona trial. Front Cardio Med. 2021;8:1–10.

    Google Scholar 

  25. Mirsoian A, Bouchlaka MN, Sckisel GD, Chen M, Pai C-CS, Maverakis E, et al. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice. J Exp Med. 2014;211:2373–83.

    PubMed  PubMed Central  CAS  Google Scholar 

  26. Donlan AN, Sutherland TE, Marie C, Preissner S, Bradley BT, Carpenter RM, et al. Il-13 is a driver of covid-19 severity. JCI insight. 2021;6:e150107.

  27. Gibellini L, De Biasi S, Meschiari M, Gozzi L, Paolini A, Borella R, et al. Plasma cytokine atlas reveals the importance of th2 polarization and interferons in predicting covid-19 severity and survival. Front Immunol. 2022;13:1030.

    Google Scholar 

  28. Marone G, Granata F, Pucino V, Pecoraro A, Heffler E, Loffredo S, et al. The intriguing role of interleukin 13 in the pathophysiology of asthma. Front Pharmacol. 2019;10:1387.

    PubMed  PubMed Central  CAS  Google Scholar 

  29. Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A. Il-13 signaling through the il-13α2 receptor is involved in induction of tgf-β1 production and fibrosis. Nature Med. 2006;12:99–106.

    PubMed  CAS  Google Scholar 

  30. Sasson J, Moreau GB, Petri Jr WA. The role of il-13 and the type 2 immune pathway in covid-19: A review. Ann Allergy, Asthma Immunol. 2023;130:727–32.

  31. Tanaka SI, 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. Clinical Endocrinol. 2001;54:347–54.

    CAS  Google Scholar 

  32. Karlsson EA, Marcelin G, Webby RJ, Schultz‐Cherry S. Review on the impact of pregnancy and obesity on influenza virus infection. Influenza Other Respiratory Viruses. 2012;6:449–60.

    PubMed  PubMed Central  Google Scholar 

  33. Greene E, MacIver NJ Targeting t cell (oxidative) metabolism to improve immunity to viral infection in the context of obesity. Front Immunol. 2022;13:1025495.

  34. Caillon A, Schiffrin EL. Role of inflammation and immunity in hypertension: Recent epidemiological, laboratory, and clinical evidence. Current Hypertens Rep. 2016;18:1–9.

    CAS  Google Scholar 

  35. Ruibal P, Oestereich L, Lüdtke A, Becker-Ziaja B, Wozniak DM, Kerber R, et al. Unique human immune signature of ebola virus disease in guinea. Nature. 2016;533:100–4.

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Hua S, Lecuroux C, Saez-Cirion A, Pancino G, Girault I, Versmisse P, et al. Potential role for hiv-specific cd38−/hla-dr+ cd8+ t cells in viral suppression and cytotoxicity in hiv controllers. PloS one. 2014;9:e101920.

    PubMed  PubMed Central  Google Scholar 

  37. Fox A, Hoa LNM, Horby P, van Doorn HR, Trung NV, Ha NH, et al. Severe pandemic h1n1 2009 infection is associated with transient nk and t deficiency and aberrant cd8 responses. PloS one. 2012;7:e31535.

    PubMed  PubMed Central  CAS  Google Scholar 

  38. Zhou R, To KK-W, Wong Y-C, Liu L, Zhou B, Li X, et al. Acute sars-cov-2 infection impairs dendritic cell and t cell responses. Immunity. 2020;53:864–77.e865.

    PubMed  PubMed Central  CAS  Google Scholar 

  39. Zeng Q, Li Y-Z, Dong S-Y, Chen Z-T, Gao X-Y, Zhang H, et al. Dynamic sars-cov-2-specific immunity in critically ill patients with hypertension. Front Immunol. 2020;11:596684.

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Majure DT, Gruberg L, Saba SG, Kvasnovsky C, Hirsch JS, Jauhar R, et al. Usefulness of elevated troponin to predict death in patients with covid-19 and myocardial injury. Am J Cardiol. 2021;138:100–6.

    PubMed  CAS  Google Scholar 

  41. Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, et al. Association of cardiac injury with mortality in hospitalized patients with covid-19 in wuhan, china. JAMA Cardiol. 2020;5:802–10.

    PubMed  PubMed Central  Google Scholar 

  42. Lala A, Johnson KW, Januzzi JL, Russak AJ, Paranjpe I, Richter F, et al. Prevalence and impact of myocardial injury in patients hospitalized with covid-19 infection. J Am College Cardiol. 2020;76:533–46.

    CAS  Google Scholar 

  43. Moll-Bernardes R, Mattos JD, Schaustz EB, Sousa AS, Ferreira JR, Tortelly MB, et al. Troponin in covid-19: To measure or not to measure? Insights from a prospective cohort study. J Clinical Med. 2022;11:5951.

    Google Scholar 

  44. Sosa-Hernandez VA, Torres-Ruiz J, Cervantes-Diaz R, Romero-Ramirez S, Paez-Franco JC, Meza-Sanchez DE, et al. B cell subsets as severity-associated signatures in covid-19 patients. Front Immunol. 2020;11:611004.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Juno JA, Tan H-X, Lee WS, Reynaldi A, Kelly HG, Wragg K, et al. Humoral and circulating follicular helper t cell responses in recovered patients with covid-19. Nature Med. 2020;26:1428–34.

    PubMed  CAS  Google Scholar 

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Acknowledgements

We are very grateful to the staff and research assistants at the D’Or Institute for Research and Education and Rede D’Or hospitals who dedicated their time to support this study.

Funding

This work was supported by intramural grants from the D’Or Institute for Research and Education, FAPERJ (nos. E-26/210.155/2020, E-26/010.000149/2020, E-26/210.191/2020, and E-26/210.253/2020, SEI-260003/002709/2020 and SEI-260003/002718/2020, CAPES, FINEP, and the Serrapilheira Institute).

Author information

Authors and Affiliations

  1. D’Or Institute for Research and Education, Rio de Janeiro, Brazil

    Renata Moll-Bernardes, Juliana R. Ferreira, Andréa Silvestre Sousa, Mariana B. Tortelly, Adriana L. Pimentel, Ana Cristina B. S. Figueiredo, Eduardo B. Schaustz, José Carlos Pizzolante Secco, Allan Robson Kluser Sales, Flavia V. O. Terzi, Adriana Xavier de Brito, Renée O. Sarmento, Marcia M. Noya-Rabelo, Sergio Fortier, Flavia A. Matos e Silva, Denilson C. Albuquerque, Paulo Rosado de-Castro, Gabriel C. Camargo, Martha V. T. Pinheiro, Olga F. Souza, Fernando A. Bozza, Ronir R. Luiz & Emiliano Medei

  2. Cardiology and Internal Medicine Department, Rede D’Or São Luiz, São Paulo, Brazil

    Juliana R. Ferreira, Mariana B. Tortelly, Adriana L. Pimentel, Ana Cristina B. S. Figueiredo, Flavia V. O. Terzi, Marcia M. Noya-Rabelo & Olga F. Souza

  3. Evandro Chagas National Institute of Infectious Disease, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

    Andréa Silvestre Sousa & Fernando A. Bozza

  4. Internal Medicine Department, Rio de Janeiro Federal State University, Rio de Janeiro, Brazil

    Renée O. Sarmento

  5. Bahia School of Medicine and Public Health, Bahia, Brazil

    Marcia M. Noya-Rabelo & Luciana Conde

  6. Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Narendra Vera

  7. Institute of Microbiology Paulo de Góes, UFRJ, Rio de Janeiro, Brazil

    Mauro Jorge Cabral-Castro

  8. Department of Pathology, Faculty of Medicine, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil

    Mauro Jorge Cabral-Castro

  9. Cardiology Department, Rio de Janeiro State University, Rio de Janeiro, Brazil

    Denilson C. Albuquerque

  10. Institute for Studies in Public Health—IESC, UFRJ, Rio de Janeiro, Brazil

    Ronir R. Luiz

  11. National Center for Structural Biology and Bioimaging, UFRJ, Rio de Janeiro, Brazil

    Emiliano Medei

Authors
  1. Renata Moll-Bernardes
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Contributions

RMB, ASS, FAB, RRL and EM contributed to the design of the study and the statistical analysis plan. JRF, MBT, ALP, ACBSF FVOT, AXB, ROS, MMNR recruited patients. NV, LC, MJCC and EM were responsible for biomarker analysis. SF and FAMS performed cellular analysis. EBS, JCPS an ARKS were involved in clinical data collection. RMB and RRL conducted the data analyses. All authors contributed to the interpretation of the analyses and the presentation of the results. RMB and EM were responsible for the drafting the manuscript. All authors contributed to reviewing and editing the manuscript, and all authors have agreed to the final version of the manuscript.

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Correspondence to Emiliano Medei.

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Moll-Bernardes, R., Ferreira, J.R., Sousa, A.S. et al. Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity. Int J Obes 48, 254–262 (2024). https://doi.org/10.1038/s41366-023-01407-0

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