The role of comorbidities (hypertension, obesity and diabetes) in the expression of the ACE 2 receptor in COVID-19: A systematic review
DOI:
https://doi.org/10.33448/rsd-v14i4.48590Keywords:
COVID-19, ACE 2, Prognosis, Comorbidities.Abstract
During the COVID-19 Pandemic, relationships between comorbidities and the severity of COVID-19 were highlighted, mainly related to the ACE 2 receptor, present in several organs and responsible for regulating the renin-angiotensin system. The entry of SARS-CoV-2 into cells deregulates ACE 2, which increases inflammation and clotting, worsening the infection. Comorbidities such as hypertension, obesity and diabetes increase the risk of complications, making it essential to understand how these conditions influence the progression of the disease. The objective was to carry out research on the role of comorbidities (hypertension, obesity and diabetes) in the expression of the ACE 2 receptor in COVID-19. A systematic review of the literature was carried out that followed the PRISMA guidelines and analyzed studies published between 2017 and 2022 in the Web of Science, Scielo and PubMed databases. After rigorous screening, 15 articles were selected for the final review. The results showed that obesity is associated with a worse prognosis in COVID-19, with reduced expression of ACE 2 in adipose tissue after weight loss, reducing susceptibility to the virus. In the case of diabetes, patients with inadequate glycemic control and cardiovascular complications were at higher risk of complications. In relation to hypertension, the dysregulation of angiotensin II by SARS-CoV-2 contributes to lung damage, worsening the disease. In relation to hypertension, the dysregulation of angiotensin II by SARS-CoV-2 contributes to lung damage, worsening the disease. The study concludes that increased expression of ACE2 in patients with these comorbidities worsens the infection. Weight loss can improve ACE 2 receptor regulation. However, more studies are needed, especially in the elderly, to assess the impact of these conditions on COVID-19 mortality.
Downloads
References
Bauer, A., Schreinlechner, M., Sappler, N., et al. (2021). Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): A prospective, parallel group, randomised, controlled, open-label trial. The Lancet Respiratory Medicine, 9(8), 863–872.
Bourgonje, A. R., Abdulle, A. E., Timens, W., Hillebrands, J. L., Navis, G. J., Gordijn, S. J., Bolling, M. C., Dijkstra, G., Voors, A. A., Osterhaus, A. D., van der Voort, P. H., Mulder, D. J., & van Goor, H. (2020). Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). Journal of Pathology, 251(3), 228–248. https://doi.org/10.1002/path.5471
Brown, J. D., Smith, S. M., Strotmeyer, E. S., et al. (2020). Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on response to a physical activity intervention in older adults: Results from the Lifestyle Interventions and Independence for Elders Study. The Journals of Gerontology: Series A, 75(5), 1010–1016.
Cariou, B., Wargny, M., Boureau, A. S., et al. (2022). Impact of diabetes on COVID-19 prognosis beyond comorbidity burden: The CORONADO initiative. Diabetologia, 65(9), 1436–1449.
Cheng, H., Wang, Y., & Wang, G. Q. (2020). Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. Journal of Medical Virology, 92(7), 726–730. https://doi.org/10.1002/jmv.25785
Conway, J., Gould, A., Westley, R., et al. (2020). Characteristics of patients with diabetes hospitalised for COVID-19 infection: A brief case series report. Diabetes Research and Clinical Practice, 169, 108460.
Cristelo, C., Azevedo, C., Marques, J. M., Nunes, R., & Sarmento, B. (2020). SARS-CoV-2 and diabetes: New challenges for the disease. Diabetes Research and Clinical Practice, 164, 108228. https://doi.org/10.1016/j.diabres.2020.108228
Davidson, A. M., Wysocki, J., & Batlle, D. (2020). Interaction of SARS-CoV-2 and other coronaviruses with ACE (angiotensin-converting enzyme)-2 as their main receptor: Therapeutic implications. Hypertension.
De Ligt, M., Hesselink, M. K. C., Jorgensen, J., et al. (2021). Resveratrol supplementation reduces ACE2 expression in human adipose tissue. Adipocyte, 10(1), 408–411.
Du, X. L., Simpson, L. M., Tandy, B. C., et al. (2021). Risk of hospitalized and non-hospitalized gastrointestinal bleeding in ALLHAT trial participants receiving diuretic, ACE-inhibitor, or calcium-channel blocker. PLOS ONE, 16(11), e0260107. https://doi.org/10.1371/journal.pone.0260107
Li, L., Spranger, L., Soll, D., et al. (2020). Metabolic impact of weight loss induced reduction of adipose ACE-2: Potential implication in COVID-19 infections? Metabolism, 113, 154401.
Marfella, R., D’Onofrio, N., Mansueto, G., et al. (2022). Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts. Cardiovascular Diabetology, 21(1), 146.
Ministério da Saúde, Datasus. (2021). Informações de saúde. Recuperado de https://susanalitico.saude.gov.br/extensions/covid-19_html/covid-19_html.html
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G., The PRISMA Group. (2015). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLOS Medicine, 6(7), e100097.
Niechciał, E., Acerini, C. L., Chiesa, S. T., et al. (2020). Medication adherence during adjunct therapy with statins and ACE inhibitors in adolescents with type 1 diabetes. Diabetes Care, 43(5), 1070–1076.
Pathangey, G., Fadadu, P. P., Hospodar, A. R., & Abbas, A. E. (2021). Angiotensin-converting enzyme 2 and COVID-19: Patients, comorbidities, and therapies. American Journal of Physiology - Lung Cell and Molecular Physiology, 320(3), L301–L330. https://doi.org/10.1152/ajplung.00259.2020
Pereira A. S. et al. (2018). Metodologia da pesquisa científica. [free e-book]. Editora UAB/NTE/UFSM
Puskarich, M. A., Ingraham, N. E., Merck, L. H., et al. (2022). Efficacy of losartan in hospitalized patients with COVID-19-induced lung injury: A randomized clinical trial. JAMA Network Open, 5(3), e222735.
Shahid, Z., Kalayanamitra, R., McClafferty, B., Kepko, D., Ramgobin, D., Patel, R., Aggarwal, C. S., Vunnam, R., Sahu, N., Bhatt, D., Jones, K., Golamari, R., & Jain, R. (2020). COVID-19 and older adults: What we know. Journal of the American Geriatrics Society, 68(5), 926–929. https://doi.org/10.1111/jgs.16472
Sieko, J., Kotowski, M., Bogacz, A., Lechowicz, K., Drozdal, S., Rosik, J., Sietnicki, M., Sieko, M., & Kotfis, K. (2020). COVID-19: The influence of ACE genotype and ACE-I and ARBs on the course of SARS-CoV-2 infection in elderly patients. Clinical Interventions in Aging.
Soll, D., Beer, F., Spranger, L., et al. (2022). Effects of weight loss on adipose and muscular neuropilin 1 mRNA expression in obesity: Potential implication in SARS-CoV-2 infections? Obesity Facts, 15(1), 90–98.
Verdecchia, P., Cavallini, C., Spanevello, A., & Angeli, F. (2020). The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. European Journal of Internal Medicine, 76, 14–20. https://doi.org/10.1016/j.ejim.2020.04.037
Yu, P., Tan, Z., Li, Z., et al. (2022). Obesity and clinical outcomes in COVID-19 patients without comorbidities: A post-hoc analysis from ORCHID trial. Frontiers in Endocrinology, 13, 936976.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Letícia Romeira Belchior; Leonardo Neres Ferreira; Eduardo Chaves Ferreira Coelho; Ana Beatriz Ferro de Melo; Isadora Garcia de Paula; Maria Eugênia Ruas Carvalho; Irmtraut Araci Hoffmann Pfrimer
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
