Pathophysiological mechanisms of coronavirus disease (COVID-19) progression and fatal complications in patients with diabetes

Authors

DOI:

https://doi.org/10.14739/2310-1237.2020.2.212812

Keywords:

SARS Coronavirus, diabetes mellitus, angiotensin-converting enzyme-2, cytokine

Abstract

 

Pandemic of the coronavirus disease (COVID-19) is still one of the most acute medical and social problem in the world. It’s well known that development of severe complications, including acute respiratory distress syndrome, is most often associated with comorbid condition and patients age (category over 50 years). Diabetes mellitus is the most common endocrine disease, clinical and epidemiological trials confirm it’s a high risk factor for progression and mortality in patients with COVID-19.

The aim of the work was to analyze the data of the scientific literature on the suspected pathophysiological mechanisms between diabetes mellitus and coronavirus disease association.

The article highlights role of angiotensin-converting enzyme-2 expression changes, which is defined as a functional target on the cell surface for SARS-CoV-2 penetration. The review analyzes the results of experimental studies about effects of medicines included in diabetes clinical protocols (insulin, glucagon like peptide-1 analogues, thiazolidinediones derivates, angiotensin-converting enzyme inhibitors, angiotensin-2 receptor blockers, statins) on ACE-2 activity. Immunological disorders in diabetes mellitus patients, may significantly affect the COVID-19 state, in particular, due late hyperinflammatory condition and cytokine storm syndrome formation, which are predictors of serious complications, including acute respiratory distress syndrome. The results of the retrospective clinical study that involves people with COVID-19 and diabetes mellitus who don’t have other comorbidities were analyzed.

Conclusions. The data presented in current review necessitate further clinical trials for objective assessment of the potential benefits and risks of medicines used in patients with diabetes under COVID-19 and for treatment regimens revision in case of adverse effect on disease progression and state. The review data indicate a high risk of unfavorable prognosis of SARS-CoV-2 infection in patients with diabetes mellitus.

 

References

Johns Hopkins University. (2020). COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins Coronavirus Resource Center. https://coronavirus.jhu.edu/

Cabinet of Ministers of Ukraine. (2020). Ofitsiinyi informatsiinyi portal Kabinetu Ministriv Ukrainy "Koronavirus v Ukraini" [COVID-19 pandemic in Ukraine. Current information about coronavirus and quarantine]. https://covid19.gov.ua/

Guan, W., Ni, Z., Hu, Y., Liang, W., Ou, C., He, J., Liu, L., Shan, H., Lei, C., Hui, D., Du, B., Li, L., Zeng, G., Yuen, K., Chen, R., Tang, C., Wang, T., Chen, P., Xiang, J., Li, S., Wang, J., Liang, Z., Peng, Y., Wei, L., Liu, Y., Hu, Y., Peng, P., Wang, J., Liu, J., Chen, Z., Li, G., Zheng, Z., Qiu, S., Luo, J., Ye, C., Zhu, S. & Zhong, N. (2020). Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine, 382(18), 1708-1720. https://doi.org/10.1056/NEJMoa2002032

Maddaloni, E., & Buzzetti, R. (2020). Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics. Diabetes/metabolism research and reviews, e33213321. Advance online publication. https://doi.org/10.1002/dmrr.3321

Remuzzi, A., & Remuzzi, G. (2020). COVID-19 and Italy: what next?. Lancet (London, England), 395(10231), 1225-1228. https://doi.org/10.1016/S0140-6736(20)30627-9

Wu, Z., & Mcgoogan, J. M. (2020). Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. Jama, 323(13), 1239. https://doi.org/10.1001/jama.2020.2648

Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., Huang, H., Zhang, L., Zhou, X., Du, C., Zhang, Y., Song, J., Wang, S., Chao, Y., Yang, Z., Xu J., Zhou, X., Chen, D., Xiong, W., Xu, L., Zhou, F., Jiang, J., Bai, C., Zheng, J., & Song, Y. (2020). Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2020.0994

Zhao, Z., Xie, J., Yin, M., Yang, Y., He, H., Jin, T., Li, W., Zhu, X., Xu, J., Zhao, C., Li, L., Li, Y., Mengist, H., Zahid, A., Yao, Z., Ding C., Qi, Y., Gao, Y., & Ma, X. (2020). Clinical and Laboratory Profiles of 75 Hospitalized Patients with Novel Coronavirus Disease 2019 in Hefei, China. MedRxiv, 2020.03.01.20029785. https://doi.org/10.1101/2020.03.01.20029785

Guo, W., Li, M., Dong, Y., Zhou, H., Zhang, Z., Tian, C., Qin, R., Wang, H., Shen, Y., Du, K., Zhao, L., Fan, H., Luo, S., & Hu, D. (2020). Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes/metabolism research and reviews, e3319. Advance online publication. https://doi.org/10.1002/dmrr.3319

Hussain, A., Bhowmik, B., & do Vale Moreira, N. C. (2020). COVID-19 and diabetes: Knowledge in progress. Diabetes research and clinical practice, 162, 108142. https://doi.org/10.1016/j.diabres.2020.108142

Muniyappa, R., & Gubbi, S. (2020). COVID-19 pandemic, coronaviruses, and diabetes mellitus. American journal of physiology. Endocrinology and metabolism, 318(5), E736-E741. https://doi.org/10.1152/ajpendo.00124.2020

Yang, J. K., Feng, Y., Yuan, M. Y., Yuan, S. Y., Fu, H. J., Wu, B. Y., Sun, G. Z., Yang, G. R., Zhang, X. L., Wang, L., Xu, X., Xu, X. P., & Chan, J. C. (2006). Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabetic medicine : a journal of the British Diabetic Association, 23(6), 623-628. https://doi.org/10.1111/j.1464-5491.2006.01861.x

Bornstein, S. R., Rubino, F., Khunti, K., Mingrone, G., Hopkins, D., Birkenfeld, A. L., Boehm, B., Amiel, S., Holt, R. I., Skyler, J. S., DeVries, J. H., Renard, E., Eckel, R. H., Zimmet, P., Alberti, K. G., Vidal, J., Geloneze, B., Chan, J. C., Ji, L., & Ludwig, B. (2020). Practical recommendations for the management of diabetes in patients with COVID-19. The lancet. Diabetes & endocrinology, 8(6), 546-550. https://doi.org/10.1016/S2213-8587(20)30152-2

Onder, G., Rezza, G., & Brusaferro, S. (2020). Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA, 323(18), 1775-1776. https://doi.org/10.1001/jama.2020.4683

U.S. Department of Health & Human Services. (2020). National Diabetes Statistics Report, 2020. 277 Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human 278 Services. Centers for Disease Control and Prevention. https://www.cdc.gov

Yang, J., Zheng, Y., Gou, X., Pu, K., Chen, Z., Guo, Q., Ji, R., Wang, H., Wang, Y., & Zhou, Y. (2020). Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 94, 91-95. https://doi.org/10.1016/j.ijid.2020.03.017

Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., Xiang, J., Wang, Y., Song, B., Gu, X., Guan, L., Wei, Y., Li, H., Wu, X., Xu, J., Tu, S., Zhang, Y., Chen, H., & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet (London, England), 395(10229), 1054-1062. https://doi.org/10.1016/S0140-6736(20)30566-3

Griffiths, M., McAuley, D. F., Perkins, G. D., Barrett, N., Blackwood, B., Boyle, A., Chee, N., Connolly, B., Dark, P., Finney, S., Salam, A., Silversides, J., Tarmey, N., Wise, M. P., & Baudouin, S. V. (2019). Guidelines on the management of acute respiratory distress syndrome. BMJ open respiratory research, 6(1), e000420. https://doi.org/10.1136/bmjresp-2019-000420

Walls, A. C., Park, Y. J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell, 181(2), 281-292.e6. https://doi.org/10.1016/j.cell.2020.02.058

Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271-280.e8. https://doi.org/10.1016/j.cell.2020.02.052

Diao, B., Feng, Z., Wang, C., Wang, H., Liu, L., Wang, C., Wang, R., Liu, Y., Liu, Y., Wang, G., Yuan, Z., Wu, Y., & Chen, Y. (2020). Human Kidney is a Target for Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. MedRxiv, 2020.03.04.20031120. https://doi.org/10.1101/2020.03.04.20031120

Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., Choe, H., & Farzan, M. (2003). Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 426(6965), 450-454. https://doi.org/10.1038/nature02145

Liu, F., Long, X., Zou, W., Fang, M., Wu, W., Li, W., Zhang, B., Zhang, W., Chen, X., & Zhang, Z. (2020). Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection. MedRxiv, 2020.02.28.20029181. https://doi.org/10.1101/2020.02.28.20029181

Zheng, Y. Y., Ma, Y. T., Zhang, J. Y., & Xie, X. (2020). COVID-19 and the cardiovascular system. Nature reviews. Cardiology, 17(5), 259-260. https://doi.org/10.1038/s41569-020-0360-5

Zou, X., Chen, K., Zou, J., Han, P., Hao, J., & Han, Z. (2020). Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Frontiers of medicine, 14(2), 185-192. https://doi.org/10.1007/s11684-020-0754-0

Lukassen, S., Chua, R. L., Trefzer, T., Kahn, N. C., Schneider, M. A., Muley, T., Winter, H., Meister, M., Veith, C., Boots, A. W., Hennig, B. P., Kreuter, M., Conrad, C., & Eils, R. (2020). SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. The EMBO journal, 39(10), e105114. https://doi.org/10.15252/embj.20105114

Roca-Ho, H., Riera, M., Palau, V., Pascual, J., & Soler, M. J. (2017). Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse. International journal of molecular sciences, 18(3), 563. https://doi.org/10.3390/ijms18030563

Wysocki, J., Ye, M., Soler, M. J., Gurley, S. B., Xiao, H. D., Bernstein, K. E., Coffman, T. M., Chen, S., & Batlle, D. (2006). ACE and ACE2 activity in diabetic mice. Diabetes, 55(7), 2132-2139. https://doi.org/10.2337/db06-0033

Tikoo, K., Patel, G., Kumar, S., Karpe, P. A., Sanghavi, M., Malek, V., & Srinivasan, K. (2015). Tissue specific up regulation of ACE2 in rabbit model of atherosclerosis by atorvastatin: role of epigenetic histone modifications. Biochemical pharmacology, 93(3), 343–351. https://doi.org/10.1016/j.bcp.2014.11.013

Wösten-van Asperen, R. M., Lutter, R., Specht, P. A., Moll, G. N., van Woensel, J. B., van der Loos, C. M., van Goor, H., Kamilic, J., Florquin, S., & Bos, A. P. (2011). Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist. The Journal of pathology, 225(4), 618-627. https://doi.org/10.1002/path.2987

Zhang, J., Dong, X., Cao, Y., Yuan, Y., Yang, Y., & Yan, Y., Akdis, C., & Gao, Y. (2020). Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy: European Journal of Allergy and Clinical Immunology. https://doi.org/10.1111/all.14238

Romaní-Pérez, M., Outeiriño-Iglesias, V., Moya, C. M., Santisteban, P., González-Matías, L. C., Vigo, E., & Mallo, F. (2015). Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression, Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and SP-B in the Lungs of Type 1 Diabetes Rats. Endocrinology, 156(10), 3559-3569. https://doi.org/10.1210/en.2014-1685

Rao, S., Lau, A., & So, H. C. (2020). Exploring Diseases/Traits and Blood Proteins Causally Related to Expression of ACE2, the Putative Receptor of SARS-CoV-2: A Mendelian Randomization Analysis Highlights Tentative Relevance of Diabetes-Related Traits. Diabetes care, 43(7), 1416-1426. https://doi.org/10.2337/dc20-0643

Pal, R., & Bhansali, A. (2020). COVID-19, diabetes mellitus and ACE2: The conundrum. Diabetes research and clinical practice, 162, 108132. https://doi.org/10.1016/j.diabres.2020.108132

Zou, Z., Yan, Y., Shu, Y., Gao, R., Sun, Y., Li, X., Ju, X., Liang, Z., Liu, Q., Zhao, Y., Guo, F., Bai, T., Han, Z., Zhu, J., Zhou, H., Huang, F., Li, C., Lu, H., Li, N., Li, D., … Jiang, C. (2014). Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nature communications, 5, 3594. https://doi.org/10.1038/ncomms4594

Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., Bao, L., Zhang, B., Liu, G., Wang, Z., Chappell, M., Liu, Y., Zheng, D., Leibbrandt, A., Wada, T., Slutsky, A. S., … Penninger, J. M. (2005). A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nature medicine, 11(8), 875-879. https://doi.org/10.1038/nm1267

Cui, J., Li, F., & Shi, Z. L. (2019). Origin and evolution of pathogenic coronaviruses. Nature reviews. Microbiology, 17(3), 181-192. https://doi.org/10.1038/s41579-018-0118-9

Su, S., Wong, G., Shi, W., Liu, J., Lai, A., Zhou, J., Liu, W., Bi, Y., & Gao, G. F. (2016). Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends in microbiology, 24(6), 490-502. https://doi.org/10.1016/j.tim.2016.03.003

Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, N.Y.), 367(6483), 1260-1263. https://doi.org/10.1126/science.abb2507

Fang, L., Karakiulakis, G., & Roth, M. (2020). Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. The Lancet. Respiratory medicine, 8(4), e21. https://doi.org/10.1016/S2213-2600(20)30116-8

Chen, D., Li, X., Song, Q., Hu, C., Su, F., & Dai, J. (2020). Hypokalemia and Clinical Implications in Patients with Coronavirus Disease 2019 (COVID-19). MedRxiv, 2020.02.27.20028530. https://doi.org/10.1101/2020.02.27.20028530

Chen, X., Hu, W., Ling, J., Mo, P., Zhang, Y., Jiang, Q., Ma, Z., Cao, Q., Deng, L., Song, S., Zheng, R., Gao, S., Ke, H., Gui, X., Lundkvist ALi, J., Lindahl, J., & Xiong, Y. (2020). Hypertension and Diabetes Delay the Viral Clearance in COVID-19 Patients. MedRxiv, 2020.03.22.20040774. https://doi.org/10.1101/2020.03.22.20040774

Fernandez, C., Rysä, J., Almgren, P., Nilsson, J., Engström, G., Orho-Melander, M., Ruskoaho, H., & Melander, O. (2018). Plasma levels of the proprotein convertase furin and incidence of diabetes and mortality. Journal of internal medicine, 284(4), 377-387. https://doi.org/10.1111/joim.12783

Hodgson, K., Morris, J., Bridson, T., Govan, B., Rush, C., & Ketheesan, N. (2015). Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections. Immunology, 144(2), 171-185. https://doi.org/10.1111/imm.12394

Kulcsar, K. A., Coleman, C. M., Beck, S. E., & Frieman, M. B. (2019). Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI insight, 4(20), e131774. https://doi.org/10.1172/jci.insight.131774

Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., Chen, J., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet (London, England), 395(10224), 565-574. https://doi.org/10.1016/S0140-6736(20)30251-8

De Wit, E., Van Doremalen, N., Falzarano, D., & Munster, V. J. (2016). SARS and MERS: recent insights into emerging coronaviruses. Nature reviews. Microbiology, 14(8), 523-534. https://doi.org/10.1038/nrmicro.2016.81

Gao, Y., Li, T., Han, M., Li, X., Wu, D., Xu, Y., Zhu, Y., Liu, Y., Wang, X., & Wang, L. (2020). Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. Journal of medical virology, 92(7), 791-796. https://doi.org/10.1002/jmv.25770

Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., Manson, J. J., & HLH Across Speciality Collaboration, UK (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (London, England), 395(10229), 1033-1034. https://doi.org/10.1016/S0140-6736(20)30628-0

Wan, S., Yi, Q., Fan, S., Lv, J., Zhang, X., Guo, L., Lang, C., Xiao, Q., Xiao, K., Yi, Z., Qiang, M., Xiang, J., Zhang, B., & Chen,Y. (2020). Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). MedRxiv, 2020.02.10.20021832. https://doi.org/10.1101/2020.02.10.20021832

Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., … Song, Y. (2020). Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2020.0994

Zupanets, I., Shebeko, S., Bezugla, N., & Otrishko, I. (2020). Patofiziolohichne obgruntuvannia efektyvnosti zastosuvannia kvertsetynu v terapii korona virusnoi khvoroby (COVID-19) [Pathophysiological substantiation of the effectiveness of quercetine use in coronavirus disease (COVID-19) therapy]. Pathologia, 17(1). https://doi.org/10.14739/2310-1237.2020.1.203844

Iacobellis, G. (2020). COVID-19 and diabetes: Can DPP4 inhibition play a role?. Diabetes research and clinical practice, 162, 108125. https://doi.org/10.1016/j.diabres.2020.108125

How to Cite

1.
Briukhanova TO, Zagayko AL, Lytkin DV. Pathophysiological mechanisms of coronavirus disease (COVID-19) progression and fatal complications in patients with diabetes. Pathologia [Internet]. 2020Sep.28 [cited 2024Dec.23];(2). Available from: http://pat.zsmu.edu.ua/article/view/212812

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Review