Twindemic of Coronavirus Disease (COVID-19) and Cardiometabolic Diseases

Gundu H. R. Rao

International Journal of Biomedicine. 2021;11(2):111-122.
DOI: 10.21103/Article11(2)_RA1
Originally published June 5, 2021


Metabolic diseases, like hypertension, excess weight, obesity, type 2 diabetes, and vascular diseases, have rapidly increased to epidemic proportions worldwide. Metabolic risks (such as oxidative stress, chronic inflammation, insulin resistance, altered glucose and lipid metabolism, changes in hemodynamics, endothelial dysfunction, and subclinical atherosclerosis) contribute significantly to the progress of vascular disease and drive it eventually to acute vascular events like heart attacks and stroke. Although this situation has been noticed and discussed extensively by the global public health experts, and professional societies, the unprecedented SARS-CoV-2 pandemic has demonstrated for the first time the interdependency or syndemic nature of metabolic diseases and a pathogenic virus that takes advantage of the compromised metabolic function in these diseases. The most common clinical symptoms reported are fever, cough, fatigue, shortness of breath, dyspnea, chest pain, sore throat, and sputum production. The main mode of transmission is through respiratory particles containing viral virions. Both asymptomatic and symptomatic patients seem to be infectious. The spike (S) protein of SARS-CoV-2 seems to have a 10- to 20-fold higher affinity to the human ACE2 receptor than that of SARS-CoV. Since these receptors are highly expressed on a variety of cells, including vascular endothelial cells and adipose tissue, individuals with compromised function of these tissues are more vulnerable to greater infection, replication, and severity with COVID-19. In most cases, the severity of the coronavirus disease is associated with pre-existing comorbidities, which include metabolic diseases such as hypertension, obesity, diabetes, and vascular diseases. Those with such diseases, or with elevated risk factors for such diseases, will have a compromised endothelium, favoring endothelial dysfunction. The infection of the endothelium by SARS-CoV-2 and resulting endothelialitis seems to add to this problem by further damaging the endothelium, causing dysfunction, disruption of vascular integrity, and endothelial cell death. These events lead to the exposure of the thrombogenic basement membrane and result in the activation of the thrombotic and clotting cascade. Because of these observations, critical care clinicians recommend aggressive anti-thrombotic and thrombolytic therapies in the management of acute COVID-19 cases. In the absence of a cure for coronavirus disease, sensible medicine proposes the following: primary prevention by following the best public health practices, such as social distancing, use of face coverings, and quarantine of COVID-positive individuals; and a gentler, moderate, and humble view and application of available treatment options and their effectiveness in patients with COVID-19. The FDA has created a special emergency program for possible coronavirus therapies, the Coronavirus Treatment Acceleration Program (CTAP). Currently, there are 590 drug development programs in planning stages, 390 trials in review, and five authorized for emergency use. None are approved for use in COVID-19 management. Currently, there are at least 51 studies listed in the COVID-19 vaccine tracker of the Regulatory Affairs Professional Society (RAPS) site. At the time of this writing, vaccines from Pfizer-BioNTech, Moderna, Oxford-AstraZeneca, and Johnson&Johnson have emergency use authorization in the US.

SARS-CoV-2 • COVID-19 • vaccine • metabolic diseases

1. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al.; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017.
2. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30; PMID: 31986264; PMCID: PMC7159299.
3. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7.
4. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum in: JAMA. 2021 Mar 16;325(11):1113. PMID: 32031570; PMCID: PMC7042881.
5. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum in: JAMA Intern Med. 2020 Jul 1;180(7):1031. PMID: 32167524; PMCID: PMC7070509.
6. Kamps BS, Hoffmann C: COVID REFERENC ENG/ (
7. Karabag SF: An unprecedented Global Crisis! The Global, Regional, National, Political, Economic and Commercial Impact of the Coronavirus Pandemic. J App. Econ. & Bus. Res. 10)10):1-6 (2020)
8. Shrestha N, Shad MY, Ulvi O, Khan MH, Karamehic-Muratovic A, Nguyen UDT, et al. The impact of COVID-19 on globalization. One Health. 2020 Dec 20;11:100180. doi: 10.1016/j.onehlt.2020.100180.
9. Haghani M, Bliemer MCJ. Covid-19 pandemic and the unprecedented mobilisation of scholarly efforts prompted by a health crisis: Scientometric comparisons across SARS, MERS and 2019-nCoV literature. Scientometrics. 2020 Sep 21:1-32. doi: 10.1007/s11192-020-03706-z.
10. Cutler DM, Summers LH. The COVID-19 Pandemic and the $16 Trillion Virus. JAMA. 2020 Oct 20;324(15):1495-1496. doi: 10.1001/jama.2020.19759.
11. Conti P, Caraffa A, Gallenga CE, Kritas SK, Frydas I, Younes A, et al. The British variant of the new coronavirus-19 (Sars-Cov-2) should not create a vaccine problem. J Biol Regul Homeost Agents. 2021 Jan-Feb;35(1):1-4. doi: 10.23812/21-3-E. PMID: 33377359.
12. Horton R: COVID-19 is not a pandemic. Lancet 2020; 396 (10255): 874.
13. Singer M, Bulled N, Ostrach B, Mendenhall E. Syndemics and the biosocial conception of health. Lancet. 2017 Mar 4;389(10072):941-950. doi: 10.1016/S0140-6736(17)30003-X. PMID: 28271845.
14. Mendenhall E. Beyond Comorbidity: A Critical Perspective of Syndemic Depression and Diabetes in Cross-cultural Contexts. Med Anthropol Q. 2016 Dec;30(4):462-478. doi: 10.1111/maq.12215.
15. Rao GHR: Global Syndemic of Metabolic Diseases: Editorial Comments. Journal of Diabetes & Clin. Res. 2018; I(1): 2-4.
16. Rao GHR: COVID-19 and Cardiometabolic Diseases.: Guest Editorial. EC Cardiol 2020; 7.6:08-12.
17. Rao GHR: Coronavirus (COVID-19), Comorbidities, and Acute Vascular Events; Guest Editorial. ECCMC EC Clinical Case Reports. 2020; 3.6:87-91.
18. Rao GHR: Coronavirus Disease (Covid-19), Comorbidities, and Clinical Manifestations. Guest Editorial. EC Diab, Met Res. 2020; 4.6 : 27-33.
19. Gussow AB, Auslander N, Faure G, Wolf YI, Zhang F, Koonin EV. Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses. bioRxiv [Preprint]. 2020 Apr 9:2020.04.05.026450. doi: 10.1101/2020.04.05.026450. Update in: Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15193-15199.
20. Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A, Li F. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A. 2020 May 26;117(21):11727-11734. doi: 10.1073/pnas.2003138117.
21. Tortorici MA, Veesler D. Structural insights into coronavirus entry. Adv Virus Res. 2019;105:93-116. doi: 10.1016/bs.aivir.2019.08.002.
22. 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 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052.
23. Ming Y, Qiang L. Involvement of Spike Protein, Furin, and ACE2 in SARS-CoV-2-Related Cardiovascular Complications. SN Compr Clin Med. 2020 Jul 11:1-6. doi: 10.1007/s42399-020-00400-2.
24. Noor FM, Islam M: Prevalence of Clinical Manifestations and Comorbidities of Coronavirus (COVID-19) Infection: A Meta-Analysis. Fortune J. Health Sci 3 (2020):55-97.
25. Rao GHR. Coronavirus Disease and Acute Vascular Events. Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029620929091. doi: 10.1177/1076029620929091.
26. Rao GHR: COVID-19 and Cardiometabolic Diseases.: Guest Editorial. EC Cardiol 2020; 7.6:08-12.
27. Rao GHR: Coronavirus (COVID-19), Comorbidities, and Acute Vascular Events; Guest Editorial. ECCMC EC Clinical Case Reports. 2020; 3.6:87-91.
28. Coronavirus Disease (Covid-19), Comorbidities, and Clinical Manifestations. Guest Editorial. EC Diab, Met Res. 2020; 4.6: 27-33.
29. Rao GHR: Coronavirus Disease (Covid-19): A Disease of the Vascular Endothelium. Series Cardiology Res 2020; 2(1): 23-27.
30. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum in: JAMA. 2020 May 26;323(20):2098.
31. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;: PMID: 31986264; PMCID: PMC7159299.
32. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y,et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7.
33. Wu C, Yang W, Wu X, Zhang T, Zhao Y, Ren W, Xia J. Clinical Manifestation and Laboratory Characteristics of SARS-CoV-2 Infection in Pregnant Women. Virol Sin. 2020 Jun;35(3):305-310. doi: 10.1007/s12250-020-00227-0.
34. Wang B, Li R, Lu Z, Huang Y. Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging (Albany NY). 2020 Apr 8;12(7):6049-6057. doi: 10.18632/aging.103000. Epub 2020 Apr 8. PMID: 32267833; PMCID: PMC7185114.
35. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648.
36. Adão R, Guzik TJ. Inside the heart of COVID-19. Cardiovasc Res. 2020 May 1;116(6):e59-e61. doi: 10.1093/cvr/cvaa086.
37. Letícia de Oliveira Toledo S, Sousa Nogueira L, das Graças Carvalho M, Romana Alves Rios D, de Barros Pinheiro M. COVID-19: Review and hematologic impact. Clin Chim Acta. 2020 Nov;510:170-176. doi: 10.1016/j.cca.2020.07.016.
38. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020 Jun 25;58(7):1021-1028. doi: 10.1515/cclm-2020-0369.
39. Borges L, Pithon-Curi TC, Curi R, Hatanaka E. COVID-19 and Neutrophils: The Relationship between Hyperinflammation and Neutrophil Extracellular Traps. Mediators Inflamm. 2020 Dec 2;2020:8829674. doi: 10.1155/2020/8829674.
40. Bg S, Gosavi S, Ananda Rao A, Shastry S, Raj SC, Sharma A, Suresh A, Noubade R. Neutrophil-to-Lymphocyte, Lymphocyte-to-Monocyte, and Platelet-to-Lymphocyte Ratios: Prognostic Significance in COVID-19. Cureus. 2021 Jan 11;13(1):e12622. doi: 10.7759/cureus.12622.
41. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417-1418. doi: 10.1016/S0140-6736(20)30937-5.
42. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020 Jul 9;383(2):120-128. doi: 10.1056/NEJMoa2015432.
43. Gralinski LE, Bankhead A 3rd, Jeng S, Menachery VD, Proll S, Belisle SE, et al. . Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. mBio. 2013 Aug 6;4(4):e00271-13. doi: 10.1128/mBio.00271-13.
44. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol. 2020 Apr;16(4):223-237. doi: 10.1038/s41581-019-0244-2.
45. Higashi Y, Kihara Y, Noma K. Endothelial dysfunction and hypertension in aging. Hypertens Res. 2012 Nov;35(11):1039-47. doi: 10.1038/hr.2012.138.
46. Panza JA, Quyyumi AA, Brush JE Jr, Epstein SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990 Jul 5;323(1):22-7. doi: 10.1056/NEJM199007053230105.
47. Wadman M: Why COVID-19 is more deadly in people with obesity-even if they are young? Science 2020; doi:10.1126/science.abe7010.
48. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9265-9. doi: 10.1073/pnas.84.24.9265.
49. Van Guilder GP, Hoetzer GL, Dengel DR, Stauffer BL, DeSouza CA. Impaired endothelium-dependent vasodilation in normotensive and normoglycemic obese adult humans. J Cardiovasc Pharmacol. 2006 Feb;47(2):310-3. doi: 10.1097/01.fjc.0000205097.29946.d3. PMID: 16495771.
50. Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD. Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance. J Clin Invest. 1996 Jun 1;97(11):2601-10. doi: 10.1172/JCI118709.
51. Tartof SY, Qian L, Hong V, Wei R, Nadjafi RF, Fischer H, et al. Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization. Ann Intern Med. 2020 Nov 17;173(10):773-781. doi: 10.7326/M20-3742.
52. Kass DA. COVID-19 and Severe Obesity: A Big Problem? Ann Intern Med. 2020 Nov 17;173(10):840-841. doi: 10.7326/M20-5677.
53. Schulz E, Gori T, Münzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res. 2011 Jun;34(6):665-73. doi: 10.1038/hr.2011.39.
54. Iantorno M, Campia U, Di Daniele N, Nistico S, Forleo GB, Cardillo C, Tesauro M. Obesity, inflammation and endothelial dysfunction. J Biol Regul Homeost Agents. 2014 Apr-Jun;28(2):169-76.
55. Rubino F, Amiel SA, Zimmet P, Alberti G, Bornstein S, Eckel RH, et al. New-Onset Diabetes in Covid-19. N Engl J Med. 2020 Aug 20;383(8):789-790. doi: 10.1056/NEJMc2018688.
56. Gerrard JM, Stuart MJ, Rao GH, Steffes MW, Mauer SM, Brown DM, White JG. Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats. J Lab Clin Med. 1980 Jun;95(6):950-8. PMID: 6445927.
57. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). 16-14 February 2020. The joint Mission consisted of 25 national and international experts from China, Germany, Japan, Korea, Russia, Singapore and the United States of America, and the World Health Organization (WHO).
58. Lindner D, Fitzek A, Bräuninger H, Aleshcheva G, Edler C, Meissner K, et al. Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiol. 2020 Nov 1;5(11):1281-1285. doi: 10.1001/jamacardio.2020.3551.
59. Hendren NS, Drazner MH, Bozkurt B, Cooper LT Jr. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation. 2020 Jun 9;141(23):1903-1914. doi: 10.1161/CIRCULATIONAHA.120.047349.
60. Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020 Sep;17(9):543-558. doi: 10.1038/s41569-020-0413-9.
61. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al.; COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 28;323(16):1574-1581. doi: 10.1001/jama.2020.5394.
62. Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, et al. Clinical Characteristics of Covid-19 in New York City. N Engl J Med. 2020 Jun 11;382(24):2372-2374. doi: 10.1056/NEJMc2010419.
63. Mahenthiran AK, Mahenthiran AK, Mahenthiran J. Cardiovascular system and COVID-19: manifestations and therapeutics. Rev Cardiovasc Med. 2020 Sep 30;21(3):399-409. doi: 10.31083/j.rcm.2020.03.124.
64. Gupta AK, Jneid H, Addison D, Ardehali H, Boehme AK, Borgaonkar S, et al. Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the JAHA Editors. J Am Heart Assoc. 2020 Jun 16;9(12):e017013. doi: 10.1161/JAHA.120.017013.
65. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul;191:145-147. doi: 10.1016/j.thromres.2020.04.013. Epub 2020 Apr 10. PMID: 32291094; PMCID: PMC7146714.
66. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1;77(6):683-690. doi: 10.1001/jamaneurol.2020.1127.
67. Tsivgoulis G, Palaiodimou L, Zand R, Lioutas VA, Krogias C, Katsanos AH, et al. COVID-19 and cerebrovascular diseases: a comprehensive overview. Ther Adv Neurol Disord. 2020 Dec 8;13:1756286420978004. doi: 10.1177/1756286420978004.
68. Akhter N, Ahmad S, Alzahrani FA, Dar SA, Wahid M, Haque S, et al. Impact of COVID-19 on the cerebrovascular system and the prevention of RBC lysis. Eur Rev Med Pharmacol Sci. 2020 Oct;24(19):10267-10278. doi: 10.26355/eurrev_202010_23251.
69. Fraiman P, Godeiro Junior C, Moro E, Cavallieri F, Zedde M. COVID-19 and Cerebrovascular Diseases: A Systematic Review and Perspectives for Stroke Management. Front Neurol. 2020 Nov 5;11:574694. doi: 10.3389/fneur.2020.574694.
70. Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, et al. Microvascular Injury in the Brains of Patients with Covid-19. N Engl J Med. 2021 Feb 4;384(5):481-483. doi: 10.1056/NEJMc2033369.
71. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al.; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032.
72. Piazza G, Morrow DA. Diagnosis, Management, and Pathophysiology of Arterial and Venous Thrombosis in COVID-19. JAMA. 2020 Dec 22;324(24):2548-2549. doi: 10.1001/jama.2020.23422.
73. Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al.; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Jun 16;75(23):2950-2973. doi: 10.1016/j.jacc.2020.04.031.
74. Rao GHR: SARS-CoV-2 biochemistry, Transmission, Clinical Manifestations, and Prevention. Int J. Biomed. 2020;10(4):303-311.
75. Krause PR, Gruber MF. Emergency Use Authorization of Covid Vaccines - Safety and Efficacy Follow-up Considerations. N Engl J Med. 2020 Nov 5;383(19):e107. doi: 10.1056/NEJMp2031373.
76. Schwartz JL. Evaluating and Deploying Covid-19 Vaccines - The Importance of Transparency, Scientific Integrity, and Public Trust. N Engl J Med. 2020 Oct 29;383(18):1703-1705. doi: 10.1056/NEJMp2026393.
77. Creech CB, Walker SC, Samuels RJ. SARS-CoV-2 Vaccines. JAMA. 2021 Apr 6;325(13):1318-1320. doi: 10.1001/jama.2021.3199. PMID: 33635317.
78. Jiang S, Zhang X, Yang Y, Hotez PJ, Du L. Neutralizing antibodies for the treatment of COVID-19. Nat Biomed Eng. 2020 Dec;4(12):1134-1139. doi: 10.1038/s41551-020-00660-2.
79. Dorans KS, Mills KT, Liu Y, He J. Trends in Prevalence and Control of Hypertension According to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline. J Am Heart Assoc. 2018 Jun 1;7(11):e008888. doi: 10.1161/JAHA.118.008888.
80. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128•9 million children, adolescents, and adults. Lancet. 2017 Dec 16;390(10113):2627-2642. doi: 10.1016/S0140-6736(17)32129-3.
81. DiBonaventura MD, Meincke H, Le Lay A, Fournier J, Bakker E, Ehrenreich A. Obesity in Mexico: prevalence, comorbidities, associations with patient outcomes, and treatment experiences. Diabetes Metab Syndr Obes. 2017 Dec 22;11:1-10. doi: 10.2147/DMSO.S129247.
82. Vrints CJM, Krychtiuk KA, Van Craenenbroeck EM, Segers VF, Price S, Heidbuchel H. Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications. Acta Cardiol. 2020 Nov 19:1-16. doi: 10.1080/00015385.2020.1846921.
83. Teuwen LA, Geldhof V, Pasut A, Carmeliet P. COVID-19: the vasculature unleashed. Nat Rev Immunol. 2020 Jul;20(7):389-391. doi: 10.1038/s41577-020-0343-0. Erratum in: Nat Rev Immunol. 2020 Jun 4.
84. Evans PC, Rainger GE, Mason JC, Guzik TJ, Osto E, Stamataki Z, et al. Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science. Cardiovasc Res. 2020 Dec 1;116(14):2177-2184. doi: 10.1093/cvr/cvaa230.
85. Nägele MP, Haubner B, Tanner FC, Ruschitzka F, Flammer AJ. Endothelial dysfunction in COVID-19: Current findings and therapeutic implications. Atherosclerosis. 2020 Dec;314:58-62. doi: 10.1016/j.atherosclerosis.2020.10.014.
86. The Lancet Public Health. COVID-19-break the cycle of inequality. Lancet Public Health. 2021 Feb;6(2):e82. doi: 10.1016/S2468-2667(21)00011-6.

Download Article
©2021 International Medical Research and Development Corporation.