Cracking the code to the 2019 novel coronavirus (COVID-19): Lessons from the eye

Neal Adams


With the recent March 11, 2020 declaration of a pandemic by the World Health Organization (WHO), further attention has turned to understanding and managing the outbreak of infectious disease termed coronavirus disease 2019 (COVID-19) caused by the novel coronavirus identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).  The SARS-CoV-2 gains entry into human cells through its ability to bind to a human ACE2 protein.  Through our understanding of diabetic retinopathy, there are genetic-based variations in ACE2 levels that confer varying risk profiles for diabetic retinopathy.  Similarly, emerging research suggests ACE2 levels confer varying risk profiles for COVID-19.  Using data comparisons between geographic prevalence rates of diabetic retinopathy and existing COVID-19 mortality rates may enable improved predictions of the rates of spread of COVID-19 in various geographic regions.  The goal of this report is to encourage cross-disciplinary horizontal vision in the field of medicine and science in order to further progress in managing and treating human disease.


2019 coronavirus; COVID-19; coronavirus 2; SARS coronavirus; SARS; SARS-CoV; SARS-CoV-2; ACE; ACE2; angiotensin converting enzyme; diabetes; diabetic retinopathy; geography; ethnicity; geographic area; geographic region; genetic; heredity; china; us


Zhang K, Ferreyra HA, Grob S, et al. Diabetic retinopathy: genetics and etiologic mechanisms. In: Ryan SJ, et al., editors. Retina, 5th ed. Philadelphia: Saunders 2013; 925-939.

Lee R, Wong TY, and Sabanayagam C. Epidemiology od diabetic retinopathy, diabetic macular edema and related vision loss. Eye and Vision 2015; 2:17-41.

Yau JWY, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35: 556-564.

Sabanayagam C, Banu R, Chee ML, et al. Incidence and progression of diabetic retinopathy: a systematic review. The Lancet: Diabetes and Endocrinology 2019; 7: 140-9.

Tikellis C, Johnston CI, Forbes JM, et al. Identification of angiotensin converting enzyme 2 in the rodent retina. Current Eye Research 2004; 29(6): 419-27.

Senanayake PD, Drazba J, Shadrach K, et al. Angiotensin II and its receptor sybtypes in the human retina. Investigative Ophthalmology and Visual Science 2007; 48: 3301-3311.

Verma A, Shan Z, Lei B, et al. ACE2 and Ang-(1-7) confer protection against development of diabetic retinopathy. Molecular Therapy 2012; 20(1): 28-36.

Foureaux G, Nogueira BS, Coutinho DCO, et al. Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina. Brazilian Journal of Medical and Biological Research 2015; 48(12): 1109-14.

Dominguez JM, Hu P, Caballero, et al. Adeno-associated virus overexpression of angiotensin-converting enzyme-2 reverses diabetic retinopathy in type 1 diabetes in mice. American Journal of Pathology 2016; 186(6): 1688-700.

Verma A, Xu K, Du T, et al. Expression of human ACE2 in lactobacillus and beneficial effects in diabetic retinopathy in mice. Molecular Therapy: Methods and Clinical Development 2019; 14: 161-170.

Duan Y, Beli E, Li Calzi S, et al. Loss of angiotensin-converting enzyme 2 exacerbates diabetic retinopathy by promoting bone marrow dysfunction. Stem Cells 2018; 36(9): 1430-40.

Qui Y, Tao L, Zheng S, et al. AAV8-mediated angiotensin-converting enzyme 2 gene delivery prevent experimental autoimmune uveitis by regulating MAPK, NF-kB and STAT3 pathways. Scientific Reports: Nature Research 2016; 6: 31912-26.

Fu X, Lin R, Qui Y, et al. Overexpression of angiotensin-converting enzyme 2 ameliorates amyloid B-induced inflammatory response in human primary retinal pigment epithelium. Investigative Ophthalmology and Visual Science 2017; 58(7): 3018-28.

Meng N, Zhang Y, Ma J, et al. Association of polymorphisms of angiotensin I converting enzyme 2 with retinopathy in type 2 diabetes mellitus among Chinese individuals. Eye 2015; 29(2): 266-71.

Rice GI, Jones AL, Grant PJ, et al. Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme2, and neprilysin in a family study. Hypertension 2006; 48: 914-20.

Burrell LM, Harrap SB, Velkoska E, et al. The ACE2 gene: its potential as a functional candidate for cardiovascular disease. Clinical Science (London) 2013; 124: 65-76.

Zhang Q, Cong M, Wang N, et al. Association of angiotensin-converting enzyme 2 gene polymorphism and enzymatic activity with essential hypertension in different gender. Medicine (Baltimore) 2018; 97(42e12917): 1-8.

Chen J. Pathogenicity and transmissibility of 2019-nCoV: a quick overview and comparison with other emerging viruses. Microbes and Infection 2020; 22(2): 69-71.

Chen Y, Guo Y, Pan Y, et al. Structure analysis of the receptor binding of 2019-nCoV. Biochemical and Biophysical Research Communications 2020 (in press).

Jia HP, Look DC, Shi L, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. Journal of Virology 2005; 79(23): 14614-21.

Hoffmann M, Kleine-Weber, Schroeder, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181: 1-10.

Li F, Li W, Farzan M, et al. Structure of SARS coronavirus spike receptor-binding domain completed with receptor. Science 2005; 309(5742): 1864-8.

Li W, Zhang C, Sui J, et al. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. The EMBO Journal 2005; 24(8): 1643-34.

Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nature Medicine 2005; 11: 875-9.

Cao Y, Li L, Feng Z, et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discovery: Nature 2020; 6(11): 1-4.

Li W, Sui J, Huang IC, et al. The S protein of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology 2007; 367(2): 367-74.

Zhao Y, Zhao Z, Want Y, et al. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRXiv 2020 (preprint, not peer-reviewed).

Cai G. Tobacco-use disparity in gene expression of ACE2, the receptor of 2019-nCov. Preprints 2020 (preprint, not peer-reviewed).

World Health Organization. Situation Report 54, 14 March 2020. Coronavirus disease (COVID-2019) situation reports: novel-coronavirus-2019/situation-reports.

Barry JM. The Great Influenza. New York: Penguin Books, 2004.



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