Nitric oxide and phosphodiesterase-5 inhibitors: possible treatments for COVID-19 in diabetes

Authors

  • Martin B Whyte University of Surrey King's College Hospital NHS Foundation Trust
  • Prash Vas King's College Hospital NHS Foundation Trust
  • Philip A Kelly King's College Hospital NHS Foundation Trust
  • Christian Heiss University of Surrey
  • Michael D Feher University of Oxford

DOI:

https://doi.org/10.15277/bjd.2020.257

Keywords:

type 2 diabetes, pulmonary microcirculation, COVID-19, nitric oxide, phosphodiesterase-5 inhibitor

Author Biographies

Martin B Whyte, University of Surrey King's College Hospital NHS Foundation Trust

Consultant Diabetologist

Clinical Senior Lecturer in Metabolic Medicine

Prash Vas, King's College Hospital NHS Foundation Trust

Consultant Diabetologist

Philip A Kelly, King's College Hospital NHS Foundation Trust

Consultant Physician

Christian Heiss, University of Surrey

Professor of Cardiovascular Medicine

Michael D Feher, University of Oxford

Honorary Professor Diabetes

References

Chen Y, Gong X, Wang L, Guo J. Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: a systematic review and meta-analysis. medRxiv 2020 (Published Online First 30 March 2020). https://doi.org/10.1101/2020.03.25.20043133. 2020

NHS England. Type 1 and type 2 diabetes and COVID-19 related mortality in England. Available from: https://www.england.nhs.uk/publication/type-1-and-type-2-diabetes-and-covid-19-related-mortality-in-england/ (accessed 28 June 2020).

Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323(13):1239–42. https://doi.org/10.1001/jama.2020.2648

Zhu L, She Z-G, Cheng X, et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metabolism 2020 (Published Online First 1 May 2020). doi: https://doi.org/10.1016/j.cmet.2020.04.021

Cariou B, Hadjadj S, Wargny M, et al, for the CORONADO Investigators. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia 2020;63(8):1500–15. https://doi.org/10.1007/s00125-020-05180-x

Stehouwer CDA. Microvascular dysfunction and hyperglycemia: a vicious cycle with widespread consequences. Diabetes 2018;67(9):1729–41. https://doi.org/10.2337/dbi17-0044

Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020;395(10234):1417–18. https://doi.org/10.1016/S0140-6736(20)30937-5

Lax SF, Skok P, Kessler HH, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series Ann Intern Med 2020 (Published Online First 14 May 2020). https://doi.org/107326/M20-2566

Brownrigg JR, Hughes CO, Burleigh D, et al. Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study. Lancet Diabetes Endocrinol 2016; 4(7):588–97. https://doi.org/10.1016/S2213-8587(16)30057-2

Davis WA, Knuiman M, Kendall P, et al. Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study. Diabetes Care 2004;27(3):752–7. https://doi.org/10.2337/diacare.27.3.752

Chance WW, Rhee C, Yilmaz C, et al. Diminished alveolar microvascular reserves in type 2 diabetes reflect systemic microangiopathy. Diabetes Care 2008;31(8):1596–601. https://doi.org/10.2337/dc07-2323

Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J 2005;26(5):948–68. https://doi.org/10.1183/09031936.05.00035205

Mori H, Okubo M, Okamura M, et al. Abnormalities of pulmonary function in patients with non-insulin-dependent diabetes mellitus. Intern Med 1992;31(2):189–93. https://doi.org/10.2169/internalmedicine.31.189

Sandler M, Bunn AE, Stewart RI. Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus. Am Rev Respir Dis 1987;135(1):223–9. https://doi.org/10.1164/arrd.1987.135.1.223

Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395(10229):1054–62. https://doi.org/10.1016/S0140-6736(20)30566-3

Ozdemir B, Yazici A. Could the decrease in the endothelial nitric oxide (NO) production and NO bioavailability be the crucial cause of COVID-19 related deaths? Med Hypotheses 2020;144:109970. https://doi.org/10.1016/j.mehy.2020.109970

Velmurugan S, Gan JM, Rathod KS, et al. Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study. Am J Clin Nutr 2016;103(1):25–38. https://doi.org/10.3945/ajcn.115.116244

Heiss C, Keen CL, Kelm M. Flavanols and cardiovascular disease prevention. Eur Heart J 2010;31(21):2583–92. https://doi.org.10.1093/eurheartj/ehq332

Balzer J, Rassaf T, Heiss C, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients: a double-masked, randomized, controlled trial. J Am Coll Cardiol 2008; 51(22):2141–9. https://doi.org/10.1016/j.jacc.2008.01.059

Barnett CF, Machado RF. Sildenafil in the treatment of pulmonary hypertension. Vasc Health Risk Manag 2006;2(4):411–22. https://doi.org/10.2147/vhrm.2006.2.4.411

Chen L, Liu P, Gao H, et al. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis 2004;39(10):1531–5. https://doi.org/10.1086/425357

Akerstrom S, Mousavi-Jazi M, Klingstrom J, et al. Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol 2005;79(3):1966–9. https://doi.org/10.1128/JVI.79.3.1966-1969.2005

ClinicalTrials.gov. Nitric oxide gas inhalation therapy for mild/moderate COVID-19 (NoCovid). NCT04305457. 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04305457 (accessed 19 May 2020).

ClinicalTrials.gov. Nitric oxide gas inhalation in severe acute respiratory syndrome in COVID-19 (NOSARSCOVID). NCT04306393. 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04306393 (accessed 19 May 2020).

McGonagle D, O'Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol 2020;2(7):437–45. https://doi.org/10.1016/S2665-9913(20)30121-1

Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol 2020;8(6):546–50. https://doi.org/10.1016/S2213-8587(20)30152-2

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Published

2020-12-13

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Editorials