COVID-19 UPDATE
A Disease of Insufficient Nitric Oxide Production By Nathan S. Bryan, PhD
COVID-19 is now a worldwide pandemic affecting millions of people around the world. As of mid-May 2021, over 160 million people have been infected, with over three million deaths. Early data coming out of China in January 2020 revealed that patients with underlying cardiovascular disease were more susceptible to infection, greater disease severity and ten times higher mortality. Among the patients studied, the median (range) age was 64 (21-95) years old, female (50.7%, and the median time to symptom onset was 10 days (interquartile range [IQR]), 1-30). Of this group, 82 (19.7%) had some type of cardiac comorbidity. It was apparent as the study went on that patients with cardiac morbidity and COVID-19 fared worse than the patients with COVID-19, but no history of cardiac morbidity. Patients with cardiac morbidity with diagnosed COVID-19, compared with patients without cardiac morbidity, had a higher mortality rate (51.2% vs 4.5%) and risk of death.1 In addition, over the past 18 months, reports from the U.S. database compiled by CDC report mortality from COVID-19 to have a racial disparity.2 A disproportionate number of COVID-19 fatalities among Hispanics and African Americans has been observed. This has been attributed to known disparities in health care, low economic resources and issues associated with social distancing: occupation, crowded residential spaces and transportation crowding. Additionally, Hispanics and African Americans have a high incidence of pre-existing and often 32
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untreated cardiovascular conditions.3 It is clear that older people with an underlying comorbidity such as high blood pressure, heart disease, kidney disease, obesity, smokers and patients with pulmonary disorders are at an increased risk of COVID infection. These are also the people that get the sickest and die from COVID. Additionally, abnormal blood clotting is an increasingly recognized complication of this disease, both systemically and within the pulmonary circulation.4 In fact, one of the greatest predictors of death is a serum blood test that indicates elevated clotting activity (D-dimer). More recent clinical observations reveal endothelial cell infection and endotheliitis in COVID patients across vascular beds in multiple organs.5 The vascular endothelium is an active paracrine, endocrine and autocrine organ that is indispensable for the regulation of vascular tone and the maintenance of vascular homoeostasis.6 COVID-19-endotheliitis could explain the systemic impaired microcirculatory function in different vascular beds and their clinical sequelae in patients with COVID-19. Endothelial dysfunction and insufficient nitric oxide (NO) production is a principal determinant of microvascular dysfunction by shifting the vascular equilibrium towards more vasoconstriction with subsequent organ ischemia, inflammation with associated tissue edema and a pro-coagulant state. See illustration. Therefore, the people that are most susceptible and vulnerable to COVID infection are exactly the patients that have insufficient nitric oxide production in their body.
