Candesartan Could Ameliorate the Cytokine Storm in COVID-19 Infection

Genesis of the Hypothesis

The authors of this study had previously shown that glutamate induces the expression of genes associated with Alzheimer's disease and aging in nerve tissue cultures and that candesartan suppresses the expression of these genes. Sartans block the effects of excessive activation of AT₁ receptors for angiotensin II, which contributes to the development of brain damage, cardiovascular issues, kidney problems, lipid and glucose metabolism disturbances, promotes inflammation and viral damage to the lungs, and shows a linear relationship with viral load and lung damage in COVID-19 patients.

Sartans were developed as antihypertensive drugs. However, they exhibit a number of pleiotropic effects, including inflammation suppression, protection of mitochondrial function, maintenance of insulin sensitivity, normalization of the coagulation cascade, protection of cognitive functions, cerebral blood flow maintenance, and protection of the blood-brain barrier, among others. Lower mortality was observed in patients hospitalized for pneumonia who were previously treated with sartans for cardiovascular disease.

Experiment Results

Researchers therefore sought to test the hypothesis that the normalization of the immune response induced by candesartan could suppress the cytokine storm in severe COVID-19. Their results showed a statistically highly significant positive correlation between the expression of hundreds of genes upregulated by glutamate and the expression profile of tissues from individuals infected with SARS-CoV-2 (lung tissue obtained postmortem, peripheral blood mononuclear leukocytes, and bronchoalveolar lavage fluid from patients compared with the same tissues in healthy individuals). They also found a marked negative correlation between the expression of these genes and the effects of candesartan. Many of these genes regulate the activity of pro-inflammatory cytokines and chemokines involved in the cytokine storm in COVID-19.

Conclusion for Clinical Practice

The authors discuss in their paper that according to their results and published literature, sartans dampen excessive inflammatory response, oxidative stress, lung fibrosis, and the expression of pro-senescence genes. They can suppress the cytokine storm typical for severe COVID-19. Therefore, they could be beneficial in treating acute SARS-CoV-2 infection and its complications, especially in older patients, protecting not only lung function but also brain function. They strongly recommend not only continuing to administer sartans to patients with SARS-CoV-2 infection but also conducting studies to confirm whether these drugs can be considered as adjunct treatment for COVID-19.

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Source: Elkahloun A. G., Saavedra J. M. Candesartan could ameliorate the COVID-19 cytokine storm. Biomed Pharmacother 2020 Nov; 131: 110653, doi: 10.1016/j.biopha.2020.110653.