Mevalonate pathway, selenoproteins, redox balance, immune system, Covid-19: Reasoning about connections

• Published in: Medical hypotheses Vol. 144; p. 110128
• Main Author: Minetti, Giampaolo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.11.2020
• Subjects: Cholesterol; Cholesterol - metabolism; Cholesterol, LDL - metabolism; COVID-19 - immunology; COVID-19 Drug Treatment; Enzyme Inhibitors - pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Immune cells; Immune System; Immunity, Innate; Inflammation; Isopentenyladenosine; LDL; Lipoproteins, LDL - metabolism; Mevalonic Acid - chemistry; Models, Theoretical; Oxidation-Reduction; Oxidative Stress; SARS-CoV-2; Selenoproteins - chemistry; Statins; SARS-CoV-2; Isopentenyladenosine; Immune cells; LDL; Statins; Cholesterol
• ISSN: 0306-9877; 1532-2777; 1532-2777
• DOI: 10.1016/j.mehy.2020.110128

It has been proposed that a degraded immune system is (one of) the condition(s) that predispose certain subjects to fatal consequences from infection by SARS-CoV-2. It is unknown whether therapeutic regimens to which these patients may have been subjected to in the months/years preceding the infection could be immunocompromising. Statins are among the most widely prescribed cholesterol-lowering drugs. As competitive inhibitors of HMG-CoA-reductase, the key enzyme of the “mevalonate pathway” through which essential compounds, not only cholesterol, are synthesized, statins decrease the levels of cholesterol, and thus LDLs, as an innate defense mechanism, with controversial results in decreasing mortality from cardiovascular disease. Moreover, statins have pleiotropic, mostly deleterious effects on many cell types, including immune cells. In the attempt to decipher the enigma of SARS-CoV-2 infectivology, the hypothesis should be tested whether the population of subjects who succumbed to Covid-19 may have developed a compromised immunity at sub-clinical levels and have become more susceptible to fatal consequences from SARS-Cov-2 infection due to statin therapy.