Homocysteine and the SARS-CoV-2 Coronavirus – The X Factor of Severe Disease and Death

Homocysteine (Hcy) is a natural, non-essential amino acid formed by the de-methylation of methionine. Pathologic elevations occur in many chronic conditions, particularly the cardiovascular conditions common with aging, and in SARS-Cov2. The most common co-existing morbidities, hypertension, cardiovascular disease, and diabetes are all strongly associated with elevated levels of Homocysteine. Homocysteine’s effects include potential mechanisms for triggering severe COVID-19 disease, or preventing its control. For instance, SARS-CoV2 enters cells through its spike proteins that attach to the Angiotensin Converting Enzyme 2 (ACE2) cellular receptors to form a tunnel through which the virus enters the celli. Homocysteine, in attaching to the enzyme, may inhibit its attachment to the receptors and allow more virus to enter the cells. High homocysteine levels increase inflammatory cytokines that are over-produced in cytokine release syndrome or “cytokine storm”, increase endothelial dysfunction, inhibit nitric oxide synthesis, and lead to thrombus formation. All of these pathologies are hallmarks of severe SARS-Cov2.