Folic Acid and Endothelial Dysfunction in COVID-19

Since 2020, recurrent waves of SARS-CoV-2 infection have persisted globally. Despite the advancements in vaccines and pharmacological treatments, a subset of patients still exhibits an aggressive form of COVID-19 requiring prolonged stays in the intensive care unit (ICU) or experiences major acute infections (or reinfections) and long-term symptoms. Endothelial dysfunction is one of the key events contributing to both the severity of acute COVID-19 and the development of long COVID (LC)/post-acute sequelae of SARS-CoV-2 infection (PASC) syndrome. Since the beginning of the pandemic, the efficacy of nutraceuticals, particularly essential micronutrients, has been investigated as a complementary treatment to prevent disease onset and improve clinical outcomes. One such bioactive molecule is folate (vitamin B9), a member of the B-vitamin family involved in the pathogenesis of multiple diseases, including viral infections and vascular disorders. This review examines the role of folic acid in COVID-19 and its interaction with homocysteine metabolism, which is frequently dysregulated in inflammatory endothelial diseases. It further discusses the potential benefits of folic acid supplementation for the prevention and treatment of COVID-19 in both the acute and long-term phases of the disease, alongside the therapeutic role of vitamin B12 supplementation in LC syndrome.