Abstract
Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.
Keywords: COVID-19; Folic acid; Hydroxychloroquine.
【저자키워드】 COVID-19, Hydroxychloroquine, Folic acid, 【초록키워드】 SARS-CoV-2, Efficacy, ACE2, Trial, Hydroxychloroquine, furin, disease severity, Variation, polymorphism, protease, hypertension, RCT, Folic acid, Laboratory, Prophylaxis, Prevalence, Interpretation, Clinical studies, Mild, Placebo, Severe patient, Other, parameters, pulmonary hypertension, Combination, Hypothesis, MTHFR, Factor, cyanocobalamin, Pyridoxine, severe patients, moderate disease, domains, failure, placebo controlled trial, benefit, lowest, reported, complicate, 【제목키워드】 Folic acid, Prophylaxis, Controlled clinical trial,