Homocysteine assessment has been proposed as a potential predictive biomarker for the severity of COVID-19 infection. The purpose of this review was to analyze the correlation between the prevalence of MTHFR 677T allele and COVID-19 incidence and mortality worldwide. There is a clear trend towards the worldwide prevalence of MTHFR 677T allele and COVID-19 incidence and mortality. The prevalence of MTHFR 677T allele in the Latino population and the incidence and mortality for COVID-19 was higher for this ethnic group than that reported for most other populations globally. Statistical analysis showed a relatively strong correlation between 677T allele and death from coronavirus. Genetic polymorphism of MTHFR C677T may modulate the incidence and severity of COVID-19 pandemic infection.