FOLIC ACID and METHOTREXATE USE and THEIR ASSOCIATION with COVID-19 DIAGNOSIS and MORTALITY: AN ANALYSIS from the UK BIOBANK

ABSTRACT

Background: Folate metabolism is implicated in SARS-CoV-2 infectivity (Ref). Objectives: To determine if methotrexate (an antifolate) or folic acid prescription were associated with a lowered and increased risk, respectively, for COVID-19 diagnosis or mortality in a large population-based cohort (UK Biobank). Methods: Data from 380,380 UK Biobank participants with general practice prescription data were used. Criteria for COVID-19 diagnosis were 1) a positive SARS-CoV-2 test and/or 2) ICD-10 code for confrmed COVID-19 (U07.1) or probable COVID-19 (U07.2) in hospital records, or death records. This defnition identifed 26,003 individuals diagnosed with COVID-19 of whom 820 were known to have died from COVID-19. Logistic regression statistical models were adjusted for age group (4 categories), sex, ethnicity, Townsend deprivation index, BMI, smoking status, presence of rheumatoid arthritis, sickle cell disease, use of anti-convulsants, statins and iron supplements. Results: Compared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had increased risk of diagnosis of COVID-19 (OR 1.51 [1.42;1.61]). The prescription of methotrexate with or without folic acid was not associated with COVID-19 diagnosis (P≥0.18). Compared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had an increased risk of death after a diagnosis of COVID-19 (OR 2.64 [2.15;3.24]) in a fully adjusted model. The prescription of methotrex-ate in combination with folic acid was not associated with an increased risk for death after a diagnosis of COVID-19 (1.07 [0.57;1.98]). (Table 1) Conclusion: We report increased risk for COVID-19 diagnosis and COV-ID-19-related death for people prescribed folic acid supplementation. The prescription and use of supplemental folic acid may confer risk of infection with the SARS-CoV-2 virus as well as the risk of death resulting from COVID-19. Our results also suggest that methotrexate might attenuate an increased risk for COVID-19 diagnosis and death conferred by folic acid.