1197: Folic Acid and Methotrexate Use and Their Association with COVID-19 Diagnosis and Mortality: An Analysis from the UK Biobank

Ruth Topless¹, Ralph Green², Sarah L Morgan³, Philip Robinson⁴, Tony Merriman¹ and Angelo Gaffo³, ¹University of Otago, Dunedin, New Zealand, ²Departments of Pathology and Medicine, University of California Davis at Sacramento, Sacramento, CA, ³University of Alabama at Birmingham, Birmingham, AL, ⁴School of Clinical Medicine, University of Queensland, Brisbane, Australia

Background/Purpose: Folate metabolism is implicated in SARS-CoV-2 infectivity. The current study seeks 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 confirmed COVID-19 (U07.1) or probable COVID-19 (U07.2) in hospital records or death records. This definition identified 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 anticonvulsants, statins and iron supplements.

Results: Compared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had an increased risk of a 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 methotrexate 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)

Conclusion: We report an increased risk for COVID-19 diagnosis and COVID-19-related death for people prescribed folic acid supplementation. The prescription and use of supplemental folic acid may confer a 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.

Disclosures: R. Topless, None; R. Green, None; S. Morgan, None; P. Robinson, Pfizer, AbbVie/Abbott, Novartis, UCB, GlaxoSmithKlein(GSK), Janssen, Eli Lilly, Kukdong, Atom Biosciences; T. Merriman, None; A. Gaffo, None.