RESUMO
BackgroundNew means of treating COVID-19 are urgently needed. Genetic validation of drugs can foreshadow trial results, and help prioritize investigations. We assessed whether common drugs, suggested as possible treatments for COVID-19 (tocilizumab, anakinra and statins) with established genetic proxies, are effective in COVID-19. We also included dexamethasone as a positive control exposure because the RECOVERY trial suggested benefit in severe COVID-19. MethodsWe assessed, using Mendelian randomization, whether genetic proxies of tocilizumab, anakinra, statins and dexamethasone use affected risk of very severe (cases=536, non-cases=329391) or hospitalized (cases=3199, non-cases=897488) COVID-19 using a recent genome-wide association study. ResultsUsing rs2228145 (IL6R) to proxy effects of tocilizumab use, no association with very severe COVID-19 was found, but possibly an inverse association with hospitalized COVID-19 (odds ratio (OR) 0.83 per standardized effect of higher soluble interleukin-6r, 95% confidence interval 0.67 to 1.02). Using rs12916 (HMGCR) to proxy effects of statins use, an inverse association with very severe COVID-19 was found (OR 0.30 per standardized effect, 95% CI 0.10 to 0.89). Using rs6743376 and rs1542176 to proxy effects of anakinra use, no associations with COVID-19 were found. Dexamethasone, instrumented by cortisol, was possibly inversely associated with very severe COVID-19 (OR 0.20 per standardized effect 95% CI 0.04 to 1.04). ConclusionOur study provides some genetic validation for the use of both tocilizumab and statins in COVID-19, but not anakinra, whilst being consistent with the findings from the RECOVERY trial about dexamethasone. Investigation of the underlying mechanisms might facilitate re-purposing and development of effective treatments.
RESUMO
Un estudio de cohorte prospectivo basado en la población danesa investigó los patrones de mortalidad a largo plazo en mujeres menopáusicas según diferentes modalidades de terapia hormonal (TH). El estudio inscribió a 29.243 mujeres posmenopáusicas entre las edades de 50 y 64 años que usaron TH en la Cohorte Dieta, Cáncer y Salud entre 1993 y 1997 y las siguieron hasta el 31 de diciembre de 2013 (mediana de seguimiento, 17,6 años).
A prospective cohort study based on the Danish population investigated long-term mortality patterns in menopausal women according to different modalities of hormone therapy (HT). The study enrolled 29,243 postmenopausal women between the ages of 50 and 64 years who used HT in the Diet, Cancer and Health Cohort between 1993 and 1997 and followed them until December 31, 2013 (median follow-up, 17.6 years) .
