Mendelian Randomization Analyses Show That Higher Acetyl-Carnitine and Carnitine Levels in Blood Protect Against Severe COVID19 (preprint)

Background: Severe Covid19 is characterised by a hyperactive immune response. Carnitine, an essential nutrient, and it’s derivative acetyl-carnitine can downregulate proinflammatory cytokines and has been suggested as a potential treatment for the disease.Methods: We carried out Mendelian randomization analyses using publicly available data from a large genome wide association study (GWAS) of metabolites and a collaborative genome wide study of Covid19 to investigate the nature of the relationship between carnitine and acetyl-carnitine and Covid19 infection, hospitalisation with Covid19 and very severe Covid19. We used the same methodology to determine whether carnitine was associated with co-morbidities commonly found among those with severe Covid19.Findings: We found evidence of a protective effect against very severe Covid19 for both carnitine and acetyl-carnitine, with around a 40% reduction in risk associated with a doubling of carnitine or acetyl-carnitine (carnitine odds ratio (OR) = 0.56, 95% confidence intervals (CI) 0.33 to 0.95, p=0.03 and acetyl-carnitine OR=0.60, 95% CI 0.35 to 1.02, p=0.06), and evidence of protective effects on hopitalisation with Covid19. For acetyl-carnitine the largest protective effect was seen in the comparison between those hospitalised with Covid19 and those infected but not hospitalised (OR=0.34, 95%CI 0.18 to 0.62, p=0.0005).Interpretation: Carnitine and acetyl-carnitine merit further investigation in respect to the prevention of severe Covid19.Funding Information: NK is supported by World Cancer Research Fund (2020/019). SJL and GDS are supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and GDS is Director of the Medical Research Council Integrative Epidemiology Unit at the University of Bristol supported by the Medical Research Council (MC_UU_00011/1). SJL and NK are affiliated with this unit. SJL and GDS are also supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre which is funded by the National Institute for Health Research (NIHR).Declaration of Interests: The authors do not have any conflicts of interest in relation to the work in this manuscript.

Mendelian randomization analyses show that higher acetyl-carnitine and carnitine levels in blood protect against severe Covid19 (preprint)

Background: Severe Covid19 is characterised by a hyperactive immune response. Carnitine, an essential nutrient, and its derivative acetyl-carnitine can downregulate proinflammatory cytokines and has been suggested as a potential treatment for the disease. Methods: We carried out Mendelian randomization analyses using publicly available data from a large genome wide association study (GWAS) of metabolites and a collaborative genome wide study of Covid19 to investigate the nature of the relationship between carnitine and acetyl-carnitine and Covid19 infection, hospitalisation with Covid19 and very severe Covid19. We used the same methodology to determine whether carnitine was associated with co-morbidities commonly found among those with severe Covid19. Results: We found evidence of a protective effect against very severe Covid19 for both carnitine and acetyl-carnitine, with around a 40% reduction in risk associated with a doubling of carnitine or acetyl-carnitine (carnitine odds ratio (OR) = 0.56, 95% confidence intervals (CI) 0.33 to 0.95, p=0.03 and acetyl-carnitine OR=0.60, 95% CI 0.35 to 1.02, p=0.06), and evidence of protective effects on hopitalisation with Covid19. For acetyl-carnitine the largest protective effect was seen in the comparison between those hospitalised with Covid19 and those infected but not hospitalised (OR=0.34, 95%CI 0.18 to 0.62, p=0.0005). Conclusion: Carnitine and acetyl-carnitine merit further investigation in respect to the prevention of severe Covid19.