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

Kazmi, N.; Davey Smith, G.; Lewis, S. J.

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.