Mendelian randomization analyses show that higher acetyl-carnitine and carnitine levels in blood protect against severe Covid19
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Abstract
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.
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.
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SciScore for 10.1101/2021.05.31.21257910: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Exposure instruments: We used single nucleotide polymorphisms (SNPs) as instruments in our Mendelian randomization analysis which have previously been identified as being associated with carnitine and acetyl-carnitine concentration measured in blood from 7,797 and 7,805 adults of European ancestry respectively. Blinding not detected. Power Analysis 34 A priori we planned to performed MR analyses on those outcomes that had power > 50%. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Natur…
SciScore for 10.1101/2021.05.31.21257910: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Exposure instruments: We used single nucleotide polymorphisms (SNPs) as instruments in our Mendelian randomization analysis which have previously been identified as being associated with carnitine and acetyl-carnitine concentration measured in blood from 7,797 and 7,805 adults of European ancestry respectively. Blinding not detected. Power Analysis 34 A priori we planned to performed MR analyses on those outcomes that had power > 50%. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Strengths and limitations of our analyses: Randomized controlled trials are expensive and are unethical where evidence of the treatment effect is weak, particularly if the drug in question has potential off target effects. In addition, trials take time and in the context of a global pandemic of a novel virus prioritization of the most promising treatments to take forward into trials is essential. Two sample Mendelian randomization analyses, such as the ones we have performed, can make use of large-scale data on common genetic variants from existing genome wide association studies,57 which means the analyses can be carried out quickly and can inform trials. In addition, using Mendelian randomization it is possible to look at effects of the treatment or exposure of interest with other outcomes using data from different GWAS to investigate whether they are on the causal pathway and to estimate any potential off-target effects. An important interpretive issue with Mendelian randomization is that genetic variants generally reflect variation in exposure over a lifetime so it is not possible to determine with certainty from our analyses the effect of short-term treatment with acetyl-carnitine and carnitine for the prevention of severe Covid19. Some of the effects we found with our secondary outcomes clearly occurred early in life (height) and are therefore very unlikely to be influenced by treatment of adults with carnitine. In addition, our analysis assumed a linear effect of the e...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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