Carnitine and COVID-19 Susceptibility and Severity: A Mendelian Randomization Study

Abstract

Background: Carnitine, a potential substitute or supplementation for dexamethasone, might protect against COVID-19 based on its molecular functions. However, the correlation between carnitine and COVID-19 has not been explored yet, and whether there exists causation is unknown.Methods: A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship between carnitine level and COVID-19. Significant single nucleotide polymorphisms from genome-wide association study on carnitine (N = 7,824) were utilized as exposure instruments, and summary statistics of the susceptibility (N = 1,467,264), severity (N = 714,592) and hospitalization (N = 1,887,658) of COVID-19 were utilized as the outcome. The causal relationship was evaluated by multiplicative random effects inverse variance weighted (IVW) method, and further verified by another three MR methods including MR Egger, weighted median, and weighted mode, as well as extensive sensitivity analyses.Results: Genetically determined one standard deviation increase in carnitine amount was associated with lower susceptibility (OR: 0.38, 95% CI: 0.19–0.74, P: 4.77E−03) of COVID-19. Carnitine amount was also associated with lower severity and hospitalization of COVID-19 using another three MR methods, though the association was not significant using the IVW method but showed the same direction of effect. The results were robust under all sensitivity analyses.Conclusions: A genetic predisposition to high carnitine levels might reduce the susceptibility and severity of COVID-19. These results provide better understandings on the role of carnitine in the COVID-19 pathogenesis, and facilitate novel therapeutic targets for COVID-19 in future clinical trials.

Whole-body metabolic modelling predicts isoleucine dependency of SARS-CoV-2 replication

“…We are currently not accounting for microbial metabolic activity, but it would be a valuable extension of the current effort as it also permits elucidate host-microbiome co-metabolism [21] . Moreover, in our models, the availability of carnitine and its derivative was limited by the defined diet uptake, while carnitine and associated lipids have been reported to change with infection and disease severity [67] . Similarly, biotin [68] is increased in COVID patients.…”

Integrative metabolomic and proteomic signatures define clinical outcomes in severe COVID-19

“…The modules identified various proteins and metabolites involved in inflammatory and vascular injury processes, such as MMP 12, Cathepsin D and RAGE which, to the best of our knowledge, have not yet been studied as targets for therapeutic intervention in COVID-19. Of note, our modules contained IL-6, which is already a mainstay of treatment for severe disease (Brown et al, 2021), and several other molecules such as carnitine, niacinamide and IFN-gamma which others have been studying in the context of COVID-19 therapies (Li et al, 2021;van Laarhoven et al, 2021;Fu et al, 2021).…”

Effects of L-carnitine supplementation in patients with mild-to-moderate COVID-19 disease: a pilot study

“…Increased percentage of oxygen saturation as a result of L-carnitine supplementation in patients can accelerate the recovery of symptoms. This improved oxygen saturation may be due to decreased ACE2 expression and thus inhibition of virus binding to lung cells [ 18 ]. In this regard, Bellamine et al showed that L-carnitine can reduce the expression of ACE2 in human pulmonary epithelial cells in vitro as well as in clinical conditions in animal models and humans [ 20 ].…”

“…Recently, it has been reported that the carnitine level of the body is negatively correlated with COVID-19 susceptibility and severity. So, an increase in the carnitine amount was associated with lower vulnerability to COVID-19 [ 18 ]. Also, another study used a combined metabolic activators regimen that included l-carnitine, and results showed that treating patients with this regimen accelerate the recovery period of COVID-19 [ 19 ].…”