Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study
- Fujian Medical University, China
- Fujian Medical University Union Hospital, China
- Lund University, Sweden
Abstract
Background: Lipid metabolism plays an important role in viral infections. We aimed to assess the causal effect of lipid-lowering drugs (HMGCR inhibitiors, PCSK9 inhibitiors and NPC1L1 inhibitior) on COVID-19 outcomes using 2-sample Mendelian Randomization (MR) study.
Methods: We used two kinds of genetic instruments to proxy the exposure of lipid-lowering drugs, including eQTLs of drugs target genes, and genetic variants within or nearby drugs target genes associated with LDL cholesterol from GWAS. Summary-data-based MR (SMR) and inverse-variance weighted MR (IVW-MR) were used to calculate the effect estimates.
Results: SMR analysis found that a higher expression of HMGCR was associated with a higher risk of COVID-19 hospitalization (OR=1.38, 95%CI=1.06-1.81). Similarly, IVW-MR analysis observed a positive association between HMGCR-mediated LDL cholesterol and COVID-19 hospitalization (OR=1.32, 95%CI=1.00-1.74). No consistent evidence from both analyses was found for other associations.
Conclusions: This 2-sample MR study suggested a potential causal relationship between HMGCR inhibition and the reduced risk of COVID-19 hospitalization.
Funding: Fujian Province Major Science and Technology Program.
Data availability
Individual-level data cannot be provided but the raw data of the eQTLGen Consortium, GTEx and COVID-19 Host Genetics Initiative can be acessed at https://www.eqtlgen.org/, https://gtexportal.org/, and https://www.covid19hg.org/ , respectively. Summary-level GWAS or eQTL data and code used to produce main results have been uploaded to GitHub(https://github.com/WH57/lipid_covid19.git). All MR results and GWAS or eQTL associations of selected SNPs were provided in theSupplementary File 1 - Tables 2 to 4.
Article and author information
Author details
Funding
Fujian Province Major Science and Technology Program (2018YZ001-1)
- Liangwan Chen
The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Edward D Janus, University of Melbourne, Australia
Ethics
Human subjects: This 2-sample MR study is based on publicly available summary-level data from genome-wide association studies (GWASs) and expression quantitative trait loci (eQTLs) studies. All these studies had been approved by the relevant institutional review boards and participants had provided informed consents.
Version history
- Preprint posted: July 24, 2021 (view preprint)
- Received: September 14, 2021
- Accepted: November 22, 2021
- Accepted Manuscript published: December 6, 2021 (version 1)
- Version of Record published: December 24, 2021 (version 2)
Copyright
© 2021, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study
eLife 10:e73873.
https://doi.org/10.7554/eLife.73873
Further reading
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- Epidemiology and Global Health
Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0%-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
