To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10), hospitalization (OR = 0.61, P = 8 × 10) and susceptibility (OR = 0.78, P = 8 × 10). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case-control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41591-021-01281-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Differential Inflammatory and Immune Response to Viral Infection in the Upper-Airway and Peripheral Blood of Mild COVID-19 Cases.
J Pers Med
November 2024
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, 38029 La Laguna, Tenerife, Spain.
Background/objectives: COVID-19 is characterised by a wide variety of clinical manifestations, and clinical tests and genetic analysis might help to predict patient outcomes.
Methods: In the current study, the expression of genes related to immune response (, , , , , and ) was analysed in the upper airway and paired-blood samples from 25 subjects infected with SARS-CoV-2. Relative gene expression was determined by RT-qPCR.
OAS1 induces endothelial dysfunction and promotes monocyte adhesion through the NFκB pathway in atherosclerosis.
Arch Biochem Biophys
January 2025
The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, China; Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangzhou, Guangdong, 510120, China. Electronic address:
Cardiovascular disease is characterized by chronic inflammation and atherosclerosis (AS) is the pathological basis. Mitigating endothelial dysfunction and mononuclear cell adhesion is a crucial approach in impeding the initial advancement of AS. As an inflammation-immune regulation-related protein, 2'-5'-oligoadenylate synthetase 1 (OAS1) plays a critical role in inflammation, but its impact on endothelial dysfunction and mononuclear cell adhesion is not well understood.
View Article and Find Full Text PDFProteome modulation triggers potent antiviral response in Japanese Encephalitis Virus infected human macrophages.
Arch Microbiol
November 2024
DBT-National Institute of Animal Biotechnology, Hyderabad, India.
Article Synopsis
- Japanese encephalitis virus (JEV) is a serious mosquito-borne infection that primarily affects children, leading to severe neurological issues and high mortality rates worldwide.
- This study investigates how human macrophages respond to JEV infection by analyzing changes in protein expression over time, revealing that 443 proteins were differentially regulated, with significant upregulation of key antiviral proteins.
- The research highlights important immune pathways activated during JEV infection, especially the type I interferon signaling pathway, offering insights that could help develop strategies for better managing this public health threat.
Evidence for a sex-dependent effect modification in the association between IFN-λ DNA polymorphisms and expression of IFN-λ and interferon-stimulated genes in human PBMCs.
Cytokine
December 2024
Biotechnology Research Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani, India; Regional Centre for Biotechnology, Faridabad, India; Biotechnology Research Innovation Council-National Institute of Animal Biotechnology (BRIC-NIAB), Hyderabad, India. Electronic address:
Human interferon (IFN) lambda (IFNL, IFN-L or IFN-λ) locus has several functional genetic variants but their role in regulating in vivo gene expression, and whether they associate with antiviral states in healthy individuals, is not clear. In this study, we recruited ∼550 healthy individuals belonging to both sexes, genotyped them for several IFNL genetic variants and measured, by qPCR, the expression of IFNL2/3, IFNL4 and four IFN-stimulated genes (ISGs) (MX1, OAS1, ISG15 and RSAD2) from their peripheral blood mononuclear cells (PBMC) both before and after stimulation with a viral mimic, poly I: C. We also measured secreted levels of several cytokines including IFN-λ1 and IFN-λ3 in poly I:C stimulated PBMCs.
View Article and Find Full Text PDFPrognostic value and molecular mechanisms of OAS1 in lung adenocarcinoma.
BMC Pulm Med
September 2024
Respiratory Department, Zibo Hospital of Integrated Traditional Chinese and Western Medicine, No. 8, Jinjing Avenue, Zhangdian District, Zibo City, 255022, Shandong Province, China.
Background: The expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) in lung cancer has been validated in numerous studies. However, the prognostic value of OAS1 expression in lung adenocarcinoma (LUAD) still remains unclear. This study aimed to reveal the prognostic value and associated molecular mechanisms of OAS1 expression in LUAD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!