Clinical implications of host genetic variation and susceptibility to severe or critical COVID-19
Publication year
2022Source
Genome Medicine, 14, 1, (2022), article 96ISSN
Publication type
Article / Letter to editor
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Organization
Internal Medicine
Human Genetics
Journal title
Genome Medicine
Volume
vol. 14
Issue
iss. 1
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Human Genetics - Radboud University Medical Center; Internal Medicine - Radboud University Medical CenterAbstract
Since the start of the coronavirus disease 2019 (COVID-19) pandemic, important insights have been gained into virus biology and the host factors that modulate the human immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 displays a highly variable clinical picture that ranges from asymptomatic disease to lethal pneumonia. Apart from well-established general risk factors such as advanced age, male sex and chronic comorbidities, differences in host genetics have been shown to influence the individual predisposition to develop severe manifestations of COVID-19. These differences range from common susceptibility loci to rare genetic variants with strongly predisposing effects, or proven pathogenic variants that lead to known or novel inborn errors of immunity (IEI), which constitute a growing group of heterogeneous Mendelian disorders with increased susceptibility to infectious disease, auto-inflammation, auto-immunity, allergy or malignancies. The current genetic findings point towards a convergence of common and rare genetic variants that impact the interferon signalling pathways in patients with severe or critical COVID-19. Monogenic risk factors that impact IFN-I signalling have an expected prevalence between 1 and 5% in young, previously healthy individuals (<60 years of age) with critical COVID-19. The identification of these IEI such as X-linked TLR7 deficiency indicates a possibility for targeted genetic screening and personalized clinical management. This review aims to provide an overview of our current understanding of the host genetic factors that predispose to severe manifestations of COVID-19 and focuses on rare variants in IFN-I signalling genes and their potential clinical implications.
This item appears in the following Collection(s)
- Academic publications [245050]
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- Faculty of Medical Sciences [93209]
- Open Access publications [105922]
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