Genetic susceptibility to severe COVID-19
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. Clinical manifestations of the disease range from an asymptomatic condition to life-threatening events and death, with more severe courses being associated with age, male sex, and comorbidities. Besides these risk factors, intrinsic characteristics of the virus as well as genetic factors of the host are expected to account for COVID-19 clinical heterogeneity. Genetic studies have long been recognized as fundamental to identify biological mechanisms underlying congenital diseases, to pinpoint genes/proteins responsible for the susceptibility to different inherited conditions, to highlight targets of therapeutic relevance, to suggest drug repurposing, and even to clarify causal relationships that make modifiable some environmental risk factors. Though these studies usually take long time to be concluded and, above all, to translate their discoveries to patients' bedside, the scientific community moved really fast to deliver genetic signals underlying different COVID-19 phenotypes. In this Review, besides a concise description of COVID-19 symptomatology and of SARS-CoV-2 mechanism of infection, we aimed to recapitulate the current literature in terms of host genetic factors that specifically associate with an increased severity of the disease.
- Publication:
-
Infection, Genetics and Evolution
- Pub Date:
- June 2023
- DOI:
- 10.1016/j.meegid.2023.105426
- Bibcode:
- 2023InfGE.11005426C
- Keywords:
-
- SARS-CoV-2;
- COVID-19;
- Severity;
- Genetics;
- Genome-wide association study;
- Mutation;
- ACE2;
- Angiotensin I converting enzyme 2;
- CCR2;
- C-C chemokine receptor type 2;
- CCR9;
- CC motif chemokine receptor 9;
- CXCR6;
- C-X motif chemokine receptor 6;
- CI;
- Confidence interval;
- COVID-19;
- Coronavirus disease 2019;
- EMT;
- Epithelial-mesenchymal transition response;
- GHS;
- Geisinger Health System;
- GRS;
- Genetic risk score;
- GWAS;
- Genome-wide association study;
- HGI;
- Host Genetics Initiative;
- ICU;
- Intensive care unit;
- IFIH1;
- Interferon induced with helicase C domain 1;
- IFN;
- Interferon;
- IRF;
- Interferon regulatory factor;
- ISG;
- Interferon-stimulated gene;
- LD;
- Linkage disequilibrium;
- LZTFL1;
- Leucine zipper transcription factor like 1;
- NGS;
- Next-generation sequencing;
- OR;
- Odds ratio;
- PMBB;
- Penn Medicine BioBank;
- PRRs;
- Pattern recognition receptors;
- PRS;
- Polygenic risk score;
- RIG-I;
- Retinoic acid-inducible gene I;
- SARS-CoV-2;
- Severe acute respiratory syndrome coronavirus 2;
- SLC6A20;
- Sodium imino-acid transporter;
- SNP;
- single-nucleotide polymorphism;
- TLR;
- Toll-like receptor;
- TMPRSS2;
- Transmembrane protease;
- serine 2;
- TLR7;
- Sensor toll-like receptor;
- UKB;
- UK Biobank;
- WGS;
- Whole-genome sequencing;
- WHO;
- World Health Organization