Genetics Insight for COVID-19 Susceptibility and Severity: A Review

Fricke-Galindo, Ingrid; Falfán-Valencia, Ramcés

doi:10.3389/fimmu.2021.622176

Cited by 162 publications

(127 citation statements)

References 108 publications

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“…[ 66 ] rs13050728—intronic variant of IFNAR2 0.9 0.69 COVID-19 H.G.I. [ 66 ] rs2236757—intronic variant of IFNAR2 1.3 0.71 Pairo-Castineira et al [ 11 ] rs3131294—intronic variant of NOTCH4 1.5 0.90 Pairo-Castineira et al [ 11 ] HLA-A*11 N.A N.A Fricke-Galindo et al [ 54 ] HLA-A*11:01:01:01 2.3 N.A Khor et al [ 56 ] HLA-A*25:01 N.A N.A Fricke-Galindo et al [ 54 ] HLA-B*46:01 2.1 N.A Lin et al [ 53 ], Fricke-Galindo et al [ 54 ] HLA-B*51:01 N.A N.A Fricke-Galindo et al [ 54 ] HLA B*54:01 5.4 N.A Lin et al [ 55 ] HLA-C*01 N.A N.A Fricke-Galindo et al [ 54 ] HLA-C*01:02 N.A N.A Fricke-Galindo et al [ 54 ] HLA-C*05 N.A N.A...…”

Section: Discussionmentioning

confidence: 99%

Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

et al. 2021

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“…XCR1 is a cytokine signaling receptor and ACE2’s 2 nd highest ranked ERC, with a highly significant evolutionary rate correlation suggestive of a protein-protein interaction. XCR1 is in a small genomic region that is implicated in severe COVID-19 by additional genome-wide association studies (Severe Covid-19 GWAS Group, 2020; Fricke-Galindo & Falfán-Valencia, 2021). Another example is Interferon alpha/beta receptor 2 (IFNAR2) which, in a genome-wide association study (GWAS) and multi-omic analysis by Pairo-Castineira et al (2021), was implicated in severe COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Evolutionary Inference Predicts Novel ACE2 Protein Interactions Relevant to COVID-19 Pathologies

Cheng

Werren

2021

Preprint

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Angiotensin-converting enzyme 2 (ACE2) is the human cell receptor that the coronavirus SARS-CoV-2 binds to and uses to enter and infect human cells. COVID-19, the pandemic disease caused by the coronavirus, involves diverse pathologies beyond those of a respiratory disease, including micro-thrombosis (micro-clotting), cytokine storms, and inflammatory responses affecting many organ systems. Longer-term chronic illness can persist for many months, often well after the pathogen is no longer detected. A better understanding of the proteins that ACE2 interacts with can reveal information relevant to these disease manifestations and possible avenues for treatment. We have undertaken a different approach to predict candidate ACE2 interacting proteins which uses evolutionary inference to identify a set of mammalian proteins that "coevolve" with ACE2. The approach, called evolutionary rate correlation (ERC), detects proteins that show highly correlated evolutionary rates during mammalian evolution. Such proteins are candidates for biological interactions with the ACE2 receptor. The approach has uncovered a number of key ACE2 protein interactions of potential relevance to COVID-19 pathologies. Some proteins have previously been reported to be associated with severe COVID-19, but are not currently known to interact directly with ACE2, while additional predicted novel interactors with ACE2 are of potential relevance to the disease. Using reciprocal rankings of protein ERCs, we have identified strongly interconnected ACE2 associated protein networks relevant to COVID-19 pathologies. ACE2 has clear connections to coagulation pathway proteins, such as coagulation factor V and fibrinogen components FGG, FGB, and FGA, the latter possibly mediated through ACE2 connections to Clusterin (which clears misfolded extracellular proteins) and GPR141 (whose functions are relatively unknown). Additionally, ACE2 has connections to proteins involved in cytokine signaling and immune response (e.g. IFNAR2, XCR1, and TLR8), and to Androgen Receptor (AR). The ERC prescreening approach has also elucidated possible functions for previously uncharacterized proteins and possible additional functions for well-characterized ones. Suggested validation approaches for ERC predicted ACE2 interacting proteins are discussed. We propose that ACE2 has novel protein interactions that are disrupted during SARS-CoV-2 infection, contributing to the spectrum of COVID-19 pathologies.

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“…The significance of deletions in immune evasion on the evolutionary trajectory of SARS-CoV-2 to an endemic virus was studied [70]. Deletions in ORF7, ORF8, and ORF10 regions found in Bangladesh and deletions in or near the furin polybasic site of the spike protein have been associated with reduced virulence [71]. The three HLA alleles (HLA-A*11, -C*01, and -DQB1*04) among Spaniards and the HLA-DRB1*08 in the Italian population correlated with mortality of COVID-19 [72].…”

Section: Impact On Clinical Manifestationsmentioning

confidence: 99%

“…Germline variants in UNC13D and AP3B1 (two typical hemophagocyticlymphohistiocytosis related genes) were found to be associated with the development of severe cytokine storm and fatal outcomes in COVID-19 [73]. Deaths during the first phase of the epidemic was found to be associated with L84S mutation (ORF8 protein involved in immune system evasion) and 2 other helicase mutations (NSP13, P504L, and Y541C) [71]. The 3p21.31 chromosome region (LZTFL1, SLC6A20, CCR9, FYCO1, CXCR6, and XCR1) and 9q34.2 (ABO) were found to have association with COVID-19 severity in genome-wide association studies [74].…”

Section: Impact On Clinical Manifestationsmentioning

confidence: 99%

Genetic and Epigenetic Variations of SARS-Cov-2 and Host Genes and Their Impact in Covid-19 Pandemic

Meethal¹,

Naseef²,

Kuruniyan³

et al. 2021

Preprint

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The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.

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Genetics Insight for COVID-19 Susceptibility and Severity: A Review

Cited by 162 publications

References 108 publications

Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

Update on human genetic susceptibility to COVID-19: susceptibility to virus and response

Evolutionary Inference Predicts Novel ACE2 Protein Interactions Relevant to COVID-19 Pathologies

Genetic and Epigenetic Variations of SARS-Cov-2 and Host Genes and Their Impact in Covid-19 Pandemic

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