CCR5Δ32 Deletion as a Protective Factor in Czech First-Wave COVID-19 Subjects

Hubacek, Jaroslav A.; Dušek, Ladislav; Májek, Ondřej; Adámek, Václav; Červinková, Tereza; Dlouhá, Dana; Pavel, Jozef; Adámková, Věra

doi:10.33549/physiolres.934647

Cited by 38 publications

(27 citation statements)

References 25 publications

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“…Thus, countries with higher deletion frequency could show the highest infection and COVID-19 mortality rates [20] , [21] . Our work and others did not support this conclusion [19] . Moreover, Spain has one of the lowest CCR5- Δ32 frequencies while having one of the highest worldwide infection and mortality rates ( https://www.worldometers.info/coronavirus ) (suppl.…”

Section: Resultscontrasting

confidence: 74%

“…Another study genotyped416 Czech first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) and compared them with a population cohort (n=2,404). The authors found a significantly higher CCR5 Δ32 frequency in asymptomatic SARS-CoV-2-positive compared to COVID-19-symptomatic patients, and concluded the CCR5 deletion might predict the severity of SARS-CoV-2 infection [19] .…”

Section: Resultsmentioning

confidence: 95%

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Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity

Cuesta‐Llavona

Gómez

Albaiceta

et al. 2021

International Immunopharmacology

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The chemokine receptor CCR5 has been implicated in COVID-19. CCR5 and its ligands are overexpressed in patients. The pharmacological targeting of CCR5 would improve the COVID-19 severity. We sought to investigate the role of the CCR5-Δ32 variant (rs333) in COVID-19. The CCR5 -Δ32 was genotyped in 801 patients (353 in the intensive care unit, ICU) and 660 healthy controls, and the deletion was significantly less frequent in hospitalysed COVID-19 than in healthy controls (p=0.01, OR=0.66 , 95%CI=0.49-0.88). Of note, we did not find homozygotes among the patients, compared to 1% of the controls. The CCR5 transcript was measured in leukocytes from 85 patients and 40 controls. We found a significantly higher expression of the CCR5 transcript among the patients, with significant difference when comparing the non-deletion carriers (controls=35; patients=n=81; p=0.01). ICU-patients showed non-significantly higher expression than no-ICU cases. Our study points to CCR5 as a genetic marker for COVID-19. The pharmacological targeting of CCR5 should be a promising treatment for COVID-19.

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Section: Resultscontrasting

confidence: 74%

Section: Resultsmentioning

confidence: 95%

Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity

Cuesta‐Llavona

Gómez

Albaiceta

et al. 2021

International Immunopharmacology

View full text Add to dashboard Cite

show abstract

“…Using RT-PCR and the TaqMan assay (ID − C_3084793_20), we analysed the APOE4 polymorphism (rs429358) in a group of 408 Czech first-wave (approximately March 2020–June 2020) SARS-CoV-2 PCR-positive (PCR test) subjects (54.7% females, mean age 44 ± 15 years, diabetes prevalence 7.8%, hypertension prevalence 13.3%). Of this total number, 164 were asymptomatic and 244 symptomatic [ 4 ]. All patients were confirmed SARS-CoV-2-negative by the time of sample collection in July 2020.…”

mentioning

confidence: 99%

Apolipoprotein E4 Allele in Subjects with COVID-19

et al. 2021

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“…C-C Motif Chemokine Receptor 5 (CCR5) forms a significant RR ERC with XCR1 as well. Several studies have implicated CCR5 variation and expression to be associated with COVID-19 severity (Gómez et al, 2020; Hubacek et al, 2021; Kasela et al, 2021), while others have not (Bernas et al, 2021). TNFSF15 is a third immune response protein in the XCR1 RR subnetwork that shows elevated expression in patients with severe COVID-19 (Jain et al, 2021).…”

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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CCR5Δ32 Deletion as a Protective Factor in Czech First-Wave COVID-19 Subjects

Cited by 38 publications

References 25 publications

Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity

Variant-genetic and transcript-expression analysis showed a role for the chemokine-receptor CCR5 in COVID-19 severity

Apolipoprotein E4 Allele in Subjects with COVID-19

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

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