Host genetic factors determining COVID-19 susceptibility and severity

EBioMedicine, Journal Year: 2021, Volume and Issue: 72, P. 103629 - 103629

Published: Oct. 1, 2021

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections range from asymptomatic severe courses of with acute respiratory distress syndrome (ARDS), multiorgan involvement and death. Risk factors for disease severity include older age, male sex, increased BMI pre-existing comorbidities. Ethnicity is also relevant susceptibility severity. Host genetic predisposition now increasingly recognized whole genome candidate gene association studies regarding have been performed. Several common rare variants in genes related inflammation or immune responses identified. We summarize research on host genetics compile associated discuss that should be investigated further understand such associations provide insights pathogenesis, risk classification, therapy response, precision medicine, drug repurposing.

Language: Английский

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Mutations in SARS-CoV-2; Consequences in structure, function, and pathogenicity of the virus

Microbial Pathogenesis, Journal Year: 2021, Volume and Issue: 154, P. 104831 - 104831

Published: March 14, 2021

Language: Английский

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Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 816 - 816

Published: March 6, 2023

The development of long-term symptoms coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela COVID-19 (PASC), can implicate persistent neurological complications in up to one third patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, peripheral neuropathy. Pathogenic mechanisms these long COVID remain largely unclear; however, several hypotheses both nervous system systemic pathogenic such SARS-CoV2 viral persistence neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, endotheliopathy. Outside the CNS, SARS-CoV-2 invade support stem cells olfactory epithelium leading alterations function. infection may induce abnormalities innate adaptive immunity including monocyte expansion, T-cell exhaustion, prolonged cytokine release, which cause neuroinflammatory responses microglia activation, white matter abnormalities, microvascular changes. Additionally, clot formation occlude capillaries endotheliopathy, due protease activity complement contribute hypoxic neuronal injury blood-brain barrier dysfunction, respectively. Current therapeutics target pathological by employing antivirals, decreasing inflammation, promoting regeneration. Thus, from laboratory evidence clinical trials literature, we sought synthesize pathophysiological pathways underlying potential therapeutics.

Language: Английский

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Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8912 - 8912

Published: Aug. 18, 2021

The year 2020 became the of outbreak coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued 2021. One unique symptoms SARS-CoV-2 disease, COVID-19, is loss chemical senses, i.e., smell taste. Smell training one methods used in facilitating recovery olfactory sense, it uses essential oils lemon, rose, clove, eucalyptus. These were not selected based on their constituents. Although scientific studies have shown that they improve recovery, there may be better combinations for recovery. Many phytochemicals bioactive properties with anti-inflammatory anti-viral effects. In this review, we describe compounds anti- inflammatory effects, list plants contain these compounds. We expand review from terpenes to less volatile flavonoids order propose combination diets can develop new taste method, as has been no so far. Finally, discuss possible use clinical settings.

Language: Английский

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ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 17, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing death of 5 million people worldwide. The genetic background represents a factor that predisposes way host responds to SARS-CoV-2 infection. In this sense, variants ACE ACE2 could explain observed interindividual variability COVID-19 outcomes. order improve understanding how are involved in severity COVID-19, we included total 481 individuals who showed clinical manifestations were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood saliva samples. insertion/deletion polymorphism evaluated high-resolution melting method; single-nucleotide (SNP) (rs4344) SNPs (rs2285666 rs2074192) genotyped using TaqMan probes. We assessed association polymorphisms with logistic regression analysis adjusted age, sex, hypertension, type diabetes, obesity. illness our study population divided as 31% mild, 26% severe, 43% critical illness; additionally, 18% died, whom 54% male. Our results codominant model contribution gene rs2285666 T/T genotype outcome [odds ratio (OR) = 1.83; 95%CI 1.01–3.29; p 0.04] require oxygen supplementation (OR 1.76; 1.01–3.04; 0.04), addition strong T allele variant develop male 1.81; 1.10–2.98; 0.02). suggest risk severe outcomes especially men, regardless obesity, diabetes.

Language: Английский

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COVID-19–associated Lung Microvascular Endotheliopathy: A “From the Bench” Perspective

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2022, Volume and Issue: 206(8), P. 961 - 972

Published: June 1, 2022

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on lung endothelium are not well defined. We hypothesized is caused by circulating host factors direct endothelial infection severe syndrome 2 (SARS-CoV-2). Objectives: aimed determine SARS-CoV-2 or sera from patients with permeability inflammatory activation microvascular cells. Methods: Human cells were treated live SARS-CoV-2; inactivated viral particles; COVID-19, without healthy volunteers. Permeability was determined measuring transendothelial resistance electrical current flow, where decreased signifies increased permeability. Inflammatory mediators quantified in culture supernatants. Endothelial biomarkers patient sera. Measurements Main Results: Viral PCR confirmed enters replicates Live SARS-CoV-2, but dead virus spike protein, induces secretion plasminogen activator inhibitor 1 vascular growth factor. There substantial variability different donors. Sera induced permeability, which correlated severity. Serum levels injury severity illness. Conclusions: infects dysregulates cell functions. Circulating also induce dysfunction. Our data point roles for both systemic acting COVID-19–associated endotheliopathy.

Language: Английский

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Causal effects of COVID‐19 on cancer risk: A Mendelian randomization study

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(4)

Published: April 1, 2023

Abstract In contemporary literature, little attention has been paid to the association between coronavirus disease‐2019 (COVID‐19) and cancer risk. We performed Mendelian randomization (MR) investigate causal associations three types of COVID‐19 exposures (critically ill COVID‐19, hospitalized respiratory syndrome 2 (SARS‐CoV‐2) infection) 33 different cancers European population. The results inverse‐variance‐weighted model indicated that genetic liabilities critically had suggestive with increased risk for HER2‐positive breast (odds ratio [OR] = 1.0924; p ‐value 0.0116), esophageal (OR 1.0004; 0.0226), colorectal 1.0010; 0.0242), stomach 1.2394; 0.0331), colon 1.0006; 0.0453). 1.1096; 0.0458), 1.0005; 0.0440) as well 1.3043; 0.0476). SARS‐CoV‐2 infection 2.8563; 0.0019) but decreasing head neck 0.9986, 0.0426). above combinations were robust through test heterogeneity pleiotropy. Together, our study effects on

Language: Английский

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Host genetic polymorphisms involved in long-term symptoms of COVID-19

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: July 27, 2023

Host genetic polymorphisms are recognized as a critical determinant of diversity in clinical symptoms Coronavirus disease 2019 (COVID-19). Accordingly, this study aimed to determine possible associations between single nucleotide (SNPs) 37 candidate variants and consequences COVID-19 - especially long-term symptoms, Long COVID. A total 260 patients, divided into mild (n = 239) severe 21) further categorized based on the presence COVID (no, n 211; yes, 49), were recruited. Genotyping selected responsible for viral entry, immune response, inflammation was performed using MassARRAY system. Out SNPs, 9 including leucine zipper transcription factor like-1 (LZTFL1) rs10490770 C allele, LZTFL1 rs11385942 dupA nicotinamide adenine dinucleotide synthetase-1 (NADSYN1) rs12785878 TT genotype, plexin A-4 (PLXNA4) rs1424597 AA rs17713054 interleukin-10 (IL10) rs1800896 TC genotype angiotensin converting enzyme-2 (ACE2) rs2285666 T plasmanylethanolamine desaturase-1 (PEDS1) rs6020298 GG G allele significantly associated with an increased risk developing COVID, whereas receptor subunit beta (IL10RB) rs8178562 reduced Kaplan-Meier curve displayed that above gene cumulative rate occurrence. Polymorphisms rs10490770, rs11385942, rs17713054, NADSYN1 rs12785878, PLXNA4 rs1424597, IL10 rs1800896, ACE2 rs2285666, PEDS1 rs6020298, IL10RB appear be factors involved development

Language: Английский

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Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies

Heliyon, Journal Year: 2024, Volume and Issue: 10(9), P. e30208 - e30208

Published: April 25, 2024

The rapid emergence of multiple strains Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has sparked profound concerns regarding the ongoing evolution virus and its potential impact on global health. Classified by World Health Organization (WHO) as variants concern (VOC), these exhibit heightened transmissibility pathogenicity, posing significant challenges to existing vaccine strategies. Despite widespread vaccination efforts, continual SARS-CoV-2 presents a formidable obstacle achieving herd immunity. Of particular is coronavirus spike (S) protein, pivotal viral surface protein crucial for host cell entry infectivity. Mutations within S have been shown enhance confer resistance antibody-mediated neutralization, undermining efficacy traditional platforms. Moreover, undergoes molecular under selective immune pressure, leading diverse with distinct mutation profiles. This review underscores urgent need vigilance adaptation in development efforts combat evolving landscape mutations ensure long-term effectiveness immunization campaigns.

Language: Английский

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Ocular neuroinflammatory response secondary to SARS-CoV-2 infection-a review

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 4, 2025

With the consistent occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, prevalence various ocular complications has increased over time. SARS-CoV-2 infection been shown to have neurotropism and therefore lead not only peripheral inflammatory responses but also neuroinflammation. Because receptor for SARS-CoV-2, angiotensin-converting enzyme (ACE2), can be found in many intraocular tissues, disease 2019 (COVID-19) may contribute persistent neuroinflammation, microcirculation dysfunction symptoms. Increased awareness neuroinflammation future research on interventional strategies are important improving long-term outcomes, reducing burden, quality life. Therefore, aim this review is focus discuss current evidence perspectives, especially possible connections between conditions potential treatment strategies.

Language: Английский

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