Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: April 5, 2023

Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent interferon (IFN) immunity or autoantibodies against IFN, account for 15–20% cases life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants remain be identified ~ 80% cases. Methods report here a genome-wide rare variant burden association analysis 3269 patients with COVID-19, 1373 SARS-CoV-2-infected individuals without pneumonia. Among 928 tested quarter (234) were positive excluded. Results No gene reached significance. Under recessive model, most significant at-risk variants was TLR7 , an OR 27.68 (95%CI 1.5–528.7, P = 1.1 × 10 −4 ) biochemically loss-of-function (bLOF) variants. replicated enrichment predicted LOF (pLOF) at 13 influenza susceptibility loci involved TLR3-dependent (OR 3.70[95%CI 1.3–8.2], 2.1 ). This further strengthened by (1) adding recently TYK2 loci, particularly under model 19.65[95%CI 2.1–2635.4], 3.4 −3 ), (2) considering as pLOF branchpoint potentially strong impacts on splicing among 15 4.40[9%CI 2.3–8.4], 7.7 −8 Finally, pLOF/bLOF these significantly younger (mean age [SD] 43.3 [20.3] years) than other (56.0 [17.3] years; 1.68 −5 Conclusions Rare genes can underlie inheritance, 60 years old.

Language: Английский

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mRNA vaccine boosters and impaired immune system response in immune compromised individuals: a narrative review

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: Jan. 27, 2024

Abstract Over the last 24 months, there has been growing evidence of a correlation between mRNA COVID-19 vaccine boosters and increased prevalence infection other pathologies. Recent works have added possible causation to correlation. may impair immune system response in compromised individuals. Multiple doses vaccines result much higher levels IgG 4 antibodies, or also impaired activation CD4 + CD8 T cells. The opportunity for needs careful consideration, as this impacts cost-to-benefit ratio boosters’ practice.

Language: Английский

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SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114076 - 114076

Published: April 1, 2024

The severe acute respiratory syndrome coronavirus 2 pandemic is characterized by the emergence of novel variants concern (VOCs) that replace ancestral strains. Here, we dissect complex selective pressures evaluating variant fitness and adaptation in human tissues. We evaluate viral properties host responses to reconstruct forces behind D614G through Omicron (BA.1) emergence. observe differential replication airway epithelia, differences cellular tropism, virus-induced cytotoxicity. accumulates most mutations after infection, supporting zoonosis airway. perform head-to-head competitions highest for Gamma Delta. Under these conditions, RNA recombination favors encoding B.1.617.1 lineage 3' end. Based on growth kinetics, Alpha, Gamma, Delta exhibit increased compared D614G. In contrast, global success likely derives from transmission antigenic variation. Our data provide molecular evidence support epidemiological observations VOC

Language: Английский

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Glucocorticoids and COVID-19

Pharmacological Research, Journal Year: 2022, Volume and Issue: 185, P. 106511 - 106511

Published: Oct. 13, 2022

Language: Английский

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Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19

Current Issues in Molecular Biology, Journal Year: 2022, Volume and Issue: 45(1), P. 33 - 50

Published: Dec. 21, 2022

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects respiratory system but can quickly become systemic, harming multiple organs leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, immune cells efficiently eliminate virus. However, 20% of develop severe organ failure. Virus replication has been described several patients who died from COVID-19, suggesting a compromised response. Immunodeficiency autoimmunity responsible for this impairment facilitate viral escape. Mutations IFN signal transduction T cell activation inadequate response young individuals. Autoantibodies accountable secondary immunodeficiency with infection prolonged Antibodies against cytokines (interferons α, γ ω, IL1β, IL6, IL10, IL-17, IL21), chemokines, nuclear proteins DNA, anticardiolipin, extracellular have reported. type titer autoantibodies depend on age gender. Organ-specific Their role is under study. Autoimmunity should be screened risk factors

Language: Английский

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The humoral and cellular response to mRNA SARS‐CoV ‐2 vaccine is influenced by HLA polymorphisms

HLA, Journal Year: 2023, Volume and Issue: 102(3), P. 301 - 315

Published: April 3, 2023

Host genetic variability contributes to susceptibility SARS-CoV-2 infection and COVID-19 evolution the role of HLA system has not clearly emerged, suggesting involvement other factors. Studying response vaccination with Spyke protein mRNA represents an ideal model highlight whether humoral or cellular responses are influenced by HLA. Four hundred sixteen workers, vaccinated Comirnaty beginning 2021, were selected within Azienda Ospedaliera Universitaria "Città della Salute e Scienza di Torino." The was determined LIAISON® kit, while analysis performed Quantiferon assay, for S1 (receptor-binding domain; Ag1) S2 (Ag2) subunits protein. Six loci typed next-generation sequencing. Associations between vaccine univariate multivariate analyses. An association found A*03:01, B*40:02 DPB1*06:01 high antibody concentration A*24:02, B*08:01 C*07:01 low responses. haplotype HLA-A*01:01 ~ B1*08:01 DRB1*03:01 DQB1*02:01 conferred increased risk response. Considering responses, 50% subjects responded against Ag1 59% Ag2. Carriers DRB1*15:01 displayed a higher both Ag2 compared rest cohort. Similarly, DRB1*13:02 predisposed robust Ag2, DRB1*11:04 showed opposite trend. Cellular Humoral is mainly associated class I alleles, previously protection severe COVID-19, vaccination, standing out. predominantly involves II DPB1*13:01 prevailing. Affinity peptides generally in line results.

Language: Английский

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miRNAs as a Potential Biomarker in the COVID-19 Infection and Complications Course, Severity, and Outcome

Diagnostics, Journal Year: 2023, Volume and Issue: 13(6), P. 1091 - 1091

Published: March 14, 2023

During the last three years, since emergence of COVID-19 pandemic, a significant number scientific publications have focused on resolving susceptibility to infection, as well course disease and potential long-term complications. is widely considered multisystem variety socioeconomic, medical, genetic/epigenetic factors may contribute severity outcome. Furthermore, SARS-COV-2 infection trigger pathological processes accelerate underlying conditions clinical entities. The development specific sensitive biomarkers that are easy obtain will allow for patient stratification, prevention, prognosis, more individualized treatments COVID-19. miRNAs proposed promising different aspects (susceptibility, severity, complication course, outcome, therapeutic possibilities). This review summarizes most relevant findings concerning miRNA involvement in pathology. Additionally, role wide range complications due accompanied and/or health discussed. importance understanding functional relationships between conditions, such pregnancy, obesity, or neurological diseases, with also highlighted.

Language: Английский

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COVID-19: A Comprehensive Review on Cardiovascular Alterations, Immunity, and Therapeutics in Older Adults

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(2), P. 488 - 488

Published: Jan. 6, 2023

Here, we present a review focusing on three relevant issues related to COVID-19 and its impact in older adults (60 years older). SARS-CoV-2 infection starts the respiratory system, but development of systemic diseases accompanied by severe clinical manifestations has also been reported, with cardiovascular immune system dysfunction being major ones. Additionally, presence comorbidities aging represent risk factors for severity poor prognosis disease. Since aging-associated decline largely alterations, sought investigate consequences underlying mechanisms these pathologies understand illness this population. Understanding effects both systems should translate into comprehensive improved medical care elderly patients, preventing as well immunological alterations Approved therapies that contribute improvement symptoms reduction mortality, new development, constitute an approach managing disorders. Among them, describe antivirals, cytokine antagonists, signaling pathway inhibitors, vaccines.

Language: Английский

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Letter to the editor: Viral load decline time offers theoretical insight rather than practical value

Eurosurveillance, Journal Year: 2025, Volume and Issue: 30(9)

Published: March 6, 2025

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Language: Английский

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Association of VDR and TMPRSS2 gene polymorphisms with COVID-19 severity: a computational and clinical study

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: March 19, 2025

Language: Английский

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