Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gene, Год журнала: 2022, Номер 844, С. 146790 - 146790

Опубликована: Авг. 17, 2022

Язык: Английский

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Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Фев. 12, 2025

The emergence of the COVID-19 pandemic made it critical to understand immune and inflammatory responses SARS-CoV-2 virus. It became increasingly recognized that response was a key mediator illness severity its mechanisms needed be better understood. Early infection both tissue cells, such as macrophages, leading pyroptosis-mediated inflammasome production in an organ system for systemic oxygenation likely plays central role morbidity wrought by SARS-CoV-2. Delayed transcription Type I III interferons may lead early disinhibition viral replication. Cytokines interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor α (TNFα), some which produced through involving nuclear kappa B (NF-κB), contribute hyperinflammatory state patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) CD8+ T-cells, B-cells, can disease reflect direct cytopathic effects or end-organ sequestration. Direct activation endothelial cells mechanism systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation microthrombi development seen lungs other organs throughout body, heart, gut, brain. kidney most impacted extrapulmonary owing high concentration ACE2 exposure kidney, acute tubular injury, myofibroblast activation, collapsing glomerulopathy select populations account COVID-19-related AKI CKD development. COVID-19-associated nephropathy (COVAN), particular, mediated IL-6 signal transducer activator 3 (STAT3) signaling, suggesting connection between chronic disease. Chronic manifestations also include conditions like Multisystem Inflammatory Syndrome Children (MIS-C) Adults (MIS-A) post-acute sequelae (PASC), spectrum clinical presentations persistent dysregulation. lessons learned those undergoing continued study have broad implications understanding infections’ immunologic consequences beyond coronaviruses.

Язык: Английский

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Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 27, 2023

Introduction While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), protein shown interact with SARS-CoV-2 proteins. However, exact role of and its key molecule MBL COVID-19 still not fully understood. Methods We therefore investigated two independent cohorts infected patients, while also analysing levels potential effects six major single nucleotide polymorphisms (SNPs) found MBL2 gene on outcome. Results show that COVID-19, indicated correlation between product MASP-1/C1-INH complex (p=0.0011) C4d (p<0.0001) severity. Despite this, genetic variations are associated susceptibility infection or outcomes such as mortality development Long COVID. Conclusion In conclusion, MBL-LP only plays minor pathogenesis, since no clinically meaningful, consistent associations were noted.

Язык: Английский

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Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review

World Journal of Experimental Medicine, Год журнала: 2022, Номер 12(4), С. 53 - 67

Опубликована: Июль 14, 2022

Coronavirus disease 2019 (COVID-19) causes acute microvascular thrombosis in both venous and arterial structures which is highly associated with increased mortality. The mechanisms leading to thromboembolism are still under investigation. Current evidence suggests that excessive complement activation severe amplification of the inflammatory response (cytokine storm) hastens progression initiates complement-dependent cytotoxic tissue damage resultant prothrombotic complications. concept thromboinflammation, involving overt inflammation coagulation cascade causing thrombotic microangiopathy end-organ damage, has emerged as one core components COVID-19 pathogenesis. system a major mediator innate immune thus an appealing treatment target. In this review, we discuss role development summarize current data on inhibitors therapeutics.

Язык: Английский

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Polymorphisms in the MBL2 gene are associated with the plasma levels of MBL and the cytokines IL-6 and TNF-α in severe COVID-19

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Апрель 17, 2023

Introduction Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, may influence synthesis inflammatory cytokines. This study investigated association MBL2 gene polymorphisms with plasma levels MBL cytokines COVID-19. Methods Blood samples from 385 individuals (208 acute COVID-19 117 post-COVID-19) were subjected real-time PCR genotyping. Plasma measurements performed by enzyme-linked immunosorbent assay flow cytometry, respectively. Results The frequencies polymorphic genotype (OO) allele (O) higher patients severe (p< 0.05). genotypes (AO OO) associated lower IL-6 TNF-α low No polymorphisms, levels, or cytokine long COVID was observed. Discussion results suggest that, besides promoting a reduction therefore its function, they also contribute development more intense process responsible for severity

Язык: Английский

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A possible association between low MBL/lectin pathway functionality and microbiota dysbiosis in endometriosis patients

Life Sciences, Год журнала: 2025, Номер unknown, С. 123427 - 123427

Опубликована: Янв. 1, 2025

Endometriosis (EM) is a chronic inflammatory disorder with multifactorial etiologies (i.e., genetics and environmental factors, hormonal immunological changes, microbiome alterations). The complement system one of the most frequently dysregulated pathways in EM. Mannose-binding lectin (MBL), carbohydrate pattern recognition molecule, first described subcomponent pathway (LP). Here, we unveiled interplay among MBL polymorphisms, plasma levels, LP functionality, microbiota as potential contributors to EM pathogenesis. A cohort 38 patients 20 healthy controls was enrolled levels functionality were assessed via ELISA assays. genetic variants endometrial vaginal investigated correlated. High related disease severity, although not accountable MBL2 genotype. MASP-2 present uterine mucosa but appeared have no function at endometriotic lesion. functional deficit displayed pathogenic bacterial species more microbiome. Moreover, women affected by showed higher frequency rare gene estrogen genes, potentially affecting levels. lower may contribute an unbalanced environment that could activate cells. Not only genotype condition, also can cause altered thus contributing changes functionality.

Язык: Английский

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Classification of C‐Type Lectins and Recognition of Pathogens

Microbiology and Immunology, Год журнала: 2025, Номер unknown

Опубликована: Март 12, 2025

ABSTRACT C‐type lectins are calcium‐dependent glycan‐binding proteins that play key roles in the innate immune response by recognizing pathogens. Soluble agglutinate and neutralize pathogens, activate complement system, promote pathogen clearance via opsonization. Membrane‐bound lectins, also known as lectin receptors (CLRs), internalize pathogens induce their degradation lysosomes, presenting pathogen‐derived antigens to MHC‐II molecules adaptive immunity. CLRs have signaling capabilities. Some contain immunoreceptor tyrosine‐based activation motif (ITAM), which induces inflammatory responses activating transcription factors, such NF‐κB NFAT. Others inhibitory (ITIM), suppresses signals phosphatases, SHP‐1. This creates a balance between inhibition. classified into 17 groups based on structural domains, with Groups II V members being particularly important for recognition. In this review, we present accumulated recent information recognition along classification basic functions.

Язык: Английский

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Elevated Levels of Mannose-Binding Lectin (MBL) in patients with Type 2 Diabetes and its Potential Association with Nephropathy and Retinopathy

Research Journal of Pharmacy and Technology, Год журнала: 2025, Номер unknown, С. 1579 - 1586

Опубликована: Апрель 12, 2025

The hepatic protein Mannose-binding lectin (MBL) serves a pivotal role in the acute-phase immune response, potentially influencing pathogenesis of type 2 diabetes (T2DM) and its associated complications, such as nephropathy retinopathy. Recent evidence suggests that elevated plasma MBL levels may serve predictive marker for albuminuria T2DM patients. Moreover, it is postulated ligands are present within kidneys diabetic individuals, thereby facilitating deposition renal parenchyma or other target organs, exacerbating pathological processes. This study aimed to assess serum patients explore potential associations between onset complications. A cross-sectional investigation was conducted, encompassing 92 participants, comprising 71 individuals diagnosed with 21 age- sex-matched healthy counterparts. Among cohort, were stratified into nephropathic non-nephropathic subgroups based on presence nephropathy, well without retinopathy status. Serum quantified utilizing Enzyme-Linked Immunosorbent Assay (ELISA). mean found be significantly compared controls (1736 vs. 730.99 ng/mL, p-value = 0.011). Furthermore, exhibited statistically significant increase microalbuminuria normoalbuminuric (p-value 0.019). Notably, association observed heightened occurrence findings this support hypothesis implicating initiation progression including Nevertheless, further warranted delineate precise underlying mechanisms governing relationship pathophysiology.

Язык: Английский

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Soluble IL-2R Levels at Baseline Predict the Development of Severe Respiratory Failure and Mortality in COVID-19 Patients

Viruses, Год журнала: 2022, Номер 14(4), С. 787 - 787

Опубликована: Апрель 10, 2022

Risk stratification of coronavirus disease-19 (COVID-19) patients by simple markers is critical to guide treatment. We studied the predictive value soluble interleukin-2 receptor (sIL-2R) for early identification at risk developing severe clinical outcomes. sIL-2R levels were measured in 197 (60.9% males; median age 61 years; moderate disease, n = 65; severe, 132, intubated and/or died, 42). All received combined immunotherapies (anakinra ± corticosteroids intravenous immunoglobulin tocilizumab) according our local treatment algorithm. The endpoint was composite event intubation due respiratory failure (SRF) or mortality. Median (interquartile range) significantly higher with compared those disease (6 (6.2) vs. 5.2 (3.4) ng/mL, p 0.017). strongest laboratory factor intubation/death (hazard ratio 1.749, 95%CI 1.041-2.939, 0.035) after adjustment other known factors. Youden's index revealed optimal cut-off predicting 9 ng/mL (sensitivity: 67%; specificity: 86%; positive and negative value: 57% 91%, respectively). Delta between day discharge minus admission date that intubated/died than who did not experience an (2.91 (10.42) 0.44 (2.88) ng/mL; 0.08)). on its dynamic changes during follow-up may reflect severity predict development SRF

Язык: Английский

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Association between mannose binding lectin gene polymorphisms and clinical severity of COVID-19 in children

Molecular Biology Reports, Год журнала: 2023, Номер 50(7), С. 5871 - 5877

Опубликована: Май 25, 2023

Язык: Английский

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