C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?

Hausburg, Melissa; Williams, Jason S.; Banton, Kaysie; Mains, Charles W.; Roshon, Michael; Bar‐Or, David

doi:10.1016/j.clicom.2022.05.001

Cited by 3 publications

(4 citation statements)

References 89 publications

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“…Although C1INH levels are increased in patients with COVID-19, it might be insufficient to control thromboinflammation. Reasons for this include a relative deficiency due to an uncontrolled activation of complement and coagulation cascades, together with the limitation of its regulatory activity caused by the interaction with SARS-CoV-2 proteins ( 63 , 64 ). Since complement activation is involved in virus neutralization and virolysis, impaired SERPING1 expression could contribute to virus dissemination and viremia ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis

Roy-Vallejo,

Fernández De Córdoba-Oñate,

Delgado-Wicke

et al. 2023

Front. Med.

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IntroductionSARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity.Materials and methodsRetrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed.ResultsThe mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia.ConclusionGenetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

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Section: Discussionmentioning

confidence: 99%

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis

Roy-Vallejo,

Fernández De Córdoba-Oñate,

Delgado-Wicke

et al. 2023

Front. Med.

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“…The frequency of each gene is calculated with the presence of each GO‐enriched term depicted in the cluster gram. The earlier part of this bioinformatic study found that the gene SERPING1 (C1‐INH), named 5DU3 in the protein data bank database, has susceptible effects against SARS‐CoV‐2 43,46,52 . The validation of the findings is examined by studying the potent vaccine candidates of SARS‐CoV‐2 from the SERPING1 gene.…”

Section: Discussionmentioning

confidence: 99%

“…Contemporary studies found that the C1 inhibitor plays a crucial role in inhibiting the SARS‐CoV‐2 virus. SERPING1 gene increases in novel coronavirus‐affected individuals and correlates with the disease severity 43,45,46 . The suppression of C1‐INF production is displayed by the nucleocapsid proteins of SARS‐CoV‐1 and the Middle East respiratory syndrome coronavirus (MERS‐CoV).…”

Section: Methodsmentioning

confidence: 99%

“…This experimental study identified 46 overlapping immune-related genetic markers as differentially expressed in blood, nasal, and saliva samples. 43,45,46 The suppression of C1-INF production is displayed by the nucleocapsid proteins of SARS-CoV-1 and the Middle East respiratory syndrome coronavirus (MERS-CoV). The target gene was identified with gender susceptibility of the infection and the severity levels in men.…”

Section: Protein-protein Interaction (Ppi) Network and Enrichment Ana...mentioning

confidence: 99%

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Molecular modeling of C1‐inhibitor as SARS‐CoV‐2 target identified from the immune signatures of multiple tissues: An integrated bioinformatics study

Sekaran

Varghese

Ramanathan

et al. 2022

Cell Biochemistry & Function

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The expeditious transmission of the severe acute respiratory coronavirus 2 (SARS-CoV-2), a strain of COVID-19, crumbled the global economic strength and caused a veritable collapse in health infrastructure. The molecular modeling of the novel coronavirus research sounds promising and equips more evidence about the pragmatic therapeutic options. This article proposes a machine-learning framework for identifying potential COVID-19 transcriptomic signatures. The transcriptomics data contains immune-related genes collected from multiple tissues (blood, nasal, and buccal) with accession number: GSE183071. Extensive bioinformatics work was carried out to identify the potential candidate markers, including differential expression analysis, protein interactions, gene ontology, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment studies. The overlapping investigation found SERPING1, the gene that encodes a glycosylated plasma protein C1-INH, in all three datasets. Furthermore, the immuno-informatics study was conducted on the C1-INH protein. 5DU3, the protein identifier of C1-INH, was fetched to identify the antigenicity, major histocompatibility (MHC) Class I and II binding epitopes, allergenicity, toxicity, and immunogenicity. The screening of peptides satisfying the vaccine-design criteria based on the metrics mentioned above is performed. The drug-gene interaction study reported that Rhucin is strongly associated with SERPING1. HSIC-Lasso (Hilbert-Schmidt independence criterion-least absolute shrinkage and selection operator), a model-free biomarker selection technique, was employed to identify the genes having a nonlinear relationship with the target class. The gene subset is trained with supervised machine learning models by a leave-one-out cross-validation method. Explainable artificial intelligence techniques perform the model interpretation analysis.

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Contactless edema via plasmin

Strickland,

Norris

2024

Blood

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C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?

Cited by 3 publications

References 89 publications

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis

Molecular modeling of C1‐inhibitor as SARS‐CoV‐2 target identified from the immune signatures of multiple tissues: An integrated bioinformatics study

Contactless edema via plasmin

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