Understanding COVID-19-associated coagulopathy

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(10), P. 639 - 649

Published: Aug. 5, 2022

Language: Английский

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The state of complement in COVID-19

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(2), P. 77 - 84

Published: Dec. 15, 2021

Language: Английский

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Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Jan. 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity reliability, monoclonal antibodies (mAbs) have emerged as powerful tools treat detect numerous diseases. Hence, many researchers begun urgently develop Ab-based kits for detection severe acute respiratory syndrome 2 (SARS-CoV-2) Ab drugs use COVID-19 therapeutic agents. detailed structure SARS-CoV-2 spike protein known, since this key infection, its receptor-binding domain (RBD) has become a major target development. Because RNA virus with mutation rate, especially under selective pressure aggressively deployed prophylactic vaccines neutralizing Abs, cocktails expected be important strategy effective treatment. Moreover, infection may stimulate overactive immune response, resulting in cytokine storm drives progression. Abs combat storms also been intense development treatments COVID-19. In addition drugs, are currently being utilized tests, including antigen immunoglobulin tests. Such tests crucial surveillance can used prevent spread Herein, we highlight some points regarding mAb-based pandemic.

Language: Английский

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Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection

Science Immunology, Journal Year: 2021, Volume and Issue: 6(59)

Published: May 13, 2021

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement is a broad indicator critical illness (and thus, no different COVID-19). It also unclear which pathways are contributing COVID-19, and if associated with certain features infection, such as endothelial injury hypercoagulability. To address these questions, we investigated plasma from patients COVID-19 prospectively enrolled at two tertiary care centers: Washington University School Medicine (n=134) Yale (n=49). We compared our non-COVID cohorts: (a) hospitalized influenza (n=54), (b) admitted intensive unit (ICU) acute respiratory failure requiring invasive mechanical ventilation (IMV, n=22). demonstrate that circulating markers elevated those non-COVID-19 failure. Further, results facilitate distinguishing who higher risk worse outcomes ICU admission, or IMV. Moreover, indicate enhanced alternative pathway most prevalent (i.e., angiopoietin-2) well hypercoagulability thrombomodulin von Willebrand factor). Our findings identify distinctive feature provide specific targets may utilized for prognostication, drug discovery personalized clinical trials.

Language: Английский

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Thein vitroantiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor

Emerging Microbes & Infections, Journal Year: 2021, Volume and Issue: 10(1), P. 317 - 330

Published: Jan. 1, 2021

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that lacks effective therapeutic interventions. SARS-CoV-2 infects ACE2-expressing cells and gains cell entry through either direct plasma membrane fusion or endocytosis. Recent studies have shown in addition to ACE2, heparan sulfate proteoglycans (HSPGs) also play important role attachment by serving as factor. Binding of viral spike protein HSPGs leads the enrichment local concentration for subsequent specific binding with ACE2. We therefore hypothesize blocking interactions between will lead inhibition replication. In this study, we report our findings broad-spectrum antiviral activity mechanism action lactoferrin (LF) against multiple common human coronaviruses well SARS-CoV-2. Our study has LF SARS-CoV-2, HCoV-OC43, HCoV-NL63, HCoV-229E culture, bovine (BLF) more potent than lactoferrin. Mechanistic revealed BLF binds HSPGs, thereby host cell. The can be antagonized HSPG mimetic heparin. Combination therapy experiment showed synergistic remdesivir culture. Molecular modelling suggests N-terminal positively charged region (residues 17-41) confers HSPGs. Overall, appears a promising drug candidate COVID-19 warrants further investigation.

Language: Английский

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Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

Viruses, Journal Year: 2020, Volume and Issue: 13(1), P. 29 - 29

Published: Dec. 26, 2020

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily illness, extrapulmonary manifestations COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction endothelium during may exacerbate these deleterious events inciting inflammatory microvascular thrombotic processes. controversial, there is evidence SARS-CoV-2 infect endothelial cells binding angiotensin-converting enzyme 2 (ACE2) cellular receptor using viral Spike protein. In this review, we explore current insights into relationship between infection, due ACE2 downregulation, pulmonary extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical clinical development therapeutic agents targeting SARS-CoV-2-mediated dysfunction. Finally, present replication primary human lung cardiac cells. Accordingly, striving understand parameters lead patients, it important consider how direct infection contribute process.

Language: Английский

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Complement activation and endothelial perturbation parallel COVID-19 severity and activity

Journal of Autoimmunity, Journal Year: 2020, Volume and Issue: 116, P. 102560 - 102560

Published: Oct. 30, 2020

Language: Английский

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SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 7, 2021

Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 123), non-COVID-19 ICU sepsis 25) and healthy controls 30). Severe acute respiratory syndrome 2 (SARS-CoV-2) RNA was detected plasma or serum (RNAemia) of when neutralizing antibody response low. RNAemia is associated higher 28-day mortality (hazard ratio [HR], 1.84 [95% CI, 1.22-2.77] adjusted for age sex). comparable performance to the best protein predictors. Mannose binding lectin pentraxin-3 (PTX3), two activators complement pathway innate immune system, are positively mortality. Machine learning identified 'Age, RNAemia' PTX3' as binary signatures In longitudinal comparisons, have a distinct proteomic trajectory mortality, recovery many liver-derived proteins indicating survival. Finally, system galectin-3-binding (LGALS3BP) interaction partners SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake spike-induced cell-cell fusion vitro.

Language: Английский

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Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(6), P. 381 - 396

Published: Dec. 19, 2022

Language: Английский

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Crosstalk between the renin–angiotensin, complement and kallikrein–kinin systems in inflammation

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 411 - 428

Published: Nov. 10, 2021

Language: Английский

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