Treatments for COVID-19

Annual Review of Medicine, Год журнала: 2023, Номер 75(1), С. 145 - 157

Опубликована: Сен. 19, 2023

The treatment for COVID-19 has evolved rapidly since the start of pandemic and now consists mainly antiviral immunomodulatory agents. Antivirals, such as remdesivir nirmatrelvir-ritonavir, have proved to be most useful earlier in illness (e.g., outpatient therapy) less severe disease. Immunomodulatory therapies, dexamethasone interleukin-6 or Janus kinase inhibitors, are disease critical illness. role anti-SARS-CoV-2 monoclonal antibodies diminished because emergence viral variants that not anticipated susceptible these treatments, there still is a consensus on use convalescent plasma. been associated with increased rates venous thromboembolism, but antithrombotic therapy limited. Multiple investigational agents continue studied, which will alter current paradigms new data released.

Язык: Английский

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Convalescent plasma therapy in COVID-19: Unravelling the data using the principles of antibody therapy

Expert Review of Respiratory Medicine, Год журнала: 2023, Номер 17(5), С. 381 - 395

Опубликована: Май 2, 2023

Introduction When the COVID-19 pandemic struck no specific therapies were available and many turned to convalescent plasma (CCP), a form of antibody therapy. The literature provides mixed evidence for CCP efficacy.Areas covered PubMed was searched using words individual study designs evaluated adherence three principles therapy, i.e. that 1) contain antibody; 2) have enough mediate biological effect; 3) be administered early in course disease. Using this approach, diverse seemingly contradictory collection clinical findings distilled into consistent picture whereby effective when used according above In addition, therapy immunocompromised patients is useful at any time disease.Expert opinion safe appropriately. Today, most humanity has some immunity SARS-CoV-2 from vaccines infection, which lessened need general population. However, major therapeutic challenge, with deauthorization all SARS-CoV-2-spike protein-directed monoclonal antibodies, only

Язык: Английский

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COVID-19 therapeutics

Clinical Microbiology Reviews, Год журнала: 2024, Номер 37(2)

Опубликована: Май 21, 2024

SUMMARYSince the emergence of COVID-19 in 2020, an unprecedented range therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy those often remains controversial or compromised by viral evolution. Uncertainties still persist regarding best therapies for high-risk patients, drug pipeline is suffering fatigue shortage funding. In this article, we review antiviral activity, mechanism action, pharmacokinetics, safety therapies. Additionally, summarize evidence from randomized controlled trials on various antivirals discuss unmet needs which should be addressed.

Язык: Английский

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Safety and Efficacy of Convalescent Plasma Combined with Other Pharmaceutical Agents for Treatment of COVID-19 in Hospitalized Patients: A Systematic Review and Meta-Analysis

Diseases, Год журнала: 2024, Номер 12(3), С. 41 - 41

Опубликована: Фев. 21, 2024

Plasma collected from people recovered COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight pandemic. CCP was, however, often in combination with other drugs, such as antiviral remdesivir and glucocorticoids. The possible effect of interaction has never been investigated systematically. To assess safety efficacy combined agents for treatment patients hospitalized COVID-19, a systematic literature search using appropriate Medical Subject Heading (MeSH) terms performed through PubMed, EMBASE, Cochrane central, medRxiv bioRxiv. main outcomes considered were mortality treatments versus alone. This review carried out accordance methodology including risk bias assessment grading quality evidence. Measure ratio (RR) together 95% confidence intervals (CIs). A total 11 studies (8 randomized controlled trials [RCTs] 3 observational) included review, 4 6 corticosteroids, all involving patients. One RCT reported information on both steroids use CCP. associated significantly reduced death (RR 0.74; CI 0.56–0.97; p = 0.03; moderate certainty evidence), while did not modify 0.72; 0.34–1.51; 0.38; very low evidence). Not enough data retrieved form analysis. current evidence suggests potential beneficial plus compared alone No significant clinical found between steroids.

Язык: Английский

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Subclass-switched anti-spike IgG3 oligoclonal cocktails strongly enhance Fc-mediated opsonization

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(15)

Опубликована: Апрель 3, 2023

Antibodies play a central role in the immune defense against SARS-CoV-2. Emerging evidence has shown that nonneutralizing antibodies are important for through Fc-mediated effector functions. Antibody subclass is known to affect downstream Fc function. However, whether antibody plays anti-SARS-CoV-2 immunity remains unclear. Here, we subclass-switched eight human IgG1 anti-spike monoclonal (mAbs) IgG3 by exchanging their constant domains. The mAbs exhibited altered avidities spike protein and more potent phagocytosis complement activation than counterparts. Moreover, combining into oligoclonal cocktails led enhanced Fc- receptor-mediated phagocytosis, superior even most single mAb when compared at equivalent concentrations. Finally, an vivo model, show opsonic of both subclasses can be protective SARS-CoV-2 infection, despite being nonneutralizing. Our results suggest promising idea explore therapy SARS-CoV-2, its emerging variants, potentially other viruses.

Язык: Английский

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Bioluminescence imaging reveals enhanced SARS-CoV-2 clearance in mice with combinatorial regimens

iScience, Год журнала: 2024, Номер 27(3), С. 109049 - 109049

Опубликована: Янв. 30, 2024

Язык: Английский

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The hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 27, 2024

Abstract Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, engineer IgG2-4 subclasses of Ab25. Despite having reduced binding, IgG3 version promotes stronger phagocytosis bacteria. Using atomic simulations, show that IgG3’s Fc tail has extensive movement in 3D space due to its extended hinge region, possibly facilitating interactions immune cells. We replaced four different IgG3-hinge segment subclasses, IgGh xx . Hinge-engineering does not diminish binding as but enhances function, where a 47 amino acid is comparable function. shows improved protection against S. systemic infection mouse model, suggesting promise preclinical therapeutic candidate. Importantly, enhanced function generalizable diverse strains from clinical isolates. versions anti-SARS-CoV-2 mAbs broaden biological applicability, and these also exhibit strongly compared subclass. The subclass two distant systems provides new insights into antibody

Язык: Английский

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Combined anti-S1 and anti-S2 antibodies from hybrid immunity elicit potent cross-variant ADCC against SARS-CoV-2

JCI Insight, Год журнала: 2023, Номер 8(15)

Опубликована: Июнь 20, 2023

Antibodies capable of neutralising SARS-CoV-2 are well studied, but Fc receptor-dependent antibody activities that can also significantly impact the course infection have not been studied in such depth. As most vaccines induce only anti-spike antibodies, here we investigated spike-specific antibody-dependent cellular cytotoxicity (ADCC). Vaccination produced antibodies weakly induced ADCC, however, from individuals who were infected prior to vaccination ('hybrid' immunity) elicited strong ADCC. Quantitative and qualitative aspects humoral immunity contributed this capability, with skewing IgG production towards S2, S1 hybrid evoking responses against both domains. targeting spike domains support NK cell activation, three regions reactivity outside receptor-binding domain (RBD) corresponding potent Consequently, ADCC by ancestral antigen was conserved variants containing neutralisation escape mutations RBD. Induction recognising a broad range epitopes eliciting durable may partially explain why provides superior protection disease than alone, demonstrates spike-only subunit would benefit strategies combined anti-S1 S2 responses.

Язык: Английский

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Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants

Medical Microbiology and Immunology, Год журнала: 2023, Номер 212(4), С. 291 - 305

Опубликована: Июль 21, 2023

Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge worldwide public health. The receptor-binding domain (RBD) is hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated impact of RBD including 5 variants concern (VOC) or interest-including Omicron (BA.2)-and 33 common point both on IgG recognition and ACE2-binding inhibition, as well FcγRIIa- FcγRIIIa-binding antibodies, in plasma from two-dose BNT162b2-vaccine recipients mild-COVID-19 convalescent subjects obtained first wave using custom-designed bead-based 39-plex array. IgG-recognition FcγR-binding antibodies were decreased against Beta mutation G446S, found several sub-variants compared wild type. Notably, while there was profound decrease inhibition less affected, suggesting that Fc functional antibody responses may be better retained comparison neutralization. Furthermore, measurement RBD-ACE2-binding affinity via biolayer interferometry showed all VOC RBDs have enhanced human ACE2, demonstrate polymorphisms, E35K (rs1348114695) has reduced VOCs, K26R (rs4646116) S19P (rs73635825) increased binding kinetics potentially affecting virus-host interaction and, thereby, host susceptibility. Collectively, our findings provide in-depth coverage mutations key facets host-virus interactions.

Язык: Английский

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In vivo determination of protective antibody thresholds for SARS-CoV-2 variants using mouse models

Emerging Microbes & Infections, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Neutralizing antibody titers have been shown to correlate with immune protection against COVID-19 and can be used estimate vaccine effectiveness. Numerous studies explored the relationship between neutralizing antibodies protection. However, there remains a lack of quantitative data directly assessing minimum effective protective titer in vivo. In this study, we utilized eight cohorts participants diverse backgrounds for evaluation response. To precisely assess lower threshold required SARS-CoV-2 infections, employed plasma adoptive transfer from different into mice. This study demonstrated that recipient mice correlated well those human donors, positive linear correlation was observed mouse recipients transferred titer. A pseudotyped virus greater than 7 identified as necessary reduce viral infected mice, establishing crucial baseline Furthermore, despite variability backgrounds, these cohorts' exhibited similar finding has significant implications design assessment competence.

Язык: Английский

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