SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

Nature Reviews Microbiology, Journal Year: 2022, Volume and Issue: 21(2), P. 112 - 124

Published: Oct. 28, 2022

Language: Английский

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Origin, virological features, immune evasion and intervention of SARS-CoV-2 Omicron sublineages

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 19, 2022

Recently, a large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continuously emerged and posed major threat to global public health. Among them, particularly, Omicron variant (B.1.1.529), first identified in November 2021, carried numerous mutations its spike protein (S), then quickly spread around the world. Currently, has expanded into more than one hundred sublineages, such as BA.1, BA.2, BA.2.12.1, BA.4 BA.5, which have already become globally dominant variants. Different from other concern (VOCs) SARS-CoV-2, sublineages exhibit increased transmissibility immune escape neutralizing antibodies generated through previous infection or vaccination, caused re-infections breakthrough infections. In this prospective, we focused on origin, virological features, evasion intervention will benefit development next-generation vaccines therapeutics, including pan-sarbecovirus universal anti-CoV combat currently circulating future emerging well SARS-CoV-2

Language: Английский

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Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients With COVID-19 (September 2022)

Clinical Infectious Diseases, Journal Year: 2022, Volume and Issue: 78(7), P. e250 - e349

Published: Sept. 5, 2022

Abstract There are many pharmacologic therapies that being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended support patients, clinicians, other healthcare professionals in their decisions about management patients COVID-19. In March 2020, the Infectious Diseases Society America (IDSA) formed a multidisciplinary guideline panel infectious pharmacists, methodologists varied areas expertise regularly review make recommendations persons process approach followed rapid recommendation development checklist. prioritized questions outcomes. A systematic peer-reviewed grey literature conducted at regular intervals. Grading Recommendations Assessment, Development, Evaluation (GRADE) assess certainty recommendations. Based on most recent search 31 May 2022, IDSA has made 32 following groups/populations: pre- postexposure prophylaxis, ambulatory mild-to-moderate disease, hospitalized mild-to-moderate, severe but not critical, critical disease. As these guidelines, can be found online at: https://idsociety.org/COVID19guidelines. At inception its work, expressed overarching goal recruited into ongoing Since then, trials were provided much-needed COVID-19 therapies. still remain unanswered as pandemic evolved, which we hope future answer.

Language: Английский

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Pathophysiological mechanisms of thrombosis in acute and long COVID-19

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 16, 2022

COVID-19 patients have a high incidence of thrombosis, and thromboembolic complications are associated with severe mortality. disease is hyper-inflammatory response (cytokine storm) mediated by the immune system. However, role inflammatory in thrombosis remains incompletely understood. In this review, we investigate crosstalk between inflammation context COVID-19, focusing on contributions to pathogenesis propose combined use anti-inflammatory anticoagulant therapeutics. Under conditions, interactions neutrophils platelets, platelet activation, monocyte tissue factor expression, microparticle release, phosphatidylserine (PS) externalization as well complement activation collectively involved immune-thrombosis. Inflammation results apoptosis blood cells, leading release PS cells microparticles, which significantly enhances catalytic efficiency tenase prothrombinase complexes, promotes thrombin-mediated fibrin generation local clot formation. Given risk importance antithrombotic therapies has been generally recognized, but certain deficiencies treatment gaps remain. Antiplatelet drugs not combination treatments, thus fail dampen procoagulant activity. Current treatments also do an optimal time for anticoagulation. The efficacy depends therapy initiation. best early possible after diagnosis, ideally stage disease. We elaborate mechanisms long COVID complications, including persistent inflammation, endothelial injury dysfunction, coagulation abnormalities. above-mentioned contents provide therapeutic strategies further improve patient outcomes.

Language: Английский

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Evolution of the SARS-CoV-2 Omicron spike

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113444 - 113444

Published: Nov. 18, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern, first identified in November 2021, rapidly spread worldwide and diversified into several subvariants. spike (S) protein accumulated an unprecedented number sequence changes relative to previous variants. In this review, we discuss how S structural features modulate host cell receptor binding, virus entry, immune evasion highlight these differentiate from We also examine key properties track across the still-evolving subvariants importance continuing surveillance evolution over time.

Language: Английский

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Efficacy and safety of tixagevimab‐cilgavimab as pre‐exposure prophylaxis for COVID‐19: A systematic review and meta‐analysis

Reviews in Medical Virology, Journal Year: 2023, Volume and Issue: 33(2)

Published: Jan. 8, 2023

Abstract Some proportions of populations, such as immunocompromised patients and organ transplant recipients might have inadequate immune responses to the vaccine for coronavirus disease 2019 (COVID‐19). For these groups administering monoclonal antibodies offer some additional protection. This review sought analyze effectiveness safety tixagevimab‐cilgavimab (Evusheld) pre‐exposure prophylaxis against COVID‐19. We used specific keywords comprehensively search potential studies on PubMed, Scopus, Europe PMC, ClinicalTrials.gov sources until 3 September 2022. collected all published articles that analyzed course Review Manager 5.4 was utilized statistical analysis. Six were included. Our pooled analysis revealed may decrease rate SARS‐CoV‐2 infection (OR: 0.24; 95% CI: 0.15–0.40, p < 0.00001, I 2 = 75%), lower COVID‐19 hospitalization 0.13; 0.07–0.24, 0%), severity risk deaths 0.17; 0.03–0.99, 0.05, 72%). In included studies, no major adverse events reported. study proposes effective safe preventing Tixagevimab‐cilgavimab be offered those who cannot vaccinated or response from give

Language: Английский

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Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19

Annals of Internal Medicine, Journal Year: 2023, Volume and Issue: 176(4), P. 496 - 504

Published: April 1, 2023

Background: Treatment guidelines and U.S. Food Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. Objective: To evaluate whether early outpatient mAbs, overall by mAb product, presumed variant, immunocompromised status, is associated reduced risk hospitalization or death at 28 days. Design: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients a propensity score–matched, nontreated control group. Setting: Large health care system. Participants: High-risk eligible under any EUA positive test result 8 December 2020 31 August 2022. Intervention: Single-dose intravenous bamlanivimab, bamlanivimab–etesevimab, sotrovimab, bebtelovimab, subcutaneous casirivimab–imdevimab administered within 2 days result. Measurements: The primary outcome was among treated versus group (no ≥3 after date). Results: 4.6% in 2571 7.6% 5135 (risk ratio [RR], 0.61 [95% CI, 0.50 0.74]). In sensitivity analyses, the corresponding RRs 1- 3-day grace periods were 0.59 0.49, respectively. subgroup those receiving mAbs when Alpha Delta be predominant had estimated 0.55 0.53, respectively, compared 0.71 Omicron variant period. Relative estimates individual products all suggested lower death. Among patients, RR 0.45 (CI, 0.28 0.71). Limitations: Observational study design, date rather than genotyping, no on symptom severity, partial vaccination status. Conclusion: Early various variants. Primary Funding Source: None.

Language: Английский

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SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(4), P. 632 - 657

Published: April 1, 2024

Over four years have passed since the beginning of COVID-19 pandemic. The scientific response has been rapid and effective, with many therapeutic monoclonal antibodies small molecules developed for clinical use. However, given ability viruses to become resistant antivirals, it is perhaps no surprise that field identified resistance nearly all these compounds. Here, we provide a comprehensive review profile each therapeutics. We hope this resource provides an atlas mutations be aware agent, particularly as springboard considerations next generation antivirals. Finally, discuss outlook thoughts moving forward in how continue manage this, next,

Language: Английский

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Multiple COVID-19 vaccine doses in CLL and MBL improve immune responses with progressive and high seroconversion

Blood, Journal Year: 2022, Volume and Issue: 140(25), P. 2709 - 2721

Published: Oct. 7, 2022

Language: Английский

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Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience

Viruses, Journal Year: 2022, Volume and Issue: 15(1), P. 118 - 118

Published: Dec. 30, 2022

Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk adverse outcomes. This has driven largely expanding field monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), long-acting antibody combination that inhibits attachment SARS-CoV-2 spike protein to surface cells, proved promising reducing incidence symptomatic or death high-risk individuals without major events when given as prophylaxis, well early treatment. Real-world data confirm combination’s prophylaxis efficacy lowering incidence, hospitalization, mortality associated solid organ transplant recipients, immune-mediated inflammatory diseases hematological malignancies, B-cell-depleting therapies. Data suggest difference neutralization efficiency between subtypes favor BA.2 over BA.1. In treating COVID-19, AZD7442 showed significant reduction severe cases course disease, within 5 days symptom onset, being events, it is addition standard care. The possibility development spike-protein mutations resist antibodies been reported; therefore, increased vigilance required view evolving variants. may be powerful ally preventing individuals. Further research include more groups assess concerns limiting its use, along evolutionary trajectory.

Language: Английский

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