Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2) specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(m Abs) in the treatment of coronavirus infectious disease 2019(COVID-19). The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied. Immunoglobulin M(Ig M) appeared earlier and lasted for a short time, while immunoglobulin G(Ig G) appeared later and last...     

Itolizumab,an anti-CD6 monoclonal antibody,as a potential treatment for COVID-19 complications

ABSTRACT

Introduction

The globally rampant SARS CoV-2 pandemic requires novel medical strategies to control the severity of disease and death due to complications. Of the 15–20% patients that develop pulmonary symptoms, a sub-set develops an acute respiratory distress syndrome (ARDS) rapidly progressing into a critical condition. Marked elevation of cytokines/chemokines is observed with elevation of additional markers of inflammation, coagulation, and organ damage such as CRP, D-dimer, LDH, Ferritin and Troponin-I. This hyperinflammation leads to worsening of oxygen saturation due to pulmonary infiltration and exudation, organ damage, and dysfunction of coagulation pathway and may lead to multi-organ failure.     

Vaginal delivery after improvement in COVID-19 by monoclonal antibody treatment: A case report and literature review

As the COVID-19 pandemic persists, pregnant women have been increasingly affected worldwide. Women during the last trimester of pregnancy are susceptible to severe COVID-19, and there are many challenges towards its treatment. Monoclonal antibody treatment (MAT) is approved for COVID-19 patients to reduce disease severity. However, there are few reports on the MAT in perinatal women. Herein, we report a 39-year-old pregnant female (36 weeks and 6 days of gestation) with improvement in COVID-19 pneumonia after treatment with casiribimab/imdevimab, resulting in successful vaginal delivery (a 2.868 kg male newborn), along with a literature review. Early diagnosis and treatment of pregnant women with COVID-19 are important. Infectious diseases doctors and/or obstetricians should be aware of the MAT option administered to perinatal COVID-19 women to reduce disease severity.     

单克隆抗体在前列腺癌诊断及治疗中的应用

目的:由于单克隆抗体在治疗肿瘤方面应用广泛,具有特异性、靶向性、亲和力强、不影响周围正常细胞和毒副作用少等优点,探讨其在前列腺癌诊断和治疗中的应用发展。资料来源:应用计算机检索Medline数据库1987-01/2004-11相关单克隆抗体在前列腺癌诊断和治疗中的文章,检索词“monoclonalantibody,prostatecancer,diagnosis,treatment”,限定文章语言种类为English。资料选择:对资料进行初审,纳入标准:①单克隆抗体在前列腺癌诊断和治疗中的作用及应用的文献。②不排除是否为随机、盲法等论证推荐的文章。排除标准:综述类文献及重复研究。资料提炼:收集到的资料中分别对单克隆抗体对前列腺癌患者放射免疫显像和治疗进行探讨,包括对不同类单克隆抗体的作用进行阐述。共收集到53篇与单克隆抗体在前列腺癌诊断和治疗中应用相关的文章。排除其中研究内容相似的文章,以近5年内发表在较权威杂志者优先。对符合标准的26篇文献进行分析。资料综合:针对单克隆抗体对前列腺癌患者放射免疫显像和治疗研究有的已进入临床试验,有的正在进行动物试验。单克隆抗体在前列腺癌诊断和治疗中的应用在于它能准确的与肿瘤细胞靶抗原位点特异结合。单克隆抗体显像既可以用于淋巴显影,又能区分肿瘤细胞;在前列腺癌治疗中,利用抗体直接与靶细胞结合,通过抗体依赖细胞毒作用、补体依赖细胞毒作用、传递细胞毒药物(放射性同位素和免疫毒素)或封闭肿瘤组织和细胞生长所必需的相关生长因子等来实施。现在,已利用基因工程技术,研究出了针对在肿瘤细胞膜外分布的前列腺特异性膜抗原的人源化单克隆抗体。结论:单克隆抗体10余年来在前列腺癌诊断和治疗中的研究与应用取得了进展,需要在以下方面开展更深入的研究:人抗单克隆抗体技术上的突破;合理的安排抗肿瘤单抗偶联物或免疫偶联物的组合,包括化学药物、毒素、放射性同位素、生物因子和基因等。随着基因工程、蛋白质工程技术的发展及单克隆抗体在临床研究的不断深入,单克隆抗体将在前列腺癌的诊断和治疗中发挥重要的作用。     

单克隆抗体在前列腺癌诊断及治疗中的应用

目的：由于单克隆抗体在治疗肿瘤方面应用广泛，具有特异性、靶向性、亲和力强、不影响周围正常细胞和毒副作用少等优点，探讨其在前列腺癌诊断和治疗中的应用发展。资料来源：应用计算机检索Medline数据库1987—01／2004-11相关单克隆抗体在前列腺癌诊断和治疗中的文章，检索词“monoclonal antibody,prostate cancer，diagnosis，treatment”，限定文章语言种类为English。资料选择：对资料进行初审，纳人标准：①单克隆抗体在前列腺癌诊断和治疗中的作用及应用的文献。②不排除是否为随机、盲法等论证推荐的文章。排除标准：综述类文献及重复研究。资料提炼：收集到的资料中分别对单克隆抗体对前列腺癌患者放射免疫显像和治疗进行探讨，包括对不同类单克隆抗体的作用进行阐述。共收集到53篇与单克隆抗体在前列腺癌诊断和治疗中应用相关的文章。排除其中研究内容相似的文章，以近5年内发表在较权威杂志者优先。对符合标准的26篇文献进行分析。资料综合：针对单克隆抗体对前列腺癌患者放射免疫显像和治疗研究有的已进人临床试验，有的正在进行动物试验。单克隆抗体在前列腺癌诊断和治疗中的应用在于它能准确的与肿瘤细胞靶抗原位点特异结合。单克隆抗体显像既可以用于淋巴显影，又能区分肿瘤细胞；在前列腺癌治疗中，利用抗体直接与靶细胞结合，通过抗体依赖细胞毒作用、补体依赖细胞毒作用、传递细胞毒药物（放射性同位素和免疫毒素）或封闭肿瘤组织和细胞生长所必需的相关生长因子等来实施。现在，已利用基因工程技术，研究出了针对在肿瘤细胞膜外分布的前列腺特异性膜抗原的人源化单克隆抗体。结论：单克隆抗体10余年来在前列腺癌诊断和治疗中的研究与应用取得了进展，需要在以下方面开展更深人的研究：人抗单克隆抗体技术上的突破；合理的安排抗肿瘤单抗偶联物或免疫偶联物的组合，包括化学药物、毒素、放射性同位素、生物因子和基因等。随着基因工程、蛋白质工程技术的发展及单克隆抗体在临床研究的不断深人，单克隆抗体将在前列腺癌的诊断和治疗中发挥重要的作用。     

Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system

IntroductionMonoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021.MethodsAccording to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan.ResultsDuring Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12–0.53) and 0.10 (95% CI: 0.01–0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event.ConclusionsThe administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.     

Clinical effect of early administration of tocilizumab following the initiation of corticosteroid therapy for patients with COVID-19

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first broke out in Wuhan in December 2019, and has since caused a global pandemic. The efficacy of several drugs has been evaluated, and it is now evident that tocilizumab has a beneficial effect, especially combined with corticosteroids, in patients with Coronavirus Disease 2019 (COVID-19). However, the optimal timing of tocilizumab administration has not yet been established. The goal of the present study was to determine the optimal timing of tocilizumab administration after starting corticosteroid therapy in patients with COVID-19.MethodsWe retrospectively analyzed the clinical characteristics of patients who were hospitalized for COVID-19 and treated with tocilizumab and corticosteroids in our hospital. The patients were divided into concurrent and sequential groups. The concurrent group received tocilizumab ≤24 h after corticosteroids, and the sequential group received tocilizumab >24 h after corticosteroid administration.ResultsThe baseline clinical characteristics of tocilizumab administration were similar between the two groups. White blood cell counts were significantly lower and C-reactive protein levels were significantly higher in the concurrent group than the sequential group. In the concurrent group, tocilizumab administration led to a significant decrease in maximum body temperature. In addition, there were significantly more oxygen-free days in the concurrent group than in the sequential group. However, survival rate was not significantly different between the concurrent and the sequential groups.ConclusionsIn the combination therapy with tocilizumab and corticosteroids, early administration of tocilizumab after starting corticosteroid treatment is effective when treating COVID-19.     

Role of the extracellular matrix in COVID-19

An outbreak of coronavirus disease 2019 (COVID-19) has spread globally, with over 500 million cases and 6 million deaths to date. COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix (ECM), which is also involved in inflammatory storms. Upon viral infection, ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism, including in the lungs. Additionally, serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets. Consequently, understanding the expression and function of ECM, particularly of the lung, during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression. In this review, we summarize the current findings on ECM, such as hyaluronic acid, matrix metalloproteinases, and collagen, which are linked to the severity and inflammation of COVID-19. Some drugs targeting the extracellular surface have been effective. In the future, these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.     

Clinical efficacy of casirivimab-imdevimab antibody combination treatment in patients with COVID-19 Delta variant

IntroductionCasirivimab-imdevimab, an antibody cocktail containing two severe acute respiratory syndrome coronavirus 2 neutralizing antibodies, reduces the viral load and the risk of coronavirus disease 2019 (COVID-19)-related hospitalization or death. The objective of this study was to evaluate the clinical efficacy of casirivimab-imdevimab in patients with COVID-19 Delta variant in Japan.MethodsThis study was conducted at five institutions and assessed a total of 461 patients with COVID-19 who met the inclusion criteria. The treatment group received a dose of casirivimab-imdevimab consisting of a cocktail of two monoclonal antibodies, (casirivimab 600 mg and imdevimab 600 mg intravenously). The control consisted of age- and sex-matched COVID-19 patients (n = 461) who sufficed the inclusion criteria but did not receive casirivimab-imdevimab. The outcome was the requirement of oxygen therapy.ResultsIn the treatment group, patients received oxygen therapy (n = 30), nasal canula (n = 23), high flow nasal cannula (n = 5), and mechanical ventilation (n = 2). In the control group, patients received oxygen therapy (n = 56), nasal canula (n = 45), high flow nasal cannula (n = 8), and mechanical ventilation (n = 3). The administration of oxygen therapy was significantly lower in the treatment group than the control group (6.5% vs. 12.1%, P = 0.0044). All these patients admitted to our hospitals and received additional therapy and recovered.ConclusionsOur results demonstrate that the casirivimab-imdevimab combination antibody treatment is associated with reduced rates of requiring oxygen therapy among high-risk patients with COVID-19 Delta variant.     

骨硬化蛋白单克隆抗体治疗骨质疏松

背景：骨硬化蛋白可负向调节骨代谢,其单克隆抗体可拮抗负向调节作用,在促进骨形成的同时抑制骨吸收。目的：旨在探讨骨硬化蛋白单克隆抗体在治疗骨质疏松中的作用机制及最新进展。方法：由第一作者应用计算机检索 PubMed、中国期刊全文数据库（CNKI）、维普数据库和万方数据库（2005年 5 月至 2013 年 5 月）相关文献。在标题、摘要、关键词中以＂osteoporosis,antibody,sclerostin,Wnt,SOST＂或＂骨质疏松,单克隆抗体,骨硬化蛋白,Wnt 通路＂为检索词进行检索。选择文章内容与骨硬化蛋白单克隆抗体有关者,同一领域文献则选择近期发表在权威杂志文章。结果与结论：初检得到 170 篇文献,根据纳入标准选择关于骨硬化蛋白单克隆抗体的 54 篇文献进行综述。骨硬化蛋白通过与 Wnt 经典信号通路共受体低密度脂蛋白受体相关蛋白 5/6 结合以阻断 Wnt 通路,从而抑制成骨细胞分化及矿化。其单克隆抗体通过与骨硬化蛋白特异性结合而间接促进骨形成、抑制骨吸收,在骨质疏松的治疗中有重大意义。同时,与其他治疗方法相比,骨硬化蛋白作用靶点的组织特异性及骨硬化蛋白单克隆抗体的结合特异性为其增加了应用优势。     

Efficacy of the current investigational drugs for the treatment of COVID-19: a scoping review

To date, there is no final FDA-approved treatment for COVID-19. There are thousands of studies published on the available treatments for COVID-19 virus in the past year. Therefore, it is crucial to synthesize and summarize the evidence from published studies on the safety and efficacy of experimental treatments of COVID-19. We conducted a systematic literature search of MEDLINE, PubMed, Cochrane Library, GHL, OpenGrey, ICTRP, and ClinicalTrials.gov databases through April 2020. We obtained 2699 studies from the initial literature search. Of them, we included 28 eligible studies that met our eligibility criteria. The sample size of the included studies is 2079 individuals. We extracted and pooled the available data and conducted a quality assessment for the eligible studies. From the 28 studies, only 13 studies provide strong evidence. Our results showed that Favipiravir and Hydroxycholoroquine shorten viral clearance and clinical recovery time and promote pneumonia absorption. On the other hand, Lopinavir-ritonavir either alone or combined with arbidol or interferons has no significant difference superior to the standard care. Corticosteroids, Convalescent plasma transfusion, and anticoagulant therapies provide a better prognosis. Remedsivir, Tocilizumab, Immunoglobulin, Mesenchymal stem cell transplantation showed effective treatment results, but further confirmatory studies are needed. In conclusion, Favipiravir and Remedsivir might be promising drugs in the treatment of COVID-19 patients.      

Effect of pulsed corticosteroids and tocilizumab on hyperinflammation in COVID-19 patients with acute respiratory distress syndrome

Objective: To compare the efficacy of pulsed-dose corticosteroids (≥250 mg methylprednisolone, 3 days) and tocilizumab in treating COVID-19-related hyperinflammation.Methods: This prospective observational study included RT-PCR positive COVID-19 patients with acute respiratory distress syndrome, who were admitted to the COVID-19 Adult Intensive Care Unit of Prof Dr. Murat Dilmener Emergency Hospital (Istanbul, Turkey) between December 1, 2020 and February 28, 2021. Clinical, laboratory and radiological examinations were used to diagnose COVID-19 associated hyperinflammation. Three cohort groups were formed: the pulsed-dose corticosteroids group (250 mg methylprednisolone for 3 days), the tocilizumab group (8 mg/day single dose or 400 mg/day for 2 days), and the combined group (pulsed-dose corticosteroid+tocilizumab). The difference in mortality rates among the groups was compared primarily. The most common cause(s) of death was determined. Furthermore, adverse events (secondary infection, acute kidney injury, arrhythmia, gastrointestinal system bleeding) for 28 days were recorded. Results: A total of 60 patients were included in this study, with 20 patients in each group. There was no statistically significant difference between the 3 groups in mortality rates (55％ in the pulsed corticosteroid group, 60％ in the tocilizumab group, 50％ in the combined group, χ2=0.404, P=0.817). Infectious causes were found to be the most common cause of mortality in all the three groups, and no difference was found between them (χ2=0.404, P=0.817). There was also no difference in the development of adverse events such as secondary infection, acute kidney injury, arrhythmia, and gastrointestinal bleeding among the groups (P>0.05). Conclusions: Corticosteroids can be used instead of tocilizumab to treat hyperinflammation in COVID-19 patients with acute respiratory distress syndrome .     

Ethical review of off-label drugs during the COVID-19 pandemic

High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019 (COVID-19) pandemic and ensure people’s health and safety. Chloroquine (CQ) and hydroxychloroquine (HCQ) have received much attention. This article comprehensively investigates the ethical review of off-label CQ and HCQ research during the COVID-19 pandemic with regard to strictly abiding by review standards, improving review efficiency, ensuring the rights and interests of subjects and that ethics committees conduct independent reviews, and achieving full ethics supervision of research conducted during an emergency. Research must be both rigorous and prudent to ensure the best outcome, with the maximization of benefits as the core principle. Standardization of the application, implementation and ethical review processes are needed to prevent unnecessary risk.     

Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19)

The recent release of the main protein structures belonging to SARS CoV-2, responsible for the coronavirus disease-19 (COVID-19), strongly pushed for identifying valuable drug treatments. With this aim, we show a repurposing study on FDA-approved drugs applying a new computational protocol and introducing a novel parameter called IVS_ratio. Starting with a virtual screening against three SARS CoV-2 targets (main protease, papain-like protease, spike protein), the top-ranked molecules were reassessed combining the Inverse Virtual Screening novel approach and MM-GBSA calculations. Applying this protocol, a list of drugs was identified against the three investigated targets. Also, the top-ranked selected compounds on each target (rutin vs. main protease, velpatasvir vs. papain-like protease, lomitapide vs. spike protein) were further tested with molecular dynamics simulations to confirm the promising binding modes, obtaining encouraging results such as high stability of the complex during the simulation and a good protein–ligand interaction network involving some important residues of each target. Moreover, the recent outcomes highlighting the inhibitory activity of quercetin, a natural compound strictly related to rutin, on the SARS-CoV-2 main protease, strengthened the applicability of the proposed workflow.

New computational protocol applied to a repurposing campaign against SARS-CoV-2.     

Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

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Role of proning and positive end-expiratory pressure in COVID-19

The novel coronavirus, which was declared a pandemic by the World Health Organization in early 2020 has brought with itself major morbidity and mortality. It has increased hospital occupancy, heralded economic turmoil, and the rapid transmission and community spread have added to the burden of the virus. Most of the patients are admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure often secondary to acute respiratory distress syndrome (ARDS). Based on the limited data available, there have been different opinions about the respiratory mechanics of the ARDS caused by coronavirus disease 2019 (COVID-19). Our article provides an insight into COVID-19 pathophysiology and how it differs from typical ARDS. Based on these differences, our article explains the different approach to ventilation in COVID-19 ARDS compared to typical ARDS. We critically analyze the role of positive end-expiratory pressure (PEEP) and proning in the ICU patients. Through the limited data and clinical experience are available, we believe that early proning in COVID-19 patients improves oxygenation and optimal PEEP should be titrated based on individual lung compliance.