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Clinical Utility of Corona Virus Disease-19 Immunoglobulin G, M, Spike Protein, and Neutralizing Antibodies in Health, Disease and Post-Vaccination 冠状病毒病-19免疫球蛋白G、M、刺突蛋白和中和抗体在健康、疾病和疫苗接种后的临床应用
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.S12.003
E. Schaefer, F. Comite, L. Dulipsingh, M. Lang, Jessica Jimison, M. Grajower, N. Lebowitz, A. Geller, M. Diffenderfer, Lihong He, G. Breton, M. Dansinger, B. Saida, C. Yuan, R. Wilkes
Objective: About 80% of corona virus disease-19 (COVID-19) deaths due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in subject’s ≥ 65 years of age, even though subjects in this age group only account for about 10% of COVID-19 cases. Our objectives were to assess age effects and the clinical utility of COVID-19 antibody levels in health, disease, and post-vaccination. Methods: We measured serum SARS-CoV-2 immunoglobulin M (IgM), IgG and neutralizing antibodies using immunoassay kits obtained from Diazyme (Poway, CA) and spike (S) protein antibodies using immunoassay kits obtained from Roche Diagnostics (Indianapolis, IN). Results: In 79,005 subjects, IgG and IgM levels were positive (≥1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively, with median IgG levels being 3.93AU/mL, 10.18 AU/mL, and 10.85 AU/mL in positive subjects <45 years, 45-64 years, and ≥65 years of age, respectively (p<0.0001). IgG antibody testing was found to be valuable for case finding in 1,111 exposed subjects with a wide variability in response. Persistently positive IgM levels were associated with chronic symptoms. Median IgG levels were 0.05 in 100 controls, 14.83 in 129 COVID-19 outpatients, and 30.61AU/mL in 49 COVID-19 hospitalized patients (p<0.0001). Neutralizing antibody levels correlated with IgG levels (r=0.875; p 2 weeks after second vaccine for Moderna, Pfizer, and AstraZeneca) in 105 subjects S protein antibody levels were all >250 U/mL and neutralizing antibodies were positive in all subjects except for 2 patients with chronic lymphocytic leukemia and 1 subject after the Johnson & Johnson vaccine. However, in all subjects, antibodies measured with the Diazyme IgG and IgM antibody and Roche total antibody levels were negative. S protein antibody levels were accurately assessed by fingerstick and micro-testing devices (Seventh Sense) in COVID-19 positive and negative subjects. Conclusions: Our data indicate that: 1) IgG levels are significantly higher in positive older subjects than in younger positive subjects, possibly in order to compensate for the decreased cellular immunity observed in the elderly, 2) IgG levels are important for case finding and there is a wide variability in response, 3) persistently elevated IgM levels are associated with chronic symptoms, 4) IgG levels are correlated with neutralizing antibody levels, both of which are significantly elevated in hospitalized COVID-19 patients, and 5) S protein antibody levels are >250 U/mL after full vaccination except for those with leukemia, and can be accurately assessed by fingerstick or micro-testing technology.
目的:严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)感染导致的COVID-19 (COVID-19)死亡中,约80%发生在年龄≥65岁的受试者中,尽管该年龄段的受试者仅占COVID-19病例的10%左右。我们的目的是评估年龄的影响以及COVID-19抗体水平在健康、疾病和疫苗接种后的临床应用。方法:使用来自Diazyme公司(Poway, CA)的免疫测定试剂盒检测血清SARS-CoV-2免疫球蛋白M (IgM)、IgG和中和抗体,使用来自Roche Diagnostics公司(Indianapolis, IN)的免疫测定试剂盒检测spike (S)蛋白抗体。结果:79,005例受试者中IgG和IgM水平阳性(≥1.0任意单位[AU]/mL)的比例分别为5.29%和3.25%,阳性受试者中IgG水平中位数分别为3.93AU/mL、10.18 AU/mL和10.85 AU/mL,阳性受试者中位数分别为250 U/mL,除2例慢性淋巴细胞白血病患者和1例接种疫苗后均为中和抗体阳性。然而,在所有受试者中,用Diazyme IgG和IgM抗体和Roche总抗体水平测量的抗体均为阴性。采用手指棒法和微量检测仪(第七感)准确检测新冠肺炎阳性和阴性受试者的S蛋白抗体水平。结论:我们的数据表明:1)老年阳性受试者的IgG水平明显高于年轻阳性受试者,这可能是为了弥补老年人细胞免疫功能的下降,2)IgG水平对病例发现很重要,并且在反应上存在很大的差异,3)持续升高的IgM水平与慢性症状有关,4)IgG水平与中和抗体水平相关。5)除白血病患者外,全疫苗接种后S蛋白抗体水平为50 ~ 250 U/mL,可通过指戳或微量检测技术准确评估。
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引用次数: 0
Autoimmune Mechanisms in Graves' Disease Graves病的自身免疫机制
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.S11.E003
Patty Lee
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引用次数: 0
Risk Factors of COVID 19 Vaccination COVID - 19疫苗接种的危险因素
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.S14.E001
W. Lee
Vaccines prevent the spread of contagious and deadly diseases. The early and nonspecific innate immune response, which can cause adverse effects like tiredness, malaise, and irritability, causes inflammatory markers to rise within hours following vaccination. The inflammatory reaction, as the first stage of the immune response, normally lasts a few days but can last longer in some people, such as those who are depressed. The adaptive immune system is in charge of the immune response's second prong. Because it focuses on certain vaccine components, it takes longer to deploy. Vaccines are intended to imbue the adaptive immune system with a long-term memory of viral or bacterial components, allowing it to respond rapidly and efficiently when challenged with infections. The adaptive immune system responds to the vaccination by (a) multiplying T cells, which can be programmed to recognize and kill pathogen-infected cells, and (b) producing antibodies, which are proteins that neutralize viruses and bacteria.
疫苗可以防止传染病和致命疾病的传播。早期和非特异性先天免疫反应可能导致疲劳、不适和烦躁等不良反应,导致接种疫苗后数小时内炎症标志物上升。作为免疫反应的第一阶段,炎症反应通常会持续几天,但在一些人身上可能会持续更长时间,比如那些抑郁的人。适应性免疫系统负责免疫反应的第二个环节。由于它侧重于某些疫苗成分,因此需要更长的时间来部署。疫苗旨在为适应性免疫系统注入病毒或细菌成分的长期记忆,使其在受到感染挑战时能够迅速有效地作出反应。适应性免疫系统对疫苗的反应是:(a)增殖T细胞,T细胞可以被编程识别和杀死病原体感染的细胞;(b)产生抗体,这是一种中和病毒和细菌的蛋白质。
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引用次数: 0
Insights of How Lung Microbiome can Contribute to COVID-19 Severity in Intensive Care Unit Patients 肺部微生物组如何影响重症监护病房患者的COVID-19严重程度
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.12.450
A. Lemenuel-Diot, B. Clinch, A. Hurt, Paul Boutry, Johann Laurent, M. Leddin, S. Frings, J. Charoin
Objective: We present a country-specific, modified Susceptible, Exposed, Infectious, and Removed (SEIR) model of SARS-CoV-2 transmission aiming to provide accurate prediction of COVID-19 cases to optimize clinical trial recruitment, inform mitigation strategies, and facilitate rapid medication development. Methods: Epidemiological data from more than 170 countries were obtained from the Johns Hopkins University COVID-19 Dashboard. Intercountry differences in initial exposure, cultural/environmental factors, and stringency of mitigation strategies were incorporated. Asymptomatic patients and “super-spreaders” were also factored into our model. Simulations were limited to a period of 2 months considering that the effects of certain parameters (e.g. seasonality of virus transmission, wearing of face masks, and deployment of vaccines) were sufficiently ambiguous to limit confidence in a longer simulation period. Results: Using these data, our model estimated 71.5% of cases as asymptomatic. Without mitigation, a mean maximum infection rate of 1.08 cases/day (Intercountry range, 0.68–1.65) was estimated in symptomatic cases. From here, symptomatic and asymptomatic people were estimated to infect 3.39 and 7.71 other people, respectively, suggesting that asymptomatic persons could be responsible for 85% of new infections. An estimated 10.6% of cases were super-spreaders with a 2.86-fold higher transmission rate than average. Mitigation strategies with a stringency index value of ≥ 45% were estimated to be required to reduce the reproduction ratio below 1 for symptomatic cases. Simulated cases over the next 2 months differed between countries, with certain countries (eg, Argentina and Japan) likely to experience an accelerated accumulation of cases. Conclusion: Together, results from our model can guide the distribution of diagnostic tests, impact clinical trial development, support medication development and distribution, and inform mitigation strategies to reduce COVID-19 spread. The large contribution of asymptomatic cases in the transmission also suggests that measures such as wearing masks, social distancing, testing, and vaccination deployment are foundational to slowing the spread of COVID-19.
目的:我们提出了一种针对特定国家的、改进的SARS-CoV-2传播的易感、暴露、感染和去除(SEIR)模型,旨在准确预测COVID-19病例,优化临床试验招募,为缓解策略提供信息,并促进快速药物开发。方法:从约翰霍普金斯大学COVID-19仪表板获取170多个国家的流行病学数据。纳入了国家间在初始暴露、文化/环境因素和缓解战略的严格程度方面的差异。无症状患者和“超级传播者”也被纳入我们的模型。考虑到某些参数(如病毒传播的季节性、戴口罩和部署疫苗)的影响足够模糊,限制了对较长模拟期的信心,模拟仅限于2个月。结果:利用这些数据,我们的模型估计71.5%的病例无症状。如果没有缓解措施,在有症状的病例中,估计平均最大感染率为1.08例/天(国家间范围为0.68-1.65例)。由此估计,有症状者和无症状者分别感染了3.39人和7.71人,这表明无症状者可能占新感染病例的85%。据估计,10.6%的病例是超级传播者,传播率是平均水平的2.86倍。据估计,要将有症状病例的繁殖比降低到1以下,需要采取严格指数值≥45%的缓解策略。未来2个月各国的模拟病例有所不同,某些国家(如阿根廷和日本)可能会加速病例积累。结论:我们的模型的结果可以指导诊断测试的分发,影响临床试验的开发,支持药物的开发和分发,并为减少COVID-19传播的缓解策略提供信息。无症状病例在传播中的巨大贡献也表明,戴口罩、保持社交距离、进行检测和接种疫苗等措施是减缓COVID-19传播的基础。
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引用次数: 0
GM-CSF: Anti-Cancer Immune Response and Therapeutic Application GM-CSF:抗癌免疫反应及治疗应用
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.S10.002
S. Mor, Monika Devanaboyina, C. Fung, Rachel Royfman, L. Filipiak, L. Stanbery, DanaeHamouda, J. Nemunaitis
A primary focus of cancer therapeutics today is precision, or target directed, therapy. Combination treatment with precision therapy can involve both immune and signal pathway targets. One approach involving the chemokine GMCSF involves enhancement of the immune system. Herein is a review of the literature and the current therapeutic role of GM-CSF, including the proposed immune mechanisms and potential applications of GM-CSF to enhance anticancer immunotherapy. GM-CSF’s potent effects on dendritic cell activation and subsequent stimulation of T-lymphocyte activity make it an attractive potential addition to combination therapeutic regimens, including radiation therapy, oncolytic viral therapy, immune checkpoint inhibition, and autologous tumor vaccines, and warrants further clinical exploration, with an emphasis on identifying concomitant molecular pathways that mediate resistance and sensitivity to the GM-CSF effect.
当今癌症治疗的一个主要焦点是精确治疗,或靶向治疗。联合治疗与精确治疗可涉及免疫和信号通路靶点。一种涉及趋化因子GMCSF的方法涉及增强免疫系统。本文综述了GM-CSF的文献和目前的治疗作用,包括提出的免疫机制和GM-CSF在增强抗癌免疫治疗中的潜在应用。GM-CSF对树突状细胞活化和随后的t淋巴细胞活性刺激的强大作用使其成为联合治疗方案(包括放射治疗、溶瘤病毒治疗、免疫检查点抑制和自体肿瘤疫苗)的一个有吸引力的潜在补充,值得进一步的临床探索,重点是确定介导对GM-CSF效应的耐药性和敏感性的伴随分子途径。
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引用次数: 0
Polyvaccine: Tying up the Loose Ends in the Type 1 Diabetes Chain 多疫苗:在1型糖尿病链中捆绑松散的末端
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.S14.E002
M. Steven
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引用次数: 0
Molecular Diversity Analysis of the Spike (S) Glycoprotein Gene from Hong Kong-China 中国香港地区穗(S)糖蛋白基因的分子多样性分析
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.12.442
Eduarda Doralice Alves Braz Da Silva, Dallynne B rbara Ramos Ven ncio, R. D. Albuquerque, Robson daSilva RamosPierre Teod sio Felix
In this work, 37 haplotypes of spike glycoprotein of SARS-CoV-2 from Hong Kong, China, were used. All sequences were publicly available on the platform of the National Center for Biotechnology Information (NCBI) and were analyzed for their Molecular Variance (AMOVA), haplotypic diversity, mismatch, demographic and spatial expansion, molecular diversity and time of evolutionary divergence. The results suggested that there was a low diversity among haplotypes, with very low numbers of transitions, transversions, indels-type mutations and with total absence of population expansion perceived in the neutrality tests. The estimators used in this study supported the uniformity among all the results found and confirm the evolutionary conservation of the gene, as well as its protein product, a fact that stimulates the use of therapies based on neutralizing antibodies, such as vaccines based on protein S.
在这项工作中,使用了来自中国香港的SARS-CoV-2刺突糖蛋白的37个单倍型。所有序列均在美国国家生物技术信息中心(NCBI)平台上公开,并分析其分子方差(AMOVA)、单倍型多样性、错配、人口统计学和空间扩张、分子多样性和进化分化时间。结果表明,单倍型之间的多样性很低,过渡、翻转、indel型突变的数量很低,并且在中性试验中完全没有发现群体扩张。本研究中使用的估计器支持所有发现的结果之间的一致性,并证实了该基因及其蛋白产物的进化保守性,这一事实刺激了基于中和抗体的治疗方法的使用,例如基于蛋白S的疫苗。
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引用次数: 0
The Current State of Safety of Allergen Immunotherapy 过敏原免疫治疗的安全性现状
Pub Date : 2021-01-01 DOI: 10.35248/2157-7560.21.S10.004
C. Incorvaia, Francesco Pucciarini, Bruena L. Gritti, Aless, Rosalba Barone, E. Ridolo
Allergen Immunotherapy (AIT) is aimed at treating allergy by modifying the immunological response to allergens. However, administration of the causative allergen by Subcutaneous Immunotherapy (SCIT) to a sensitized patient may result in severe, and rarely fatal, systemic reactions. The identification of risk factors for anaphylaxis, especially concomitant uncontrolled asthma, has led to a significant reduction, but not yet elimination, in fatalities. The option of Sublingual Immunotherapy (SLIT) has been shown to be safer, with no fatalities reported thus far and including rare episodes of anaphylaxis, but the fact that the treatment is self-administered by the patient requires precautions and careful education.
过敏原免疫疗法(AIT)旨在通过改变对过敏原的免疫反应来治疗过敏。然而,通过皮下免疫治疗(SCIT)致敏患者的致敏原管理可能导致严重的,很少致命的,全身反应。确定过敏反应的危险因素,特别是伴随不受控制的哮喘,已导致死亡人数显著减少,但尚未完全消除。舌下免疫疗法(SLIT)的选择已被证明是更安全的,迄今为止没有死亡报告,包括罕见的过敏反应发作,但治疗是由患者自行进行的,这一事实需要预防措施和仔细的教育。
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引用次数: 0
Efficacy of “Essential Iodine Drops” Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) “必需碘滴剂”抗SARS-CoV-2的疗效观察
Pub Date : 2020-09-18 DOI: 10.21203/rs.3.rs-69394/v1
K. Zoltán
Background: Aerosolization of respiratory droplets is considered the main route of coronavirus disease 2019 (COVID-19). Therefore, reducing the viral load of Severe Acute Respiratory SyndromeCoronavirus 2 (SARS-CoV-2) shed via respiratory dropletsis potentially an ideal strategy to prevent the spread of the pandemic. The in vitro virucidal activity of intranasal Povidone-Iodine (PVP-I) has been demonstrated recently to reduce SARS-CoV-2 viral titres. This study evaluated the virucidal activity of the aqueous solution of Iodine-V (a clathrate complex formed by elemental iodine and fulvic acid) as in Essential Iodine Drops (EID) with 200 µg elemental iodine/ml content against SARS-CoV-2 to ascertain whether it is a better alternative to PVP-I. Methods: SARS-CoV-2 (USAWA1/2020 strain) virus stock was prepared by infecting Vero 76 cells (ATCC CRL-1587) until cytopathic effect (CPE). The virucidal activity of EID against SARS-CoV-2 was tested in three dilutions (1:1; 2:1 and 3:1) in triplicates by incubating at room temperature (22 ± 2°C) for either 60 or 90 seconds. The surviving viruses from each sample were quantified by a standard end-point dilution assay. Results: EID (200 µg iodine/ml) after exposure for 60 and 90 seconds was compared to controls. In both cases, the viral titre was reduced by 99% (LRV 2.0). The 1:1 dilution of EID with virus reduced SARS-CoV-2 virus from 31,623 cell culture infectious dose 50% (CCCID50) to 316 CCID50 within 90 seconds. Conclusion: Substantial reductions in LRV by Iodine-V in EID confirmed the activity of EID against SARSCoV-2 in vitro, demonstrating that Iodine-V in EID is effective at inactivating the virus in vitro and therefore suggesting its potential application intranasally to reduce SARS-CoV-2 transmission from known or suspected COVID-19 patients.
背景:呼吸道飞沫雾化被认为是2019冠状病毒病(COVID-19)的主要途径。因此,减少通过呼吸道飞沫传播的严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)的病毒载量可能是防止大流行传播的理想策略。鼻内聚维酮碘(PVP-I)的体外杀病毒活性最近已被证明可以降低SARS-CoV-2病毒的滴度。本研究评价了碘滴剂(EID)中碘- v(元素碘和黄腐酸形成的包合物)的水溶液(元素碘含量为200µg /ml)对SARS-CoV-2的抗病毒活性,以确定其是否优于PVP-I。方法:通过感染Vero 76细胞(ATCC CRL-1587)制备SARS-CoV-2 (USAWA1/2020株)病毒库,直至产生细胞病变效应(CPE)。以三种稀释浓度(1:1;2:1和3:1),在室温(22±2°C)下孵育60或90秒。通过标准终点稀释法对每个样本中的存活病毒进行定量。结果:暴露60秒和90秒后的EID(200µg碘/ml)与对照组比较。在这两种情况下,病毒滴度降低了99% (LRV 2.0)。EID与病毒1:1稀释后,在90秒内将SARS-CoV-2病毒从31,623细胞培养感染剂量的50% (CCCID50)降低到316 CCID50。结论:EID中碘- v对LRV的显著降低证实了EID对SARSCoV-2的体外活性,表明EID中的碘- v在体外可有效灭活病毒,因此提示其可能应用于鼻内以减少已知或疑似COVID-19患者的SARS-CoV-2传播。
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引用次数: 4
Racial/Ethnic Disparities in COVID-19 Hospital Admissions COVID-19住院的种族/民族差异
Pub Date : 2020-07-17 DOI: 10.1101/2020.07.12.20152017
V. A. Retamales, Oswaldo Madrid Suarez, O. Lara-Garcia, S. Ranjha, R. Maini, S. Hingle, V. Sundareshan, Robert Robinson
Importance: COVID-19 has affected millions of people worldwide. Furthermore, with its increasing incidence, more has been learned about the risk factors that can make certain groups more at risk of contracting the disease or have worse outcomes. We aim to identify any discrepancy in the hospitalization rate by race/ethnicity of patients who tested positive for COVID-19, and through this, analyze the risks of these groups in an effort to call out for attention to the circumstances that make them more vulnerable and susceptible to disease. Observations: Analysis indicates that patients identified as non-Hispanic White and Asian/Pacific Islander in hospital admission data are underrepresented in COVID-19 admissions. Patients identified as non-Hispanic Black, Hispanic/Latino, and American Indian have a disproportionate burden of hospital admissions, suggesting an increased risk of more severe disease. Conclusions and Relevance: There is a disproportionate rate of COVID-19 hospitalizations found among non-Hispanic Blacks. Further investigation is imperative to identify and remediate the reason(s) for increased vulnerability to COVID-19 infections requiring hospital admission. These efforts would likely reduce the COVID-19 morbidity and mortality in the non-Hispanic Black population.
重要性:COVID-19影响了全世界数百万人。此外,随着发病率的增加,人们对可能使某些群体更容易感染该疾病或产生更糟糕结果的风险因素了解得更多。我们的目标是确定COVID-19检测呈阳性的患者按种族/民族住院率的差异,并通过此分析这些群体的风险,以呼吁人们关注使他们更脆弱和更容易感染疾病的环境。观察结果:分析表明,入院数据中被确定为非西班牙裔白人和亚洲/太平洋岛民的患者在COVID-19入院中代表性不足。非西班牙裔黑人、西班牙裔/拉丁裔和美洲印第安人的住院负担不成比例,表明患更严重疾病的风险增加。结论和相关性:在非西班牙裔黑人中,COVID-19住院率不成比例。必须进行进一步调查,以确定和纠正需要住院治疗的COVID-19感染易感性增加的原因。这些努力可能会降低非西班牙裔黑人中COVID-19的发病率和死亡率。
{"title":"Racial/Ethnic Disparities in COVID-19 Hospital Admissions","authors":"V. A. Retamales, Oswaldo Madrid Suarez, O. Lara-Garcia, S. Ranjha, R. Maini, S. Hingle, V. Sundareshan, Robert Robinson","doi":"10.1101/2020.07.12.20152017","DOIUrl":"https://doi.org/10.1101/2020.07.12.20152017","url":null,"abstract":"Importance: COVID-19 has affected millions of people worldwide. Furthermore, with its increasing incidence, more has been learned about the risk factors that can make certain groups more at risk of contracting the disease or have worse outcomes. We aim to identify any discrepancy in the hospitalization rate by race/ethnicity of patients who tested positive for COVID-19, and through this, analyze the risks of these groups in an effort to call out for attention to the circumstances that make them more vulnerable and susceptible to disease. Observations: Analysis indicates that patients identified as non-Hispanic White and Asian/Pacific Islander in hospital admission data are underrepresented in COVID-19 admissions. Patients identified as non-Hispanic Black, Hispanic/Latino, and American Indian have a disproportionate burden of hospital admissions, suggesting an increased risk of more severe disease. Conclusions and Relevance: There is a disproportionate rate of COVID-19 hospitalizations found among non-Hispanic Blacks. Further investigation is imperative to identify and remediate the reason(s) for increased vulnerability to COVID-19 infections requiring hospital admission. These efforts would likely reduce the COVID-19 morbidity and mortality in the non-Hispanic Black population.","PeriodicalId":17656,"journal":{"name":"Journal of Vaccines and Vaccination","volume":"21 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2020-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87673670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of Vaccines and Vaccination
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