关键词： 实验室感染防控   LAI   生物安全   感染控制体系   综述  

摘要： 新型冠状病毒感染的全球蔓延凸显了医学实验室在传染病防控中的核心地位,但实验室感染事件频发暴露了医学实验室在感染控制方面的不足。新冠感染后,医学实验室感染控制面临多重挑战。本文探讨了医学实验室感染控制体系的现状与挑战,并从人为因素、管理体系、技术设备等多个维度剖析问题根源,提出构建实验室感染防控长效机制的路径,旨在提升医学实验室的感染控制能力。

关键词： 新型冠状病毒   COVID-19   心肌炎   心肌损伤  

摘要： 随着近年来新型冠状病毒的大流行，心肌炎是新型冠状病毒感染侵犯心血管系统最常见的心脏表现，可能与以下三种机制相关：病毒直接损伤心肌细胞引发心肌炎，诱导的多系统炎性综合症相关的心肌炎，新型冠状病毒疫苗相关心肌炎。临床上可通过临床表现、心肌损伤标志物、心电图检查、超声心动图、心肌核磁等辅助检查进行诊断及鉴别。

关键词： 新型冠状病毒   听力损失   耳鸣   远期  

摘要： 目的 分析新型冠状病毒(coronavius disease 2019,COVID-19)感染后远期听力损失及耳鸣的发生率、听力学特征及影响因素,探究COVID-19对听觉系统的远期影响。方法 以感染过COVID-19的成年人761例为研究对象,在症状问卷和专科查体后,对其中感染后新发听力损失和/或耳鸣且症状持续超过3～6个月的患者进行纯音听阈测试、声导抗、耳声发射等检查,分析年龄、基础疾病等因素与听觉系统症状的相关性。结果 761例中分别有60例(7.88%)、79例(10.38%)感染后有新发听力损失、耳鸣症状,其中分别有38例(4.99%)、33例(4.34%)在新发听力损失或耳鸣后远期(3～6个月)症状仍存在。卡方检验显示,年龄、糖尿病、既往听力损失史与感染后听力损失有相关性;高脂血症、失眠、既往耳鸣史、感染次数与感染后耳鸣有相关性。听力学检查提示,在感染后新发听力损失的45耳中,感音神经性听力损失12耳(26.67%),隐性听力损失25耳(55.56%),低频听力损失3耳(6.67%),高频听力损失4耳(8.89%),传导性听力损失1耳(最终确诊为耳硬化症)。结论 COVID-19感染后新发的听力损失和耳鸣可在远期持续存在。高龄、糖尿病及有听力损失史者是COVID-19感染后新发听力损失的高危人群;多次感染、有耳鸣史和失眠者是感染后新发耳鸣的高危人群。

关键词： SARS-CoV-2   变体   策略   中和性纳米抗体   假病毒  

摘要： 目的：开发广谱靶向严重急性呼吸系统综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2及其变体的纳米抗体（nanobody,Nb），并确立一种能够广泛用于制备广谱中和病毒及其多种变体Nb的策略。方法：使用SARS-CoV-2野生型菌株刺突蛋白的受体结合域（wild type receptor-binding domain,WT-RBD）免疫羊驼，构建出纳米抗体噬菌体文库，通过Delta变体的RBD结合域（Delta-RBD）对文库进行免疫管筛选、ELISA实验等操作筛选得到Nb，毕赤酵母系统表达Nb并纯化，通过ELISA、生物膜干涉技术、假病毒中和实验、以及Alphafold2建模和分子对接等多种手段验证纳米抗体的性质及功能。结果：得到4个Nb不仅均对WT-RBD具有较高的亲和力，还能有效地结合Delta-RBD及Omicron变体的RBD结合域（Omicron-RBD）。Nb34、Nb42和Nb45对Delta-RBD和Omicron-RBD表现出较强的结合能力，同时Nb45可以有效地中和Omicron变体的假病毒。这些Nb能够结合SARS-CoV-2及其变体的作用机制可能与其结合RBD上的保守位点相关。结论：得到的4个Nb具有防治SARS-CoV-2及其变体的巨大潜力，同时本研究中确立和使用的这种策略也可以广泛用于制备广谱中和易变异病毒及其多种变体的Nb。

关键词： 新型冠状病毒感染   荆花解毒方   无症状感染者   临床评价  

摘要： 目的：评价荆花解毒合剂治疗新型冠状病毒感染无症状感染者的临床疗效及安全性。方法：研究纳入250例新型冠状病毒感染无症状感染者，随机分为试验组和对照组，每组125例，试验组给予荆花解毒方合剂，对照组给予荆花解毒方安慰剂，治疗周期14d，符合解除隔离标准即可停药。比较两组治疗后核酸转阴时间、核酸转阴率、转型的时间/比例、症状发生时间/发生率和不良事件发生率。结果：研究脱落29例（试验组13例、对照组16例），形成符合方案集221例（试验组112例、对照组109例）。①试验组核酸转阴时间9.57 d明显短于对照组11.03 d（P<0.05），治疗7天、10天、14天试验组核酸转阴率均高于对照组（P<0.05）。②试验组平均转型时间7.00 d较对照组的5.13 d明显延迟（P<0.05），治疗4d时试验组转型比例低于对照组（P<0.05）。③发热、胸闷、气短症状发生率试验组低于对照组（P<0.05），症状出现时间试验组较对照组延迟（P<0.05）。④两组均未发生重症及死亡，亦未观察到严重不良事件。结论：对于新型冠状病毒感染无症状感染者，荆花解毒方可有效缩短病毒核酸转阴时间，提高核酸转阴率，减少临床症状发生，降低转型比例，具有较好的安全性。

关键词： Antibody dynamics   COVID-19 vaccines   SARS-CoV-2   Health workers   Mali   2019-nCoV   Novel Coronavirus   Ab   Antibody   ACE2   Angiotensin Converting Enzyme 2   AZ   AstraZeneca   COVID-19   Coronavirus Disease 2019   CSREF   Centre de Santé de Référence (Referral health center)   ELISA   Enzyme-linked Immunosorbent Assay   HCW   Healthcare Worker   HD   Hospital of Dermatology   HDC   Health District Centers   HM   Hospital of Mali   HW   Health Worker   J&J   Johnson & Johnson   MoH   Ministry of Health   mRNA   messenger Ribonucleic Acid   N   Nucleoprotein   OD   Optical Density   ORF   Open Reading Frame   RDT   Rapid Diagnosis test   REDCap   Research Electronic Data Capture   RNA   Ribonucleic Acid   RT-PCR   Reverse Transcription Polymerase Chain Reaction   S   Spike   SARS-CoV-2   Severe Acute Respiratory Syndrome Coronavirus 2   UCRC   University Clinical Research Center   USTTB   University of Sciences, Techniques and Technologies of Bamako   WHO   World Health Organization  

摘要： Background This prospective study aimed to evaluate the dynamics and seroprevalence of anti-SARS-CoV-2 antibodies in a cohort of vaccinated and unvaccinated health workers (HWs) in Bamako, Mali. The study also measured antibody responses as a function of SARS-CoV-2 infections, socio-demography, vaccination status and associated comorbidities. Method 685 vaccinated and 413 unvaccinated HWs (total = 1098) were monitored over a 15-month periods with follow-up visits every 3 months for the first 6 months and a final visit after 15 months. Anti-spike and anti-nucleoprotein antibodies were assessed using ELISA. Non-parametric tests and logistic regression analyses were performed to compare antibody levels and to investigate associated factors. Results Overall, anti-SARS-CoV-2 antibodies tended to increase over the first 3 months in both vaccinated and unvaccinated groups. Spike (>98 %) and nucleoprotein (>91 %) antibodies remained high and relatively stable after 3 months and correlated inversely with the rate attack of symptomatic and asymptomatic COVID-19. Males demonstrated lower antibody responses, particularly for nucleoprotein ( p  < 0.05) compared to females. HWs with comorbidities demonstrated higher antibody responses. Participants with active SARS-CoV-2 infections exhibited decreased antibody levels. Vaccinated participants exhibited a trend toward higher spike antibodies. Virus-inactivated type vaccination increased nucleoprotein antibodies. Furthermore, there was no increase of antibody levels after receiving, two or more vaccine doses, independently of whether the same or a different type of used vaccines. Nucleoprotein antibodies varied significantly at inclusion among participants across blood groups. Conclusion This study identified a progressive increase in anti-spike and anti-nucleoprotein antibodies in both vaccinated and unvaccinated HWs, correlating with reduced COVID-19 infection rates. These findings highlight the significance of both natural and va

关键词： Age   Cardiovascular adverse events   COVID-19 vaccine   Number of doses   Obesity   Timing of vaccine   Vaccine safety  

摘要： Rationale: Studies on determinants of cardiovascular adverse events (CVAEs) in ChAdOx1-nCoV-19 vaccine recipients are scarce. Methods: This is a subgroup analysis of our published one-year prospective study (February 2021 to April 2022) on the safety of the ChAdOx1-nCoV-19 vaccine. Healthcare workers and the elderly were the core study participants (priority vaccine recipients) who were followed up telephonically for one year after vaccination. Patterns of CVAEs and their risk factors were analyzed. Results: Out of 1650 enrolled participants, the data on CVAEs were available for 1525. Cardiac AEs and vascular AEs occurred in 1.4 % and 1.8 %, respectively. CVAEs were serious in 0.45 % of participants. Obese individuals had 3.8-and 2-times higher odds of cardiac and vascular AEs, respectively. Individuals aged 40 years and above had 3 times higher odds of vascular AEs. Cardiac AEs were significantly more common after the first dose of the vaccine. No association was seen between CVAEs and COVID-19 before or after vaccination. The rates of persistent CVAEs were 2.4-3.1 %, 1.1-1.3 %, and 0.5-0.9 % in the Vaccine After COVID (VAC) group, COVID After Vaccine (CAV) group, and Vaccine NO COVID (VNC) group, respectively. Conclusion: The occurrence of CVAEs might be governed by the number of vaccine doses, age, obesity, and timing of the vaccine with respect to natural SARS-CoV-2 infection. While no causality can be established between the observed events and vaccination, individuals receiving any dose of vaccine after recovery from COVID-19 need extended monitoring for CVAEs. Larger studies including unvaccinated individuals are required to understand the predictors of CVAEs for the individualization of future vaccination policies.

关键词： Paediatric vaccinology   Viral vectors   SARS-CoV-2  

摘要： Background Paediatric COVID-19 vaccination programmes were initiated in response to the coronavirus pandemic declared by the World Health Organisation (WHO) in 2020. Ten COVID-19 vaccines received WHO Emergency Use Listing, however, only five were approved for use in children. ChAdOx1 nCoV-19 (AZD1222) was approved in adults in a two-dose regimen. We previously reported interim findings of a phase 2 study of ChAdOx1 nCoV-19 in children with immunogenicity, comparable with adults. Final results after 12 month follow-up are reported. Methods Single-blind, randomised controlled trial across four UK centres, recruiting 261 children and adolescents (aged 6-17 years). Participants received either two doses of ChAdOx1 nCoV-19 or Bexsero vaccine (controls). The primary outcome was safety (adverse events for 28 days following vaccination and serious adverse events throughout), and secondary outcome was immunogenicity (measured by SARS-CoV-2 anti-spike enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot (ELISpot)). Findings Five serious adverse events and four adverse events of special interest were reported. None were related to study vaccinations, and there were no deaths. Geometric mean titres (GMTs) from an anti-spike (Wuhan) ELISA in participants aged 6-11 years were 1 EU/ml (95% CI 1-2) at baseline versus 796 EU (95% CI 161-3948, n =4) at D364. In participants aged 12-17 years, GMTs were 1 EU/ml (95% CI 1-2, n=3) at baseline versus 1432 EU/ml (95% CI 2337-6083; n=6) at D364 (2 dose regimen at 112-day interval), compared to 3 EU/ml (95% CI 0-62) at baseline versus 392 EU/ml (95% CI 24, 6493; n=3) at D364 (2 dose regimen at a 28-day interval). Interpretation A two-dose regimen of ChAdOx1 nCoV-19 was immunogenic and safe in the trial population. No vaccine-related serious adverse events were reported. Immune responses persisted to 12 months in participants who did not experience breakthrough infection, This trial was registered with ISRCTN, trial

关键词： Type 2 diabetes   ChAdOx1 nCoV-19 vaccine   Lymphocyte proliferation   B cell memory   Hybrid immunity  

摘要： Introduction: Despite the success of vaccination, isolated cases of COVID-19 infection are being reported in the vulnerable subjects worldwide. Given that individuals with type-2 diabetes (T2D) often exhibit immune dysregulation, this study aimed to characterize SARS-CoV-2-specific immunity following ChAdOx1 nCoV-19 vaccination in subjects with T2D. Methods: We recruited 55 T2D and 60 healthy control (HC) subjects and monitored their immunological parameters at baseline, 3rd, 6th, and 12th month post-ChAdOx1 nCoV-19 vaccination. The frequency of SARS-CoV-2 epitope-specific CD8+ T cells were determined using MHC-I dextramers. The SARS-CoV-2 specific recall responses were assessed by lymphocyte proliferation, intracellular (TNF-alpha, IFN-gamma) and extracellular (IL-2, IL-4, IL-6, IL-10, IFN-gamma, TGF-beta) cytokine estimation following in-vitro stimulation with SARS-CoV-2 S-protein peptide pool (SP). The anti-S antibody titers and the frequency of memory B cells (CD19+ CD27+), plasmablasts (CD19+ CD27hiCD38hi), and plasma cells (CD38hi CD138+) were also determined. Results: Following vaccination, the incidence of COVID-19 disease was significantly higher in T2D individuals, suggesting an increased rate of breakthrough infections. The T2D cohort also exhibited lower frequency of SARS-CoV-2-specific peripheral CD8+ T cells and demonstrated diminished recall responses, as evidenced by reduced in-vitro lymphocyte proliferation. During breakthrough COVID-19 disease, systemic levels of IFN-gamma were elevated in T2D subjects, whereas higher IL-10 levels were observed only in HC. Upon SP stimulation, a greater proportion of CD8+ and CD4+ T cells from HC expressed IFN-gamma and TNF-alpha, indicating a more robust antiviral cell-mediated immune response. Additionally, B cell immunophenotyping revealed a reduced frequency of memory B cells in T2D. Conclusion: The data indicate that individuals with T2D exhibit impaired vaccine-induced SARS-CoV-2-specific immunological memory

关键词： 蔗糖质量浓度   高效液相色谱法   示差折光检测器   新型冠状病毒mRNA疫苗  

摘要： 采用氨丙基键合硅胶色谱柱（4.6 mm×250 mm，5.0 μm），以乙腈-水溶液为流动相，对流动相比例、流速以及柱温进行优化，建立了高效液相色谱-示差折光检测器法（HPLC-RID）测定新型冠状病毒mRNA疫苗中蔗糖质量分数的方法，该方法在5.05～30.30 mg/mL的质量浓度范围内具有良好的线性关系，专属性、重复性、准确性、及耐用性均较好，定量限和检测限均满足使用需求。该方法不仅为新型冠状病毒mRNA疫苗中蔗糖质量浓度测定提供了可靠的分析手段，也为其他mRNA类疫苗中的蔗糖质量浓度测定提供研究基础。