全球自然感染SARS-CoV-2人群的抗体水平研究

新型冠状病毒肺炎（COVID-19）已蔓延至全球二百二十多个国家和地区,造成了全球大流行。通过SARS-CoV-2的特异性抗体的血清学检测可以估计人群感染的状况,有助于回顾性评估研究人群中疫情的规模或感染程度。本文对全球自然感染SARS-CoV-2一般人群和医务工作者、儿童、孕妇等特殊人群的血清抗体水平研究进行综述,以期更好地理解COVID-19流行期间人群的血清学特征和规律,对疾病的认识和后期疫情防控提供重要借鉴。综述发现全球范围内报告的自然感染SARS-CoV-2血清抗体阳性率在不同国家或地区有所不同,阳性率从低于0.1%到超过20%,其高低与不同血清学检测方法、检测时所处的疫情流行阶段有关。儿童的血清抗体阳性率低于其他年龄组,医务工作者、孕妇的血清抗体阳性率则与一般人群相似。未来有必要进一步持续监测血清抗体阳性水平,以评估COVID-19所致的疾病负担,为COVID-19疫情控制提供科学证据。     

Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants

The recent pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has raised global health concerns. The viral 3-chymotrypsin-like cysteine protease (3CL^pro) enzyme controls coronavirus replication and is essential for its life cycle. 3CL^pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV. Therefore, herein, we analysed the 3CL^pro sequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. Our analyses revealed that the top nine hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.     

新型冠状病毒对循环系统影响的研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)是由新型冠状病毒(SARS-CoV-2)引起的,以发热、咳嗽及呼吸困难为主要临床症状的一种可在人群中广泛传播的疾病。截至目前,2019新型冠状病毒已在全球范围内造成大流行,随着国内疫情防治工作的有效开展,以及对于新型冠状病毒肺炎的认识与研究不断加深,发现很多新冠肺炎患者出现以循环系统损害症状为首发或继发的临床症状。SARS-CoV-2可直接通过血管紧张素转换酶2 (angiotensin converting enzyme 2,ACE2)受体损伤心肌细胞,也可以通过异常激活免疫系统、释放大量细胞因子从而导致急、慢性的心肌损伤。当心功能受损严重时,可能会通过RAS系统影响到肾脏功能,从而导致患者同时出现心脏和肾脏损害的临床表现。此外,对于COVID-19患者来说,还存在着动、静脉血栓栓塞的风险。本文结合近日来公布的新冠肺炎病例的资料和各团队最新的研究发现,对新型冠状病毒对于循环系统影响的研究进展做一简要概述,以期为进一步了解新型冠状病毒感染对循环系统的损害提供帮助。      

SARS-CoV-2暴露剂量与COVID-19潜伏期及病情发展趋势的相关性研究

尽管SARS-CoV-2暴露剂量和暴露者机体抵抗力都是受多种因素影响难以确定的变量,但COVID-19的发生是SARS-CoV-2暴露剂量与暴露者机体抵抗力相互作用的结果。本文通过比较中国湖北内外发病情形、湖北之外其他省市不同日期COVID-19发病的潜伏期、以及散发病例与聚集性发病情形,发现SARS-CoV-2感染率高低与疫情时程及潜伏期均相关,显示SARS-CoV-2暴露剂量与是否发病、以及发病后的严重程度均可能具有相关性。从而提示COVID-19的治疗,需要对潜伏期偏短的患者提防其重症化和死亡风险。     

Peak IgG antibody titers against SARS-CoV-2 spike protein following immunization with the Pfizer/BioNTech BNT162b2 vaccine

This study investigated the immune response and outcome of BNT162b2 vaccination among 12 staff at a hospital in Fukushima, Japan. Blood samples were collected from participants before their first vaccination, with subsequent sampling performed during the participants’ work days for six weeks thereafter. Antibody titers peaked 6-13 days after the second vaccination (days 27-34 after the first), followed by a steady decrease. Six males had significantly lower peak antibody titers than six females (p = 0.016 with t-test); the older six (median age 53 years) had lower antibody titers than the younger six (median age 35 years) but without statistical significance (p value=0.24 with t-test).     

多部位样本核酸检测持续阳性的新型冠状病毒肺炎患者1例分析

目前新型冠状病毒肺炎（COVID-19）正在我国及世界其他国家流行,患者感染病毒后的临床症状不一,甚至呈现为无症状感染状态,这给整个疫情的防控提出了更高的要求。新型冠状病毒（SARS-CoV-2）核酸检测作为COVID-19诊断的主要手段,在抗击疫情的过程中发挥着重要的作用,因此备受关注。本文报告一例无明显消化道症状,但粪便及肛拭子核酸检测持续阳性的COVID-19病例。患者为武汉某大学在校学生,在校期间即出现呼吸道症状,后放假回家,因病情加重而就诊入院,根据病情发展和诊疗需要,该患者进行了多次核酸检测,在症状明显好转,咽拭子核酸检测转阴后,其痰液、肛拭子及粪便样本的核酸检测仍持续阳性,由此,讨论多部位样本核酸检测对COVID-19诊疗的临床意义,并探讨疫情防控策略。     

Targeting SARS-CoV-2 Main Protease: A Computational Drug Repurposing Study

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Evaluation of hematological parameters and thrombocytopenia following Pfizer-BioNTech (BNT162b2) SARS-CoV-2 vaccination

Objectives:To evaluate hematological parameters and thrombotic profiles of healthy individuals who received Pfizer-BioNTech (BNT162b2) vaccines in Saudi Arabia.Methods:Hematological parameters and the incidence of anti-platelet factor-4 (anti/PF-4) antibodies were evaluated in 40 participants who were eligible for COVID-19 vaccination in Saudi Arabia (above 18 years old) at Jazan University Hospital. These parameters were assessed at 2 different timepoints; at day 0 (the day of receiving the first dose of Pfizer- BioNTech (BNT162b2) and prior to vaccination) and 14-21 days after receiving the vaccine.Results:Among the participants, 38 (80%) were men, while 12 (20%) were women, with a mean age of 27 years. A total of 15% of the participants reported previous infection with SARS-CoV-2 and 3 patients had a history of diabetes mellitus and hypertension. Hematological parameters results in those vaccines showed no significant changes between the 2 timepoints, such as, day 0 (just before receiving vaccination) and 14 to 21 days post vaccination. Further, anti/PF4 antibodies were negative for all participants following vaccination.Conclusion:Our data showed that the incidence of hematological abnormalities or induction of anti/PF4 antibodies following Pfizer-BioNTech (BNT162b2) vaccination is not common, which is consistent with several previous reports. However, larger studies with more participants evaluated at different timepoints following vaccination are warranted to exclude potential transient hematological abnormalities.     

经9次核酸检测终确诊的新型冠状病毒肺炎患者1例分析

目前新型冠状病毒肺炎(COVID-19)疫情在全球蔓延,形势严峻,并对全球公共卫生事业构成巨大挑战,快速准确的诊断COVID-19对疫情的防控有重要意义。本文报道1例COVID-19患者的调查和确诊过程,以对COVID-19确诊和疫情防控提供有价值的参考。患者为赴渝务工于2020年1月23日返乡人员,在渝期间,其同工地的一同事确诊为COVID-19,之后该工地接连有另外8位同事被确诊。患者返乡后2月2日被当地疫情防控单位采取医学隔离。患者于隔离后不久出现咳嗽,阵发性,干咳为主,偶可咳出黄色痰液等COVID-19相关临床症状,遂被当地新型冠状病毒肺炎定点医疗单位收治,后经市级新型冠状病毒肺炎诊治专家组远程视频会诊转入四川大学华西医院资阳医院。患者先后经历9次核酸检测,在前8次核酸检测均为阴性的情况下,于第9次核酸检测结果为阳性,2月21日最终确诊为新型冠状病毒肺炎。     

The potential of miRNA-based therapeutics in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: A review

Since the World Health Organization (WHO) declared COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as a pandemic in March 2020, and more than 117 million people worldwide have been confirmed to have been infected. Scientists, medical professionals, and other stakeholders are racing against time to find and develop effective medicines for COVID-19. However, no drug with high efficacy to treat SARS-CoV-2 infection has been approved. With the increasing popularity of gene therapy, scientists have explored the utilization of small RNAs such as microRNAs (miRNAs) as therapeutics. miRNAs are non-coding RNAs with high affinity for the 3′-UTRs of targeted messenger RNAs (mRNAs). Interactions between host cells and viral genomes may induce the upregulation or downregulation of various miRNAs. Therefore, understanding the expression patterns of these miRNAs and their functions will provide insights into potential miRNA-based therapies. This review systematically summarizes the potential targets of miRNA-based therapies for SARS-CoV-2 infection and examines the viability of possible transfection methods.     

当前新冠病毒的主要检测手段

2019年,由新型冠状病毒(SARS-CoV-2)感染引起的新型冠状病毒肺炎(COVID-19)被报道,随后疫情在世界上各个国家和地区暴发且迅速流行.COVID-19的传染性强、病死率高,为有效控制疫情的发展,新冠病毒的检测至关重要,国内外各研究团队及机构已研发出各种检测新冠病毒的有效手段和仪器设备,本文从背景原理、应...     

新型冠状病毒Omicron变异株的流行病学特征及防控研究

Omicron（B.1.1.529）变异株于2021年11月24日首次从南非报告给世界卫生组织,截至2021年12月8日全球共有57个国家和地区报告了Omicron感染病例。目前Omicron变异株在部分非洲国家已成为主导毒株,且传播速度快。尽管Omicron变异株引起的疾病症状较轻,多数病例为无症状感染者和轻型患者,但病例数量的快速增长可能给全球卫生系统带来沉重压力。此外,Omicron变异株的变异来源、传播特征、疫苗抗性等尚不明确,给各国和地区的疫情防控带来很大挑战。本文就Omicron变异株的病原学特征、变异来源、传播特征及可能的机制、流行现状、疫苗对其保护效果、防控措施等方面的研究进展进行综述,以期为科学防控Omicron变异株所致疫情提供参考。     

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy

Objective: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2(ACE2) receptor and viral spike protein by virtual screening. Methods: The three-dimensional(3 D)-coordinate file of the receptor-binding domain(RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration(FDA)-approved drugs from Drug Bank and natural compounds from Traditional Chinese Medicine Systems Pharmacology(TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine(CM) herb sources were listed in this paper. Results: It was found that digitoxin, a cardiac glycoside in Drug Bank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen(莲花清瘟), a CM formula reportedly exerting activity against severe acute respiratory syndrome(SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. Conclusions: A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-Co V-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.     

No Effects of Meteorological Factors on the SARS-CoV-2 Infection Fatality Rate

Objective Previous studies have shown that meteorological factors may increase COVID-19 mortality, likely due to the increased transmission of the virus. However, this could also be related to an increased infection fatality rate (IFR). We investigated the association between meteorological factors (temperature, humidity, solar irradiance, pressure, wind, precipitation, cloud coverage) and IFR across Spanish provinces (n = 52) during the first wave of the pandemic (weeks 10–16 of 2020).Methods We estimated IFR as excess deaths (the gap between observed and expected deaths, considering COVID-19-unrelated deaths prevented by lockdown measures) divided by the number of infections (SARS-CoV-2 seropositive individuals plus excess deaths) and conducted Spearman correlations between meteorological factors and IFR across the provinces. Results We estimated 2,418,250 infections and 43,237 deaths. The IFR was 0.03％ in < 50-year-old, 0.22％ in 50–59-year-old, 0.9％ in 60–69-year-old, 3.3％ in 70–79-year-old, 12.6％ in 80–89-year-old, and 26.5％ in ≥ 90-year-old. We did not find statistically significant relationships between meteorological factors and adjusted IFR. However, we found strong relationships between low temperature and unadjusted IFR, likely due to Spain's colder provinces' aging population. Conclusion The association between meteorological factors and adjusted COVID-19 IFR is unclear. Neglecting age differences or ignoring COVID-19-unrelated deaths may severely bias COVID-19 epidemiological analyses.     

银丹解毒颗粒治疗SARS-CoV-2变异株B.1.1.7 COVID-19临床观察

目的:观察银丹解毒颗粒治疗SARS-CoV-2变异株B.1.1.7新型冠状病毒肺炎(coronavirus disease 2019,COⅥD-19)的临床疗效.方法:前瞻性收集2021年1月18日至2月1日北京地坛医院收治的17例服用银丹解毒颗粒的SARS-CoV-2变异株B.1.1.7 COVID-19患者,其中9...     

PCR-核酸飞行时间质谱系统检测新型冠状病毒方法的建立及应用研究

背景　新型冠状病毒肺炎（COVID-19）在全球暴发,实验室检测结果是疾病诊断的重要依据,检测方法的灵敏度和特异度是影响实验结果的关键因素,现实时荧光定量聚合酶链反应（PCR）核酸检测方法是COVID-19确诊的通用方法,但其检测灵敏度有方法局限性,依赖标本病毒含量。通过对PCR-核酸飞行时间质谱检测方法的优化,从而提高对低新型冠状病毒（SARS-CoV-2）含量病例检测的灵敏度,可为现有方法做有效补充。目的　应用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）原理,在Clin-ToF Ⅱ飞行时间质谱系统上,建立PCR-核酸飞行时间质谱（PCR-TOF MS）系统检测SARS-CoV-2的方法,并评估其实际应用价值。方法　2020年2-3月于上海市临床检验中心室间质评阳性样本40份、阴性样本7份,国家卫生健康委员会室间质评阳性样本41份、阴性样本33份,本实验室购买阳性质粒及稀释样本32份,健康人样本28份,空白对照超纯水5份,共186份样本作为建立PCR-TOF MS系统数据。于2020年1-2月收集安徽省内临床送检到安徽省疾病预防控制中心的疑似COVID-19患者上呼吸道样本80份（咽拭子样本55份、痰液样本25份）及健康人群样本20份（均为咽拭子样本）作为评估PCR-TOF MS系统效果的数据。建立PCR-TOF MS系统试验体系步骤,包括PCR扩增、虾碱性磷酸酶（SAP）消化、单碱基延伸和质谱检测;并基于阳性质粒优化模版量,根据186份样本检测质谱峰的信噪比（SNP）确定该方法在SARS-CoV-2检测时的判读标准。对80份疑似SARS-CoV-2样本和20份健康人群样本进行检测分析,并与实时荧光定量PCR法进行对比。结果　通过对PCR-TOF MS 模板条件的优化,模版量6 μl时,扩增产物可获得典型的质谱峰图。建立的PCR-TOF MS反应体系可以对SARS-CoV-2核酸的开放读码框1ab（ORF1ab）基因和核壳蛋白（N）基因进行有效扩增检测。本研究PCR-TOF MS方法对临床疑似病例样本的检出率为90.00%,高于实时荧光定量PCR法的75.00%,同时,结果显示,实时荧光定量PCR法检出中含有25.00%的可疑结果,而PCR-TOF MS则无可疑结果。对于痰液和咽拭子两种样本的检出率,PCR-TOF MS法分别为100.00%和85.45%,高于荧光定量PCR法的64.00%和43.64%。阴性样本两种方法均未检出。结论　通过PCR技术与飞行时间质谱技术的结合,使得检测SARS-CoV-2目标片段指数级扩大,从而提高样本的检测灵敏度。MALDI-TOF MS技术通过对离子分子量的检测分析,具有较高的准确性和特异性,同时证实了痰液样本优于咽拭子样本。该方法可作为实时荧光定量PCR法的补充和协同,在一定程度上有利于弥补假阴性的问题,从而降低临床漏诊率,提高检测效率,为疫情的研判缩短时间。     

不同新型冠状病毒变异株感染的COVID-19潜伏期研究

从新型冠状病毒肺炎（COVID-19）疫情初始至今,COVID-19的病原体新型冠状病毒（SARS-CoV-2）不断进化和变异,产生传播力和毒力变化的变异株,如Alpha（B.1.1.7）、Beta（B.1.351）、Gamma（P.1）、Delta（B.1.617.2）以及Omicron（B.1.1.529）变异株。深入研究不同变异株感染所致的COVID-19潜伏期有助于追溯传染源,确定密切接触者的留验、检疫和医学观察期限,为及时调整COVID-19疫情防控措施提供依据。本文主要综述了国内外感染SARS-CoV-2野生株和不同变异株的COVID-19潜伏期的相关研究,研究发现,感染SARS-CoV-2野生株的潜伏期在4~8 d,中位潜伏期约为5.5 d。感染Beta、Gamma变异株的潜伏期与野生株基本类似,约为5 d。感染Alpha、Delta和Omicron变异株的潜伏期则低于其他毒株,分别为4 d、4 d和3 d。