简介：摘要COVID-19的全球大流行使冠状病毒再次引起重视。在本世纪大流行的三种高致病性冠状病毒(SARS-CoV、MERS-CoV、SARS-CoV-2)研究中，已有直接证据证明SARS-CoV及SARS-CoV-2可引起人眼部感染。冠状病毒感染除引起眼部症状外，也可通过眼部感染引发全身多种临床表现。两种高致病性冠状病毒(SARS-CoV和SARS-CoV-2)具有更强的流行性及更高的病死率，两种病毒眼部症状相似，病毒结构及眼部感染过程也具有相似性，主要是通过其特异性S蛋白与细胞表面相关受体结合，使其核酸进入细胞内并借用细胞内的蛋白合成通路对自身蛋白进行转录、组装、折叠并通过其受体蛋白激发多种细胞因子表达。本文就2003年流行的SARS-CoV以及2019年末流行的SARS-CoV-2两种高致病性冠状病毒的特点、眼部感染通路的研究进展及病毒眼部感染相关的研究现状进行综述，阐述眼部病毒防护及患者眼部检查的必要性。(国际眼科纵览，2020, 45: 374-379)

简介：摘要人冠状病毒OC43(human coronavirus OC43，HCoV-OC43)与SARS-CoV-2(severe acute respiratory syndrome coronavirus 2)同属于β冠状病毒属，自1967年发现以来在人群中持续流行，现已成为常见的季节性呼吸道病毒之一。致病率和致死率更高的SARS-CoV-2在2019年底出现，后又伴随多种变异株的出现，其传播和感染能力不断增强。HCoV-OC43与SARS-CoV-2在基因组结构和功能、物种进化、流行特点及临床表现上可能具有一定的相似性。本综述对HCoV-OC43和SARS-CoV-2的流行病学、基因组学、种系进化等方面进行分析，有助于了解这两种病毒的关联与差异，为认识HCoV-OC43存在的潜在威胁提供参考。

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简介：AbstractIn December of 2019, several cases of atypical pneumonia caused by an unknown agent were reported in Wuhan, the capital city of Hubei Province in China. In early January 2020, it was announced that these cases were caused by a novel coronavirus. The virus was later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes a disease associated with atypical pneumonia termed Corona virus disease 2019 (COVID-19). Several respiratory viruses, including coronaviruses and influenza viruses tend to have prominent peaks of infection during colder seasons, especially in temperate regions. The cold temperatures, along with accompanying dry conditions can drive respiratory tract infections by assisting with viral transmission, weakening the human immune system, and increasing viral molecular stability. Though the topic of SARS-CoV-2 transmission and warm weather has been associated with misinformation campaigns, it is worth investigating since an informative answer may give an indication of the future behavior of SARS-CoV-2.

简介：AbstractCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid spread worldwide. In this study, we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2, using 22 virus genome sequences reported by three different laboratories in Morocco till June 7,2020, as well as 40,366 virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations, of which 30 were mis-sense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K, which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred once in Moroccan sequences, with no record in other sequences worldwide. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses belonging to Clade 20A, 9 to Clade 20B and 2 to Clade 20C, suggesting that the epidemic spread in Morocco did not display a predominant SARS-CoV-2 route. Therefore, multiple and unrelated introductions of SARS-CoV-2 into Morocco through different routes have occurred, giving rise to the diversity of virus genomes in the country. Further, in all probability, the SARS-CoV-2 circulated in a cryptic way in Morocco, starting from January 15, 2020 before the first case was officially discovered on March 2, 2020.

简介：AbstractHost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in children, are still under investigation. Children with coronavirus disease 2019 (COVID-19) constitute a significant study group of immune responses as they rarely present with severe clinical manifestations, require hospitalization, or develop complications such as multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. The deciphering of children's immune responses during COVID-19 infection will provide information about the protective mechanisms, while new potential targets for future therapies are likely to be revealed. Despite the limited immunological studies in children with COVID-19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS-CoV-2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues. Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS-CoV-2 infection and adaptive memory immunity is vital to prevent reinfection.

简介：AbstractThe global spread of SARS-CoV-2 is currently continuing, and the World Health Organization has announced the risk assessment of the viruses as high. In this study, we analyzed virology features of SARS-CoV-2 causing a family cluster outbreak. Among the six family members, five have been laboratory-confirmed infection of SARS-CoV-2 viruses. A total of five SARS-CoV-2 viruses have been isolated from the nasopharyngeal swabs. The complete genome of the viruses exhibited 100% nucleotide identity with each other. Only two nucleotide differences have been observed between genomes of the isolated viruses and the HCoV/Wuhan/IVDC-HB-01/2019 strain. Therefore, SARS-CoV-2 has been confirmed as the causation of the family cluster infections.

简介：AbstractIn malaria-endemic regions, people often get exposed to various pathogens simultaneously, generating co-infection scenarios. In such scenarios, overlapping symptoms pose serious diagnostic challenges. The delayed diagnosis may lead to an increase in disease severity and catastrophic events. Recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected various areas globally, including malaria-endemic regions. The Plasmodium and SARS-CoV-2 co-infection and its effect on health are yet unexplored. We present a case report of a previously healthy, middle-aged individual from the malaria-endemic area who suffered SARS-CoV-2 and Plasmodium falciparum co-infection. The patient developed severe disease indications in a short time period. The patient showed neurological symptoms, altered hematological as well as liver-test parameters, and subsequent death in a narrow time span. We hereby discuss the various aspects of this case regarding treatment and hematological parameters. Further, we have put forward perspectives related to the mechanism behind severity and neurological symptoms in this fatal parasite-virus co-infection case. In malaria-endemic regions, due to overlapping symptoms, suspected COVID-19 patients should also be monitored for diagnosis of malaria without any delay. The SARS-CoV-2 and Plasmodium co-infection could increase the disease severity in a short time span. In treatment, dexamethasone may not help in severe cases having malaria as well as COVID-19 positive status and needs further exploration.

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简介：AbstractIntroduction:Liver injury during SARS-CoV-2 infection has a multifactorial pathogenesis and it is frequent in pediatric cases.Case presentation:We report a case with severe hypertransaminasemia associated with mild SARS-CoV-2 infection.Conclusion:This highlights the potential need of hepatic function evaluation during acute illness and follow-up even in non-critically ill children with COVID-19.

简介：AbstractBackground:The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is pandemic. However, the origins and global transmission pattern of SARS-CoV-2 remain largely unknown. We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics.Methods:Using the full-length sequences of SARS-CoV-2 with intact geographic, demographic, and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020, we constructed the transmission tree to depict the evolutionary process by the R package "outbreaker" . The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2 (ACE2) was predicted using mCSM-PPI2 software. Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test.Results:From 26 December 2019 to 8 March 2020, early stage of the COVID-19 pandemic, SARS-CoV-2 strains identified worldwide were mainly composed of three clusters: the Europe-based cluster including two USA-based subclusters; the Asia-based cluster including isolates in China, Japan, the USA, Singapore, Australia, Malaysia, and Italy; and the USA-based cluster. The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade. After 8 March 2020, the clusters of SARS-CoV-2 strains tended to be independent and became "pure" in each of the major countries. Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2. Of all predicted mutants, the number of E484K was the largest one with 86 585 sequences, followed by S477N with 55 442 sequences worldwide. In more than ten countries, the frequencies of the isolates with E484K and S477N increased significantly. V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses (P < 0.001). SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart (P < 0.001).Conclusions:SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure. Travel restrictions might cause location-specific SARS-CoV-2 clustering. The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion.

简介：AbstractThe present pandemic has posed a crisis to the economy of the world and the health sector. Therefore, the race to expand research to understand some good molecular targets for vaccine and therapeutic development for SARS-CoV-2 is inevitable. The newly discovered coronavirus 2019 (COVID-19) is a positive sense, single-stranded RNA, and enveloped virus, assigned to the beta CoV genus. The virus (SARS-CoV-2) is more infectious than the previously detected coronaviruses (MERS and SARS). Findings from many studies have revealed that S protein and RdRp are good targets for drug repositioning, novel therapeutic development (antibodies and small molecule drugs), and vaccine discovery. Therapeutics such as chloroquine, convalescent plasma, monoclonal antibodies, spike binding peptides, and small molecules could alter the ability of S protein to bind to the ACE-2 receptor, and drugs such as remdesivir (targeting SARS-CoV-2 RdRp), favipir, and emetine could prevent SASR-CoV-2 RNA synthesis. The novel vaccines such as mRNA1273 (Moderna), 3LNP-mRNAs (Pfizer/BioNTech), and ChAdOx1-S (University of Oxford/Astra Zeneca) targeting S protein have proven to be effective in combating the present pandemic. Further exploration of the potential of S protein and RdRp is crucial in fighting the present pandemic.

简介：摘要目的了解乙型肝炎病毒(hepatitis B virus，HBV)合并人类免疫缺陷病毒(human immunodeficiency virus，HIV)感染对抗反转录病毒治疗(anti-retroviral therapy, ART)效果的影响。方法纳入2016年9月至2019年10月重庆市公共卫生医疗救治中心收治的269例HIV感染者，将其分为HIV单独感染组和HBV合并HIV感染组，比较2组患者ART启动时和ART后不同时间点(2、4、8、12、24、36、48和96周)的肝功能、CD4+T淋巴细胞计数、HIV RNA变化情况。统计学分析采用独立样本t检验、秩和检验和χ2检验。结果HIV单独感染组145例，HBV合并HIV感染组124例。ART启动时两组患者肝功能指标[天冬氨酸转氨酶(t＝9.566)、丙氨酸转氨酶(t＝-4.652)、总胆红素(t＝-25.476)]差异均无统计学意义(均P>0.05)。ART后24、48和96周时，HIV单独感染组与HBV合并HIV感染组CD4+T淋巴细胞计数分别为(305.9±156.9)/μL比(266.2±172.5)/μL、(388.5±226.1)/μL比(380.8±287.4)/μL、(369.5±191.4)/μL比(453.6±179.6)/μL；ART后48、72和96周时，CD4+T淋巴细胞计数增长值为121.0(-52.5, 144.5)/μL比156.0(-35.8，185.8)/μL、139.0(-116.0，176.8)/μL比114.5(-59.5, 229.0)/μL、-91.0(-110.0, 153.3)/μL比-94.0(-130.8, 114.3)/μL，差异均无统计学意义(t＝-0.516、-0.066、-1.414、Z＝-1.715、-0.802、-1.602，均P>0.05)。ART后24、48和96周时，HIV单独感染组的HIV RNA抑制率分别为89.7%(130/145)、96.6%(140/145)和96.6%(140/145)，HBV合并HIV感染组分别为87.1%(108/124)、92.7%(115/124)和94.4%(117/124)，差异均无统计学意义(χ2＝0.026、0.053、0.017，均P>0.05)。ART后第2周、第4周HIV单独感染组肝功能异常率分别为3.4%(5/145)、6.2%(9/145)，低于HBV合并HIV感染组的21.0%(26/124)、13.7%(17/124)，差异均有统计学意义(χ2＝20.121、4.309，均P<0.05)；而第8周[10.3%(15/145)比9.7%(12/124)]、第12周[9.0%(13/145)比9.7%(12/124)]、第24周[9.7%(14/145)比8.9%(11/124)]、第36周[9.7%(14/145)比10.5%(13/124)]、第48周[8.3%(12/145)比8.1%(10/124)]、第96周[2.8%(4/145)比0(0/124)]的肝功能异常率差异均无统计学意义(χ2＝0.330、0.040、0.049、0.051、0.004、3.472，均P>0.05)。结论合并HBV感染对HIV感染者的ART效果无不良影响。

简介：AbstractIndirect effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are difficult to calculate. Fear of intrahospital infection has led to a decrease in the use of emergency services and the performance of elective procedures. Several low- and middle-income countries have seen the number of institutional deliveries reduced, even in the absence of a follow-up program for home births. We present the case of a patient with adequate prenatal care and an institutional delivery plan who, due to the SARS-CoV-2 pandemic, chose to have a home delivery with unsafe conditions. The lack of supervision by health personnel and the absence of an immediate consultation plan facilitated the presentation of postpartum hemorrhage and poor neonatal results. Little attention has been paid during the pandemic to pregnant women who decide to have their birth at home. A broad discussion is necessary in this regard, to regain the confidence of the population and strengthen institutional births, or to strengthen midwife-assisted home births programs. Patients’ fear to acquiring SARS-CoV-2 infection inside hospitals is a factor that must be taken into account in prenatal care programs.

简介：摘要目的探讨新型冠状病毒（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）非结构蛋白1（nonstructural protein 1，NSP1）对I型干扰素（type I interferon，IFN-I）应答的影响及其作用机制。方法为研究SARS-CoV-2的NSP1对I型IFN产生的影响，构建NSP1表达质粒，并通过免疫荧光检测其蛋白表达能力。通过双荧光素酶报告基因实验检测NSP1对IFN-β启动子激活的作用。构建NSP1突变体M1（K163AH164A）和M2（△161-180），验证突变位点对IFN-β启动子激活的影响。结果NSP1显著抑制维甲酸诱导基因蛋白I、黑色素瘤分化相关蛋白5、线粒体抗病毒信号蛋白、TANK结合激酶1、干扰素调节因子3、干扰素调节因子7诱导的下游IFN-β启动子的激活，并对I型IFN通路的各关键分子的蛋白表达具有抑制作用，NSP1 C端的KH基序是其发挥抑制作用的关键位点。结论SARS-CoV-2 NSP1能够拮抗宿主I型干扰素免疫应答，实现病毒的天然免疫逃逸。

简介：AbstractMany factors have been identified as having the ability to affect the sensitivity of rapid antigen detection (RAD) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to identify the impact of sample processing on the sensitivity of the RAD tests. We explored the effect of different inactivation methods, viral transport media (VTM) solutions, and sample preservation on the sensitivity of four RAD kits based on two SARS-CoV-2 strains. Compared with non-inactivation, heat inactivation significantly impacted the sensitivity of most RAD kits; however, β-propiolactone inactivation only had a minor effect. Some of the VTM solutions (VTM2, MANTACC) had a significant influence on the sensitivity of the RAD kits, especially for low viral-loads samples. The detection value of RAD kits was slightly decreased, while most of them were still in the detection range with the extension of preservation time and the increase of freeze-thaw cycles. Our results showed that selecting the appropriate inactivation methods and VTM solutions is necessary during reagent development, performance evaluation, and clinical application.

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简介：摘要目的探讨人乳头瘤病毒（HPV）-DNA、巨细胞病毒（CMV）-DNA病毒含量与子宫内膜癌（EC）危险因素关系及预测模型。方法选取安徽医科大学附属宿州医院2017年1月至2020年6月EC患者58例作为观察组，根据1∶1匹配病例对照原则选取同期子宫内膜增生（EH）患者58例作为对照组。比较两组临床资料、HPV-DNA、CMV-DNA阳性率及病毒含量，经由单因素分析将P<0.05的自变量纳入Logistic回归模型，分析EC危险因素，评价HPV-DNA、CMV-DNA与EC危险因素的相关性，采用似然比卡方、拟合优度检验评价Logistic回归模型，受试者工作特征（ROC）曲线分析模型对EC的预测价值。结果观察组年龄≥ 55岁、体质量指数（BMI）≥ 24 kg/m2、有高血压史、有糖尿病史、有恶性肿瘤家族史、有激素替代治疗史均高于对照组[72.41%（42/58）比39.66%（23/58）、70.69%（41/58）比43.10%（25/58）、36.21%（21/58）比10.34%（6/58）、31.03%（18/58）比8.62%（5/58）、29.31%（17/58）比5.17%（3/58）、27.93%（17/58）比8.62%（5/58）]，差异有统计学意义（P<0.05）；观察组HPV阳性率、CMV阳性率、HPV-DNA、CMV-DNA病毒含量高于对照组[62.07%（36/58）比29.31%（17/58）、81.03%（47/58）比41.38%（24/58）、（471.16 ± 33.58）copies/ml比（240.08 ± 17.41）copies/ml、（256.19 ± 24.77）copies/ml比（132.27 ± 13.20）copies/ml]（P<0.05）；年龄≥ 55岁、BMI ≥ 24 kg/m2、高血压史、糖尿病史、恶性肿瘤家族史、激素替代治疗史、HPV阳性、CMV阳性是EC发生的危险因素（P<0.05）；HPV-DNA病毒含量与EC患者年龄、恶性肿瘤家族史、糖尿病史呈正相关（P<0.05），CMV-DNA病毒含量与年龄、恶性肿瘤家族史、高血压史呈正相关（P<0.05）；根据Logistic回归模型预测值和真实值绘制ROC曲线，曲线下面积为0.930（95% CI 0.885~0.976），当个体发生医院感染的预测概率>0.528时，预测灵敏度为84.48%，特异度为89.66%。结论EC发生与多种因素有关，而HPV-DNA、CMV-DNA病毒含量均是其发生的危险因素，构建基于EC病理特征及HPV-DNA、CMV-DNA病毒含量的Logistic回归模型，整体预测价值较高，具有临床应用前景。

简介：摘要目的探讨人乳头瘤病毒（HPV）-DNA、巨细胞病毒（CMV）-DNA病毒含量与子宫内膜癌（EC）危险因素关系及预测模型。方法选取安徽医科大学附属宿州医院2017年1月至2020年6月EC患者58例作为观察组，根据1∶1匹配病例对照原则选取同期子宫内膜增生（EH）患者58例作为对照组。比较两组临床资料、HPV-DNA、CMV-DNA阳性率及病毒含量，经由单因素分析将P<0.05的自变量纳入Logistic回归模型，分析EC危险因素，评价HPV-DNA、CMV-DNA与EC危险因素的相关性，采用似然比卡方、拟合优度检验评价Logistic回归模型，受试者工作特征（ROC）曲线分析模型对EC的预测价值。结果观察组年龄≥ 55岁、体质量指数（BMI）≥ 24 kg/m2、有高血压史、有糖尿病史、有恶性肿瘤家族史、有激素替代治疗史均高于对照组[72.41%（42/58）比39.66%（23/58）、70.69%（41/58）比43.10%（25/58）、36.21%（21/58）比10.34%（6/58）、31.03%（18/58）比8.62%（5/58）、29.31%（17/58）比5.17%（3/58）、27.93%（17/58）比8.62%（5/58）]，差异有统计学意义（P<0.05）；观察组HPV阳性率、CMV阳性率、HPV-DNA、CMV-DNA病毒含量高于对照组[62.07%（36/58）比29.31%（17/58）、81.03%（47/58）比41.38%（24/58）、（471.16 ± 33.58）copies/ml比（240.08 ± 17.41）copies/ml、（256.19 ± 24.77）copies/ml比（132.27 ± 13.20）copies/ml]（P<0.05）；年龄≥ 55岁、BMI ≥ 24 kg/m2、高血压史、糖尿病史、恶性肿瘤家族史、激素替代治疗史、HPV阳性、CMV阳性是EC发生的危险因素（P<0.05）；HPV-DNA病毒含量与EC患者年龄、恶性肿瘤家族史、糖尿病史呈正相关（P<0.05），CMV-DNA病毒含量与年龄、恶性肿瘤家族史、高血压史呈正相关（P<0.05）；根据Logistic回归模型预测值和真实值绘制ROC曲线，曲线下面积为0.930（95% CI 0.885~0.976），当个体发生医院感染的预测概率>0.528时，预测灵敏度为84.48%，特异度为89.66%。结论EC发生与多种因素有关，而HPV-DNA、CMV-DNA病毒含量均是其发生的危险因素，构建基于EC病理特征及HPV-DNA、CMV-DNA病毒含量的Logistic回归模型，整体预测价值较高，具有临床应用前景。

简介：摘要目的建立基于SYBR Green I颜色判定的检测新型冠状病毒（severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）ORF1ab基因的逆转录环介导等温扩增方法（reverse transcription loop-mediated isothermal amplification，RT-LAMP），为诊断SARS-CoV-2提供简便、快速和准确可靠的工具。方法基于GenBank中SARS-CoV-2 ORF1ab基因序列保守区设计引物，经引物筛选和RT-LAMP反应体系优化后进行灵敏度和特异性评价，并与实时荧光定量RT-PCR（quantitative real-time PCR，qRT-PCR）方法进行比较。结果基于颜色判定的RT-LAMP方法可在65℃45 min内完成SARS-CoV-2的快速检测，检测限为3 copies/reaction，与qRT-PCR的敏感度一致。RT-LAMP检测人冠状病毒OC43、人冠状病毒NL63和乙型流感病毒核酸样本结果为阴性，具有较好的特异性。经SARS-CoV-2临床样本验证，RT-LAMP与qRT-PCR的检测符合率达100%。结论基于颜色判定的RT-LAMP方法灵敏度高、特异性强，适用于SARS-CoV-2的快速可视化检测，具有应用于SARS-CoV-2样本的初筛及基层卫生医疗机构和现场推广的潜力。