简介：摘要严重急性呼吸系统综合症冠状病毒2(severe acute respiratory syndrome coronavirus 2，SARS-CoV-2)感染造成的新型冠状病毒肺炎(coronavirus disease 2019，COVID-19)是人类本世纪来面临的威胁最大的传染病之一。目前，全球范围内有4类疫苗已经获批上市或授权紧急使用—灭活疫苗、mRNA疫苗、腺病毒载体疫苗和重组蛋白疫苗。随着COVID-19大流行的持续，已进行全程免疫人群的抗体水平逐渐降低，加强免疫是必要的措施，而序贯免疫策略似乎是一种更好的疫苗接种策略。本文将对四类不同技术路线疫苗在序贯免疫中的研究进行综述。

简介：摘要严重急性呼吸综合征冠状病毒2 （severe acute respiratory syndrome coronavirus 2，SARS-CoV-2）感染导致的新型冠状病毒肺炎（coronavirus disease 2019，COVID-19）引发全球大流行。HIV感染者/艾滋病患者是一个特殊人群，由于其免疫系统受损及各种并发症，对SARS-CoV-2的感染风险、疾病严重程度和预后等产生重要影响。本文对HIV-1/SARS-CoV-2合并感染的流行病学特点、临床特征和转归等进行综述。

简介：摘要目的分析新型冠状病毒在不同食品和加工材料表面存活规律，为制定预防病毒通过食品和加工材料传播的防控措施和风险评估提供参考。方法将病毒培养物接种至常见进口食品和加工材料表面，使用荧光定量PCR方法测定在不同温度和时间条件下样本表面病毒核酸载量；使用半数组织培养感染剂量实验测定病毒滴度，观察病毒存活时间。使用线性回归模型计算病毒半衰期。结果食品和加工材料表面病毒核酸载量随时间下降，且温度越高病毒核酸载量下降越快。不同种类食品和加工材料表面病毒存活时间不同，室温条件下，猪肉和车厘子表面病毒存活24 h；其次为带鱼和鲜橙表面。加工材料表面病毒存活时间均较短，小于24 h。4 ℃条件下，病毒在猪肉表面至少存活1周，其次为车厘子和带鱼。-20 ℃条件下，病毒在猪肉和塑料包装表面的活性下降缓慢，8周后病毒滴度仍然较高，而在带鱼和纸板表面的活性下降明显。结论不同食品和加工材料表面的病毒核酸存续时间和存活规律不同，且温度越低病毒存活时间越长，应根据食品、加工材料类型，以及生产环境条件制定针对性预防和消毒措施。

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简介：【摘要】目前针对新冠病毒的特效药的研发策略主要有三种：抗体研发，感染阻断，以及从天然药材中提取有效物质。本文讨论了通过阻断以达到阻止病毒入侵的药物研发策略。与 SARS-CoV相似， SARS-CoV-2使用人体酶 ACE2作为入侵的结合位点并且需要蛋白酶 TMPRSS2的辅助进行膜融合。因此，针对这一特点可有两种阻断策略：抑制宿主蛋白或阻止受体结合。而阻止受体结合的过程中可有三个目标：受体结合域，突刺蛋白，以及 ACE2。

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简介：摘要越来越多的证据表明，严重急性呼吸系统综合征2型冠状病毒（SARS-CoV-2）对人体损害不局限于呼吸道，还可侵入中枢神经系统，诱发神经系统疾病。SARS-CoV-2病毒作为一种新兴的病毒，可能会对神经系统产生短期及长期影响。加之，目前SARS-CoV-2的临床治疗仅限于对症支持治疗以及使用多种抗RNA病毒药物（如法匹拉韦、羟氯喹），尽管专门针对SARS-CoV-2的疫苗和治疗性抗体在测试中，但这种解决方案具有长期性，需要对其安全性进行彻底测试。因此，了解SARS-CoV-2潜在的神经侵袭机制就显得尤为重要，对其防治工作具有重要的指导意义。本文就SARS-CoV-2的病原学、神经侵袭的可能机制以及与神经系统疾病的关系作一综述，旨在为SARS-CoV-2的有效防控治疗提供依据和参考。

简介：摘要:严重急性呼吸系统综合征(SARS)的流行表明，人畜共患病向人类和动物冠状病毒(COV)的传播对公众健康构成严重威胁，因此有必要制定防治对策。由于缺乏对SARS-CoV-2引起的COVID-19的有效治疗，为了开发更有效的抑制剂，我们发现非共价片段X1249的设计提供了进一步的有益信息。

简介：AbstractBackground:Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student's t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

简介：AbstractThe coronavirus disease 2019 (COVID-19) is still causing a wide range of infections and deaths due to the high variability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, it is necessary to establish a reliable and convenient pseudovirus-based neutralization assay to develop drug targeted variants of SARS-CoV-2. Based on the HIV-1 backbone, we generated a high titer luciferase (Luc)-expressing pseudovirus packaging system. Three dominant S mutant substitution pseudovirus were also established and identified compared to wide type in hACE2-overexpressing HEK-293T cells (293T-ACE2 cells). Compared to serine protease inhibitor camostat mesylate, the cysteine protease inhibitor E-64d could significantly block all SARS-CoV-2 mutant S pseudovirus infection in 293T-ACE2 cells. Furthermore, the neutralization ability of two antibodies targeted receptor-binding domain (RBD) of SARS-CoV-2 spike protein (S) was evaluated, which showed different inhibition dose-effect curves among four types of S pseudovirus. Overall, we developed a pseudovirus-based neutralization assay for SARS-CoV-2, which would be readily adapted to SARS-CoV-2 variants for evaluating antibodies.

简介：AbstractThe immune responses and the function of immune cells among asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cases, especially in immuno-compromised individuals, remain largely unknown. Here we present a case of asymptomatic SARS-CoV-2 infection that lasted for at least 67 days. The patient has administrated Thymalfasin as 1.6 mg per dose every other day from Day 45 to 70, plus 200 mg per dose Arbidol antiviral therapy three doses per day from Day 48 to 57. Throughout the infection, no anti-SARS-CoV-2 specific IgM or IgG antibodies were detected. Instead, the patient showed either a low percentage or an absolute number of non-classical monocytes, dendritic cells (DCs), CD4+ T cells, and regulatory T cells (Tregs), which may account for the clinical feature and absence of antibody response. This case may shed new light on the outbreak management related to control/prevention, treatment, and vaccination of SARS-CoV-2 and other virus infections in immunocompromised individuals.

简介：AbstractSince severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified during late 2019, the sustained spread of this pathogen within the human population has caused worldwide disruption with staggering infection rates and death tolls. Due to the accumulation of mutations in SARS-CoV-2, the virus has evolved into many variants, five of which have been listed as variants of concern VOCs by the World Health Organization (WHO). Multiple animal models of SARS-CoV-2 have been developed to evaluate vaccines and drugs and to assess the pathogenicity, transmissibility and antiviral measures of these VOCs. Here, we review the cutting-edge research based on mouse, hamster, ferret and non-human primate models for evaluating SARS-CoV-2 with a focus on the Omicron variant, and highlight the importance of updating vaccines in a timely manner in order to mitigate the negative effects of SARS-CoV-2 infections in the human population.

简介：AbstractA series of stringent non-pharmacological and pharmacological interventions were implemented to contain the pandemic but the pandemic continues. Moreover, vaccination breakthrough infection and reinfection in convalescent coronavirus disease 2019 (COVID-19) cases have been reported. Further, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerged with mutations in spike (S) gene, the target of most current vaccines. Importantly, the mutations exhibit a trend of immune escape from the vaccination. Herein the scientific question that if the vaccination drives genetic or antigenic drifts of SARS-CoV-2 remains elusive. We performed correlation analyses to uncover the impacts of wide vaccination on epidemiological characteristics of COVID-19. In addition, we investigated the evolutionary dynamics and genetic diversity of SARS-CoV-2 under immune pressure by utilizing the Bayesian phylodynamic inferences and the lineage entropy calculation respectively. We found that vaccination coverage was negatively related to the infections, severe cases, and deaths of COVID-19 respectively. With the increasing vaccination coverage, the lineage diversity of SARS-CoV-2 dampened, but the rapid mutation rates of the S gene were identified, and the vaccination could be one of the explanations for driving mutations in S gene. Moreover, new epidemics resurged in several countries with high vaccination coverage, questioning their current pandemic control strategies. Hence, integrated vaccination and non-pharmacological interventions are critical to control the pandemic. Furthermore, novel vaccine preparation should enhance its capabilities to curb both disease severity and infection possibility.

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：摘要SARS-CoV-2是引起COVID-19大流行的病原体，对人类的生命健康和社会稳定造成严重危害。在重型COVID-19病例中，病毒感染引发细胞因子风暴，导致多器官炎症反应过度直至衰竭，最终导致患者死亡。最近研究显示，核苷酸结合寡聚化结构域样受体蛋白3 (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3, NLRP3)炎症小体的激活是SARS-CoV-2致病的重要机制，SARS-CoV-2可通过多种途径激活NLRP3炎症小体，从而诱发大量促炎细胞因子释放。本文综述了SARS-CoV-2感染激活NLRP3炎性小体及其分子机制，并总结靶向抑制NLRP3炎症小体的研究进展，为治疗SARS-CoV-2感染提供新策略。

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简介：AbstractThe novel betacoronavirus (Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2) is a pathogen that causes deadly respiratory disease named coronavirus disease 2019 (COVID-19). The incidence of this disease has increased in the last few months affecting 257,832,881 people in 221 countries and 51,68,069 deaths worldwide according to Worldometer at 04:03 GMT on November 22, 2021. Thus, the emergence of this disease creates a challenge for health care providers in handling this pathogen and reducing its risk of transmission. In developing countries, this virus is treated in biosafety level 2 laboratories, where a high concentration of pathogen can easily affect the laboratory staff and cause the spread of this disease. Based on the epidemiology and characteristics of the SARS-CoV-2 virus already discussed in recent studies, we will provide biosafety guidelines and suggestions for safe handling and transportation of the SARS-CoV-2 virus in dealing with the current pandemic situation with a focus on increased infectivity of emerging new variants.

简介：AbstractThe pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented social and economic disruption. Many nucleic acid testing (NAT) laboratories in China have been established to control the epidemic better. This proficiency testing (PT) aims to evaluate the participants’ performance in qualitative and quantitative SARS-CoV-2 NAT and to explore the factors that contribute to differences in detection capabilities. Two different concentrations of RNA samples (A, B) were used for quantitative PT. Pseudovirus samples D, E (different concentrations) and negative sample (F) were used for qualitative PT. 50 data sets were reported for qualitative PT, of which 74.00% were entirely correct for all samples. Forty-two laboratories participated in the quantitative PT. 37 submitted all gene results, of which only 56.76% were satisfactory. For qualitative detection, it is suggested that laboratories should strengthen personnel training, select qualified detection kits, and reduce cross-contamination to improve detection accuracy. For quantitative detection, the results of the reverse transcription digital PCR (RT-dPCR) method were more comparable and reliable than those of reverse transcription quantitative PCR (RT-qPCR). The copy number concentration of ORF1ab and N in samples A and B scattered in 85, 223, 50, and 106 folds, respectively. The differences in the quantitative result of RT-qPCR was mainly caused by the non-standard use of reference materials and the lack of personnel operating skills. Comparing the satisfaction of participants participating in both quantitative and qualitative proficiency testing, 95.65% of the laboratories with satisfactory quantitative results also judged the qualitative results correctly, while 85.71% of the laboratories with unsatisfactory quantitative results were also unsatisfied with their qualitative judgments. Therefore, the quantitative ability is the basis of qualitative judgment. Overall, participants from hospitals reported more satisfactory results than those from enterprises and universities. Therefore, surveillance, daily qualitiy control and standardized operating procedures should be strengthened to improve the capability of SARS-CoV-2 NAT.

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.