Clinical Effect of Yinhuang Qingfei Capsules in Treatment of Asymptomatic and Mild/Common Severe Acute Respiratory Syndrome Coronavirus 2 Infection:An Analysis of 242 Cases

[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.

Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic

The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions.

Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

A Case of Severe Acute Respiratory Syndrome (SARS) Coronavirus 2 in Pregnancy: A Multidisciplinary Approach

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is a truly novel, multifaceted disease that has negatively impacted the lives of many including the pregnant women. We present a 34-year-old pregnant patient at 35 weeks with SARS-COV-2 requiring emergent cesarean section under general endotracheal anesthesia and a prolonged postoperative course in the ICU with multiple end organ function derangement of this disease. After nearly 1 month, she was discharged home. Her baby did not have any manifestations of SARS-COV-2 and was able to go home after 5 days.

Biology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the humoral immunoresponse:a systematic review of evidence to support global policy-level actions and research

Background Both population-level epidemiological data and individual-level biological data are needed to control the coronavirus disease 2019(COVID-19)pandemic.Population-level data are widely available and efforts to combat COVID-19 have generated proliferate data on the biology and immunoresponse to the causative pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).However,there remains a paucity of systemized data on this subject.Objective In this review,we attempt to extract systemized data on the biology and immuno-response to SARS-CoV-2 from the most up-to-date peer-reviewed studies.We will focus on the biology of the virus and immunological variations that are key for determining long-term immunity,transmission potential,and prognosis.Data Sources and Methods Peer-reviewed articles were sourced from the PubMed database and by snowballing search of selected publications.Search terms included:“Novel Coronavirus”OR“COVID-19”OR“SARS-CoV-2”OR“2019-nCoV”AND“Immunity”OR“Immune Response”OR“Antibody Response”OR“Immunologic Response”.Studies published from December 31,2019 to December 31,2020 were included.To ensure validity,papers in pre-print were excluded.Results Of 2889 identified papers,36 were included.Evidence from these studies suggests early seroconversion in patients infected with SARS-CoV-2.Antibody titers appear to markedly increase two weeks after infection,followed by a plateau.A more robust immune response is seen in patients with severe COVID-19 as opposed to mild or asymptomatic presentations.This trend persists with regard to the length of antibody maintenance.However,overall immunity appears to wane within two to three months post-infection.Conclusion Findings of this study indicate that immune responses to SARS-CoV-2 follow the general pattern of viral infection.Immunity generated through natural infection appears to be short,suggesting a need for long-term efforts to control the pandemic.Antibody testing will be essential to gauge the epidemic and inform decision-making on effective strategies for treatment and prevention.Further research is needed to illustrate immunoglobulin-specific roles and neutralizing antibody activity.

Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na^(+)/H^(+) exchanger

The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.

Clinical and Spatial Characteristics of Severe Acute Respiratory Syndrome by COVID-19 in Indigenous of Brazil

The new coronavirus (SARS-CoV-2) broke out in Wuhan in China in December 2019, causing severe pneumonia and deaths, soon in March 2020, it reached pandemic level, affecting several countries including Brazil. The disease was named COVID-19, with characteristics of most infected having mild and moderate symptoms and a part severe symptom. The disease has already reached 158 ethnic groups, which have high vulnerability and limited access to health services. The objective is to investigate the clinical and spatial characteristics of Severe Acute Respiratory Syndrome of COVID-19 in the indigenous peoples of Brazil. It is an epidemiological, cross-sectional, analytical ecological study, based on data from the OpenDataSUS platform from 01/01/2020 to 31/08/2020. Profile variables, signs and symptoms and risk factors/comorbidities. The data were analyzed by Bioestat 5.3. There were 1,207 cases and 470 deaths. Profile: male gender (59.48%) means age 53 years. Signs and symptoms: fever (74.23%), cough (77.71%), sore throat (35.62%), dyspnea (69.34%), respiratory discomfort (62.80%), O2 saturation < 95% (56.42%);and associated with mortality: dyspnea (80.0%) and O2 saturation < 95% (69.36%). Risk factors and comorbidities (45.89%) were associated with deaths (54.04%). About comorbidities, chronic cardiovascular diseases represented (18.97%) and Diabetes Mellitus (18.97%), and associated with deaths: Chronic Cardiovascular Disease (24.46%). Being admitted to the ICU has a risk of death in (OR-3.96- < 0.0001-CI-2913/5383) followed by not being vaccinated against influenza (OR-1.85- < 0.0001-CI-1358/2528). The public and health policies of Brazil should be directed to control the dissemination of COVID-19 in this population, that COVID-19 evolves in the same intensity, however, the indigenous have vulnerabilities that can increase the impact of the pandemic in this population.

Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China

Background:Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and coronavirus disease 2019(COVID-19)development.Currently,it is unclear whether mitochondrial DNA(mtDNA)variants,which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production,are associated with COVID-19 risk.Methods:A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls(n=615)and COVID-19 patients(n=536).COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning.The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment.MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny.Student’s t-test was used for continuous variables,and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables.To assess the independent effect of each mtDNA variant defining mtDNA haplogroups,multivariate logistic regression analyses were performed to calculate the odds ratios(OR)and 95%confidence intervals(CI)with adjustments for possible confounding factors of age,sex,smoking and diseases(including cardiopulmonary diseases,diabetes,obesity and hypertension)as determined through clinical and radiographic examinations.Results:Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations(>10%in the control population)at C5178 a(in NADH dehydrogenase subunit 2 gene,ND2)and A249 d(in the displacement loop region,D-loop)/T6392 C(in cytochrome c oxidase I gene,CO1)/G10310 A(in ND3)were associated with a reduced risk of severe COVID-19(OR=0.590,95%CI 0.428–0.814,P=0.001;and OR=0.654,95%CI 0.457–0.936,P=0.020,respectively),while A4833 G(ND2),A4715 G(ND2),T3394 C(ND1)and G5417 A(ND2)/C16257 a(D-loop)/C16261 T(D-loop)were related to an increased risk of severe COVID-19(OR=2.336,95%CI 1.179–4.608,P=0.015;OR=2.033,95%CI 1.242–3.322,P=0.005;OR=3.040,95%CI 1.522–6.061,P=0.002;and OR=2.890,95%CI 1.199–6.993,P=0.018,respectively).Conclusions:This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19.Based on the case–control study,we concluded that the common mtDNA variants at C5178 a and A249 d/T6392 C/G10310 A might contribute to an individual’s resistance to developing severe COVID-19,whereas A4833 G,A4715 G,T3394 C and G5417 A/C16257 a/C16261 T might increase an individual’s risk of developing severe COVID-19.

SARS-CoV-2 viral load in the upper respiratory tract and disease severity in COVID-19 patients

Due to the disease's broad clinical spectrum,it is currently unclear how to predict the future prognosis of patients at the time of diagnosis of coronavirus disease 2019(COVID-19).Real-time reverse transcription-polymerase chain reaction(RTPCR)is the gold standard molecular technique for diagnosing COVID-19.The number of amplification cycles necessary for the target genes to surpass a threshold level is represented by the RT-PCR cycle threshold(Ct)values.Ct values were thought to be an adequate proxy for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral load.A body of evidence suggests that SARS-CoV-2 viral load is a possible predictor of COVID-19 severity.The link between SARS-CoV-2 viral load and the likelihood of severe disease development in COVID-19 patients is not clearly elucidated.In this review,we describe the scientific data as well as the important findings from many clinical studies globally,emphasizing how viral load may be related to disease severity in COVID-19 patients.Most of the evidence points to the association of SARS-CoV-2 viral load and disease severity in these patients,and early anti-viral treatment will reduce the severe clinical outcomes.

成人接种2剂新冠灭活疫苗12个月后T细胞免疫应答特点

目的评估成年人接种新型冠状病毒(SARS-CoV-2)灭活疫苗12个月后不同抗原特异性T细胞免疫应答的特点。方法解放军总医院第五医学中心2022年4-6月招募15名健康成年人,于接种2剂新冠灭活疫苗12个月后采集其静脉血标本,以基于多色流式细胞术的活化诱导标记法(AIM)检测SARS-CoV-2抗原特异性T淋巴细胞水平,并分析其记忆表型与亚群分化特点。结果成年人接种2剂灭活疫苗12个月后,90%以上个体可检测到Spike及Non-spike特异性CD4^(+)T细胞反应(S:14/15,P=0.0001;NS:15/15,P<0.0001);80%个体检测到Spike及Non-spike特异性CD8^(+)T细胞反应(S:12/15,P=0.0463;NS:12/15,P=0.0806)。抗原特异性CD4^(+)T细胞主要表现为中央记忆细胞(CM)、1型效应记忆细胞(EM1)记忆表型,以及1/17型辅助性T细胞(Th1/17)、2型辅助性T细胞(Th2)辅助表型。结论灭活疫苗接种后能诱导广泛且持久的抗原特异性CD4^(+)T细胞反应,可能是当前国内新型冠状病毒感染重症化比例较低的关键因素。

上海市某方舱医院2897例新型冠状病毒Omicron变异株轻型/无症状感染者住院时间影响因素分析

目的探讨上海市某方舱医院新型冠状病毒奥密克戎(Omicron)变异株轻型/无症状感染者住院时间的影响因素。方法回顾性收集上海宝山泾灿路(罗泾京东)方舱医院收治的2897例Omicron变异株轻型/无症状感染者的病历资料,分析其一般资料、住院时间等基本情况,探究不同特征的新冠病毒Omicron变异株感染者住院时间差异,采用多重线性回归方法分析住院时间的影响因素。根据单因素分析结果,采用二元logistic回归分析住院时间≥14 d可能的影响因素。结果2897例Omicron变异株轻型/无症状感染者的平均住院时间为(9.1±4.6)d,不同年龄段、入舱前核酸阳性时间以及伴有咳嗽、咳痰、咽痛、发热、流涕、鼻塞、口干咽燥、头痛、乏力、肌痛、腹泻、恶寒、恶心呕吐、头晕症状的感染者住院时间不同,差异具有统计学意义(P<0.05)。多重线性回归结果显示,年龄增加、患有糖尿病史以及咽痛、发热、流涕、肌痛症状会增加住院天数,而入舱前核酸阳性时间长则会减少住院天数。住院时间≥14 d者,高龄、糖尿病史以及出现咽痛、发热、口干咽燥、肌痛、恶心呕吐症状的占比更高,入舱前核酸阳性时间相对更短,接种2针及以上疫苗占比更低,差异具有统计学意义(P<0.05)。二元Logistic回归结果显示,高龄、入舱前核酸阳性时间短、糖尿病史以及发热和口干咽燥症状可能是导致住院时间超过14 d的危险因素,接种2针及以上疫苗可能是保护因素。结论Omicron变异株轻型/无症状感染者平均住院时间约为9 d,高龄、疫苗接种2针及以上、患有糖尿病史、入舱前核酸阳性时间短以及咽痛、发热、流涕、口干咽燥、肌痛等正气虚衰、病邪入里、化热伤阴表现对于住院时间可能产生重要影响。通过尽早识别核酸转阴慢、住院时间长的高危患者,以期为缩短核酸转阴时间、指导重点人群精准防控提供指导方向。

Cold chain and severe acute respiratory syndrome coronavirus 2 transmission:a review for challenges and coping strategies

Since June 2020,the re-emergence of coronavirus disease 2019(COVID-19)epidemics in parts of China was linked to the cold chain,which attracted extensive attention and heated discussions from the public.According to the typical characteristics of these epidemics,we speculated a possible route of transmission from cold chain to human.A series of factors in the supply chain contributed to the epidemics if the cold chain were contaminated by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),such as temperature,humidity,personal hygiene/protection,and disinfection.The workers who worked in the cold chain at the receiving end faced a higher risk of being infected when they were not well protected.Facing the difficult situation,China put forward targeted and powerful countermeasures to block the cold chain-related risk.However,in the context of the unstable pandemic situation globally,the risk of the cold chain needs to be recognized and evaluated seriously.Hence,in this review,we reviewed the cold chain-related epidemics in China,analyzed the possible mechanisms,introduced the Chinese experience,and suggested coping strategies for the global epidemic prevention and control.

Evolutionary dynamics of the severe acute respiratory syndrome coronavirus 2 genomes

The coronavirus disease 2019(COVID-19)pandemic has caused immense losses in human lives and the global economy and posed significant challenges for global public health.As severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of COVID-19,has evolved,thousands of single nucleotide variants(SNVs)have been identified across the viral genome.The roles of individual SNVs in the zoonotic origin,evolution,and transmission of SARS-CoV-2 have become the focus of many studies.This review summarizes recent comparative genomic analyses of SARS-CoV-2 and related coronaviruses(SC2r-CoVs)found in non-human animals,including delineation of SARS-CoV-2 lineages based on characteristic SNVs.We also discuss the current understanding of receptor-binding domain(RBD)evolution and characteristic mutations in variants of concern(VOCs)of SARS-CoV-2,as well as possible co-evolution between RBD and its receptor,angiotensin-converting enzyme 2(ACE2).We propose that the interplay between SARS-CoV-2 and host RNA editing mechanisms might have partially resulted in the bias in nucleotide changes during SARS-CoV-2 evolution.Finally,we outline some current challenges,including difficulty in deciphering the complicated relationship between viral pathogenicity and infectivity of different variants,and monitoring transmission of SARS-CoV-2 between humans and animals as the pandemic progresses.

Expert Recommendation for Novel Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in HIV-Infected Adults

The outbreak of coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a pandemic.SARS-CoV-2 vaccination is currently being actively promoted worldwide as a promising measure to combat the pandemic.However,human immunodeficiency virus(HIV)-infected individuals who manifest varying degrees of immunodeficiency and chronic inflammation may require special consideration with regards to vaccine types and the timing of immunization depending on specific clinical situations.The present recommendation provides a reference for SARS-CoV-2 vaccination in HIV-infected patients.

Variation analysis of the severe acute respiratory syndrome coronavirus putative non-structural protein 2 gene and construction of three-dimensional model

Background The rapid transmission and high mortality rate made severe acute respiratory syndrome (SARS) a global threat for which no efficacious therapy is available now. Without sufficient knowledge about the SARS coronavirus (SARS-CoV), it is impossible to define the candidate for the anti-SARS targets. The putative non-structural protein 2 (nsp2) (3CL pro , following the nomenclature by Gao et al, also known as nsp5 in Snidjer et al) of SARS-CoV plays an important role in viral transcription and replication, and is an attractive target for anti-SARS drug development, so we carried on this study to have an insight into putative polymerase nsp2 of SARS-CoV Guangdong (GD) strain. Methods The SARS-CoV strain was isolated from a SARS patient in Guangdong, China, and cultured in Vero E6 cells. The nsp2 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into eukaryotic expression vector pCI-neo (pCI-neo/nsp2). Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein. The expressive protein of SARS-CoV nsp2 was analyzed by 7% sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). The nucleotide sequence and protein sequence of GD nsp2 were compared with that of other SARS-CoV strains by nucleotide-nucleotide basic local alignment search tool (BLASTN) and protein-protein basic local alignment search tool (BLASTP) to investigate its variance trend during the transmission. The secondary structure of GD strain and that of other strains were predicted by Garnier-Osguthorpe-Robson (GOR) Secondary Structure Prediction. Three-dimensional-PSSM Protein Fold Recognition (Threading) Server was employed to construct the three-dimensional model of the nsp2 protein.Results The putative polymerase nsp2 gene of GD strain was amplified by RT-PCR. The eukaryotic expression vector (pCI-neo/nsp2) was constructed and expressed the protein in COS-7 cells successfully. The result of sequencing and sequence comparison with other SARS-CoV strains showed that nsp2 gene was relatively conservative during the transmission and total five base sites mutated in about 100 strains investigated, three of which in the early and middle phases caused synonymous mutation, and another two base sites variation in the late phase resulted in the amino acid substitutions and secondary structure changes. The three-dimensional structure of the nsp2 protein was successfully constructed. Conclusions The results suggest that polymerase nsp2 is relatively stable during the phase of epidemic. The amino acid and secondary structure change may be important for viral infection. The fact that majority of single nucleotide variations (SNVs) are predicted to cause synonymous, as well as the result of low mutation rate of nsp2 gene in the epidemic variations, indicates that the nsp2 is conservative and could be a target for anti-SARS drugs. The three-dimensional structure result indicates that the nsp2 protein of GD strain is high homologous with 3CL pro of SARS-CoV urbani strain, 3CL pro of transmissible gastroenteritis virus and 3CL pro of human coronavirus 229E strain, which further suggests that nsp2 protein of GD strain possesses the activity of 3CL pro .

SARS-COV-2 M^(pro)抑制剂2-(2-氯苯基)-7-(异喹啉-4-基)-5,7-二氮杂螺[3.4]辛-6,8-二酮的合成

目的研究SARS-COV-2 M^(pro)抑制剂2-(2-氯苯基)-7-(异喹啉-4-基)-5,7-二氮杂螺[3.4]辛-6,8-二酮(1)的合成方法,为其深入研究和其衍生物的合成提供借鉴方法。方法以(2-氯苯基)乙酸甲酯为起始原料,经亲电取代、还原、磺酰化、环化、选择性水解得到3-(2-氯苯基)-1-乙氧羰基环丁烷-1-甲酸(6),在三乙胺存在下,化合物6与叠氮磷酸二苯酯反应,生成的酰基叠氮化合物经Curtius重排生成相应的异氰酸酯;再与4-氨基异喹啉反应,并在碳酸钠的作用下进一步环合生成目标化合物。结果中间体及目标化合物的化学结构经^(1)H-NMR、^(13)C-NMR、ESI-MS确证。结论对化合物6的合成路线进行了优化;通过化合物6获得了一条更精简的化合物1的合成路线,该路线既避免了有毒的三光气的使用,也避免了副反应的发生;通过制备型HPLC得到化合物1的两个顺反异构体,并使用NOESY确定了化合物的构型。

SARS-CoV-2靶向CypA/CD147受体途径诱导心肌细胞凋亡

目的探究SARS-CoV-2靶向亲环素A(CypA)/细胞外金属蛋白酶诱导剂(CD147)受体途径诱导心肌细胞凋亡的可能机制。方法构建pEncmv-SARS-CoV-2 S-3xflag重组载体质粒转染H9c2细胞,TUNEL实验、流式细胞术和DNA ladder分析细胞凋亡,免疫共沉淀(CoIP)验证CD147与SARS-CoV-2 S蛋白之间相互作用,Western blotting法检测细胞凋亡信号通路相关蛋白表达。结果与对照组比较,TUNEL实验和流式细胞术结果显示转染组细胞凋亡显著增加(P<0.05),DNA ladder分析发现DNA降解明显。Western blotting法检测显示Caspase12、DR3表达显著升高(P<0.001),FAS表达升高(P<0.01),TRF1、DR4表达降低(P<0.01)。结论SARS-CoV-2 S蛋白靶向CypA/CD147受体入侵宿主细胞,激活内质网通路(Caspase12)和死亡受体通路(DR3、FAS),以内源性和外源性凋亡途径诱导心肌细胞凋亡。

自然杀伤(NK)细胞与2019冠状病毒病(COVID-19)发生发展的研究进展

自然杀伤(NK)细胞在清除病毒,执行免疫调节方面发挥着重要的作用,它通过分泌趋化因子以及与其他天然免疫细胞协同作用,被赋予天然免疫调节功能和获得性免疫反应。随着对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的2019冠状病毒病(COVID-19)的研究深入,发现NK细胞在其中发挥着重要作用。SARS-CoV-2感染会影响NK细胞的分布和效应功能,NK细胞的免疫应答或可影响新冠肺炎患者的预后。本文总结了近年来NK细胞在COVID-19感染中作用的研究现状,并且讨论了以NK细胞作为治疗剂的可能性,以期为防治SARS-CoV-2的免疫损害提供潜在思路。

Long, thin transmission chains of Severe Acute Respiratory Syndrome Coronavirus 2 may go undetected for several weeks at low to moderate reproduction numbers: Implications for containment and elimination strategy

Severe Acute Respiratory Syndrome Coronavirus 1(SARS-CoV-1)infections almost always caused overt symptoms,so effective case and contact management enabled its effective eradication within months.However,Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)usually causes only mild symptoms,so transmission chains may grow to include several individuals before at least one index case becomes ill enough to self-report for diagnosis and care.Here,simple mathematical models were developed to evaluate the implications of delayed index case detection for retrospective contact tracing and management responses.Specifically,these simulations illustrate how:(1)Contact tracing and management may effectively contain most but not all large SARS-CoV-2 clusters arising at foci with high reproduction numbers because rapidly expanding transmission chains ensure at least one overtly symptomatic index case occurs within two viral generations a week or less apart.(2)However,lower reproduction numbers give rise to thinner transmission chains extending through longer sequences of non-reporting asymptomatic and paucisymptomatic individuals,often spanning three or more viral generations(2 weeks of transmission)before an overtly symptomatic index case occurs.(3)Consequently,it is not always possible to fully trace and contain such long,thin transmission chains,so the community transmission they give rise to is underrepresented in surveillance data.(4)Wherever surveillance systems are weak and/or transmission proceeds within population groups with lower rates of overt clinical symptoms and/or self-reporting,case and contact management effectiveness may be more severely limited,even at the higher reproduction numbers associated with larger outbreaks.(5)Because passive surveillance platforms may be especially slow to detect the thinner transmission chains that occur at low reproduction numbers,establishing satisfactory confidence of elimination may require that no confirmed cases are detected for two full months,throughout which presumptive preventative measures must be maintained to ensure complete collapse of undetected residual transmission.(6)Greater scope exists for overcoming these limitations by enhancing field surveillance for new suspected cases than by improving diagnostic test sensitivity.(7)While population-wide active surveillance may enable complete traceability and containment,this goal may also be achievable through enhanced passive surveillance for paucisymptomatic infections,combining readily accessible decentralized testing with population hypersensitization to self-reporting with mild symptoms.Containment and elimination of SARS-CoV-2 will rely far more upon presumptive,population-wide prevention measures than was necessary for SARS-CoV-1,necessitating greater ambition,political will,investment,public support,persistence and patience.Nevertheless,case and contact management may be invaluable for at least partially containing SARS-CoV-2 transmission,especially larger outbreaks,but only if enabled by sufficiently sensitive surveillance.Furthermore,consistently complete transmission chain containment may be enabled by focally enhanced surveillance around manageably small numbers of outbreaks in the end stages of successful elimination campaigns,so that their endpoints may be accelerated and sustained.

沈阳市1209例新型冠状病毒感染者“长新冠”特征及风险因素分析

本研究旨在探究新型冠状病毒(简称新冠)感染者长新冠的临床特点及相关风险因素。选取2023年8月以前至少感染过一次新冠病毒的感染者1209例,随访收集人口学资料、长新冠症状,进行血常规等实验室检查,并通过单因素和多因素logistic回归分析长新冠的相关风险因素。结果显示,1209例感染者中有146例(12.08%)报告长新冠症状,主要以乏力、咳嗽、记忆力减退等症状为主,同时实验室检查结果和非长新冠感染者相比无明显异常。多因素logistic回归分析结果显示,长新冠的风险因素包括女性(aOR=1.69,P=0.007)、合并3种及以上基础疾病(aOR=4.07,P<0.001)以及再感染(aOR=1.94,P=0.002)。本研究发现疫情防控措施优化后,以奥密克戎毒株感染为主的感染者长新冠的发生率较既往毒株低,女性、合并较多基础疾病(≥3)以及再感染是长新冠的风险因素。