Huu S. TIEU’s Predicting Outcome of Severe Acute Respiratory Syndrome (SARS) and Preparing the Treatment for COVID-19 (Coronavirus) and Other Viral Pandemics

This project paper is to give a prediction for the future of other viral pandemics and to provide recommendations for preparing therapies that could help in the success of effective treatments and benefits for patients in life-threatening situations. The theory of prediction was proposed by Huu S. TIEU on March 25, 2019, and he hypothesized that any malfunctioning cell in the body could have a damaging effect. This paper discusses the prediction that Localized Oxygen Deprivation could be a contributing factor for a future epidemic or other viral pandemics that could affect body function. This paper is based on opinion and does not have sufficient evidence to support the claims made. Therefore, further in-depth study is needed to prove the findings. The author cites Hypoxia to support his idea, but he is not claiming that Hypoxia-Inducible Factor (HIF) has worked on his predictions. The author also tested a theory using cow blood curd for body function, but this test was not a structured test and the findings were not supported by other evidence. To further prove the idea or theory, further study into the subject should be conducted.

Elevated Plasma Tissue-type Plasminogen Activator (t-PA) and Soluble Throm-bomodulin in Patients Suffering From Severe Acute Respiratory Syndrome (SARS) as a Possible Index for Prognosis and Treatment Strategy

To detect the presence of endothelial injury in patients with severe acute respiratory syndrome （SARS） via enhanced levels of tissue-type plasminogen activator （t-PA） and soluble thrombomodulin （sTM）. Methods Case patients were from Xuanwu Hospital （Capital University of Medical Sciences, Beijing, China）, and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA： 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L （P〈0.0001）, and sTM： 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L （P〈0.05）]. The only patient who died had extremely high levels of these endothelial injury markers （t-PA： 2.77 nmol/L and sTM： 1.01 nmol/L）. The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 （P〈0.05）. Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.

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.

The role of immunoinformatics in analysis of immune response against severe acute respiratory syndrome (SARS) coronavirus

In order to analyze the immune response to severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), immunoinformatics and computational analyses were performed to study the immunological characters of SARS-CoV. According to the results of immunoinformatics analysis, the obvious variation of HLA-A2 associated T cell epitopes between SARS virus and HCoV-229E was found as follows: (1) Disappearance of HLA-A2 binding site; (2) variation sequence on the HLA-A2 associated epitope; (3) emergence of a new HLA-A2 associated epitope. The immunoinformatics results were evidenced by T2 cell binding assay, ELISPOT and DimerX staining. In conclusion, immunoinformatics is a useful method to analyze the immunological character of a new finding infectious pathogen, like SARS-CoV. These findings of immunoinformatics are confirmed by lab and clinical experiments. In this case, immunoinformatics seems a very useful tool in the study of immune response and the evaluation of vaccine in infectious diseases, such as SARS.

Epidemiological Characteristics of An Outbreak of Severe Acute Respiratory Syndrome in Dongcheng District of Beijing From March to May 2003

Objective To describe epidemiologic features of an outbreak of severe acute respiratory syndrome (SARS) in Dongcheng District, Beijing occurred in a period between March and May 2003. Methods Data of SARS cases notified from Dongcheng District Center for Disease Control and Prevention (CDC )and supplemented by other channels were collected. Clinicians and officials of local hospitals were interviewed in groups and medical records of fatal cases of SARS were reviewed to verify the diagnosis. Stored serum specimens of the patients were detected for IgG antibody against SARS Co-V by enzyme-linked immunosorbent assay (ELISA). All the data were input into dataset files by Microsoft Excel-2000 software and analyzed with SPSS version 10.0 software. Results Outbreak of SARS in Dongcheng District started on March 14, 2003 with a peak in mid- and late April, and dropped in early May. A total of 572 reported cases were collected during this period in Dongcheng District, Beijing, and 99 of them were excluded from SARS, because of diagnosis of common cold, regular pneumonia, measles and rubella, etc. Actually, 473 SARS cases, which included 390 (82.5%) probable cases and 83 (17.5%) suspect cases, were analyzed. About 90% of the probable cases were positive for IgG antibody. Attack rate of SARS in permanent residents of Dongcheng District was 28.3 per 100 000. Forty-one of them died, with a case-fatality rate of 8.7%. Persons were all susceptible to infection of SARS Co-V, with the highest proportion at ages of 20-50 years, which accounted for 68.7% of the total cases. Average age of the patients at their onset was 40.7 years. No gender difference in SARS cases was found. Number of SARS cases in health-care workers (HCWs) accounted for 18.0% and that in retired workers accounted for 15.4% of the total cases. Cases occurred in all 10 sub-districts of Dongcheng, with the highest in Beixinqiao and Andingmen Sub-districts. Totally, 230 of the 572 notified cases (40.2%) were hospitalized at local hospitals under the jurisdiction of Dongcheng District. Eighteen of 85 cases of SARS occurred in HCWs of local hospitals, accounting for 4.5% of the total number of HCWs working at wards caring for SARS patients or fever clinics. There were 34.7% of SARS cases without any histories of contact before the onset of the disease. Familial aggregation phenomena were observed in 41.8% of the cases and 18.1% of households. And 7.4% (attack rate ) of those exposed to SARS cases suffered from the illness during the periods of quarantine. Conclusions SARS appeared to be infectious in origin and caused outbreak in Dongcheng District, Beijing introduced by an imported case traveling from Hong Kong in a period between March and May 2003. People are all susceptible to infection of SARS Co-V, which mainly threatens the young adults and the middle-aged, as well as HCWs and the retired workers. The main mode of transmission is direct exposure to SARS patients in a near distance at hospitals or families via droplets spread. Prevention and control of SARS should be focused on early isolation of patients and quarantine for close contacts. Current available measures to prevent and control SARS are proved to be effective.

Analysis and Comparison of the Tongue Picture of 34 Patients with Severe Acute Respiratory Syndrome

Objective: To explore the changes of tongue pictures in the developing process of disease in patients with severe acute respiratory syndrome (SARS), and to compare the tongue pictures of SARS patients with those of suspected SARS patients. Methods: Materials of tongue picture were dynamically collected from 34 SARS patients and 35 suspected SARS patients, and the difference and similarity between them were analyzed. Meanwhile, the changes in clinic symptoms and tongue picture after integrative medicinal treatment were observed. Results: Characteristics of tongue picture in SARS patients were changed along with the progress of the disease, showing that there existed a tendency of the pathogen invading from exterior to interior, from surface to the deep. Also the tongue pictures were varied due to the coexistence of dampness pathogen; the time of the early stage was generally 1 - 1.5 days, shorter than that of other stages. While in the patients with suspected SARS, the tongue picture was mostly red with thin white or yellow coating, comparatively steady and showing no obvious change along with the development of the disease. Conclusion: Observing the tongue picture and its changes in different stages can be helpful to understanding the property of pathogenic evil and its developing rules, thus offering a basis for clinical treatment.

Severe Acute Respiratory Syndrome-Retrospect and Lessons of 2004 Outbreak in China

Objective To summarize lessons learned from an outbreak of severe acute respiratory syndrome （SARS） in China during the spring of 2004. Methods Data of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention （BCDC） and Anhui Provincial Center for Disease Control and Prevention （APCDC） and results of epidemiological investigations were collected and analyzed. Results Three generations of 11 cases of SARS were identified during the outbreak, Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients, Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases, Conclusions SARS outbreak in 2004 has yielded following lessons for public health globally. （1） Lab bio-safety programs should be made and should be strictly abided by, Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious, （2） Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.

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.

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.

Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identifi-

中医药治疗SARS疗效Meta分析及对新冠肺炎防治的启示

目的目前新冠肺炎疫情肆虐全球,与SARS同属冠状病毒感染。系统评价中医药治疗SARS的疗效,为新冠治疗提供参考。方法检索中医药治疗SARS的随机对照试验,由两名评价者对检索文献进行分析,将符合标准的文献纳入本次系统评价范畴,并进行Meta分析。结果16个研究符合纳入标准,系统研究中共纳入患者1574例,其中试验组820例,对照组754例。16项研究中有效率的研究,通过异质性检验,χ^(2)=12.22,df=14,P=0.59,I2=0%,采用固定效应模型,OR=5.23(95%CI=3.38~8.08),Z=7.45,P<0.01,提示中医药治疗SARS有效率高,且有统计学意义。结论中医药治疗SARS疗效显著,明显优于西医疗法,对新冠肺炎的防治有参考意义。

Pushing past the tipping points in containment trajectories of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)epidemics:A simple arithmetic rationale for crushing the curve instead of merely flattening it

Countries with ambitious national strategies to crush the curve of their Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)epidemic trajectories include China,Korea,Japan,Taiwan,New Zealand and Australia.However,the United States and many hard-hit European countries,like Ireland,Italy,Spain,France and the United Kingdom,currently appear content to merely flatten the curve of their epidemic trajectories so that transmission persists at rates their critical care services can cope with.Here I present a simple set of arithmetic modelling analyses that are accessible to non-specialists and explain why preferable crush the curve strategies,to eliminate transmission within months,would require only a modest amount of additional containment effort relative to the tipping point targeted by flatten the curve strategies,which allow epidemics to persist at supposedly steady,manageable levels for years,decades or even indefinitely.

基于分子对接和分子动力学模拟技术筛选SARS-CoV-23CL蛋白酶抑制剂

目的 以分子对接和分子动力学模拟技术相结合的方法筛选得到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) 3CL蛋白酶的小分子抑制剂。方法 基于SARS-CoV-2 3CL蛋白酶的晶体结构(PDB ID:7K3T和7SI9),从PubChem数据库中筛选得到SARS-CoV-2 3CL蛋白酶的特异性抑制剂nirmatrelvir的结构类似物,使用Autodock进行非共价分子对接,使用AutoDockFR进行共价分子对接,采用Pymol和Ligplot软件对SARS-CoV-2 3CL蛋白酶和小分子进行相互作用模式分析,最后使用AMBER18进行小分子化合物与SARS-CoV-2 3CL蛋白酶复合物的分子动力学模拟,进一步验证分子对接结果,使用SwissADME对化合物进行成药性分析。结果 将78个nirmatrelvir结构类似物与SARS-CoV-2 3CL蛋白酶进行虚拟筛选和分子对接,得到了2个与nirmatrelvir作用相当的小分子化合物(PubChem ID:57842182和156619968),共价对接发现化合物57842182和化合物156619968与SARS-CoV-2 3CL蛋白酶间不存在共价结合。分子动力学模拟结果表明化合物57842182、化合物156619968与SARS-CoV-2 3CL蛋白酶的结合自由能(ΔE_(total))分别为-23.96 kcal·mol^(-1)和-27.11 kcal·mol^(-1),二者主要通过与MET165、GLU166、ASN142、CYS145、LEU50、MET49等氨基酸残基的相互作用占据SARS-CoV-2 3CL蛋白酶亚活性位点,具有潜在抑制SARS-CoV-2 3CL蛋白酶活性的功能。化合物57842182和化合物156619968的成药性略差于nirmatrelvir。结论 筛选得到的nirmatrelvir结构类似物57842182和156619968具有作为新型冠状病毒SARS-CoV-2 3CL蛋白酶小分子抑制剂的潜力,其与SARS-CoV-2 3CL蛋白酶的结合特点可为SARS-CoV-2 3CL蛋白酶抑制剂的药物设计提供线索。

COVID-19 Patient with Multifocal Pneumonia and Respiratory Difficulty Resolved Quickly: Possible Antiviral and Anti-Inflammatory Benefits of Quercinex (Nebulized Quercetin-NAC) as Adjuvant

Background: SARS-CoV-2 (COVID-19) is a viral pandemic with no current vaccine or effective treatment. Hydroxychloroquine and azithromycin are not without cardiovascular risk or complications, and these treatments can fail to aid in full recovery from COVID-19. As new treatments become approved for the pandemic, an inexpensive, non-toxic, and safe adjunctive therapy is needed. Case Presentation: A 59-year-old male presented with respiratory symptoms. Chest X-ray revealed classic indications of COVID-19 pneumonia. A PCR nasopharyngeal swab test confirmed a COVID-19 infection and hospital doctors prescribed Rocephin, azithromycin, and hydroxychloroquine. The patient was then prescribed Quercinex, a nebulized formula of quercetin-(cyclodextrin) (20 mg/mL) and N-acetylcysteine (100 mg/mL) three times daily for 14 days by physicians at Envita Medical Center for continued COVID-19 respiratory symptoms. Following 30 minutes after each nebulization treatment, the patient experienced immediate deep breathing relief that lasted for multiple hours. Within the following 48 hours after the first treatment, respiratory symptoms continued to diminish and resolve quickly. Finally, post-treatment follow-up chest X-rays revealed no pulmonary fibrosis (scarring) and clear lung fields. Conclusion: The Quercinex formula appeared to greatly alleviate the unresolved respiratory symptoms rapidly. Several mechanisms of the formula, namely antiviral and anti-inflammatory action, with direct administration via nebulizer to the deep lung tissue, could potentially explain the fast and complete recovery. We recommend that the Quercinex formula be considered for further clinical study as an adjuvant or on its own for COVID-19 and possibly other viral pulmonary conditions.

The difference of immunologic parameters between SARS patients of mild type and severe type

The aim of this study is to study the difference of immunologic parameters between severe acute respiratory syndrome (SARS) patients of mild type and severe type. Data including white blood cell (WBC) count, lymphocyte count, CD3, CD4 and CD8 T lymphocyte count, levels of C3, C4, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) from 1291 patients with SARS in each week from onset of illness were recorded. The clinical progress of each sign was analysed and the difference between mild type and severe type was compared. Lymphocyte count, CD8 T lymphocyte count declined in the first two weeks and recovered from the third week, while CRP and C4 levels rose in the first week and then recovered gradually. Lymphocyte count and CD8 T lymphocyte count of severe cases were much lower than that of mild type (P<0.01), while CRP and C4 levels in severe type were much higher than that of mild type (P<0.01). Lymphocyte count, CD8 T lymphocyte count, CRP and C4 levels are useful signs for the diagnosis of SARS of severe type and are valuable for the evaluation of its severity.

Consensus for the management of severe acute respiratory syndrome

INTRODUCTIONSince recognition of the first case of severe acute respiratory syndrome (SARS) in Guangdong Province in November 2002, health care workers engaged in basic medicine, clinical medicine and preventive medicine, have done much work and made encouraging progress in the understanding of the etiology, epidemiology, diagnosis, treatment and prevention of SARS. The "Proposed Criteria for Diagnosis of Infectious Atypical

新型冠状病毒疫苗的研究进展

新型冠状病毒感染是近年来全球最关注的紧急公共卫生事件之一,严重威胁着世界人民的生命健康。接种新型冠状病毒疫苗(简称新冠疫苗)是降低新冠病毒对人群危害的最经济有效的措施,各国积极开展新冠疫苗研发和接种工作,其中重组蛋白疫苗、病毒载体疫苗、灭活疫苗、mRNA疫苗占据了主要市场。随着变异株传播能力和变异逃避能力增强,新冠疫苗的保护效果和持久性成为了当前的研究热点。该文就新冠疫苗的研究进展作一简要综述,以期为新冠疫苗的研发工作提供借鉴。

Severe acute respiratory syndrome coronavirus protein 6 mediates ubiquitin-dependent proteosomal degradation of N-Myc(and STAT) interactor

Severe acute respiratory syndrome coronavirus(SARS-Co V) encodes eight accessory proteins, the functions of which are not yet fully understood. SARS-Co V protein 6(P6) is one of the previously studied accessory proteins that have been documented to enhance viral replication and suppress host interferon(IFN) signaling pathways. Through yeast two-hybrid screening, we identified eight potential cellular P6-interacting proteins from a human spleen c DNA library. For further investigation, we targeted the IFN signaling pathway-mediating protein, N-Myc(and STAT) interactor(Nmi). Its interaction with P6 was confirmed within cells. The results showed that P6 can promote the ubiquitin-dependent proteosomal degradation of Nmi. This study revealed a new mechanism of SARS-Co V P6 in limiting the IFN signaling to promote SARS-Co V survival in host cells.

肾上腺糖皮质激素治疗SARS的回顾性分析

目的 :了解我院严重急性呼吸道综合征 (SevereAcuteRespiratorySyndrome,SARS ,即非典型肺炎 )治疗中肾上腺糖皮质激素的使用。方法 :对 4 3例SARS患者进行回顾性研究 ,分析肾上腺糖皮质激素的初始使用剂量、最高剂量。根据是否在使用初始剂量后需要将肾上腺糖皮质激素加量将患者分为糖皮质激素加量组和非加量组 ,分别比较两组在临床表现、初始剂量和疗效上的差异。结果 :根据初始 3天肾上腺糖皮质激素的剂量 ,甲泼尼龙 (甲基强的松龙 )的初始剂量为 (170 .82± 15 .89)mg·d-1,范围 4 8～ 5 0 0mg·d-1,最大甲泼尼龙剂量为 (2 91.4 4±37.6 3)mg·d-1,剂量范围 4 8～ 80 0mg·d-1。 4例未用糖皮质激素。 2 5例用初始剂量激素后未再加量 ,14例初始剂量激素未能有效控制病情 ,根据病情追加了糖皮质激素剂量。糖皮质激素加量组甲泼尼龙剂量明显增高 ,达到病情稳定所需时间也较长 ,使用糖皮质激素的天数也延长。但两组从病情严重程度并无显著差异。结论 :本组患者绝大多数使用亚冲击剂量的糖皮质激素即可获满意疗效 ,部分患者尚需增加皮质激素剂量 ,可能与这些患者对糖皮质激素的反应性差有关 。