Antiviral,immunomodulatory, and anticoagulant effects of quercetin and its derivatives: Potential role in prevention and management of COVID-19

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a devastating health crisis worldwide. In this review, we have discussed that prophylactic phytochemical quercetin supplementation in the form of foods or nutraceuticals may help manage the COVID-19 pandemic. The following evidence supports our argument. First, nuclear factor erythroid-derived 2-like 2 (NRF2) agonists abrogate replication of SARS-CoV-2 in lung cells, and quercetin is a potent NRF2 agonist. Second, quercetin exerts antiviral activity against several zoonotic coronaviruses, including SARS-CoV-2, mainly by inhibiting the entry of virions into host cells. Third, inflammatory pathways activated by nuclear factor kappa B, inflammasome, and interleukin-6 signals elicit cytokine release syndrome that promotes acute respiratory distress syndrome in patients with COVID-19, and quercetin inhibits these pro-inflammatory signals. Fourth, patients with COVID-19 develop thrombosis, and quercetin mitigates coagulation abnormalities by inhibiting plasma protein disulfide isomerase. This review provides a strong rationale for testing quercetin for the management of COVID-19.     

The latest research progress of COVID-19 mutant strain "Mu" virus strain

Novel coronavirus pneumonia(COVID-19) is a highly pathogenic infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Until now, the new crown pneumonia has caused hundreds of millions of people worldwide to be infected. Novel coronavirus pneumonia is still a high level of variation. Due to the high variability of COVID-19, there are already a large number of COVID-19 variant strains that are still at a high level of infection worldwide. Recently, WHO (WHO) released a new variant, "Mu" (μ, B.1.621) may be a high vaccine tolerance. This paper reviews the latest research progress of "Mu" virus strain in detail.     

巴瑞替尼在新型冠状病毒感染中对Ⅰ型干扰素信号通路的影响

目的 探讨巴瑞替尼在新型冠状病毒感染中的抗病毒作用及对细胞因子表达的影响。方法 首先使用SARS-CoV-2 （MOI=0.1）感染Calu-3 细胞系,通过RT-qPCR分析新冠病毒感染过程中炎症因子（IL-6、IL-8、TNF-α和IL-1β）、干扰素β（IFN-β）和干扰素刺激基因（IFIT2）mRNA表达水平。下一步用巴瑞替尼预处理Calu-3细胞2 h,之后感染SARS-CoV-2 （MOI=0.1）,分别在感染后0、24、36、48 h时间点收集细胞,比较药物处理组和未处理组中上述基因mRNA表达水平及对病毒复制的影响作用。结果 SARS-CoV-2感染Calu-3细胞后,可诱导促炎因子（IL-6、TNF-a、IL-1β）和干扰素及干扰素刺激因子（IFN-β和IFIT2）mRNA水平发生不同程度的显著上调,病毒感染组在感染48 h相对于未感染组上调了近100倍或以上（P<0.000 1）,上述因子的mRNA表达水平随感染时间延长持续增加（P<0.001或P<0.000 1）。IL-8 mRNA水平上升幅度尽管无上述基因显著,但也呈现2~4倍的增加。巴瑞替尼预处理Calu-3细胞后,对胞内SARS-CoV-2的复制水平无显著抑制作用（P>0.05）。然而,该药物可显著抑制SARS-CoV-2感染诱导的IL-6和TNF-α水平的上调（分别下调5.25倍和3.90倍,P<0.01）,对IL-8和IL-1β的水平影响不大。另外,该药物也可明显下调病毒感染对IFN-β和IFIT2水平的增加（分别下调10.51倍和90.78倍,P<0.000 1）。结果 巴瑞替尼药物尽管对新冠病毒在细胞内病毒载量水平无显著抑制效应,但可不同程度抑制新冠病毒感染诱导的炎症因子的大量释放,尤其对干扰素和干扰素刺激基因表达的抑制作用更加显著。考虑到IFN-Ⅰ反应在病毒感染过程中发挥重要作用,临床必须谨慎使用巴瑞替尼治疗 COVID-19 患者。     

从一对夫妻患者的诊治过程探讨2019冠状病毒病(COVID-19)疑似患者的管理

观察2例2019冠状病毒病（COVID-19）疑似患者诊断、治疗以及隔离管理的过程,结合文献分析COVID-19疑似患者的临床特征和管理重点。COVID-19是由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染所致的疾病,SARS-CoV-2具有很强的传染性,甚至无症状感染者也可能传播病毒。SARS-CoV-2可通过接触传播、飞沫传播,并可能通过气溶胶传播。在临床发热门诊的患者管理中,准确识别并管理好疑似患者,采取严格的隔离措施,对院内感染的防控极为重要。     

SARS-CoV-2与宿主固有免疫系统的相互作用

2019冠状病毒病(coronavirus disease 2019,COVID-19,我国通称新型冠状病毒肺炎,简称新冠肺炎)是由严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的一种以肺部病变为主的呼吸道传染病,...     

严重急性呼吸综合征冠状病毒2与新型冠状病毒肺炎

目前正在暴发流行的新型冠状病毒肺炎（COVID-19）的病原体是严重急性呼吸综合征冠状病毒2（SARS-CoV-2）,这是近年来继严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERSCoV）之后发现的能够感染人的第7种冠状病毒。SARS-CoV-2系单股正链RNA病毒,传染性强,人群普遍对其缺乏免疫力,疫情目前仍在持续。2020年1月30日（当地时间）,WHO将此次疫情列为国际关注的突发公共卫生事件（PHEIC）。本文就SARS-CoV-2病原学、致病性及COVID-19的检测诊断、预防控制和临床治疗等领域的进展进行讨论。     

院内感染为主引起的多家庭新冠肺炎聚集性疫情调查

目的 调查分析一起院内感染为主的新型冠状病毒肺炎（COVID-19）多家庭聚集疫情特点,为聚集性疫情的防控提供科学依据。方法 应用描述流行病学方法分析潍坊市某新冠肺炎聚集疫情特点,采用实时荧光定量 RT-PCR 法对采集的呼吸道标本、深咳痰液等进行新型冠状病毒(SARS-CoV-2)核酸检测,确诊病例和无症状感染者判定按照《国家卫生健康委新型冠状病毒感染的肺炎诊疗方案（试行第四版）》要求进行。结果 首代病例就诊时隐瞒外出旅行史,导致由院内感染和家庭接触引发的8个二代病例和7个三代病例发生,涉及4个家庭内聚集,没有引起医护人员的感染或发病。结论 详细询问病人外出旅行史和其他接触史对病例的诊断至关重要,做好医护人员个人防护可有效降低院内感染的发生,家庭成员间的密切接触传播是聚集疫情发生的重要危险因素。     

COVID-19全球疫情及其应对策略留给我们的思索

由新型冠状病毒（SARS-CoV-2）所引起的新型冠状病毒肺炎（COVID-19）仍在继续肆虐全球,给公共卫生体系带来巨大挑战,并威胁人类健康和生存。此次疫情留给我们太多思索:要关注呼吸道感染性疾病尤其人畜共患的新发呼吸道传染病;明确病毒病原的重要性,这关系到儿童肺炎的防治策略。由于COVID-19具有高传染性和病毒快速变异的特点,且缺乏特异性药物,故疫苗是目前最有效的预防手段,必须尽早建立全球免疫屏障。     

用于新型冠状病毒核酸检测的即时检测方法研究进展

新型冠状病毒(SARS-CoV-2)引起的新型冠状病毒肺炎(corona virus disease 2019,COVID-19)在全世界范围内快速传播,截至2020年9月30日全球感染人数已达3 300万人,造成100多万人死亡,给公众的生命健康造成严重威胁。基于实验室的标准化核酸检测方法周转时间长、成本高,因此急需开发便捷检测新冠病毒的方法,实现在资源有限的情况下快速测试以及时控制疫情。本文从提取、扩增、检测3个方面总结了针对新型冠状病毒所开发的核酸即时检测方法(point-ofcare testing,POCT),并对整合了这3个步骤的商业化即时检测装置进行简要介绍,以期为COVID-19及其他新兴传染病的紧急应对和快速部署提供参考。     

Molecular immune pathogenesis and diagnosis of COVID-19

Coronavirus disease 2019(COVID-19)is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus(SARS-CoV)and the Middle East respiratory syndrome coro-navirus(MERS-CoV)in the twenty-first century.In this minireview,we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis,diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections,which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.     

2019冠状病毒病相关肾损伤研究进展

2019 冠状病毒病(coronavirus disease 2019,COVID-19)目前已在世界范围内暴发流行,是世界性的重大 公共卫生问题。严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)传染性 极强,主要侵袭患者的肺,导致呼吸窘迫综合征甚至多器官衰竭。肾也是病毒攻击的主要器官之一,病毒通过血管 紧张素转换酶2(ACE2)直接损伤肾小管,并引起细胞因子风暴导致肾损伤,增加患者的死亡风险。早期排查COVID- 19患者肾损伤危险因素,检测肾损伤指标,对存在肾损伤的患者及时进行支持治疗及肾脏替代治疗,可降低病死率。     

Symptomatic and Asymptomatic SARS-CoV-2 Infection and Follow-up of Neutralizing Antibody Levels

ObjectiveTo investigate neutralizing antibody levels in symptomatic and asymptomatic patients with coronavirus disease 2019 (COVID-19) at 6 and 10 months after disease onset.MethodsBlood samples were collected at three different time points from 27 asymptomatic individuals and 69 symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus-neutralizing antibody titers against SARS-CoV-2 in both groups were measured and statistically analyzed.ResultsThe symptomatic and asymptomatic groups had higher neutralizing antibodies at 3 months and 1–2 months post polymerase chain reaction confirmation, respectively. However, neutralizing antibodies in both groups dropped significantly to lower levels at 6 months post-PCR confirmation.ConclusionContinued monitoring of symptomatic and asymptomatic individuals with COVID-19 is key to controlling the infection.     

COVID-19与心血管代谢性疾病的临床研究进展

COVID-19与心血管代谢性疾病（CVMD）之间高共患病率和死亡率，及其潜在的心血管损伤风险，为其临床诊治带来巨大挑战。最新研究发现：高龄状态、免疫功能缺陷、炎症因子风暴及氧化应激损伤等是二者高共患病率的潜在机制；病毒直接侵袭、心肌氧供需失衡以及血管内皮与凝血功能障碍则可能是COVID-19患者心血管损伤的重要机制。此外，SARS-CoV-2细胞膜受体ACE2在各脏器与循环系统中的表达水平，不仅介导病毒对脏器直接侵袭损伤，还可参与机体炎症与氧化应激平衡的调节，从而影响患者COVID-19易感性与预后结局。本文将就COVID-19合并心血管代谢性疾病的上述研究进展进行回顾，并探讨SARS-CoV-2引起心血管损伤机制，以期为COVID-19合并CVMD患者的临床诊治提供理论依据。     

Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage: Comparative analytical study of physicochemical quality attributes

COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has produced a serious emergency for global public health, placing enormous stress on national health systems in many countries. Several studies suggest that cytokine storms (interleukins) may play an important role in severe cases of COVID-19. Neutralizing key inflammatory factors in cytokine release syndrome (CRS) could therefore be of great value in reducing the mortality rate. Tocilizumab (TCZ) in its intravenous (IV) form of administration -RoActemra® 20 mg/mL (Roche)-is indicated for treatment of severe CRS patients. Preliminary investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe, with several ongoing clinical trials. This has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals, which has resulted in drug shortages. Here, we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion, at 6 mg/mL and 4 mg/mL, prepared from RoActemra® 20 mg/mL (IV form) and from RoActemra® 162 mg (0.9 mL solution pre-filled syringe, subcutaneous(SC) form), to evaluate the use of the latter for preparing clinical solutions required for IV administration, so that in a situation of shortage of the IV medicine, the SC form could be used to prepare the solutions for IV delivery of TCZ. It is important to remember that during the current pandemic all the medicines are used off-label, since none of them has yet been approved for the treatment of COVID-19.     

A Comprehensive Review of COVID-19 Virology,Vaccines,Variants,and Therapeutics

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative pathogen of the coronavirus disease 2019(COVID-19),has caused more than 179 million in...     

2019冠状病毒病(COVID-19)诊疗浙江经验

当前2019冠状病毒病（COVID-19）疫情仍处于胶着状态。浙江大学医学院附属第一医院是国家感染性疾病临床医学中心,浙江省COVID-19患者救治中心。疫情一线的专家集智攻关,以国家卫生健康委员会和国家中医药管理局发布的COVID-19诊治指南为依据,以抗病毒、抗休克、抗低氧血症、抗继发感染、维持水电解质和酸碱平衡、维持微生态平衡的“四抗二平衡”救治策略为核心,总结完善诊治方案,聚焦临床实践的一些具体问题,为COVID-19患者临床诊治提供借鉴。推荐以多学科协作诊治个性化治疗提高COVID-19患者救治质量。建议病原学检测、炎症指标监测和肺部影像学动态观察指导临床诊治。痰液的病毒核酸检测阳性率最高,约10%的急性期患者血液中检测到病毒核酸,50%的患者粪便中检测到病毒核酸,粪便中可分离出活病毒,须警惕粪便是否具有传染性;开展细胞因子等炎症指标监测有助于发现是否出现细胞因子风暴,判断是否需要人工肝血液净化治疗。通过以“四抗二平衡”为核心的综合治疗提高治愈率、降低病死率;早期抗病毒治疗能减少重症、危重症发生,前期使用阿比多尔联合洛匹那韦/利托那韦抗病毒显示出一定效果。休克和低氧血症多为细胞因子风暴所致,人工肝血液净化治疗能迅速清除炎症介质,阻断细胞因子风暴,对维持水电解质酸碱平衡也有很好的作用,可以提高危重型患者的疗效。重型病例疾病早期可适量、短程应用糖皮质激素。氧疗过程中,患者氧合指数小于200 mmHg时应及时转入重症医学科治疗;采用保守氧疗策略,不推荐常规进行无创通气;机械通气患者应严格执行集束化呼吸机相关性肺炎预防管理策略;氧合指数大于150 mmHg时,及早减、停镇静剂并撤机拔管。不推荐预防性使用抗菌药物,对于病程长,体温反复升高和血降钙素原水平升高的患者可酌情使用抗菌药物;要关注COVID-19患者继发真菌感染的诊治。COVID-19患者有肠道微生态紊乱,肠道乳酸杆菌、双歧杆菌等有益菌减少,推荐对所有患者进行营养和胃肠道功能评估,以营养支持和补充大剂量肠道微生态调节剂,纠正肠道微生态失衡,减少细菌移位和继发感染。COVID-19患者普遍存在焦虑和恐惧心理,应建立动态心理危机干预和处理。提倡中西医结合辨证施治;优化重型患者护理促进康复。严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染后病毒清除规律仍不明了,出院后仍须居家隔离2周,并定期随访。以上经验和建议在本中心实行,取得较好效果,但COVID-19是一种新的疾病,其诊治方案及策略仍有待进一步探索与完善。     

SARS-CoV-2对神经系统损害的研究进展

由严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)所引起 的2019 冠状病毒病(coronavirus disease 2019,COVID-19)疫情在全球大暴发。SARS-CoV-2 感染除了可累及呼吸系统 外,还可导致严重的神经系统损伤。研究表明SARS-CoV-2 可通过血行和跨神经元途径入侵神经系统,并可能通过抑 制细胞免疫、低氧血症及炎症作用,诱导神经元变性与细胞凋亡,以及血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2)机制造成COVID-19 患者的神经系统损害,导致患者颅内感染、中毒性脑病、急性脑血管疾病、肌 肉损害、周围神经系统损伤、急性脊髓炎、脱髓鞘疾病或其他神经系统疾病。     

Association between 25 Hydroxyvitamin D Concentrations and the Risk of COVID-19: A Mendelian Randomization Study

Coronavirus disease 2019 (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic[1]. Primary prevention, which is aimed at delaying disease onset by modulating modifiable risk factors, has been proposed to address the global challenge posed by COVID-19. Vitamin D plays a critical role in the immune system, and vitamin D deficiency is a risk factor for several adverse health outcomes, such as cancer, cardiovascular diseases, metabolic disorders, infectious diseases, and autoimmune diseases. Some studies have shown that low 25 hydroxyvitamin D (25OHD) concentrations are associated with a high risk of COVID-19[2], but other studies have found no association[3]. Therefore, the association between 25OHD concentrations and the risk of COVID-19 has not been established. The above studies were observational, and traditional epidemiological studies are vulnerable to reverse causality and residual confounding.     

新型冠状病毒肺炎患者6例临床特征和影像学表现

目的 总结6例新型冠状病毒肺炎（COVID-19）患者的临床特征和影像学表现，为COVID-19早期确诊和临床干预提供依据。方法 选择上海中医药大学附属第七人民医院2020年1月1日至2020年2月22日严重急性呼吸综合征冠状病毒2（SARS-CoV-2）核酸检测阳性的6例COVID-19患者，回顾性分析流行病学史、临床表现、影像学资料和实验室检查。结果 6例患者均有明确的武汉旅行或居住史，4例患者有发热，3例有咳嗽，2例有流涕、咽痛等上呼吸道症状，2例有头痛、肌肉酸痛等全身症状。6例患者胸部CT检查均可见肺部异常表现，病灶均为双侧分布，下肺病灶多于上肺，主要表现为双侧肺野外带多发磨玻璃影、实变影、“铺路石”征及不同程度纤维化。发病后较晚行胸部CT检查可见肺实变和明显纤维化。结论 COVID-19影像学具有一定的特征性表现，结合患者流行病学史、临床表现和SARS-CoV-2核酸检测能早期诊断。     

蝙蝠相关的冠状病毒

2019年12月,新型冠状病毒肺炎（COVID-19）暴发,继2003年严重急性呼吸综合征（SARS）暴发后又给人类敲响了一记警钟。研究者通过溯源分析,发现COVID-19病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的自然宿主可能是中华菊头蝠。21世纪以来,全球共出现4次冠状病毒[严重急性呼吸综合征冠状病毒（SARS-CoV）、中东呼吸综合征冠状病毒（MERS-CoV）、猪急性腹泻综合征冠状病毒（SADS-CoV）、SARS-CoV-2]的暴发,给人类健康、公共卫生、经济发展及社会稳定造成了巨大的威胁与损失。大量证据表明,这4种冠状病毒的自然宿主可能均为蝙蝠。本文对蝙蝠相关冠状病毒的种类、全球地理分布及引起暴发的蝙蝠相关冠状病毒作一综述。