Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on in-hospital mortality among patients with COVID-19: a systematic review and meta-analysis

INTRODUCTIONThere are concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may worsen the outcomes of patients with COVID-19. This systematic review and meta-analysis aimed to study the in-hospital mortality among COVID-19 patients who were on ACEIs/ARBs as compared to those not on ACEIs/ARBs.METHODSWe searched PubMed, EMBASE, clinicaltrials.gov and Google Scholar between 1 January 2020 and 30 May 2020 to identify all studies that evaluated the use of ACEIs/ARBs and reported the in-hospital mortality outcomes of COVID-19 patients. Nine non-randomised studies were eligible for inclusion in the analysis. The primary outcome studied was the in-hospital mortality of COVID-19 patients who were on ACEIs/ARBs compared with those not on ACEIs/ARBs.RESULTSOf the 8,313 patients in the nine studies, 7,622 (91.7%) were from studies with all-comers, while 691 (8.3%) were from studies involving only patients with hypertension. 577 (14.6%) in-hospital deaths were observed out of a total of 3,949 patients with an outcome in the nine studies. Overall, no significant difference was observed in the in-hospital mortality between patients on ACEIs/ARBs and those not on ACEIs/ARBs (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.75–1.50; p = 0.73). Further sensitivity analysis in the hypertension group and the all-comers group showed similar results (OR 0.88, 95% CI 0.58–1.32; p = 0.53 and OR 1.85, 95% CI 1.00–3.43; p = 0.05, respectively).CONCLUSIONWe observed that ACEIs/ARBs had no significant impact on the in-hospital mortality of COVID-19 patients and can be used safely in patients with indications.     

新型冠状病毒肺炎心脏损伤及其与血管紧张素转化酶Ⅱ的关系研究进展

新型冠状病毒肺炎(COVID-19)是由新型冠状病毒(SARS-CoV-2)引起的疾病。COVID-19患者主要表现为发热、乏力、干咳等典型呼吸系统症状,但也有部分患者有心悸、胸闷等不适,出现心电图、心肌酶谱、心功能等改变,表现为心脏损害。血管紧张素转化酶Ⅱ(ACE2)作为SARS-CoV-2侵入细胞的受体,可能与COVID-19患者心脏损伤有密切联系。文章就COVID-19患者心脏损伤及其与ACE2的关系作一综述。     

男性新型冠状病毒肺炎患者生殖系统损伤机制研究进展

新型冠状病毒肺炎(COVID-19)在发病率和严重程度上存在显著的性别差异,同年龄段中男性患者多于女性患者。新型冠状病毒(SARS-CoV-2)利用血管紧张素转换酶(ACE)2受体进入人体细胞。由于ACE2在人类多个器官系统上有不同程度的表达,SARS-CoV-2除感染呼吸系统外,同样可以感染消化系统、神经系统、免疫系统等。睾丸为富含ACE2的器官之一,部分男性COVID-19患者精液中检出SARS-CoV-2,SARS-CoV-2可能损伤生殖系统。但SARS-CoV-2参与男性生殖系统损害的机制尚未完全阐明,目前研究主要集中在SARS-CoV-2对男性生殖的短期影响,并越来越重视其长期影响。本文总结了SARS-CoV-2介导男性COVID-19患者的生殖细胞损伤、性腺功能减退、睾丸炎症的可能机制,并指出目前研究存在的问题,为男性COVID-19患者生殖系统损伤的机制研究扩宽思路。     

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。     

抑制肾素-血管紧张肽系统药物研究

肾素-血管紧张肽系统(RAS)是药物治疗心血管系统疾病的关键作用靶点。目前的主要药物是血管紧张肽转化酶抑制剂(ACEI)和血管紧张肽Ⅰ受体拮抗剂(ARBs),因此被认为是作用于RAS治疗心血管疾病的经典药物,但是还有许多能够通过其他途径而产生对RAS的抑制作用。本文综述了目前发现的一些其他途径以及和经典途径的联系以及阻断它们产生的可能效应,包括ACEI抑制剂、ARBs、肾素抑制剂、糜蛋白酶抑制剂、血管紧张肽转化酶2、中性肽链内切酶抑制剂、醛固酮抑制剂以及针对RAS的基因治疗和免疫治疗。     

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。     

Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants

The recent pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has raised global health concerns. The viral 3-chymotrypsin-like cysteine protease (3CL^pro) enzyme controls coronavirus replication and is essential for its life cycle. 3CL^pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV. Therefore, herein, we analysed the 3CL^pro sequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. Our analyses revealed that the top nine hits might serve as potential anti- SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.     

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。     

新型冠状病毒对循环系统影响的研究进展

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)是由新型冠状病毒(SARS-CoV-2)引起的,以发热、咳嗽及呼吸困难为主要临床症状的一种可在人群中广泛传播的疾病。截至目前,2019新型冠状病毒已在全球范围内造成大流行,随着国内疫情防治工作的有效开展,以及对于新型冠状病毒肺炎的认识与研究不断加深,发现很多新冠肺炎患者出现以循环系统损害症状为首发或继发的临床症状。SARS-CoV-2可直接通过血管紧张素转换酶2 (angiotensin converting enzyme 2,ACE2)受体损伤心肌细胞,也可以通过异常激活免疫系统、释放大量细胞因子从而导致急、慢性的心肌损伤。当心功能受损严重时,可能会通过RAS系统影响到肾脏功能,从而导致患者同时出现心脏和肾脏损害的临床表现。此外,对于COVID-19患者来说,还存在着动、静脉血栓栓塞的风险。本文结合近日来公布的新冠肺炎病例的资料和各团队最新的研究发现,对新型冠状病毒对于循环系统影响的研究进展做一简要概述,以期为进一步了解新型冠状病毒感染对循环系统的损害提供帮助。      

基于刺突蛋白靶点的抗新型冠状病毒药物研究进展

重症急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的新型冠状病毒肺炎(COVID-19)目前仍在不断蔓延,但针对该病毒的特效治疗药物尚在研发当中。本文基于冠状病毒生物学特点和病毒复制过程中的关键蛋白——刺突蛋白,介绍了相关药物作用位点及研究进展,为抗SARS-CoV-2药物的临床应用提供信息依据,为治疗COVID-19药物研发提供思路。     

Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease,Nsp12 polymerase and Nsp13 helicase

Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health safety. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are under way to test possible therapies. During this urgent situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated the highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach has facilitated the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.     

奥密克戎(Omicron)变异株及其对口腔诊疗的潜在影响

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)感染引起的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)疫情已经在全世界蔓延超过两年,每日的新增感染人数及死亡人数仍在持续增长。最新出现的奥密克戎(Omicron)变异株因其刺突蛋白出现多位点突变,导致病毒传染性与致病性发生显著变化,给公共卫生带来了新的挑战。WHO将Omicron变异株列为“需要关注的变异株”(variants of concern, VOC)。SARS-CoV-2及其变异株的传播扰乱了世界范围内的口腔诊疗工作。口腔诊疗过程中,近距离面对面交流、飞沫、气溶胶、接触唾液、血液等,增加了口腔诊疗机构中的传播风险,特别是Omicron等新发变异株的流行,对口腔诊疗带来新的挑战。口腔舌部、黏膜等组织可高表达血管紧张素转换酶2(angiotensin converting enzyme 2, ACE2),ACE2是SARS-CoV-2的结合受...     

当前新冠病毒的主要检测手段

2019年,由新型冠状病毒(SARS-CoV-2)感染引起的新型冠状病毒肺炎(COVID-19)被报道,随后疫情在世界上各个国家和地区暴发且迅速流行.COVID-19的传染性强、病死率高,为有效控制疫情的发展,新冠病毒的检测至关重要,国内外各研究团队及机构已研发出各种检测新冠病毒的有效手段和仪器设备,本文从背景原理、应...     

肾素-血管紧张素系统拮抗剂对非肌层浸润性膀胱癌的预后影响

目的 探讨血管紧张素转化酶抑制剂（ACEIs）和血管紧张素受体拮抗剂（ARBs）对非肌层浸润性膀胱癌（NMIBC）患者术后预后的影响。 方法 回顾性分析2009年1月至2011年12月收治的388例NMIBC患者的临床资料,术前因高血压服用ACEIs/ARBs者为用药组,术前未用ACEIs/ARBs者为对照组,再按高血压因素分层。总结两组患者病理组织学特征和临床特征,分析患者术后复发的独立危险因素。 结果 所有纳入的患者均为非肌层浸润后膀胱尿路上皮癌,行经尿道膀胱肿瘤切除术后均完成膀胱维持灌注化疗,其中306例术后完成了即刻膀胱灌注化疗,82例患者术后未行即刻膀胱灌注化疗。161例患者确诊高血压,其中,107例术前服用ACEIs/ARBs（用药组）,54例未服用ACEIs/ARBs。对照组281例,包括54例高血压患者,227例非高血压患者。两组患者在年龄、性别、吸烟状态、肿瘤分期分级、肿瘤数量、肿瘤直径以及是否行膀胱即刻灌注化疗等方面比较差异无统计学意义,按血压、用药（ACEIs/ARBs）因素分层后上述指标差异仍无统计学意义。中位随访时间60月,用药组中36例复发,对照组中129例复发,两组肿瘤无复发生存时间分别为（48.43±23.50）月、（41.15±23.64）月,差异有统计学意义（P=0.007）,5年肿瘤无复发生存率分别为66.36%、54.09%,差异有统计学意义（P=0.027）。Cox多因素回归分析显示,未服用ACEIs/ARBs[标准偏回归系数（β）=0.174]是影响NMIBC术后复发的独立危险因素（P<0.05）,排在肿瘤直径≥ 3 cm（β=0.193）、吸烟（β=0.191）、G3期肿瘤（β=0.181）之后,且权重排位不受血压影响。 结论 服用ACEIs/ARBs可改善NMIBC患者预后,降低术后复发率。     

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.     

Reducing SARS-CoV-2 pathological protein activity with small molecules

Coronaviruses are dangerous human and animal pathogens. The newly identified coronavirus SARS-CoV-2 is the causative agent of COVID-19 outbreak, which is a real threat to human health and life. The world has been struggling with this epidemic for about a year, yet there are still no targeted drugs and effective treatments are very limited. Due to the long process of developing new drugs, reposition of existing ones is one of the best ways to deal with an epidemic of emergency infectious diseases. Among the existing drugs, there are candidates potentially able to inhibit the SARS-CoV-2 replication, and thus inhibit the infection of the virus. Some therapeutics target several proteins, and many diseases share molecular paths. In such cases, the use of existing pharmaceuticals for more than one purpose can reduce the time needed to design new drugs. The aim of this review was to analyze the key targets of viral infection and potential drugs acting on them, as well as to discuss various strategies and therapeutic approaches, including the possible use of natural products. We highlighted the approach based on increasing the involvement of human deaminases, particularly APOBEC deaminases in editing of SARS-CoV-2 RNA. This can reduce the cytosine content in the viral genome, leading to the loss of its integrity. We also indicated the nucleic acid technologies as potential approaches for COVID-19 treatment. Among numerous promising natural products, we pointed out curcumin and cannabidiol as good candidates for being anti-SARS-CoV-2 agents.     

新型冠状病毒肺炎流行病学特点 和治疗药物研究进展

严重急性呼吸综合征冠状病毒2（SARS-CoV-2）于2019 年12 月在中国武汉被发现。由 于该病毒具有较强的传染性,爆发了以湖北省为中心,借助春运快速波及至全国的新型冠状病毒肺炎 (COVID-19）疫情。认清疫情变化规律和了解临床针对性的药物研发进展,对疫情控制具有重要意义。该文 从SARS-CoV-2 的特性、COVID-19 疫情的流行病学表现、治疗药物研发和应用等进行综述。     

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.     

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。     

COVID-19 vaccine candidates and vaccine development platforms available worldwide

The pandemic caused by the worldwide spread of the coronavirus, which first appeared in 2019, has been named coronavirus disease 19 (COVID-19). More than 4.5 million deaths have been recorded due to the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), according to the World Health Organization. COVID-19 Dashboard in September 2021. Apart from the wildtype, other variations have been successfully transmitted early in the outbreak although they were not discovered until March 2020. Modifications in the SARS-CoV-2 genetic material, such as mutation and recombination, have the ability to modify the viral life span, along with transitivity, cellular tropism, and symptom severity. Several processes are involved in introducing novel vaccines to the population, including vaccine manufacturing, preclinical studies, Food and Drug Administration permission or certification, processing, and marketing. COVID-19 vaccine candidates have been developed by a number of public and private groups employing a variety of strategies, such as RNA, DNA, protein, and viral vectored vaccines. This comprehensive review, which included the most subsequent evidence on unique features of SARS-CoV-2 and the associated morbidity and mortality, was carried out using a systematic search of recent online databases in order to generate useful knowledge about the COVID-19 updated versions and their consequences on the disease symptoms and vaccine development.