冠状病毒疾病2019发病机制若干热点问题的思考

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）所致冠状病毒疾病2019（COVID-19）已构成国际关注的突发公共卫生事件。COVID-19传染性强,可导致患者出现严重呼吸道感染和多器官系统功能损害。COVID-19发病机制尚不明确,我们推测SARS-CoV-2直接致宿主靶细胞损伤及机体免疫炎症反应紊乱可能是COVID-19的主要致病机制。本文基于相关研究领域的进展,对COVID-19发病机制中的若干热点问题进行分析和讨论,并提出思考。     

A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis

The gold standard for the diagnosis of coronavirus disease 2019 (COVID-19) is a nucleic acid detection test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may occasionally reveal false-positive or false-negative results. Herein, we describe a case of a patient infected with human coronavirus NL63 (HCoV-NL63) who was falsely diagnosed with COVID-19 using the Ampdirect? 2019-nCoV detection kit (Shimadzu Corporation, Japan) and SARS-CoV-2 Detection Kit (TOYOBO co., ltd.), and was admitted to a COVID-19 hospital ward. We suspected a cross-reaction between HCoV-NL63 and SARS-CoV-2; however, the reported genome sequences of HCoV-NL63 and N1/N2 primers for SARS-CoV-2 do not correspond. Thus, the PCR result was supposed to be a false positive possibly due to contamination or human error. Although the issue of a false-negative result has been the focus of much attention to prevent the spread of the disease, a false positive is fraught with problems as well. Physicians should recognize that unnecessary isolation violates human rights and a careful diagnosis is indispensable when the results of laboratory testing for COVID-19 are unclear. Generally, in cases such as a duplicate PCR test was partially positive, either N1 or N2 alone was positive, PCR testing for two or more target regions resulted in a positive only for single region, a high cycle threshold >35 was obtained, a false positive should be suspected. Especially, when these conditions coincide, we should recognize the high likelihood of a false positive.     

新型冠状病毒肺炎相关性急性胰腺炎：证据，挑战与思考

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）自2019年12月发病以来,现已全球大流行。COVID-19除影响呼吸系统外,还可造成全身多系统、多脏器的损害。目前关于COVID-19累及胰腺的证据十分有限,COVID-19患者中急性胰腺炎（AP）的发病率存在不确定性,其临床特征和发病机制也存在诸多疑问。在全球COVID-19流行仍未得到完全控制的背景下,由于目前对COVID-19与AP之间相互作用知之甚少,我们必须警惕他们之间可能存在的联系。临床上诸多治疗程序需要合理化,应采取有效的防护措施,在科学诊治患者的同时有效避免医护人员SARS-CoV-2感染。     

Severe Acute Respiratory Syndrome Coronavirus 2 and Blood Safety: An Updated Review

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus first identified in late 2019 and subsequently declared a worldwide pandemic in March 2020. In this review, we provide an overview of the implications of SARS-CoV-2 for blood safety and sufficiency.SummaryApproximately one-third of SARS-CoV-2 infections are asymptomatic. The reported mean incubation period typically varies from 2 to 11 days, but longer periods up to 22 days have been reported. The blood phase of SARS-CoV-2 appears to be brief and low level, with RNAaemia detectable in only a small proportion of patients, typically associated with more severe disease and not demonstrated to be infectious virus. A small number of presymptomatic and asymptomatic blood phase cases have been reported. Transfusion-transmission (TT) of SARS-CoV-2 has not been reported. Therefore, the TT risk associated with SARS-CoV-2 is currently theoretical. To mitigate any potential TT risk, but more importantly to prevent respiratory transmission in donor centers, blood services can implement donor deferral policies based on travel, disease status, or potential risk of exposure and encourage staff vaccination.Key MessagesThe TT risk of SARS-CoV-2 appears to be low. The biggest risk to blood services in the current COVID-19 pandemic is to maintain the sufficiency of the blood supply while minimizing respiratory transmission of SARS-CoV-2 to donors and staff while donating blood.     

COVID-19: Focus on the lungs but do not forget the gastrointestinal tract

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.     

新型冠状病毒在环境中的存活潜力和感染风险

新型冠状病毒肺炎(COVID-19)传播速度快、范围广,主要通过飞沫和接触传播.本研究通过整理新型冠状病毒(SARS-CoV-2)在不同物体表面的存活时间及主要影响因素的相关研究,发现SARS-CoV-2的稳定性与重症急性呼吸综合征冠状病毒(SARS-CoV)相近,室温下可在多种物体表面或介质中存活数天(不锈钢表面2 ...     

Stem cell therapy: A promising treatment for COVID-19

Novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. SARS-CoV-2 is an RNA virus and has a glycosylated spike (S) protein used for genome encoding. COVID-19 can lead to a cytokine storm and patients usually have early respiratory signs and further secondary infections, which can be fatal. COVID-19 has entered an emergency phase, but there are still no specific effective drugs for this disease. Mesenchymal stem cells (MSCs) are multipotent stromal cells, which cause antiapoptosis and can repair damaged epithelial cells. Many clinical trials have proved that MSC therapy could be a potential feasible therapy for COVID-19 patients, especially those with acute respiratory distress syndrome, without serious adverse events or toxicities. However, more studies are needed in the future, in order to confirm the effect of this therapy.     

新型冠状病毒IgM/IgG抗体在病程监测中的临床意义

目的评价新型冠状病毒(SARS-CoV-2)IgM/IgG抗体检测(化学发光法)在新型冠状病毒肺炎(COVID-19)病程监测和转归方面的临床意义。方法回顾性研究。收集2020年1月20日至2020年3月1日在天津市疾病预防控制中心核酸检测阳性的COVID-19确诊患者88例(115例血清样本)作为疾病组,排除COVID-19(核酸检测阴性)的其他疾病患者245例(245例血清样本)作为对照组。用化学发光法检测SARS-CoV-2 IgM和IgG抗体。结果 SARS-CoV-2 IgM抗体检测的敏感性、特异性分别为90.91%、100%;SARS-CoV-2 IgG抗体检测的敏感性、特异性分别为88.64%、100%;IgM和IgG抗体联合检测敏感性显著提高至96.59%,特异性为100%,与核酸检测的总符合率高达99.10%。SARS-CoV-2 IgM抗体水平在COVID-19病程中呈现先升高后降低的趋势,IgG抗体水平随着病程的进展逐渐升高。结论 SARS-CoV-2 IgM和IgG抗体化学发光法联合检测敏感性高,可作为COVID-19一种有效的辅助诊断,在病程监测和转归方面有一定的意义。     

2例新型冠状病毒肺炎粪便SARS-CoV-2核酸阳性临床启示

目前中国新型冠状病毒肺炎(COVID-19)疫情仍十分严峻,及时、早期地识别COVID-19患者是控制疫情的关键步骤。而新型冠状病毒(SARS-CoV-2)核酸检测作为诊断COVID-19的金标准,不但对检测技术提出更高的要求,同时对不同病程患者如何选择标本类型也是一个挑战。本文报道2例COVID-19确诊病例的诊疗经过,并分析采用不同类型标本检测SARS-CoV-2核酸的检出情况,为临床诊断COVID-19时如何选择标本类型和如何提高核酸检出率提供参考。     

SARS-CoV-2抗体用于COVID-19诊断的Meta分析

目的 采用Meta分析探讨严重急性呼吸综合征冠状病毒2(SARS-CoV-2)抗体对新型冠状病毒肺炎(COVID-19)的诊断价值.方法 检索PubMed、Embase、Cochrane Library、中国知网、万方和维普数据库,收集相关文献.计算合并敏感性、合并特异性、诊断比值比(DOR),分析文献的异质性,采用综...     

新型冠状病毒IgM和IgG抗体不同检测方法在新型冠状病毒感染中的临床应用评价

目的探讨新型冠状病毒(SARS-CoV-2)IgM和IgG抗体不同检测方法在新型冠状病毒肺炎(COVID-19)中的应用。方法选取25例COVID-19患者,以同期20例排除SARS-CoV-2感染的患者作为对照组,分别采用磁微粒化学发光法和胶体金法检测所有对象的血清SARS-CoV-2 IgM和IgG抗体。同时检测COVID-19患者血清降钙素原(PCT)、铁蛋白及C反应蛋白(CRP)。结果化学发光法检测血清SARSCoV-2 IgM和IgG抗体的敏感性分别为48%和56%,特异性均为100%,胶体金法检测血清SARS-CoV-2 IgM和IgG抗体的敏感性分别为88%和76%,临床特异性均为100%。2种方法检测血清SARS-CoV-2 IgM和IgG抗体总符合率分别为68.9%和73.3%。25例COVID-19患者中有36%的患者血清PCT升高、72%的患者血清CRP升高、84%的患者血清铁蛋白水平升高。结论SARS-CoV-2 IgM和IgG抗体不同检测方法之间差异较大,用于COVID-19患者的临床诊断时应综合考虑。     

Healthy neonate born to a SARS-CoV-2 infected woman: A case report and review of literature

BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus that has generated a worldwide outbreak of infections. Many people with coronavirus disease-2019 (COVID-19) have developed severe illness, and a significant number have died. However, little is known regarding infection by the novel virus in pregnant women. We herein present a case of COVID-19 confirmed in a woman delivering a neonate who was negative for SARS-CoV-2 and related it to a review of the literature on pregnant women and human coronavirus infections.CASE SUMMARYThe patient was a 36-year-old pregnant woman in her third trimester who had developed progressive clinical symptoms when she was confirmed as infected with SARS-CoV-2. Given the potential risks for both the pregnant woman and the fetus, an emergency cesarean section was performed, and the baby and his mother were separately quarantined and cared for. As a result, the baby currently shows no signs of SARS-CoV-2 infection (his lower respiratory tract samples were negative for the virus), while the mother completely recovered from COVID-19.CONCLUSIONAlthough we presented a single case, the successful result is of great significance for pregnant women with SARS-CoV-2 infection and with respect to fully understanding novel coronavirus pneumonia.     

Cross-protective immunity following coronavirus vaccination and coronavirus infection

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have shown efficacy against SARS-CoV-2, it is unknown if coronavirus vaccines can also protect against other coronaviruses that may infect humans in the future. Here, we show that coronavirus vaccines elicited cross-protective immune responses against heterologous coronaviruses. In particular, we show that a severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) vaccine developed in 2004 and known to protect against SARS-CoV-1 conferred robust heterologous protection against SARS-CoV-2 in mice. Similarly, prior coronavirus infections conferred heterologous protection against distinct coronaviruses. Cross-reactive immunity was also reported in patients with coronavirus disease 2019 (COVID-19) and in individuals who received SARS-CoV-2 vaccines, and transfer of plasma from these individuals into mice improved protection against coronavirus challenges. These findings provide the first demonstration to our knowledge that coronavirus vaccines (and prior coronavirus infections) can confer broad protection against heterologous coronaviruses and establish a rationale for universal coronavirus vaccines.     

COVID-19 Susceptibility in chronic obstructive pulmonary disease

In barely nine months, the pandemic known as COVID-19 has spread over 200 countries, affecting more than 22 million people and causing over than 786 000 deaths. Elderly people and patients with previous comorbidities such as hypertension and diabetes are at an increased risk to suffer a poor prognosis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although the same could be expected from patients with chronic obstructive pulmonary disease (COPD), current epidemiological data are conflicting. This could lead to a reduction of precautionary measures in these patients, in the context of a particularly complex global health crisis. Most COPD patients have a long history of smoking or exposure to other harmful particles or gases, capable of impairing pulmonary defences even years after the absence of exposure. Moreover, COPD is characterized by an ongoing immune dysfunction, which affects both pulmonary and systemic cellular and molecular inflammatory mediators. Consequently, increased susceptibility to viral respiratory infections have been reported in COPD, often worsened by bacterial co-infections and leading to serious clinical outcomes. The present paper is an up-to-date review that discusses the available research regarding the implications of coronavirus infection in COPD. Although validation in large studies is still needed, COPD likely increases SARS-CoV-2 susceptibility and increases COVID-19 severity. Hence, specific mechanisms to monitor and assess COPD patients should be addressed in the current pandemic.     

Clinical features and potential mechanism of coronavirus disease 2019-associated liver injury

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has posed a serious threat to global public health security. With the increase in the number of confirmed cases globally, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Despite atypical pneumonia as the primary symptom, liver dysfunction has also been observed in many clinical cases and is associated with the mortality risk in patients with COVID-19, like severe acute respiratory syndrome and Middle East respiratory syndrome. Here we will provide a schematic overview of the clinical characteristics and the possible mechanisms of liver injury caused by severe acute respiratory syndrome coronavirus 2 infection, which may provide help for optimizing the management of liver injury and reducing mortality in COVID-19 patients.     

Post-COVID-19 interstitial lung disease presenting with profound hypoxemia: Report of three cases demonstrating a good response to high-dose corticosteroid therapy

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to critical pneumonia, although the clinical courses vary. In some cases, COVID-19 pneumonia causes secondary pulmonary fibrosis, which can retain radiological changes and prolong respiratory symptoms. Interstitial lung disease (ILD) secondary to COVID-19 is thought to be caused by multiple pathologies, such as excessive cytokines and abnormal repair processes elaborated by lung cells (epithelium, mesenchyme, and alveolar macrophages) after lung injury rather than viral invasion itself. Immunosuppression therapy may improve chronic respiratory symptoms and radiological changes in post-COVID-19 ILD, although the treatment is not yet established. Herein, we report three patients with post-COVID-19 ILD who presented with profound hypoxemia that had a good response to high-dose corticosteroid therapy. Further and larger studies are needed to establish post-COVID-19 ILD.     

Fatal gastrointestinal bleeding associated with acute pancreatitis as a complication of Covid-19: a case report

Clinical manifestations of Covid-19 vary widely among patients. Recent studies suggest that up to 15% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. The location of virus–host cell receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 has an important role in the pathophysiology and presentation of disease. They are expressed in the respiratory tract, as well as other organs and tissues including exocrine and endocrine pancreatic cells. These cells are therefore a possible target for the virus, which could explain the relationship between SARS-CoV-2 infection and pancreatic injury. We report a disastrous collateral effect of the Covid-19 pandemic on a 33-year-old man with chronic renal insufficiency and asymptomatic SARS-CoV-2 infection, who developed acute pancreatitis. Inflammation progressed rapidly toward necrosis and the development of a peripancreatic pseudoaneurysm which subsequently ruptured, causing death.     

Histopathological features of SARS-CoV-2 infection and relationships with organoid technology

Coronavirus disease 2019 (COVID-19) following infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic that is still having serious effects worldwide. This virus, which targets the lungs in particular, can also damage other tissues. Angiotensin converting enzyme 2 (ACE-2) plays a key role in viral entry into host cells. The presence of ACE-2 in various tissues may permit viral infection. Studies of COVID-19 often make use of postmortem tissues. Although this information provides various useful results, it is also necessary to conduct in vitro studies to understand optimal treatment approaches. Because the virus may show species-specific differences, in vitro technologies using human cells are particularly important. Organoid technologies, three-dimensional structures that can be obtained from human cells, are playing increasingly important roles in studies of SARS-CoV-2. This technology offers a significant advantage in terms of mimicking in vivo tissue structures and testing antiviral compounds. In this mini-review, we summarize studies of SARS-CoV-2 using both histopathological and organoid technology approaches.     

Circulating angiotensin converting enzyme 2 and COVID-19

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a widespread outbreak since December 2019. The SARS-CoV-2 infection-related illness has been dubbed the coronavirus disease 2019 (COVID-19) by the World Health Organization. Asymptomatic and subclinical infections, a severe hyper-inflammatory state, and mortality are all examples of clinical signs. After attaching to the angiotensin converting enzyme 2 (ACE2) receptor, the SARS-CoV-2 virus can enter cells through membrane fusion and endocytosis. In addition to enabling viruses to cling to target cells, the connection between the spike protein (S-protein) of SARS-CoV-2 and ACE2 may potentially impair the functionality of ACE2. Blood pressure is controlled by ACE2, which catalyzes the hydrolysis of the active vasoconstrictor octapeptide angiotensin (Ang) II to the heptapeptide Ang-(1-7) and free L-Phe. Additionally, Ang I can be broken down by ACE2 into Ang-(1-9) and metabolized into Ang-(1-7). Numerous studies have demonstrated that circulating ACE2 (cACE2) and Ang-(1-7) have the ability to restore myocardial damage in a variety of cardiovascular diseases and have anti-inflammatory, antioxidant, anti-apoptotic, and anti-cardiomyocyte fibrosis actions. There have been some suggestions for raising ACE2 expression in COVID-19 patients, which might be used as a target for the creation of novel treatment therapies. With regard to this, SARS-CoV-2 is neutralized by soluble recombinant human ACE2 (hrsACE2), which binds the viral S-protein and reduces damage to a variety of organs, including the heart, kidneys, and lungs, by lowering Ang II concentrations and enhancing conversion to Ang-(1-7). This review aims to investigate how the presence of SARS-CoV-2 and cACE2 are related. Additionally, there will be discussion of a number of potential therapeutic approaches to tip the ACE/ACE-2 balance in favor of the ACE-2/Ang-(1-7) axis.