脂质在人冠状病毒感染中的作用

冠状病毒是一类阳性单链RNA病毒。目前已发现有7种冠状病毒可感染人类,包括人类冠状病毒229E(hCoV-229E)、中东呼吸综合征冠状病毒(MERSr-CoV)、严重急性呼吸综合征冠状病毒(SARSrCoV)、人类冠状病毒OC43、人类冠状病毒HKU1、人类冠状病毒NL63及严重急性呼吸综合征冠状病毒2(SARS-CoV-2)。脂质,如磷脂、脂肪酸及胆固醇等与人类致病性冠状病毒感染密切相关。文章综述了脂质及脂质相关调节酶在冠状病毒感染中的作用。     

Recent endemic coronavirus infection is associated with less-severe COVID-19

Four different endemic coronaviruses (eCoVs) are etiologic agents for the seasonal common cold, and these eCoVs share extensive sequence homology with human SARS coronavirus 2 (SARS-CoV-2). Here, we show that individuals with, as compared with those without, a recent documented infection with eCoV were tested at greater frequency for respiratory infections but had a similar rate of SARS-CoV-2 acquisition. Importantly, the patients with a previously detected eCoV had less-severe coronavirus disease 2019 (COVID-19) illness. Our observations suggest that preexisting immune responses against endemic human coronaviruses can mitigate disease manifestations from SARS-CoV-2 infection.     

Convalescent plasma as a therapeutic agent for SARS-CoV,MERS-CoV and SARS-CoV-2: A scoping review

Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 are three kinds of coronaviruses that are exceptionally pathogenic to humans via zoonotic infections. The outbreaks of SARS-CoV and MERS-CoV, and SARS-CoV-2, to some extent, posed a severe threat to human health, daily activities as well as the economic status of many countries. When faced with these emerging viruses and no accessible vaccines and drugs, convalescent plasma (CP) is required as passive immunotherapy, since CP has the potential to neutralize and eliminate the virus from blood circulation. The sources of CP are individuals who have recovered from the viruses. Currently, CP is administered as emergency use and investigational treatment. Some studies have shown that CP is effective to treat infected individuals with viral pandemics such as influenza A, Ebola virus, SARS-CoV, and MERS-CoV. Moreover, following the deadly outbreak of SARS-CoV-2 in 2019, plenty of non-randomized clinical studies have been done on the effectiveness of CP for the treatment of Coronavirus Disease 2019 (COVID-19), and most of these studies have indicated that CP therapy is promising and saved many critically-ill patients. Therefore, CP is a helpful immune therapeutic agent for the immediate response of such pandemics because of its clinical efficacy, immediate availability, cost-effectiveness, ease of production, delivery, and storage. This review aims to summarize the effectiveness of CP in the treatment of these three coronaviruses, i.e. SARS-CoV, MERS-CoV, and SARS-CoV-2.     

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。     

关注SARS-CoV-2致病机制的研究

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）传染性强,可导致患者出现严重急性呼吸道感染（SARI）和多器官系统功能损害。SARS-CoV-2致病机制尚不明确,推测免疫炎症反应紊乱在其发生发展中发挥至关重要的作用。结合相关领域的研究进展,梳理SARS-CoV-2可能的致病机制,厘清未来研究方向,具有重要临床意义。     

Does common cold coronavirus infection protect against severe SARS-CoV-2 disease?

The coronavirus disease 2019 (COVID-19) pandemic continues to cause morbidity and mortality. Since SARS coronavirus 2 (SARS-CoV-2) was identified as the cause for COVID-19, some have questioned whether exposure to seasonal common cold coronaviruses (CCCs) could provide tangible protection against SARS-CoV-2 infection or disease. In this issue of the JCI, Sagar et al. examined SARS-CoV-2 infections and outcomes of patients who had previously tested positive or negative for CCC infection (CCC⁺ or CCC^–) by a comprehensive respiratory panel using PCR. No differences were seen between groups in terms of susceptibility to SARS-CoV-2 infection. However, hospitalized patients with a documented history of CCC infection had lower rates of intensive care unit (ICU) admissions and higher rates of survival than hospitalized CCC^– patients. While these findings are associative and not causative, they highlight evidence suggesting that previous CCC infection may influence the disease course of SARS-CoV-2 infection.     

Stability and infectivity of coronaviruses in inanimate environments

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a highly contagious virus that can transmit through respiratory droplets,aerosols,or contacts.Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission.The inanimate surfaces have often been described as a source of nosocomial infections.However,summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present.This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces.The literature was systematically searched on Medline without language restrictions.All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included.Most viruses from the respiratory tract,such as coronaviruses,influenza,SARS-CoV,or rhinovirus,can persist on surfaces for a few days.Persistence time on inanimate surfaces varied from minutes to up to one month,depending on the environmental conditions.SARSCoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity.The most common coronaviruses may well survive or persist on surfaces for up to one month.Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature.Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection.The risk of transmission via touching contaminated paper is low.Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.     

新型冠状病毒的研究现状与实验室诊断

新型冠状病毒(SARS-CoV-2)在全球范围内的传播对世界公共健康构成了巨大威胁。目前,预防和治疗SARS-CoV-2的选择仍然非常有限。解析病毒感染宿主的致病机制及治疗性疫苗的研制迫在眉睫。与此同时,研发快速、有效的SARS-CoV-2实验室检测技术,对于实现快速确诊感染病例、排除疑似病例、促进疫情的防控与临床救治至关重要。该文首先从SARS-CoV-2的结构特征、分子遗传变异特征、致病机制及潜在的药物靶点等方面介绍了“如何认识SARS-CoV-2”;同时立足于临床检验,重点介绍了现有的病毒实验室检测技术及问题解析、即时检验及高通量病毒筛查芯片等病毒筛查新技术,回答了“如何检测SARS-CoV-2”。最后对实验室从业人员如何安全防护进行了要点总结。     

Evaluation of four commercial severe acute respiratory coronavirus 2 antibody tests

IntroductionNumerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital.MethodsThis study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses.ResultsThe varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11–15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed.ConclusionsOur results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis.     

Coronavirus Disease 2019: Coronaviruses and Blood Safety

With the outbreak of unknown pneumonia in Wuhan, China, in December 2019, a new coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), aroused the attention of the entire world. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19). The World Health Organization declared COVID-19 in China as a Public Health Emergency of International Concern. Two other coronavirus infections—SARS in 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2012—both caused severe respiratory syndrome in humans. All 3 of these emerging infectious diseases leading to a global spread are caused by β-coronaviruses. Although coronaviruses usually infect the upper or lower respiratory tract, viral shedding in plasma or serum is common. Therefore, there is still a theoretical risk of transmission of coronaviruses through the transfusion of labile blood products. Because more and more asymptomatic infections are being found among COVID-19 cases, considerations of blood safety and coronaviruses have arisen especially in endemic areas. In this review, we detail current evidence and understanding of the transmission of SARS-CoV, MERS–CoV, and SARS-CoV-2 through blood products as of February 10, 2020, and also discuss pathogen inactivation methods on coronaviruses.     

Alternative Screening Approaches for Discovery of Middle East Respiratory Syndrome Coronavirus Inhibitors

Two coronaviruses causing severe respiratory disease and high mortality rates emerging within the past dozen years reinforces the need for clinically efficacious antivirals targeting coronaviruses. Alternative screening approaches for antivirals against the recently emergent Middle East respiratory syndrome coronavirus (MERS-CoV) may provide lead compounds to address this need. Two Antimicrobial Agents and Chemotherapy (AAC) papers screened libraries of approved compounds that may potentially be repurposed as MERS-CoV antivirals. A third AAC paper showed that a previously described severe acute respiratory syndrome coronavirus (SARS-CoV) helicase inhibitor also has activity against MERS-CoV.     

Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation,infectivity, transmission,and vaccine resistance

The appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has caused panic responses around the world because of its high transmission rate and number of mutations. This review summarizes the highly mutated regions, the essential infectivity, transmission, vaccine breakthrough and antibody resistance of the Omicron variant of SARS-CoV-2. The Omicron is highly transmissible and is spreading faster than any previous variant, but may cause less severe symptoms than previous variants. The Omicron is able to escape the immune system’s defenses and coronavirus disease 2019 vaccines are less effective against the Omicron variant. Early careful preventive steps including vaccination will always be key for the suppression of the Omicron variant.     

Should people with chronic liver diseases be vaccinated against COVID-19?

Hepatic impairment in coronavirus disease 2019 (COVID-19) may derive from cholangiocyte damage in the beginning, but not from direct infection of hepatocytes. Chronic liver disease patients co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited overexpression of angiotensin-converting enzyme 2 receptors and overwhelming cytokine storm. Consensus has been reached that we should encourage as many people as possible to be vaccinated in order to achieve herd immunity. SARS-CoV-2 vaccines can prevent or alleviate severe infection and cytokine storm. It is recommended that all adult patients with chronic liver diseases and liver transplant recipients should receive COVID-19 vaccines using the standard dose and schedule. Data is not yet sufficient to compare the efficacy of different types of vaccines used in chronic liver disease patients.     

Distinctive features of severe SARS-CoV-2 pneumonia

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.     

Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.     

新型冠状病毒感染的临床表现及其实验室检测技术进展

新型冠状病毒(SARS-CoV-2)属于冠状病毒属,是一种主要通过呼吸道传播的RNA病毒,具有极高传染性,被世界卫生组织列为对人类危害最严重的病毒之一。目前尚无批准上市的用于预防SARS-CoV-2的疫苗,该病毒导致的2019年新型冠状病毒肺炎(COVID-19)需要通过实验室检测才能明确。为了解SARS-CoV-2的研究进展,该文综述了该病毒的特征、感染的流行病学、实验室检测技术,以期为诊断和防控新型冠状病毒病提供参考。     

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.     

Transmission of severe acute respiratory syndrome coronavirus 2 via fecal-oral: Current knowledge

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 93 million cases and 2 million deaths in the world. SARS-CoV-2 respiratory tract infection and its main clinical manifestations such as cough and shortness of breath are well known to the scientific community. However, a growing number of studies have reported SARS-CoV-2-related gastrointestinal involvement based on clinical manifestations, such as diarrhea, nausea, vomiting, and abdominal pain as well as on the pathophysiological mechanisms associated with coronavirus disease 2019. Furthermore, current evidence suggests SARS-CoV-2 transmission via the fecal-oral route and aerosol dissemination. Moreover, studies have shown a high risk of contamination through hospital surfaces and personal fomites. Indeed, viable SARS-CoV-2 specimens can be obtained from aerosols, which raises the possibility of transmission through aerosolized viral particles from feces. Therefore, the infection by SARS-CoV-2 via fecal-oral route or aerosolized particles should be considered. In addition, a possible viral spread to sources of drinking water, sewage, and rivers as well as the possible risk of viral transmission in shared toilets become a major public health concern, especially in the least developed countries. Since authors have emphasized the presence of viral RNA and even viable SARS-CoV-2 in human feces, studies on the possible fecal-oral coronavirus disease 2019 transmission become essential to understand better the dynamics of its transmission and, then, to reinforce preventive measures against this infection, leading to a more satisfactory control of the incidence of the infection.     

全球冠状病毒研究态势分析及其启示

2019年12月发生于中国武汉的不明原因肺炎最终被确定是一种新型冠状病毒感染所致,后者暂被命名为2019新型冠状病毒(2019-nCoV)。冠状病毒是一个大型病毒家族,可诱发禽类、哺乳动物和人类的诸多疾病,包括2003年严重急性呼吸综合征(severe acute respiratory syndrome,SARS)、2012年中东呼吸综合征(Middle East respiratory syndrome,MERS)等。近20年来,全球科学家已开展了一系列冠状病毒相关的传播机制及致病机制等各方面研究。本文基于文献计量学、引文分析和知识图谱等方法,分析了全球冠状病毒研究的现状和趋势,梳理了冠状病毒相关研究的知识脉络,为当下及今后冠状病毒所致疾病的防控提供参考。     

SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals

Characterization of the T cell response in individuals who recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8⁺ T cell recognition in a cross-sectional sample of 30 coronavirus disease 2019 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis and from humoral and inflammatory responses. There were 132 SARS-CoV-2–specific CD8⁺ T cell responses detected across 6 different HLAs, corresponding to 52 unique epitope reactivities. CD8⁺ T cell responses were detected in almost all convalescent individuals and were directed against several structural and nonstructural target epitopes from the entire SARS-CoV-2 proteome. A unique phenotype for SARS-CoV-2–specific T cells was observed that was distinct from other common virus-specific T cells detected in the same cross-sectional sample and characterized by early differentiation kinetics. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8⁺ T cell response. Overall, T cells exhibited distinct differentiation into stem cell and transitional memory states (subsets), which may be key to developing durable protection.