2019冠状病毒病的发病机制研究进展

由严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的病毒性肺炎已经扩散到全球200多个国家和地区,导致了数十万人死亡。2019冠状病毒病(coronavirus disease 19,COVID-19)的流行病学、致病机制和临床治疗方法成为各国政府以及科研界亟待研究解决的重大问题。本文对SARS-CoV-2的病原学特征及COVID-19的发病机制、病理学研究进展进行综述,重点评述病毒受体人血管紧张素转换酶Ⅱ (human angiotensin-converting enzyme 2,ACE2)与病毒致病机制的相关性,为后续研究与防治提供参考。     

Incidence and impact of cardiac arrhythmias in coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

BackgroundStudies have shown that cardiac arrhythmias may occur in up to 44% of patients with severe coronavirus disease 2019 (COVID-19) and has been associated with an increased risk of death. This systematic review and meta-analysis aimed to evaluate the incidence of cardiac arrhythmias in patients with COVID-19 and their implications on patient prognosis.MethodsWe performed a systematic literature search from PubMed, SCOPUS, Europe PMC, Cochrane Central Databases, and Google Scholar + Preprint Servers. The primary endpoint of the study was poor outcomes including mortality, severe COVID-19, and the need for ICU care.ResultsA total of 4 studies including 784 patients were analyzed. The incidence of arrhythmia in patients with COVID-19 was 19% (9–28%; I²: 91.45). Arrhythmia occurred in 48% (38–57%; I²: 48.08) of patients with poor outcome and 6% (1–12%; I²: 85.33%) of patients without poor outcome. Patients with COVID-19 experiencing arrhythmia had an increased risk of poor outcome (RR 7.96 [3.77, 16.81], p < 0.001; I²: 71.1%). The funnel-plot analysis showed an asymmetrical funnel plot with most of the studies on the right side of the effect estimate. The regression-based Egger’s test showed indication of small-study effects (p = 0.001).ConclusionCardiac arrhythmias were significantly associated with an increased risk of poor outcome in COVID-19. Arrhythmias were observed in 19% of patients with COVID-19 and in 48% of patients with COVID-19 and poor outcomes.     

新型冠状病毒上海株(nCoV-SH01)的分离和鉴定

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情对人类生命健康构成极大威胁。病毒的分离是构建新型冠状病毒(2019 novel coronavirus, 2019-nCoV)细胞感染模型和动物感染模型的基础。本研究利用冠状病毒易感的Vero E6细胞,从1例上海感染者的咽拭子中分离到一株2019-nCoV,命名为nCoV-SH01。对该毒株全基因组采用一代Sanger和二代Illumina法测序,发现该毒株与GenBank MN908947的同源性＞99.99%。免疫荧光检测显示,该毒株与COVID-19康复者的血清呈阳性反应。当nCoV-SH01感染Vero E6细胞后,导致典型的合胞体病变,细胞病变效应明显且进展迅速,提示nCoV-SH01可用于进一步建立2019-nCoV的细胞感染和动物感染模型,为开展致病性研究以及抗病毒药物和疫苗研发奠定了基础。     

A novel coronavirus from patients with pneumonia in China, 2019

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide. The global pandemic poses a serious challenge to the medical community. Detection of serum immunoglobulin G (IgG) and immunoglobulin M (IgM) is crucial for the diagnosis of COVID-19. IgG is particularly important for antiviral response assessment. Our study divided 51 patients into \     

Dysregulation of the immune response in coronavirus disease 2019

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger a cytokine storm in the pulmonary tissue by releasing various types of mediators, leading to acute respiratory distress syndrome (ARDS). Increased neutrophil-to-lymphocyte ratio, as well as CD4+ T lymphopenia, is reported in cases with novel coronavirus disease (COVID-19), meanwhile, lymphopenia is a significant finding in the majority of COVID-19 cases with a severe phenotype. Moreover, excessive activation of monocyte/macrophage and cytokine storms are associated with the severity of the disease and the related complications in SARS-CoV-2 infection. Understanding the immune response dysregulation in COVID-19 is essential to develop more effective diagnostic, therapeutic, and prophylactic strategies in this pandemic.     

密切关注新型冠状病毒肺炎并发、继发侵袭性真菌感染

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)在中国武汉暴发波及全国,截至2月14日,死亡人数已经超过 1 300,严重威胁人类的生命。《新型冠状病毒感染的肺炎诊疗方案(试行第五版)》中采用的抗病毒、抗细菌、激素、机械通气和循环支持等治疗手段,均为引发真菌感染的高危因素。当患者继发真菌感染时,病死率会大幅提升。因此,应制定科学、规范的预警技术,以便早期发现真菌感染;研发便捷、高效、低廉和覆盖面广的抗高发侵袭性真菌感染的诊断试剂盒以及新型抗菌材料防护物品,确保做到早期预警、明确诊断、精准治疗和有效防护,以应对可能出现的COVID-19继发严重真菌感染的状况。密切关注COVID-19并发、继发性真菌感染具有重要的现实意义。     

DNA repair pathway genes and lung cancer susceptibility: A meta-analysis

Objective

DNA repair pathway genes have been implicated to play an important role in the development of lung cancer. However, contradictory results are often reported by various studies, making it difficult to interpret them. So in this meta-analysis, we have assessed the association between lung cancer risk and two DNA repair pathway genes. XRCC1 and ERCC2, by analyzing 67 published case–control studies.

Research design and methods

We searched PubMed, Embase and Web of Science using terms “XRCC1” or “XPD” or “ERCC2” and “lung cancer” on August 1, 2012. Three criteria were applied to select included studies for resulting studies. Information was carefully extracted by two investigators independently. We used pooled odds ratio (OR) to assess the effect of a polymorphism, and a dominant model was applied where genotypes that contain the non-reference allele were combined together. All the calculations were performed using STATA version 11.0.

Main outcome measures and results

Three common nonsynonymous polymorphisms in XRCC1, codon 194, codon 280 and codon 399, and two common nonsynonymous polymorphisms in ERCC2, codon 312 and codon 751, were analyzed. The result showed in total population, Lys751Gln in ERCC2 is associated with an increase of lung cancer risk, with a summary OR as 1.15. No association was found for any other polymorphisms. When studies were stratified by ethnicity, the risk effect of Lys751Gln in ERCC2 was found only in Caucasians, not in Asians.

Conclusions

In conclusion, Lys751Gln in ERCC2 is associated with lung cancer, and the risk effect probably exists in Caucasians. By contrast, polymorphisms in XRCC1 are less likely to be susceptible to lung cancer risks.     

The effect of silica exposure on the risk of lung cancer: A meta-analysis

Lung cancer is an incurable disease with an increased mortality rate caused by the inhalation of dust-containing crystalline silica particles. Silica exposure is one of the most important occupational hazards in the world. Whether the association between silica exposure and lung cancer is because of the fibrotic process or to the effect of respirable silica itself is unclear. The International Agency for Research on Cancer (IARC) classified silica as a human lung carcinogen. The opinion of lung cancer is a question that has been addressed in this review. Three electronic databases, including MEDLINE, Scopus, and Web of Science, were used to search for relevant literature from 2000 to 2022. To evaluate the relationship between exposure to silica and developing lung cancer, we performed a meta-analysis using the random-effects model. For each study, the overall odds ratio (OR), relative risk (RR) with 95% confidence intervals (CI), and p values were calculated. An extensive database search resulted in the selection of 20 (case‒control and nested case‒control studies were selected) out of 527 studies. Among the 20 selected studies, 7 studies showed a significant association between silica exposure and an increased risk of lung cancer. Further analysis showed that among the selected studies, six studies showed a significant correlation between combined exposure to silica and smoking with an increased risk of lung cancer. The data from the present study showed that smoking habits increased the impact of silica exposure on the initiation of lung carcinogenesis in exposed workers.     

Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review

Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1st_, 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.     

Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial

BackgroundTreatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy.MethodsFrom January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients).ResultsA total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups.ConclusionsOur findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.     

Cell-based therapies for coronavirus disease 2019: proper clinical investigations are essential

The serious consequences of the global coronavirus disease 2019 (COVID-19) pandemic have prompted a rapid global response to develop effective therapies that can lessen disease severity in infected patients. Cell-based approaches, primarily using mesenchymal stromal cells (MSCs), have demonstrated a strong safety profile and possible efficacy in patients with acute respiratory distress syndrome (ARDS), but whether these therapies are effective for treating respiratory virus-induced ARDS is unknown. According to the World Health Organization International Clinical Trials Registry Platform and the National Institutes of Health ClinicalTrials.gov databases, 27 clinical investigations of MSC-based cell therapy approaches have begun in China since the onset of the COVID-19 outbreak, with a growing number of academic and industry trials elsewhere as well. Several recent published reports have suggested potential efficacy; however, the available data presented are either anecdotal or from incomplete, poorly controlled investigations. Therefore, although there may be a potential role for MSCs and other cell-based therapies in treatment of COVID-19, these need to be investigated in a rationally designed, controlled approach if safety and efficacy are to be demonstrated accurately. The authors urge that the field proceed by finding a balance between swift experimentation and communication of results and scientifically coherent generation and analysis of clinical data.     

XPA A23G polymorphism and lung cancer risk: a meta-analysis

Case–control studies on the association between XPA A23G and lung cancer have provided either controversial or inconclusive results. To clarify the effect of XPA A23G on the risk of lung cancer, a meta-analysis of all case–control observational studies was performed. Pooled odds ratios (ORs) for various polymorphisms were estimated using random and fixed effects models. The Q-statistic was used to evaluate the homogeneity, and Egger and Begg tests were used to assess publication bias. For the homozygote GG and G allele carriers (GA + GG), the pooled ORs were 1.24 (95% CI 1.05–1.46; P = 0.27 for heterogeneity) and 1.30 (95% CI 1.13–1.51; P = 0.45 for heterogeneity) compared to the homozygous genotype (AA). In the stratified analysis by ethnicity, the ORs of the G allele carriers and the homozygote GG were 1.28 (95% CI 1.10–1.49; P = 0.07 for heterogeneity) and 1.42 (95% CI 1.04–1.93; P = 0.39 for heterogeneity) among non-Caucasians. No significant associations were found in the Caucasian population in any of the genetic models. When studies that were not in Hardy–Weinberg equilibrium (HWE) were corrected, the pattern of the results remained the same. Our results indicated a significantly decreased risk of lung cancer in non-Caucasians with the G allele.     

Epidemiological and clinical features in patients with coronavirus disease 2019 outside of Wuhan,China: Special focus in asymptomatic patients

ObjectivesIn December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan City and rapidly spread across the world. The clinical characteristics of affected patients in different regions and populations may differ. Thus, this study aimed to identify the characteristics of the disease to provide an insight about the prevention and treatment of COVID-19.MethodsData on the demographic characteristics and clinical findings of the patients admitted at the First Hospital of Changsha from January 1, 2020 to February 10, 2020 were assessed.ResultsIn this study, there were 8 (3.8%) asymptomatic, 21 (10.0%) mild upper respiratory tract infection (URTI), and 180 (86.1%) pneumonia cases. In total, 47 (22.5%) patients resided in Wuhan, and 45 (21.5%) had recently traveled to Wuhan before disease onset. Moreover, 19 (9.1%) had contact with people from Wuhan, and 69 (33.0%) were family cluster cases. The median incubation period was approximately 6.3 (range: 1.0–20.0) days. Fever and cough were the most common initial symptoms: 99 (49.3%) patients presented with fever, without cough; 59 (29.4%) with cough, without fever; and 33 (16.4%) with both fever and cough.ConclusionThe symptoms of patients with COVID-19 were relatively mild outside Wuhan, and family cluster was a remarkable epidemic characteristic. Special attention should be paid to asymptomatic patients.     

The effect of silica exposure on the risk of lung cancer: A dose-response meta-analysis

BackgroundThe relationship between silica and the risk of developing lung cancer has been established in previous literature, but how much the level of exposure to silica can increase the risk of lung cancer is a question that has been addressed in this review.MethodsThree electronic databases, including MEDLINE, Scopus, and Web of Science were searched for relevant literature. For the dose-response relationship between exposure to silica and developing lung cancer, we performed a meta-analysis using the random-effects model. For each level of exposure, we calculated the overall risk ratio (RR) with 95% confidence intervals (CI).ResultsNineteen studies were included in the meta-analysis. There was a positive and significant increasing dose-response trend between silica exposure and the risk of developing lung cancer as follows: < 0.50 mg/m³ 1.14 (95% CI: 1.05, 1.23; I² = 79%), 0.50–0.99 mg/m³ 1.34 (95% CI: 1.05, 171; I² = 45%), 1.00–1.99 mg/m³ 1.14 (95% CI: 1.00, 1.30; I² = 70%), 2.00–2.99 mg/m³ 1.47 (95% CI: 1.05, 2.06; I² = 57%), 3.00–3.99 mg/m³ 1.44 (95% CI: 0.99, 2.11; I² = 58%), and ≥ 4.00 mg/m³ 1.64 (95% CI: 1.20, 2.24; I² = 88%). The heterogeneity across studies was mild to moderate.ConclusionsThe presence of a dose-response relationship favors the causal relationship between exposure to silica and developing lung cancer.     

Mesenchymal stem cells: a new front emerges in coronavirus disease 2019 treatment

Currently, treating coronavirus disease 2019 (COVID-19) patients, particularly those afflicted with severe pneumonia, is challenging, as no effective pharmacotherapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Severe pneumonia is recognized as a clinical syndrome characterized by hyper-induction of pro-inflammatory cytokine production, which can induce organ damage, followed by edema, dysfunction of air exchange, acute respiratory distress syndrome, acute cardiac injury, secondary infection and increased mortality. Owing to the immunoregulatory and differentiation potential of mesenchymal stem cells (MSCs), we aimed to outline current insights into the clinical application of MSCs in COVID-19 patients. Based on results from preliminary clinical investigations, it can be predicted that MSC therapy for patients infected with SARS-CoV-2 is safe and effective, although multiple clinical trials with a protracted follow-up will be necessary to determine the long-term effects of the treatment on COVID-19 patients.     

Stem cell therapy in coronavirus disease 2019: current evidence and future potential

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.     

Sex- and age-specific clinical and immunological features of coronavirus disease 2019

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8⁺ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8⁺ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8⁺ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.     

The outlook for diagnostic purposes of the 2019-novel coronavirus disease

At the end of December 2019, a novel acute respiratory syndrome coronavirus 2 (SARS-CoV2) appeared as the third unheard of outbreak of human coronavirus infection in the 21st century. First, in Wuhan, China, the novel SARS-CoV2 was named by the World Health Organization (WHO), as 2019-nCOV (COVID-19), and spread extremely all over the world. SARS-CoV2 is transmitted to individuals by human-to-human transmission leading to severe viral pneumonia and respiratory system injury. SARS-CoV2 elicits infections from the common cold to severe conditions accompanied by lung injury, acute respiratory distress syndrome, and other organ destruction. There is a possibility of virus transmission from asymptomatic cases as active carriers, in addition to symptomatic ones, which is a crucial crisis of COVID-19 that should be considered. Hence, paying more attention to the accurate and immediate diagnosis of suspected and infected cases can be a great help in preventing the rapid spread of the virus, improving the disease prognosis, and controlling the pandemic. In this review, we provide a comprehensive and up-to-date overview of the different types of Clinical and Para-clinical diagnostic methods and their practical features, which can help understand better the applications and capacities of various diagnostic approaches for COVID-19 infected cases.     

对新型冠状病毒肺炎继发真菌感染的思考

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情十分严重,给民众的健康带来了巨大威胁。COVID-19患者可能继发侵袭性真菌感染,会严重威胁患者的生命,因此,在诊治策略上应该给予重视。除了加强高危患者中病原真菌的常规检查外,还应加大力度支持和扶持病原真菌先进检测技术的研发;此外,还应重点支持针对医疗单位、公共场所和家庭等常温环境以及体表和器物表面灭活病毒、细菌、真菌等病原体的新型技术和方法的研发。最终为国家战胜COVID-19和继发感染疫情提供新措施和新策略。     

新型冠状病毒肺炎疫情下医务工作者的自我心理防护

近来,新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)疫情成为“国际关注的突发公共卫生事件”,大量医务工作者积极投入应对疫情的战役,在承担繁重工作的同时,也承受着巨大的心理压力。本文分析在重大传染病疫情下,一线医务工作者可能面临的心理问题,并提出自我解决的方案,这将有助于医务人员以良好的情绪状态投入防疫和抗疫工作。