ABSTRACT
The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.
Subject(s)
Severe Acute Respiratory Syndrome , Cerebrospinal Fluid LeakABSTRACT
It is widely accepted that the zinc element is crucial in human beings. Zinc has gained more attention during the COVID-19 pandemic due to its utilization for the treatment and prevention of respiratory tract infections. However, some studies also pointed out that zinc intake might cause unwanted side effects and even be dangerous when overdosed. To reveal the relationship between zinc intake and health outcomes, we performed an umbrella review from human studies. In total, the umbrella review included 43 articles and identified 11 outcomes for dietary zinc intake and 86 outcomes for supplementary zinc intake. Dietary zinc intake in the highest dose would decrease the risk of overall and specific digestive tract cancers, depression, and type 2 diabetes mellitus (T2DM) in adults. Supplementary zinc consumption in adults was linked to an improvement of depression, antioxidant capacity and sperm quality, higher serum zinc concentration, and lower concentration of inflammatory markers. Zinc supplementation in children would reduce the incidence of diarrhea and pneumonia, improve zinc deficiency and boost growth. However, zinc might not decrease all-cause mortality in adults or the in-hospital mortality of COVID-19. And better maternal and neonatal outcomes may not derive from pregnant women who consumed higher or lower doses of zinc supplementation (>20 mg/day and <20 mg/day, respectively). Dose-response analyses revealed that a daily 5 mg increment of zinc would lower the risk of colorectal and esophageal cancer, whereas a large dose of zinc supplementation (daily 100 mg) showed no benefit in reducing prostate cancer risk.
ABSTRACT
The second COVID‐19 outbreak in Beijing was controlled by non‐pharmaceutical interventions, which avoided a second pandemic. Until mass vaccination achieves herd immunity, cities are at risk of similar outbreaks. It is vital to quantify and simulate Beijing's non‐pharmaceutical interventions to find effective intervention policies for the second outbreak. Few models have achieved accurate intra‐city spatio‐temporal epidemic spread simulation, and most modeling studies focused on the initial pandemic. We built a dynamic module of infected case movement within the city, and established an urban spatially epidemic simulation model (USESM), using mobile phone signaling data to create scenarios to assess the impact of interventions. We found that: (1) USESM simulated the transmission process of the epidemic within Beijing;(2) USESM showed the epidemic curve and presented the spatial distribution of epidemic spread on a map;and (3) to balance resources, interventions, and economic development, nucleic acid testing intensity could be increased and restrictions on human mobility in non‐epidemic areas eased.
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Objective: Researching the prognostic value of myocardial enzymes in COVID-19 patients. Materials &methods: We collected 113 confirmed COVID-19 patients. The dynamic changes of CK, LDH and α-HBDH in patients were studied retrospectively, the correlation between myocardial enzyme index, clinical classification and outcome of patients and its significance to prognosis. Results: There are significant statistical differences between LDH, α-HBDH, CK and the clinical classification, and patient’s outcome. In the receiver operating characteristic curve analysis, LDH, α-HBDH and CK have a good diagnostic value for the death outcome of patients. Conclusion: LDH, α-HBDH and CK were the components of myocardial enzyme profiles, and our results found that they were significantly positively correlated with clinical classification and prognosis of COVID-19 patients. The values of LDH, α-HBDH and CK increased with the increase of the severity of admission clinical classification and the deterioration of outcome. Therefore, we propose that continuous monitoring of LDH, α-HBDH and CK indicators can warn the deterioration of COVID-19 to a certain extent, regardless of whether patients with cardiovascular diseases are combined or not, and prompt early intervention.
ABSTRACT
The novel coronavirus disease 2019 (COVID-19) is a global epidemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 has a similar structure to severe acute respiratory syndrome coronavirus-1(SARS-CoV-1). The S protein on the surface of the virus is cleaved by host proprotein convertases (PCs) to expose the active N-terminal S1 extracellular domain. Its receptors are angiotensin-converting enzyme 2 (ACE2), and the C-terminal S2 membrane anchoring protein is responsible for translocating the virus into the cell. Among patients with COVID-19, there is a higher prevalence of cardiovascular disease, and more than 7% of patients have suffered myocardial damage due to the infection, but the internal mechanism is still poorly understood. There is currently no specific and effective targeted treatment. Reduction of the patient's morbidity and mortality is an urgent problem that needs to be solved clinically. By exploring the theoretical analysis of PCs and ACE2 in COVID-19 cardiovascular susceptibility, some insights on how to prevent and alleviate adverse cardiovascular prognosis have been provided in this study.
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Objective: To investigate the mechanism of Qingkailing Injection in the treatment of coronavirus disease 2019 (COVID-19). Methods: The active components and target proteins of Gardeniae Fructus, Isatidis Radix, Lonicerae Japonicae Flos, and other materials in Qingkailing Injection were obtained by means of literature search and TCMSP. Uniprot database was used to search the target genes corresponding to the active ingredients, and Cytoscape 3.7.2 was used to construct the drug-compound-target network. The enrichment analysis of KEGG pathway was carried out with the help of DAVID database to predict its mechanism. Core active components and potential targets of anti-COVID-19 drugs were verified by molecular docking. Results: The drug-compound- target network consisted of five drugs, 62 compounds and 70 targets. The KEGG pathway enrichment analysis included 41 signaling pathways (P < 0.05), which were mainly involved in cell apoptosis, Fc epsilon RI signaling pathway, TNF signaling pathway, etc. Molecular docking results showed that acacetin and syrigin had strong affinity with potential targets of anti-COVID-19 drugs. Conclusion: In this study, the effect of Qingkailing Injection has the characteristics of multiple components, multiple targets and multiple pathways. The active component, acacetin, can regulate the apoptosis pathway and TNF pathway by acting on CASP3, CASP8, FASLG, and other targets, so as to realize the potential therapeutic effect on COVID-19.
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COVID-19 virus has currently caused major outbreaks worldwide. ACE2 is a major cellular-entry receptor for the COVID-19 virus. Although ACE2 is known to be expressed in many organs, whether it is expressed by the conjunctival tissue is largely unknown. Human conjunctival tissues from 68 subjects were obtained, which included 10 subjects with conjunctival nevi, 20 subjects with conjunctivitis, 9 subjects with conjunctival papilloma, 16 subjects with conjunctival cyst, 7 subjects with conjunctival polyps, and 6 ocular traumas as normal subjects. Expression of ACE2 was evaluated by immunohistochemistry, immunofluorescence, reverse transcriptase-quantitative polymerase chain reaction, and western blot assay. We observed the expression of ACE2 by conjunctival tissues, expecially in conjunctival epithelial cells. ACE2 was significantly (p<0.001) overexpressed in conjunctival cells obtained from subjects with conjunctivitis, conjunctival nevi, conjunctival papilloma, conjunctival cyst, and conjunctival polyps epithelial cells when compared to that in conjunctival epithelial cells obtained from control subjects. Collectively, clinical features of reported COVID-19 patients combined with our results indicate that COVID-19 is likely to be transmitted through the conjunctiva.
Subject(s)
Papilloma , Conjunctivitis , Wounds and Injuries , Polyps , COVID-19ABSTRACT
Since December 2019, COVID-19 has raged in Wuhan and subsequently all over China and the world. We propose a Cybernetics-based Dynamic Infection Model (CDIM) to the dynamic infection process with a probability distributed incubation delay and feedback principle. Reproductive trends and the stability of the SARS-COV-2 infection in a city can then be analyzed, and the uncontrollable risks can be forecasted before they really happen. The infection mechanism of a city is depicted using the philosophy of cybernetics and approaches of the control engineering. Distinguished with other epidemiological models, such as SIR, SEIR, etc., that compute the theoretical number of infected people in a closed population, CDIM considers the immigration and emigration population as system inputs, and administrative and medical resources as dynamic control variables. The epidemic regulation can be simulated in the model to support the decision-making for containing the outbreak. City case studies are demonstrated for verification and validation.
Subject(s)
COVID-19 , Hallucinations , Auditory Perceptual DisordersABSTRACT
A newly identified novel coronavirus (2019-nCoV) has caused numerous acute respiratory syndrome cases in Wuhan China from December 2019 to Feb 2020. Its fast spreading to other provinces in China and overseas is very likely causing a pandemic. Since the novel coronavirus has been reported to be capable of endangering thousands of lives, it is extremely important to find out how the coronavirus is transmitted in human organs. Apart from fever and respiratory complications, gastrointestinal symptoms are observed in some patients with 2019-nCoV but the significance remains undetermined. The cell receptor angiotensin covering enzyme II (ACE2), which is the major receptor of SARS-nCoV, has been reported to be a cellular entry receptor of 2019-nCoV as well. Here, to more precisely explore the potential pathogen transmission route of the 2019-nCoV infections in the gastrointestinal tract, we analyzed the ACE2 RNA expression profile in the colon tissue of healthy adults and colorectal cancer patients of our cohort and other databases. The data indicates that ACE2 is mainly expressed in epithelial cells of the colon. The expression of ACE2 is gradually increased from healthy control, adenoma to colorectal cancer patients in our cohort as well as in the external Asian datasets. According to the expression profile of ACE2 in colon epithelial cells, we speculate adenoma and colorectal cancer patients are more likely to be infected with 2019-nCoV than healthy people. Our data may provide a theoretical basis for the classification and management of future 2019-nCoV susceptibility people in clinical application.