Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are being deployed, but the global need greatly exceeds the supply, and different formulations might be required for specific populations. Here we report Day 42 interim safety and immunogenicity data from an observer-blinded, dose escalation, randomized controlled study of a virus-like particle vaccine candidate produced in plants that displays the SARS-CoV-2 spike glycoprotein (CoVLP: NCT04450004
 ). The co-primary outcomes were the short-term tolerability/safety and immunogenicity of CoVLP formulations assessed by neutralizing antibody (NAb) and cellular responses. Secondary outcomes in this ongoing study include safety and immunogenicity assessments up to 12 months after vaccination. Adults (18–55 years, n = 180) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 μg, 7.5 μg, and 15 μg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate. Safety and immunogenicity results in humans of a two-dose SARS-CoV-2 vaccine made from plants support further assessment of potential efficacy.

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Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19.

Background Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). Methods In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

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Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

COVID-19 is a complex disease, and many difficulties are faced today especially in the proper choice of pharmacological treatments. The role of antiviral agents for COVID-19 is still being investigated and evidence for immunomodulatory and anti-inflammatory drugs is quite conflicting, whereas the use of corticosteroids is supported by robust evidence. The use of heparins in hospitalized critically ill patients is preferred over other anticoagulants. There are conflicting data on the use of convalescent plasma and vitamin D. According to the World Health Organization (WHO), many vaccines are in Phase III clinical trials, and some of them have already received marketing approval in European countries and in the United States. In conclusion, drug repurposing has represented the main approach recently used in the treatment of patients with COVID-19. At this moment, analysis of efficacy and safety data of drugs and vaccines used in real-life context is strongly needed.

Therapeutic strategies to fight COVID-19: Which is the status artis?

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Transcript of Press Conference

Background High incidence of venous thromboembolic complications in coronavirus disease 2019 (COVID-19) patients was noted recently. Objective This study aimed to explore the factors associated with prevalence of venous thromboembolism (VTE) in COVID-19 patients. Methods A literature search was conducted in several online databases. Fixed effects meta-analysis was performed for the factors associated with prevalence of VTE in COVID-19 patients. Results A total of 39 studies were analysed in this analysis. The incidence of pulmonary embolism and VTE in severe COVID-19 patients were 17% (95% CI, 13-21%) and 42% (95% CI, 25-60%), respectively. VTE were more common among individuals with COVID-19 of advance age. Male COVID-19 patients are more likely to experience VTE. Higher levels of white blood cell (WBC; WMD = 1.34 × 109/L; 95% CI, 0.84-1.84 × 109/L), D-dimer (WMD = 4.21 μg/ml; 95% CI, 3.77-4.66 μg/ml), activated partial thromboplastin time (APTT; WMD = 2.03 s; 95% CI, 0.83-3.24 s), fibrinogen (WMD = 0.49 μg/ml; 95% CI, 0.18-0.79 g/L) and C-reactive protein (CRP; WMD = 21.89 mg/L; 95% CI, 11.44-32.34 mg/L) were commonly noted in COVID-19 patients with VTE. Patients with lower level of lymphocyte (WMD = -0.15 × 109/L; 95% CI, -0.23--0.07 × 109/L) was at high risk of developing VTE. The incidence of severe condition (OR = 2.66; 95% CI, 1.95-3.62) was more likely to occur among COVID-19 patients who developed VTE. Conclusion VTE is a common complication in severe COVID-19 patients and thromboembolic events are also associated with adverse outcomes.

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Venous thromboembolic events in patients with COVID-19: A systematic review and meta-analysis.

Background Because of the lack of vaccination, it is urgent to find effective antiviral agents for COVID-19 treatment. Method Online databases were searched for articles published before or on 22 June 2020. Studies reporting the effectiveness and safety of antiviral agents for COVID-19 were analysed. Results A total of 42 studies were included in this analysis. Hydroxychloroquine (HCQ) was not associated with the incidence of death (risk ratio (RR)=1.08; 95% CI 0.81 to 1.44) and severe cases (RR=1.05; 95% CI 0.61 to 1.81). Patients treated with HCQ obtained few benefits with respect to the clearance of viral RNA and were more likely to have adverse reactions. HCQ treatment could shorten the body temperature recovery time (weighted mean difference = −1.04; 95% CI −1.64 to −0.45). Lopinavir/ritonavir (LPV/r) (RR=0.90; 95% CI 0.76 to 1.07) and Arbidol (RR=1.09; 95% CI 0.92 to 1.29) were not associated with the negative conversion rate. Integrative Chinese-Western medicine alleviated clinical symptoms and decreased the incidence of severe cases (RR=0.38; 95% CI 0.25 to 0.59). Remdesivir treatment reduced the 14-day mortality rate of patients with severe COVID-19 (RR=0.64; 95% CI 0.44 to 0.94). Convalescent plasma (CP) tended to increase the negative conversion rate (RR=2.47; 95% CI 1.70 to 3.57). Conclusion HCQ, LPV/r and Arbidol bring little benefit in COVID-19 treatment. Integrative Chinese-Western medicine improved the clinical symptoms of patients with COVID-19. Remdesivir and CP might be the potential treatments for patients with severe COVID-19. However, large-scale clinical randomised trials are needed to validate our conclusions.

https://spcare.bmj.com/content/bmjspcare/11/1/45.full.pdf

Evaluation of current medical approaches for COVID-19: a systematic review and meta-analysis.

A novel coronavirus first discovered in late December 2019 has spread to many countries around the world. An increasing number of asymptomatic patients have been reported and their ability to spread the virus has been proven. This brings major challenges to the control of the transmission. The discovery and control of asymptomatic patients with COVID-19 are the key issues in future epidemic prevention and recovery. In this narrative review, we summarise the existing knowledge about asymptomatic patients and put forward detection methods that are suitable for finding such patients. Besides, we compared the characteristics and transmissibility of asymptomatic patients in different populations in order to find the best screening, diagnosis and control measures for different populations. Comprehensive preventive advice is also provided to prevent the spread of infection from asymptomatic patients.

https://spcare.bmj.com/content/bmjspcare/early/2021/07/29/bmjspcare-2020-002813.full.pdf

Asymptomatic COVID-19 infection: diagnosis, transmission, population characteristics.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to public concern worldwide. Although a variety of hypotheses about the hosts of SARS-CoV-2 have been proposed, an exact conclusion has not yet been reached. Initial clinical manifestations associated with COVID-19 are similar to those of other acute respiratory infections, leading to misdiagnoses and resulting in the outbreak at the early stage. SARS-CoV-2 is predominantly spread by droplet transmission and close contact; the possibilities of fecal-oral, vertical, and aerosol transmission have not yet been fully confirmed or rejected. Besides, COVID-19 cases have been reported within communities, households, and nosocomial settings through contact with confirmed COVID-19 patients or asymptomatic individuals. Environmental contamination is also a major driver for the COVID-19 pandemic. Considering the absence of specific treatment for COVID-19, it is urgent to decrease the risk of transmission and take preventive measures to control the spread of the virus. In this review, we summarize the latest available data on the potential hosts, entry receptors, clinical features, and risk factors of COVID-19 and transmission routes of SARS-CoV-2, and we present the data about development of vaccines.

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Original Hosts, Clinical Features, Transmission Routes, and Vaccine Development for Coronavirus Disease (COVID-19)

Banded travertines are important parts of fissure ridge systems, but studies on geochemical characterization of banded travertines are limited. This study investigated the lithofacies and stable carbon and oxygen isotopic features of banded travertines from Xiagei (southwestern China) to examine their formation mechanisms. Petrographic analyses of the banded travertines revealed two lithotypes: thick-laminated palisade crystalline crust and thin-laminated composite crystalline crust. δ13C and δ18O of the Xiagei banded travertines range from 2.82‰ to 4.50‰ V-PDB, and from −25.86‰ to −20.90‰ V-PDB. Parent CO2 evaluation shows that the Xiagei banded travertines mainly received CO2 from the decarbonation of marine carbonates, but the contributions of magmatic CO2 and the dissolution of marine carbonates are also unneglectable. Significantly, the magmatic-derived CO2 might indicate that the delamination of the lithosphere along with the asthenosphere upwelling could be taking place in the eastern Tibetan plateau. Paleotemperature calculation shows that the Xiagei travertines were precipitated from moderate- to high-temperature hot springs (44.3 to 86.8 °C). Interestingly, the thick-laminated palisade crystalline crust and thin-laminated composite crystalline crust display calculated paleotemperature between 66.6 and 86.8 °C and between 56.6 and 77.7 °C, respectively, reflecting the great role of water temperature in controlling the lithofacies of banded travertines. A comparison between the banded travertines at Xiagei and other areas also shows temperature is a non-negligible factor controlling banded travertine precipitation. However, this does not mean that water temperature is the decisive controlling factor and more studies on banded travertines are still indispensable to disclose the potential factors controlling the factors/processes affecting banded travertine lithofacies. This study provides a good example for understanding the relationship between lithofacies and stable isotopic geochemical characteristics of travertine deposits.

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Yaxian You

Papers

Evaluation of current medical approaches for COVID-19: a systematic review and meta-analysis.

Asymptomatic COVID-19 infection: diagnosis, transmission, population characteristics.

Original Hosts, Clinical Features, Transmission Routes, and Vaccine Development for Coronavirus Disease (COVID-19)

Stable Carbon and Oxygen Isotopic Features of Banded Travertines from the Xiagei Fissure Ridge System (Shangri-La, China)