Safety and Efficacy of Oral administrated Cepharathine in Non-hospitalized, asymptomatic or mild COVID-19 patients: A Double-blind, Randomized, Placebo-controlled Trial (preprint)

Cepharanthine (CEP) is a natural remedy that potently inhibits SARS-CoV-2 activity both in vitro and in vivo. We conducted a proof-of-concept, double-blind, randomized, placebo-controlled trial among adults with asymptomatic or mild coronavirus disease 2019 (COVID-19). Patients were stratified randomly to de novo infection or viral rebound, and assigned in a 1:1:1 ratio to receive 60 mg/day or 120 mg/day of CEP or placebo. Primary outcome the time from randomization to negative nasopharyngeal swab, and safety were evaluated. A total of 262 de novo infected and 124 viral rebound patients underwent randomization. In the 188 de novo patients included in modified intention-to-treat (mITT) population, when compared with placebo, 60 mg/day CEP slightly shortened the time to negative (difference=-0.77 days, hazard ratio (HR)=1.40, 95% CI 0.97 to 2.01, p=0.072), and 120 mg/day CEP did not show the trend. Among de novo patients in the per-protocol set (PPS), 60 mg/day CEP significantly shortened the time to negative (difference=-0.87 days, HR=1.56, 95% CI 1.03 to 2.37, p=0.035). Among viral rebound patients in the mITT population, neither 120 mg/day nor 60 mg/day CEP significantly shortened the time to negative compared to placebo. Adverse events were not different among the three groups, and no serious adverse events occurred. Treatment of asymptomatic or mild Covid-19 with 120 mg/day or 60 mg/day CEP did not shorten the time to negative compared with placebo, without evident safety concerns. Among de novo infected patients with good compliance, 60 mg/day CEP significantly shortened the time to negative compared with placebo ( NCT05398705 ).

Coronavirus Usurps the Autophagy-Lysosome Pathway and Induces Membranes Rearrangement for Infection and Pathogenesis

Autophagy is a crucial and conserved homeostatic mechanism for early defense against viral infections. Recent studies indicate that coronaviruses (CoVs) have evolved various strategies to evade the autophagy–lysosome pathway. In this minireview, we describe the source of double-membrane vesicles during CoV infection, which creates a microenvironment that promotes viral RNA replication and virion synthesis and protects the viral genome from detection by the host. Firstly, CoVs hijack autophagy initiation through non-structural proteins and open-reading frames, leading to the use of non-nucleated phagophores and omegasomes for autophagy-derived double-membrane vesicles. Contrastingly, membrane rearrangement by hijacking ER-associated degradation machinery to form ER-derived double-membrane vesicles independent from the typical autophagy process is another important routine for the production of double-membrane vesicles. Furthermore, we summarize the molecular mechanisms by which CoV non-structural proteins and open-reading frames are used to intercept autophagic flux and thereby evade host clearance and innate immunity. A comprehensive understanding of the above mechanisms may contribute to developing novel therapies and clinical drugs against coronavirus disease 2019 (COVID-19) in the future.

Therapeutic Mechanism of Xiaoqinglong Decoction against COVID-19 Based on Network Pharmacology and Molecular Docking Technology.

BACKGROUND: A xiaoqinglong decoction (XQLD) has been proven effective in treating severe coronavirus disease 2019 (COVID-19) cases; however, the mechanism remains unclear. OBJECTIVE: In the current study, we used network pharmacology and molecular docking technology to identify the effective components, potential targets, and biological pathways of XQLD against COVID-19. METHODS: Public databases were searched to determine the putative targets of the active compounds of XQLD and COVID-19-related targets. STRING and Cytoscape were used to establish the protein-protein interaction network and drug component, along with the target-pathway network. The DAVID database was used to enrich the biological functions and signaling pathways. AutoDock Vina was used for virtual docking. RESULTS: We identified 138 active compounds and 259 putative targets of XQLD. Biological network analysis showed that quercetin, beta-sitosterol, kaempferol, stigmasterol, and luteolin may be critical ingredients of XQLD, whereas VEGFA, IL-6, MAPK3, CASP3, STAT3, MAPK1, MAPK8, CASP8, CCL2, and FOS may be candidate drug targets. Enrichment analysis illustrated that XQLD could function by regulating viral defense, inflammatory response, immune response, and apoptosis. Molecular docking results showed a high affinity between the critical ingredients and host cell target proteins. CONCLUSION: This study uncovered the underlying pharmacological mechanism of XQLD against COVID-19. These findings lay a solid foundation for promoting the development of new drugs against severe acute respiratory syndrome coronavirus-2 infection and may contribute to the global fight against the COVID-19 pandemic.

Regular testing of asymptomatic healthcare workers identifies cost-efficient SARS-CoV-2 preventive measures (preprint)

Protecting healthcare professionals is crucial in maintaining a functioning healthcare system. The risk of infection and optimal preventive strategies for healthcare workers during the COVID-19 pandemic remain poorly understood. Here we report the results of a weekly testing regime that has been performed since the beginning of the COVID-19 pandemic to identify pre- and asymptomatic healthcare workers. Based on these observations we have developed a mathematical model of SARS-CoV-2 transmission that integrates the sources of infection from inside and outside the hospital. The data were used to study how regular testing and a desynchronisation protocol are effective in preventing transmission of COVID-19 infection at work, and compared both strategies in terms of workforce availability and cost-effectiveness. We showed that case incidence among healthcare workers is higher than would be explained solely by community infection. Furthermore, while testing and desynchronisation protocols are both effective in preventing nosocomial transmission, regular testing maintains work productivity with implementation costs.

The Association of Incidence of Face-Touching Behaviors with Masks Wearing Rates During the Coronavirus Disease 2019 Pandemic (preprint)

Background: Mandatory mask wearing policy for general population in public areas were the most controversial mitigative measure for the coronavirus disease 2019 (COVID-19) pandemic. Thus, it was imperative to investigate its influence on the incidence of face touching behaviors. Methods: Videos displaying mask-wearing and face-touching behaviors of general population in public areas were analyzed. Period before the COVID-19 epidemic were defined as January 2018 to October 2019, and those during the pandemic were from February 2020 to August 2020 in East Asia, and March to August 2020 in Europe and United States (US). Findings: 37 videos (4699 individuals) before the pandemic with 135 videos (8217 individuals) were included. The mask wearing rates all increased significantly during the pandemic. However, the incidence of face touching behaviors maintained. The incidence of eyes, nose and mouth touching behaviors decreased in East Asia and Europe, instead of US. Mask wearing rates was negatively related to incidences of face touching behaviors, especially in East Asia. Surprisingly, when mask wearing rates were >0% and <75%, mask wearing rates was positively related to the incidence of face touching behaviors in East Asia significantly (p=0.017). Interpretation: The incidence of face touching behaviors of general population in public areas was negatively associated with mask wearing rates. However, Mandatory mask wearing polices were risky in population with low adherence to masks, among whom, the face touching behaviors in public areas might increase with mask wearing rates rise. Funding: This study was supported by Guangzhou Science and Technology Project (201904010461).Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Clinical Ethics Review Board of the Third Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University. Informed consent was waived according to ethical review of biomedical research involving humans by Order of the National Health and Family Planning Commission of the People’s Republic of China No. 11.

Expression and immunoreactivity of a recombinant multi-epitope antigen designed based on four major structural proteins of avian infectious bronchitis virus.

The development of rapid, simple, and sensitive diagnostic methods for identification of avian infectious bronchitis virus (IBV) is crucial for the effective control of avian infectious bronchitis. In the present study, a tandemly arranged multiepitope peptide (named SEMN) was designed with four antigenic regions derived from four major structural proteins of IBV. Then, we performed codon optimization of SEMN gene by changing the codon-adaptation index from 0.45 to 0.94 and expressed the optimized gene in codon bias-adjusted Escherichia coli Rosetta (DE3), followed by determination of the immunoreactivity of the purified protein. Bioinformatics analysis of SEMN showed a high antigenicity, surface probability and hydrophilicity. The recombinant protein rSEMN was expressed both in soluble forms and as inclusion bodies, and the molecular weight of rSEMN was about 39 kDa. The preliminary diagnostic performance of rSEMN was confirmed by Western blotting analysis using chicken anti-IBV polyclonal antibodies. Further studies are needed to evaluate the immunogenicity in animal models and to give a final assessment of the diagnostic utility of this recombinant multi-epitope antigen.

Pharmacotherapics Advice in Guidelines for COVID-19.

Since December 2019 to May 2020, coronavirus disease 2019 (COVID-19) has infected over 6 million people worldwide. Due to its sudden and rapid outbreak, effective treatment for COVID-19 is scarce. Based on national clinical trials of novel treatments, China, Italy, Germany, and other countries and organizations have published multiple guidelines for COVID-19 and advised many medicines, such as chloroquine and tocilizumab. In this paper, we summarize the pharmacotherapy for COVID-19 according to those guidelines, highlight updates of the pharmacotherapy guidelines, and review the efficacy and safety of the indicated anti-COVID-19 drugs.

An experimental trial of recombinant human interferon alpha nasal drops to prevent coronavirus disease 2019 in medical staff in an epidemic area (preprint)

Objective To investigate the efficacy and safety of recombinant human interferon alpha (rhIFN-) nasal drops in healthy medical staff to prevent coronavirus disease 2019 (COVID-19). Methods A prospective, open-label study was conducted in January 21, 2020at Taihe Hospital in Shiyan City, Hubei Province. Totally, 2944 medical staff members were recruited and allocated into low-risk group or high-risk group according to whether they were directly exposed to COVID-19 patients. Participants in the low-risk group received rhIFN- nasal drops (2-3 drops/nostril/time, 4 times/day) for 28 days with first-level protection; those in the high-risk group received identical rhIFN- nasal drops combined with thymosin-1 (1.6 mg, hypodermic injection, once a week) along with secondary-level or third-level protection. The primary outcome was new-onset COVID-19 over 28 days. The secondary outcome was new-onset fever or respiratory symptoms but with negative pulmonary images. The results were compared with new-onset COVID-19 in medical staff in Hubei Province (including Wuhan) during the same period. Adverse reactions to interferon nasal drops were also observed. Results Among the 2944 subjects in our study, 2415 were included in the low-risk group, including 997 doctors and 1418 nurses with average ages of 37.38 and 33.56 years, respectively; 529 were included in the high-risk group, including 122 doctors and 407 nurses with average ages of 35.24 and 32.16 years, respectively. The 28-day incidence of COVID-19 was zero in both the high and low-risk groups. The 28-day incidence of new-onset clinical symptoms with negative images for pneumonia was also zero in both the high and low-risk groups. As control, a total of 2035 medical personnel with confirmed COVID-19 from the same area (Hubei Province) was observed between January 21 to February 23, 2020. No serious adverse events were observed in our trial during the intervention period. Conclusion In this investigator-initiated open-label study, we observed that rhIFN- nasal drops may effectively prevent COVID-19 in medical staff, as an enhancement protection on the basis of standard physical isolation. Our results also indicate that rhIFN- nasal drops have potential promise for protecting susceptible healthy people during the coronavirus pandemic.

An Environmental Data Collection for COVID-19 Pandemic Research

The COVID-19 viral disease surfaced at the end of 2019 and quickly spread across the globe. To rapidly respond to this pandemic and offer data support for various communities (e.g., decision-makers in health departments and governments, researchers in academia, public citizens), the National Science Foundation (NSF) spatiotemporal innovation center constructed a spatiotemporal platform with various task forces including international researchers and implementation strategies. Compared to similar platforms that only offer viral and health data, this platform views virus-related environmental data collection (EDC) an important component for the geospatial analysis of the pandemic. The EDC contains environmental factors either proven or with potential to influence the spread of COVID-19 and virulence or influence the impact of the pandemic on human health (e.g., temperature, humidity, precipitation, air quality index and pollutants, nighttime light (NTL)). In this platform/framework, environmental data are processed and organized across multiple spatiotemporal scales for a variety of applications (e.g., global mapping of daily temperature, humidity, precipitation, correlation of the pandemic to the mean values of climate and weather factors by city). This paper introduces the raw input data, construction and metadata of reprocessed data, and data storage, as well as the sharing and quality control methodologies of the COVID-19 related environmental data collection.