The Effects of Health Education on Acute Intermittent Porphyria Attacks : A Retrospective Cohort Study (preprint)

Background: Acute Intermittent Porphyria (AIP) is characterized by acute attacks of neurovisceral symptoms. Infection and negative emotions are factors that can trigger acute AIP attacks, thus avoiding these potential triggers can effectively reduce the risk of acute attacks. During the COVID-19 pandemic, online health education provides patients with a convenient and safe way to receive health education, thus effectively improving their quality of life（QoL）. We explored the effect of online health education on acute AIP attacks during the COVID-19 pandemic. Methods：This study retrospectively included 47 patients with AIP who were infected with COVID-19 and completed a questionnaire from November 2022 to March 2023. These participants were divided into two groups based on whether they had received centralized health education during COVID-19. The primary outcomes were acute AIP attacks, AIP attack severity, and QoL. Secondary outcomes were negative emotions and positive coping styles. Results: In comparison to the non-health education group, the health education group showed a significant decrease in the incidence of acute AIP attacks (P < .05), a reduction in the severity of AIP attacks (P < .05), and an improvement in QoL (P < .05). Additionally, the health education group had a significant decrease in negative emotions (P < 0.05) and a substantial increase in positive coping styles (P < 0.05). Conclusions: Health education may enhance patients' cognition and coping skills, and reduce negative emotions, thereby reducing the occurrence and severity of acute AIP attacks, and improving the patients' QoL.

Absence of platelet overactivation and thrombosis formation among patients with coronary atherosclerosis disease after vaccination against SARS-CoV-2 (preprint)

Background Association of Coronavirus disease 2019 vaccines with thrombosis has raised concerns among patients with coronary atherosclerosis disease (CAD).Objectives After vaccination against SARS-CoV-2, to detect thrombosis formation in atherosclerosis ApoE−/− mice, and platelet activation, coagulation, the profile of prothrombotic antibodies, and the production of platelet factor 4 (PF4) antibodies in patients with CAD.Methods Atherosclerotic ApoE−/− mice were immunized with saline or inactivated SARS-CoV vaccines. We investigated FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. Inpatients undergoing percutaneous coronary intervention (PCI) were consecutively enrolled and defined according to vaccination status. We evaluated coagulation by thrombelastograph (TEG), platelet activation makers by flow cytometry, PF4 antibody and antiphospholipid antibodies by ELISA, and SARS-CoV-2 neutralizing antibody.Results In atherosclerotic ApoE−/− mice, FeCl3-induced thrombus formation and thrombus formation under flow conditions were similar between saline-treated and inactivated SARS-CoV-2 vaccines-treated groups. A total of 182 patients undergoing PCI were included in the final analysis, of whom 92 had been vaccinated. Baseline characteristics were well balanced between unvaccinated and vaccinated groups. The expression of PAC-1 and P-selectin, the prevalence of positivity for PF4 antibodies and antiphospholipid antibodies were similar between these two groups.Conclusions Inactivated SARS-CoV-2 vaccines did not potentiate thrombosis formation in atherosclerotic mice. Inactivated SARS-CoV-2 vaccines did not enhance platelet activation, or trigger the production of PF4 and antiphospholipid antibodies in patients with CAD. Our data adds evidence to the safety profile of the inactivated SARS-CoV-2 vaccines.

Modeling and optimization of triclosan biodegradation by the newly isolated Bacillus sp. DL4: Kinetics and metagenomics analysis (preprint)

Overusing triclosan (TCS) endangered ecological safety and human health, and the pandemic of COVID-19 aggravates the accumulation of TCS in the aquatic environment. Therefore, reducing residual TCS concentrations in the environment is an urgent issue. An aerobic bacterium, Bacillus sp. DL4 was isolated with the capability of TCS biodegradation. Response surface methodology (RSM) and artificial neural network (ANN) were carried out to optimize and verify the different condition variables. All the variables were linear and the interaction of the three factors significantly affected TCS removal at the quadratic level (p < 0.001). Under the optimal conditions (35℃, initial pH 7.31, and 5% strain DL4), the TCS removal rate of 95.89 ± 0.68% was observed and found to be consistent with the predicted values from RSM and ANN models. In addition, statistical comparisons between the models indicated that the ANN model had a stronger predictive capability than the RSM model. Kinetic studies showed that TCS degradation was consistent with a pseudo-first-order kinetic model. Whole genome sequencing indicated that many functional genes were involved in and facilitated TCS degradation. Main metabolite products were detected and identified during the biodegradation process by LC-MS, and a possible degradation pathway was tentatively hypothesized. Overall, this study provides a theoretical foundation for the characterization and mechanism of TCS biodegradation in the environment by Bacillus sp. DL4.

Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor (preprint)

SARS-CoV-2 has demonstrated extraordinary ability to evade antibody immunity by antigenic drift. Small molecule drugs may provide effective therapy while being part of a solution to circumvent SARS-CoV-2 immune escape. In this study we report an alpha-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease (Mpro), RAY1216. Enzyme inhibition kinetic analysis established that RAY1216 is a slow-tight inhibitor with a Ki of 8.6 nM; RAY1216 has a drug-target residence time of 104 min compared to 9 min of PF-07321332 (nirmatrelvir), the antiviral component in Paxlovid, suggesting that RAY1216 is approximately 12 times slower to dissociate from the protease-inhibitor complex compared to PF-07321332. Crystal structure of SARS-CoV-2 Mpro:RAY1216 complex demonstrates that RAY1216 is covalently attached to the catalytic Cys145 through the alpha-ketoamide warhead; more extensive interactions are identified between bound RAY1216 and Mpro active site compared to PF-07321332, consistent with a more stable acyl-enzyme inhibition complex for RAY1216. In cell culture and human ACE2 transgenic mouse models, RAY1216 demonstrates comparable antiviral activities towards different SARS-CoV-2 virus variants compared to PF-07321332. Improvement in pharmacokinetics has been observed for RAY1216 over PF-07321332 in various animal models, which may allow RAY1216 to be used without ritonavir. RAY1216 is currently undergoing phase III clinical trials (https://clinicaltrials.gov/ct2/show/NCT05620160) to test real-world therapeutic efficacy against COVID-19.

Inhalable SARS-CoV-2 vaccines for single-dose dry-powder aerosol immunization and orchestrated mucosal/systemic immune responses (preprint)

The ongoing coronavirus disease pandemic has fostered major advances in vaccination technologies; however, there are urgent needs of mucosal immune responses and single-dose, non-invasive administration. Here, we develop a SARS-CoV-2 vaccine for single-dose, dry-powder aerosol inhalation that induces potent systemic and mucosal immune responses. Our vaccine encapsulates proteinaceous cholera toxin B subunit-assembled nanoparticles displaying the SARS-CoV-2 RBD antigen (R-CNP) within microcapsules of optimal aerodynamic size, and such unique nano-micro coupled structure supports efficient alveoli delivery, sustained R-CNP release, and antigen presenting cell uptake, which are favorable for invocation of immune responses. Moreover, our vaccine successfully induces robust serological IgG and secretory IgA production, collectively conferring effective protection from SARS-CoV-2 challenge (including pseudovirus and the authentic virus) in mice, hamsters, and non-human primates. Finally, we also demonstrate a “mosaic iteration” of our vaccine that co-displays ancestral and Omicron’s antigens, thus extending the breadth of antibody response against co-circulating strains and transmission of Omicron variant. These findings support our inhalable vaccine as a promising candidate to prevent SARS-CoV-2 infection, disease, and transmission.

Genetic characterization of SARS-CoV-2 from cross-border trucks and containers in Kashgar Prefecture, Xinjiang Uygur Autonomous Region, China

Kashgar is a prefecture in Xinjiang Uygur Autonomous Region. China. Kashgar Prefecture (KP) is a land-cargo port connecting China with central Asian countries and Europe. Frequent transportation of cargo has increased the risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) introduction into China, which has increased the pressure on coronavirus disease-2019 (COVID-19) prevention and control. In November 2020, an imported virus-induced COVID-19 outbreak occurred in KP. To investigate the genetic characterization of SARS-CoV-2 that contaminated the trucks and containers, and the potential of border rapid logistics system to serve as carriers for SARS-CoV-2 transmission, thirty-five SARS-CoV-2-positive nucleic-acid samples collected from KP cross-border trucks and containers from 6-10 November 2020 were subjected into SARS-CoV-2 genomic sequencing and comparative analyses. The results showed that the median (minimum to maximum) Ct value of ORF1ab was 37.64 (28.91-39.81) . and that of the N gene was 36.50 (26.35-39.30), and the median (minimum to maximum) of the reads mapping ratio to SARS-CoV-2 was 51.95% (0.86%-99.31%), which indicated low viral loads in these environmental samples. Eighteen of 35 samples had genomic coverage >70%. According to the Pango nomenclature, 18 SARS-CoV-2 sequences belonged to six lineages (B.1, B.I.1, B.1.9. B.1.1.220, B.1.153 and B.1.465), three of which (B.I. B.1.1 and 8.1.153) were found in case samples from the same period of four China-neighboring countries. Analyses of nucleotide mutations and phylogenetic trees showed that the genome sequences of SARS-CoV-2 collected from the same location were similar. Four of 18 sequences were in a sub-lineage with the representative strain of COVID-19 outbreak in KP, one of which had 1 or 2 differences in nucleotide mutation sites with the strain that caused the COVID-19 outbreak in KP, which indicated high homology in the viral genome. We showed that cross-border trucks and containers were contaminated by various genotypes of SARS-CoV-2 from other countries during the outbreak in KP. and in which contained the parental virus of the KP cases. These trucks and containers served as carriers for SARS-CoV-2 introduction from other countries to cause local transmission. Our results provide important references for COVID-19 prevention-and-control strategies in border ports and tracing of outbreak sources in China.

Virome characterization of game animals in China reveals a spectrum of emerging pathogens

Wild animals may be closely related to the outbreak of infectious diseases in recent years. For example, it has been reported that there are closely related SARS-CoV and new coronavirus (SARS-CoV-2) in civet cats, raccoon dogs and pangolins. Therefore, it is of great significance to identify existing or potential pathogens in wild animals that may be in close contact with humans, in order to trace the origin of a specific epidemic and to carry out risk assessment of the most likely source of future epidemics.

Reduced sera neutralization to Omicron SARS-CoV-2 by bothinactivated and protein subunit vaccines and the convalescents (preprint)

Omicron variant continues to spread all over the world. There are lots of scientific questions remaining to be answered for such a devastating variant. There are a dozen of vaccines already in clinical use. The very urgent scientific question would be whether or not these vaccines can protect Omicron variant. Here, we tested the sera from both convalescents and vaccine recipients receiving either inactivated or protein subunits vaccines (CoronaVac from Sinovac, or BBIBP-CoV from Sinopharm, or ZF2001 from Zhifei longcom) for the binding antibody titers (ELISA) and neutralization antibodies titers (pseudovirus neutralization assay). We showed that Omicron do have severe immune escape in convalescents, with 15 of 16 were negative in neutralization. By contrast, in vaccinees who received three jabs of inactivated or protein subunit vaccine, the neutralizing activity was much better preserved. Especially in the ZF2001 group with an extended period of the second and third jab (4-6 months) remains 100% positive in Omicron neutralization, with only 3.1-folds reduction in neutralizing antibody (NAb) titer. In this case, we proposed that, the multi-boost strategy with an extended interval between the second and third jab for immune maturation would be beneficial for NAb against devastating variants such as Omicron.

Will individuals visit hospitals when suffering heat-related illnesses? Yes, but…

Under heat problem, the combined effects of heatwaves and urban heat island effects, has been one of the deadliest climate-related disasters. Uncovering heat-induced health problems is of significance to inform people about urban heat impacts and improve people's awareness of addressing urban heat problems. Existing studies have primarily done this through panel analysis based on second-hand data from local or national authorities. However, there are limited studies directly concentrating on the heat responses of people. To address this gap, this study aims to investigate public responses to urban heat and heat-related illness on the individual side. The study was conducted through a questionnaire survey in three Chinese cities including Nanchang, Shenyang and Xi'an. Based on 1154 valid responses, this study analysed respondents understanding of urban heat problems, symptoms of physiological illnesses and their behaviours of hospitalisation. The results indicate that the knowledge of heat-related risks (2.29 out of 5) was significantly lower than the perceived urban heat severity (3.24) and the perceived severity of physiological impacts (2.40). The skin heat damage (44.7%), among 873 respondents who underwent physiological impacts, was the most frequent physiological illness, followed by the digestive systems (34.0%) and then respiratory (24.1%) and cardiovascular diseases (18.2%). Among the 873 respondents, only 4.0% and 17.7% of respondents would like or were mostly yes to visit hospitals, while 14.2% and 26.4% of the respondents would not like or were mostly not to visit hospitals. Moreover, perceived urban heat severity, knowledge of heat-related risks, perceived severity of physiological impacts, symptoms of physiological illnesses and behaviours of hospitalisation were city-specific and demography-dependent. Overall, the empirical analysis provides new evidence of urban heat problems and generates theoretical and policy implications for heat-induced impact estimation and prevention.

Neutralization of recombinant RBD-subunit vaccine ZF2001-elicited antisera to SARS-CoV-2 variants including Delta (preprint)

SARS-CoV-2 variants brought new waves of infection worldwide. In particular, Delta variant (B.1.617.2 lineage) has become predominant in many countries. These variants raised the concern for their potential immune escape to the currently approved vaccines. ZF2001 is a subunit vaccine received emergency use authorization (EUA) in both China and Uzbekistan, with more than 100-million doses administrated with a three-dose regimen. The tandem-repeat dimer of SARS-CoV-2 spike protein receptor binding domain (RBD) was used as the antigen. In this work, we evaluated the neutralization of ZF2001-elicited antisera to SARS-CoV-2 variants including all four variants of concern (Alpha, Beta, Gamma and Delta) and other three variants of interest (Epsilon, Eta and Kappa) by pseudovirus-based assay. We found antisera preserved majority of the neutralizing activity against these variants. E484K/Q substitution is the key mutation to reduce the RBD-elicited sera neutralization. Moreover, ZF2001-elicited sera with a prolonged intervals between the second and third dose enhanced the neutralizing titers and resilience to SARS-CoV-2 variants.

'It's Getting People More Engaged in Things': Responses to Solutions-Oriented News in the Context of COVID-19 (preprint)

This preprint presents preliminary findings from a major new study that examines UK audience perceptions of solutions-oriented journalism in the context of the COVID-19 pandemic. Using a nationally representative survey (n=2015) and in-depth interviews (n=59), members of the UK public were asked about their evaluations of problems-focussed news and solutions-orientated news. Findings suggest that UK audiences are – on the whole – positive towards the concept of solutions-oriented news, identifying its potential to enhance their interest in the news, feel more positive about the potential for change, and empower them to take actions in their local community. We also reveal some of the demographic factors that are associated with support for solutions journalism.

Pandemic News Experience: COVID-19, News Consumption, Mental Health, and the Demand for Positive News (preprint)

COJO for COVID Recovery is a UKRI/AHRC-funded rapid COVID-19 response research project that addresses the role that constructive journalism (COJO), particularly solution-focused journalism, can play in the pandemic recovery. The research set out in this report details the findings of the project’s initial in-depth interviews and survey with UK news audiences. Four key sets of findings regarding COVID-19 news consumption and experience emerge from this analysis. 1. The high interest in COVID-19 news was associated with the need to monitor and navigate the uncertain evolution of the pandemic as it affected audiences. 2. There was a clear fluctuation that followed “an inverse Bell curve” (up-down-up) pattern of COVID-19 news consumption which was in parallel with the severity of the pandemic and its associated lockdown restrictions. 3. Many of our participants reported switching off from the news or avoiding it for reasons linked to mental and emotional health, including negativity, repetitive reporting and information overload. 4. Participants demanded the media provide more positive news that helps to lift the mood of the public and/or offers ways out of the pandemic.

Rapid Resolution of severe feline infectious peritonitis using natural products (preprint)

This is the first report of a successful treatment of a severe feline infectious peritonitis (FIP) case using Lianhuaqingwen (LH) capsule, a Chinese patent medicine （natural products）and it has been used for the treatment of coronavirus disease 2019. A 1-year-old cat was diagnosed FIP and presented with severe ascites, aphagia, inflammation, breathing difficulties and weight loss. Within 22 days of LH capsule treatment, all indicators of the cat eventually returned to normal, and the ascites gradually disappeared. This case report is the first description of the clinical recovery features of a cat with a systemic FCoV infection using LH capsules.

Characterization of a pathogenic variant in GBA for Parkinson's disease with mild cognitive impairment patients

Parkinson's disease (PD) is the second most common neurodegenerative disease, and mild cognitive impairment (MCI) is a well-established risk factor for the development of dementia in PD. A growing body of evidence suggests that low expression of glucocerebrosidase (GBA) promotes the transmission of &#945;-synuclein (&#945;-Syn) interpolymers and the progression of PD. However, how GBA mutations affect the pathogenesis of PD via abnormal aggregation of &#945;-Syn is unclear, and no clinically valid PD-MCI genetic markers have been identified. Here, we first located a GBA eQTL, rs12411216, by analysing DHS, eQTL SNP, and transcription factor binding site data using the UCSC database. Subsequently, we found that rs12411216 was significantly associated with PD-MCI (P <0.05) in 306 PD patients by genotyping. In exploring the relationship between rs12411216 and GBA expression, the SNP was found to be associated with GBA expression in 50 PD patients through qPCR verification. In a further CRISPR/Cas9-mediated genome editing module, the SNP was identified to cause a decrease in GBA expression, weaken enzymatic activity and enhance the abnormal aggregation of &#945;-Syn in SH-SY5Y cells. Additionally, using an electrophoretic mobility shift assay, we confirmed that the binding efficiency of transcription factor E2F4 was affected by the rs12411216 SNP. In conclusion, our results showed that rs12411216 regulated GBA expression, supporting its potential role as a PD-MCI genetic biomarker and highlighting novel mechanisms underlying Parkinson's disease.

The Impact of Coronavirus Disease 2019 (COVID-19) on Liver Injury in China: A Systematic Review and Meta-analysis (preprint)

Abstract Background: The evidence for the incidence and severity of liver injury in Chinese patients with COVID-19 is still controversial. Aims: The purpose of this study was to summarize the incidence of liver injury and the differences between liver injury markers among different patients with COVID-19 in China. Methods: Computer searches of PubMed, Embase, CNKI and medRxiv were used to obtain reports on the incidence and markers of liver injury in Chinese patients with COVID-19, from January 1, 2020 to April 10, 2020. (No. CRD42020181350) Results: A total of 57 reports from China were included, including 9889 confirmed cases of COVID-19 infection. The results of the meta-analysis showed that among the patients with early COVID-19 infection in China, the incidence of liver injury events was 24.7% (95% CI, 23.4%-26.4%). Liver injury in severe patients was more common than that in non-severe patients, with a risk ratio of 2.07 (95% CI, 1.77 to 2.43). Quantitative analysis showed that the severe the coronavirus infection, the higher the level of AST, ALT, TB, ALP, GGT and the lower the level of ALB. The changing trend of the appeal index was similar in ICU patients and dead patients. Conclusion: There is a certain risk of liver injury in Chinese patients with COVID-19, and the risk and degree of liver injury are related to the severity of COVID-19.

Transmission of corona virus disease 2019 during the incubation period may lead to a quarantine loophole (preprint)

Background: The ongoing outbreak of novel corona virus disease 2019 (COVID-19) in Wuhan, China, is arousing international concern. This study evaluated whether and when the infected but asymptomatic cases during the incubation period could infect others. Methods: We collected data on demographic characteristics, exposure history, and symptom onset day of the confirmed cases, which had been announced by the Chinese local authorities. We evaluated the potential of transmission during the incubation period in 50 infection clusters, including 124 cases. All the secondary cases had a history of contact with their first-generation cases prior to symptom onset. Results: The estimated mean incubation period for COVID-19 was 4.9 days (95% confidence interval [CI], 4.4 to 5.4) days, ranging from 0.8 to 11.1 days (2.5th to 97.5th percentile). The observed mean and standard deviation (SD) of serial interval was 4.1{+/-}3.3 days, with the 2.5th and 97.5th percentiles at -1 and 13 days. The infectious curve showed that in 73.0% of the secondary cases, their date of getting infected was before symptom onset of the first-generation cases, particularly in the last three days of the incubation period. Conclusions: The results indicated the transmission of COVID-9 occurs among close contacts during the incubation period, which may lead to a quarantine loophole. Strong and effective countermeasures should be implemented to prevent or mitigate asymptomatic transmission during the incubation period in populations at high risk.