Enhancing Biocidal Capability in Cuprite Coatings.

The SARS-CoV-2 global pandemic has reinvigorated interest in the creation and widespread deployment of durable, cost-effective, and environmentally benign antipathogenic coatings for high-touch public surfaces. While the contact-kill capability and mechanism of metallic copper and its alloys are well established, the biocidal activity of the refractory oxide forms remains poorly understood. In this study, commercial cuprous oxide (Cu2O, cuprite) powder was rapidly nanostructured using high-energy cryomechanical processing. Coatings made from these processed powders demonstrated a passive "contact-kill" response to Escherichia coli (E. coli) bacteria that was 4× (400%) faster than coatings made from unprocessed powder. No viable bacteria (>99.999% (5-log10) reduction) were detected in bioassays performed after two hours of exposure of E. coli to coatings of processed cuprous oxide, while a greater than 99% bacterial reduction was achieved within 30 min of exposure. Further, these coatings were hydrophobic and no external energy input was required to activate their contact-kill capability. The upregulated antibacterial response of the processed powders is positively correlated with extensive induced crystallographic disorder and microstrain in the Cu2O lattice accompanied by color changes that are consistent with an increased semiconducting bandgap energy. It is deduced that cryomilling creates well-crystallized nanoscale regions enmeshed within the highly lattice-defective particle matrix. Increasing the relative proportion of lattice-defective cuprous oxide exposed to the environment at the coating surface is anticipated to further enhance the antipathogenic capability of this abundant, inexpensive, robust, and easily handled material for wider application in contact-kill surfaces.

Circulating eosinophils associated with responsiveness to COVID-19 vaccine and the disease severity in patients with SARS-CoV-2 omicron variant infection.

OBJECTIVE: This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China. METHODS: We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.2 variant in Shanghai, China. These patients were diagnosed or admitted between Feb 20, 2022, and May 10, 2022, and were classified as asymptomatic (n = 705), mild (n = 286) and severe (n = 166) groups. We compiled and analyzed data of patients' clinical demographic characteristics, laboratory findings, and clinical outcomes. RESULTS: COVID-19 vaccine reduced the incidence of severe cases. Severe patients were shown to have declined peripheral blood EOS. Both the 2 doses and 3 doses of inactivated COVID-19 vaccines promoted the circulating EOS levels. In particular, the 3rd booster shot of inactivated COVID-19 vaccine was shown to have a sustained promoting effect on circulating EOS. Univariate analysis showed that there was a significant difference in age, underlying comorbidities, EOS, lymphocytes, CRP, CD4, and CD8 T cell counts between the mild and the severe patients. Multivariate logistic regression analysis and ROC curve analysis indicate that circulating EOS (AUC = 0.828, p = 0.025), the combination of EOS and CD4 T cell (AUC = 0.920, p = 0.017) can predict the risk of disease severity in patients with SARS-CoV-2 Omicron BA.2 variant infection. CONCLUSIONS: COVID-19 vaccine promotes circulating EOS and reduces the risk of severe illness, and particularly the 3rd booster dose of COVID-19 vaccine sustainedly promotes EOS. Circulating EOS, along with T cell immunity, may have a predictive value for the disease severity in SARS-CoV-2 Omicron infected patients.

Changes in tobacco use in the early phase of COVID-19 pandemic in Hong Kong: a qualitative study.

INTRODUCTION: Changes in tobacco use and related personal and environmental factors amid the COVID-19 pandemic can be captured by qualitative studies, but they are few in non-Western populations. We assessed the perceived links between tobacco use and COVID-19, and changes in the use of cigarettes, electronic cigarettes (ECs) and heated tobacco products (HTPs) in the early phase of the pandemic in Hong Kong, where lockdown was not implemented. METHODS: Semi-structured telephone interviews were conducted from January to June 2021 in 95 participants (36 EC users, 28 HTP users, 32 exclusive cigarette users). Transcriptions were coded using deductive and inductive approaches, and factors for changes were nested in the social-ecological model. RESULTS: Two-thirds of participants perceived their infection susceptibility was the same as never tobacco users, and 44.2% perceived more severe COVID-19 disease if infected. Amid the pandemic, tobacco use decreased overall but increased indoors for all three products. Increased tobacco use was mostly attributed to increased emotional distress, while decreases were attributed to various personal (health concerns) and environmental factors (e.g. COVID-19 regulations). Perceived convenience and lower costs were reasons for increased EC use. Limited access to HTPs was compensated by cigarette use. CONCLUSIONS: Many participants were unaware of the potential harm of tobacco use on COVID-19. Overall tobacco use decreased due to COVID-19 regulations, which may not be sustainable post-pandemic. Indoor consumption increased, supporting a comprehensive smoke-free policy that covers private indoor areas. Better cessation services targeting EC, HTP and cigarette use are needed. IMPLICATIONS: Smokers need better awareness of the risk of tobacco use on COVID-19. Smoking cessation services can be improved by offering brief advice, strengthening advocacy against secondhand smoke, and covering EC and HTP use, highlighting their potential harms to users and others, and their risk of addiction and relapse to cigarette use.

Neglected Aspects of SARS-CoV-2 Aerosol Transmission in Bathrooms of Multistory and High-Rise Buildings - Beijing Municipality, China, October 2022.

What is already known about this topic?: There is a toilet flush-soil stack-floor drain pathway of aerosol transmission in multistory and high-rise buildings, but the influencing factors are not completely clear. What is added by this report?: The poor airtightness of the connecting parts of the floor drain, as well as pressure fluctuations in the sewage pipe during toilet flushing caused by blockage of the soil stack vent, may lead to the cross-floor transmission of viral aerosols through the soil stack and floor drains. What are the implications for public health practice?: In multistory and high-rise buildings, the bathroom floor drains should be kept sealed, and floor drain connecting parts should be airtight. Furthermore, the soil stack vent should not be blocked. In this way, the cross-floor transmission of viral aerosols can be effectively reduced.

Cigarettes, heated tobacco products and dual use: exhaled carbon monoxide, saliva cotinine and total tobacco consumed by Hong Kong tobacco users.

BACKGROUND: Independent studies on exhaled carbon monoxide (CO) and saliva cotinine levels in regular heated tobacco product (HTP) users, and how they compare with conventional cigarette (CC) smokers, are lacking. METHODS: A total of 3294 current users of CCs, HTPs or electronic cigarettes (ECs) from a household survey and a smoking hotspot survey were classified into seven groups: exclusive users of CCs, HTPs, ECs; dual users of CCs and HTPs, CCs and ECs, HTPs and ECs; and triple users. We measured exhaled CO level using the piCo Smokerlyzer (n=780) and saliva cotinine using NicAlert cotinine test strips (n=620). Among the seven groups, the differences in (1) CO and cotinine levels were examined using Kruskal-Wallis test, and (2) the average daily tobacco consumption in the past 30 days was examined using multivariable linear regression. RESULTS: Both exclusive and dual users of CCs had a higher CO level than exclusive HTP or EC users (p<0.05). Exhaled CO levels were similar between HTP and EC users, as were saliva cotinine levels among the seven groups. Compared with exclusive CC users, those who also used HTPs or ECs smoked fewer CCs (CCs+HTPs: adjusted coefficient -2.79, 95% CI -3.90 to -1.69; CCs+ECs: -1.34, 95% CI -2.34 to -0.34), but consumed more tobacco sticks equivalent in total (2.79 (95% CI 1.61 to 3.96); 1.95 (95% CI 0.79 to 3.12)). CONCLUSIONS: HTP or EC use showed lower exhaled CO but similar saliva cotinine levels compared with CC use. Dual users of CCs and HTPs/ECs smoked fewer CCs than exclusive CC users, but consumed more tobacco in total.

Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration.

Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-[Formula: see text]1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-[Formula: see text]1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-[Formula: see text]1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-[Formula: see text]1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration.

The prevalence of adverse reactions among individuals with three-dose COVID-19 vaccination.

BACKGROUND: Considering the adverse reactions to vaccination against coronavirus disease 2019 (COVID-19), some people, particularly the elderly and those with underlying medical conditions, are hesitant to be vaccinated. This study aimed to explore the prevalence of adverse reactions and provide direct evidence of vaccine safety, mainly for the elderly and people with underlying medical conditions, to receive COVID-19 vaccination. METHODS: From 1st March to 30th April 2022, we conducted an online survey of people who had completed three doses of COVID-19 vaccination by convenience sampling. Adverse reaction rates and 95% confidence intervals were calculated. In addition, conditional logistic regression was used to compare the differences in adverse reactions among the elderly and those with underlying medical conditions with the general population. RESULTS: A total of 3339 individuals were included in this study, of which 2335 (69.9%) were female, with an average age of 32.1 ± 11.4 years. The prevalence of adverse reactions after the first dose of inactivated vaccine was 24.6% (23.1-26.2%), 19.2% (17.8-20.7%) for the second dose, and 19.1% (17.7-20.6%) for the booster dose; among individuals using messenger RNA vaccines, the prevalence was 42.7% (32.3-53.6%) for the first dose, 47.2% (36.5-58.1%) for the second dose, and 46.1% (35.4-57.0%) for the booster dose. Compared with the general population, the prevalence of adverse events did not differ in individuals with underlying medical conditions and those aged 60 and above. CONCLUSIONS: For individuals with underlying medical conditions and those aged 60 and above, the prevalence of adverse reactions is similar to that of the general population, which provides a scientific basis regarding vaccination safety for these populations.

Respiratory Syncytial Virus Two-Step Infection Screen Reveals Inhibitors of Early and Late Life Cycle Stages.

Human respiratory syncytial virus (hRSV) infection is a leading cause of severe respiratory tract infections. Effective, directly acting antivirals against hRSV are not available. We aimed to discover new and chemically diverse candidates to enrich the hRSV drug development pipeline. We used a two-step screen that interrogates compound efficacy after primary infection and a consecutive virus passaging. We resynthesized selected hit molecules and profiled their activities with hRSV lentiviral pseudotype cell entry, replicon, and time-of-addition assays. The breadth of antiviral activity was tested against recent RSV clinical strains and human coronavirus (hCoV-229E), and in pseudotype-based entry assays with non-RSV viruses. Screening 6,048 molecules, we identified 23 primary candidates, of which 13 preferentially scored in the first and 10 in the second rounds of infection, respectively. Two of these molecules inhibited hRSV cell entry and selected for F protein resistance within the fusion peptide. One molecule inhibited transcription/replication in hRSV replicon assays, did not select for phenotypic hRSV resistance and was active against non-hRSV viruses, including hCoV-229E. One compound, identified in the second round of infection, did not measurably inhibit hRSV cell entry or replication/transcription. It selected for two coding mutations in the G protein and was highly active in differentiated BCi-NS1.1 lung cells. In conclusion, we identified four new hRSV inhibitor candidates with different modes of action. Our findings build an interesting platform for medicinal chemistry-guided derivatization approaches followed by deeper phenotypical characterization in vitro and in vivo with the aim of developing highly potent hRSV drugs.

Diagnostic efficiency of RPA/RAA integrated CRISPR-Cas technique for COVID-19: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic value of recombinase polymerase/ aided amplification (RPA/RAA) integrated clustered regularly interspaced short palindromic repeats (CRISPR) in the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We searched relevant literature on CRISPR technology for COVID-19 diagnosis using "novel coronavirus", "clustered regularly interspaced short palindromic repeats" and "RPA/RAA" as subject terms in PubMed, Cochrane, Web of Science, and Embase databases. Further, we performed a meta-analysis after screening the literature, quality assessment, and data extraction. RESULTS: The pooled sensitivity, specificity and a rea under the summary receiver operator characteristic curve (AUC) were 0.98 [95% confidence interval (CI):0.97-0.99], 0.99 (95% CI: 0.97-1.00) and 1.00 (95% CI: 0.98-1.00), respectively. For CRISPR-associated (Cas) proteins-12, the sensitivity, specificity was 0.98 (95% CI: 0.96-1.00), 1.00 (95% CI: 0.99-1.00), respectively. For Cas13, the sensitivity and specificity were 0.99 (95% CI: 0.97-1.00) and 0.95 (95% CI: 0.91-1.00). The positive likelihood ratio (PLR) was 183.2 (95% CI: 28.8, 1166.8); the negative likelihood ratio (NLR) was 0.02 (95% CI: 0.01, 0.03). CONCLUSION: RPA/RAA integrated with CRISPR technology is used to diagnose coronavirus disease-19 (COVID-19) with high accuracy and can be used for large-scale population screening.

A comparative study of spike protein of SARS-CoV-2 and its variant Omicron (B.1.1.529) on some immune characteristics.

The emergence of Omicron variant raises great concerns because of its rapid transmissibility and its numerous mutations in spike protein (S-protein). S-protein can act as a pathogen-associated molecular pattern and complement activator as well as antigen. We compared some immune characteristics of trimer S-proteins for wild type (WT-S) and B.1.1.529 Omicron (Omicron-S) to investigate whether the mutations have affected its pathogenicity and antigenic shift. The results indicated that WT-S and Omicron-S directly activated nuclear factor-κB (NF-κB) and induced the release of pro-inflammatory cytokines in macrophages, but the actions of Omicron-S were weaker. These inflammatory reactions could be abrogated by a Toll-like receptor 4 antagonist TAK-242. Two S-proteins failed to induce the production of antiviral molecular interferon-ß. In contrast to pro-inflammatory effects, the ability of two S-proteins to activate complement was comparable. We also compared the binding ability of two S-proteins to a high-titer anti-WT-receptor-binding domain antibody. The data showed that WT-S strongly bound to this antibody, while Omicron-S was completely off-target. Collectively, the mutations of Omicron have a great impact on the pro-inflammatory ability and epitopes of S-protein, but little effect on its ability to activate complement. Addressing these issues can be helpful for more adequate understanding of the pathogenicity of Omicron and the vaccine breakthrough infection.

Car Purchase Intention Modeling in the Context of COVID-19: An Integrated Analysis of Impact Range and Impact Asymmetry

The car purchase intention of noncar owners is closely related to the growth of car ownership and may be changed in the context of COVID-19. This paper aims to investigate the decision-making mechanism of the car purchase intention before COVID-19 and the change of car purchase intention after COVID-19. The contributions of influencing factors are derived from the gradient boosting decision tree model and the asymmetric effects of attitudinal factors are further analyzed based on the three-factor theory. The comprehensive importance hierarchies of the two dependent variables are constructed through the integrated analysis of impact range and impact asymmetry. The results show that people who were previously more willing to buy cars are more likely to increase their willingness to buy after COVID-19. The pre–COVID-19 car purchase intention is primarily determined by shared mobility-related attitudes, while attitudes toward private car use have a greater impact on the post–COVID-19 intention change. These two attitudes are mainly manifested as intention relievers and discouragers before COVID-19, but they are more likely transformed into intention strengtheners and encouragers after COVID-19. The availability of shared mobility has the maximum comprehensive importance to the post–COVID-19 intention change. Therefore, maintaining and promoting the ridership of shared mobility will be the most important prerequisite for alleviating the car purchase intention after COVID-19 pandemic. [ FROM AUTHOR] Copyright of Journal of Advanced Transportation is the property of Hindawi Limited and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The Impact of COVID-19 on Travel Mode Choice Behavior in Terms of Shared Mobility: A Case Study in Beijing, China.

Shared mobility is growing rapidly and changing the mobility landscape. The COVID-19 pandemic has complicated travel mode choice behavior in terms of shared mobility, but the evidence on this impact is limited. To fill this gap, this paper first designs a stated preference survey to collect mode choice data before and during the pandemic. Different shared mobility services are considered, including ride hailing, ride sharing, car sharing, and bike sharing. Then, latent class analysis is used to divide the population in terms of their attitudes toward shared mobility. Nested logit models are applied to compare travel mode choice behavior during the two periods. The results suggest that shared mobility has the potential to avoid the high transmission risk of public transport and alleviate the intensity of private car use in the COVID-19 context, but this is limited by anxiety about shared spaces. As the perceived severity of the pandemic increases, preference for ride hailing and ride sharing decreases, and a price discount for ride hailing is more effective than that for ride sharing at maintaining the ridership despite the impact of COVID-19. These findings contribute to understanding the change in travel demand and developing appropriate strategies for shared mobility services to adapt to the pandemic.

The association of intensity and duration of non-pharmacological interventions and implementation of vaccination with COVID-19 infection, death, and excess mortality: Natural experiment in 22 European countries.

BACKGROUND: Critical questions remain regarding the need for intensity to continue NPIs as the public was vaccinated. We evaluated the association of intensity and duration of non-pharmaceutical interventions (NPIs) and vaccines with COVID-19 infection, death, and excess mortality in Europe. METHODS: Data comes from Our Word in Data. We included 22 European countries from January 20, 2020, to May 30, 2021. The time-varying constrained distribution lag model was used in each country to estimate the impact of different intensities and duration of NPIs on COVID-19 control, considering vaccination coverage. Country-specific effects were pooled through meta-analysis. RESULTS: This study found that high-intensity and long-duration of NPIs showed a positive main effect on reducing infection in the absence of vaccines, especially in the intensity above the 80th percentile and lasted for 7 days (RR = 0.93, 95% CI: 0.89-0.98). However, the adverse effect on excess mortality also increased with the duration and intensity. Specifically, it was associated with an increase of 44.16% (RR = 1.44, 95% CI: 1.27-1.64) in the excess mortality under the strict intervention (the intensity above the 80th percentile and lasted for 21 days). As the vaccine rollouts, the inhibition of the strict intervention on cases growth rate was increased (RR dropped from 0.95 to 0.87). Simultaneously, vaccination also alleviated the negative impact of the strict intervention on excess mortality (RR decreased from 1.44 to 1.25). Besides, maintaining the strict intervention appeared to more reduce the cases, as well as avoids more overall burden of death compared with weak intervention. CONCLUSIONS: Our study highlights the importance of continued high-intensity NPIs in low vaccine coverage. Lifting of NPIs in insufficient vaccination coverage may cause increased infections and death burden. Policymakers should coordinate the intensity and duration of NPIs and allocate medical resources reasonably with widespread vaccination.

Changes in tobacco use at the early stage of the COVID-19 pandemic: Results of four cross-sectional surveys in Hong Kong.

INTRODUCTION: Changes in tobacco use since the COVID-19 outbreak differed by countries and little is known about changes in the use of specific tobacco products. METHODS: We analyzed data from four cross-sectional telephone/online surveys from April to June 2020 to investigate such changes since the 1st and 2nd wave outbreaks (February to April 2020) in Hong Kong. The respondents were 1595 adults (83.2% male) who used tobacco before the COVID-19 outbreak from our previous intervention study and surveys. We investigated the changes in tobacco use, intention to quit and quit attempts during the outbreak. RESULTS: About two-thirds (65.3%) of respondents reported no change in overall tobacco use, while 23.1% used less (including cessation) and 11.6% used more, resulting in a net decrease of 11.5 percentage points. A greater net decrease was observed for cigarettes (14.3% points) than heated tobacco products (HTPs, 3.3% points) and electronic cigarettes (e-cigarettes, 2.5% points). Decreased use was mainly due to the more extended stay at home (63.2%), health considerations (52.6%) and mask-wearing (47.4%), while increased use was for passing time (75.0%) and releasing stress (46.4%). Eight percent of cigarette, HTP and e-cigarette users reported a higher intention to quit since the pandemic outbreak. Nineteen percent of tobacco users (176/948) attempted to quit during the pandemic. Only 2.9% (46/1569) were abstinent at the time of the survey. CONCLUSIONS: Overall tobacco use decreased after the first two waves of the COVID-19 outbreak in Hong Kong. A greater proportion of cigarette users decreased use than HTP and e-cigarette users. Given the different methods used in the four surveys, future studies should aim for a large and representative sample.

Cryptocurrency price discrepancies under uncertainty: Evidence from COVID-19 and lockdown nexus.

The past decades have witnessed recurrent price discrepancies in cryptocurrency markets across countries. In addition to prior explanations that generally attribute this phenomenon to domestic capital controls during normal periods, we provide another explanation that investors perceive cryptocurrency as an alternative (hedging) investment, especially under uncertainty. Using the emerging of the COVID-19 pandemic in 2020 and the subsequent lockdown policies implemented by a group of countries as natural experiments, we adopt a difference-in-difference framework to examine how the nexus affects Bitcoin price discrepancies. We find that price discrepancies are larger in countries with confirmed cases of COVID-19 and rigorously implementing lockdown policies. We then verify our "alternative investment" hypothesis on the mechanism by showing that countries with intensified exposure to media hype on COVID-19 topics and with more panic emotion among citizens during the pandemic generally experienced larger Bitcoin price discrepancies than their counterparts. We also find that domestic capital control, sanitary policy stringency, uncertainty aversion, individualistic culture, and governmental power could moderate the general effect.

Analysis of microstructure and protective performance of melt-blown materials for medical protective masks

Since the end of 2019, the Corona Virus Disease 2019 (COVID-19) pandemic has led to a surge in the use of all kinds of medical supplies, especially surgical masks. Based on the microstructure and anti-virus mechanism of melt-blown materials used for medical masks, this paper introduces the research status of nonwoven filter materials used for protective masks. At the same time, the surface interface structure of four disposable medical protective masks from different manufacturers was analyzed by scanning electron microscope, and the difference of melt-blown materials of these masks was studied. The results show that the fiber diameter of melt-blown mask with better protective effect is fine and compact, and the aperture formed between fibers is smaller. This reasearch provides new ideas for further research and development of non-woven materials for medical masks.

LCOS-SLM Based Intelligent Hybrid Algorithm for Beam Splitting

The iterative Fourier transform algorithm (IFTA) is widely used in various optical communication applications based on liquid crystal on silicon spatial light modulators. However, the traditional iterative method has many disadvantages, such as a poor effect, an inability to select an optimization direction, and the failure to consider zero padding or phase quantization. Moreover, after years of development, the emergence of various variant algorithms also makes it difficult for researchers to choose one. In this paper, a new intelligent hybrid algorithm that combines the IFTA and differential evolution algorithm is proposed in a novel way. The reliability of the proposed algorithm is verified by beam splitting, and the IFTA and symmetrical IFTA algorithms, for comparison, are introduced. The hybrid algorithm improves the defects above while considering the zero padding and phase quantization of a computer-generated hologram, which optimizes the directional optimization in the diffraction efficiency and the fidelity of the output beam and improves the results of these two algorithms. As a result, the engineers’ trouble in the selection of an algorithm has also been reduced.

Enzymatic Beacons for Specific Sensing of Dilute Nucleic Acid.

Enzymatic beacons, or E-beacons, are 1 : 1 bioconjugates of the nanoluciferase enzyme linked covalently at its C-terminus to hairpin forming ssDNA equipped with a dark quencher. We prepared E-beacons biocatalytically using HhC, the promiscuous Hedgehog C-terminal protein-cholesterol ligase. HhC attached nanoluciferase site-specifically to mono-sterylated hairpin oligonucleotides, called steramers. Three E-beacon dark quenchers were evaluated: Iowa Black, Onyx-A, and dabcyl. Each quencher enabled sensitive, sequence-specific nucleic acid detection through enhanced E-beacon bioluminescence upon target hybridization. We assembled prototype dabcyl-quenched E-beacons specific for SARS-CoV-2. Targeting the E484 codon of the virus Spike protein, E-beacons (80×10-12  M) reported wild-type SARS-CoV-2 nucleic acid at ≥1×10-9  M by increased bioluminescence of 8-fold. E-beacon prepared for the SARS-CoV-2 E484K variant functioned with similar sensitivity. Both E-beacons could discriminate their target from the E484Q mutation of the SARS-CoV-2 Kappa variant. Along with mismatch specificity, E-beacons are two to three orders of magnitude more sensitive than synthetic molecular beacons.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.