Safety of COVID-19 vaccine in patients with myasthenia gravis: a self-controlled case series study.

Background: The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients. Methods: The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression. Results: Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination. Conclusion: COVID-19 vaccination has no long-term impact on MG relapse.

How Connected is Crude Oil to Stock Sectors Before and After the COVID-19 Outbreak? Evidence from a Novel Network Method

A novel network with Wavelet denoising-GARCHSK and Mixed CoVaR method is proposed to construct full-sample and dynamic networks for investigating the risk spillover effects across international crude oil and Chinese stock sectors before and after the COVID-19 outbreak. The empirical results denote that the total bidirectional oil-sector risk spillover effects increase rapidly after the COVID-19 outbreak. Interestingly, sectors shift from net risk receivers to net risk contributors in the oil-sector risk transfer effects during the pandemic period. Second, unlike the pre-COVID-19 period, Shanghai crude (SC) replaces Brent as the largest oil risk transmitter to stocks during the COVID-19 period. Third, there are notable sectoral features in the oil-sector risk spillovers, which differ across different periods. After the burst, Energy has an incredibly weak connection with crude oil, while the sectors, which oil products are input for, become close with crude oil. Far more surprising is that the petroleum-independent sectors have increasing closer risk transfer effects with crude, even becoming the largest risk contributors to oil, after that. Finally, the oil-sector relationships during the same period are time-varying but stable. This paper provides policymakers and investors with new method and insight into the oil-sector relationships. [ABSTRACT FROM AUTHOR] Copyright of Fluctuation & Noise Letters is the property of World Scientific Publishing Company 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 abstract 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 abstract. (Copyright applies to all Abstracts.)

Development of receptor binding domain-based double-antigen sandwich lateral flow immunoassay for the detection and evaluation of SARS-CoV-2 neutralizing antibody in clinical sera samples compared with the conventional virus neutralization test.

Vaccination is an effective strategy to fight COVID-19. However, the effectiveness of the vaccine varies among different populations in varying immune effects. Neutralizing antibody (NAb) level is an important indicator to evaluate the protective effect of immune response after vaccination. Lateral flow immunoassay (LFIA) is a rapid, safe and sensitivity detection method, which has great potential in the detection of SARS-CoV-2 NAb. In this study, a fluorescent beads-based lateral flow immunoassay (FBs-LFIA) and a latex beads-based LFIA (LBs-LFIA) using double antigen sandwich (DAS) strategy were established to detect NAbs in the serum of vaccinated people. The limit of detection (LoD) of the FBs-LFIA was 1.13 ng mL- 1 and the LBs-LFIA was 7.11 ng mL- 1. The two LFIAs were no cross-reactive with sera infected by other pathogenic bacteria. Furthermore, the two LFIAs showed a good performance in testing clinical samples. The sensitivity of FBs-LFIA and LBs-LFIA were 97.44% (95%CI: 93.15%-99.18%) and 98.29% (95%CI: 95.84%-99.37%), and the specificity were 98.28% (95%CI: 95.37%-99.45%) and 97.70% (95%CI: 94.82%-99.06%) compared with the conventional virus neutralization test (cVNT), respectively. Notably, the LBs-LFIA was also suitable for whole blood sample, requiring only 3 µL of whole blood, which provided the possibility to detect NAbs at home. To sum up, the two LFIAs based on double antigen sandwich established by us can rapidly, safely, sensitively and accurately detect SARS-CoV-2 NAb in human serum.

Targeting autophagy regulation in NLRP3 inflammasome-mediated lung inflammation in COVID-19.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late stage of COVID-19. Here, we discuss the autophagy regulation at different stages of COVID-19. Specifically, we highlight the therapeutic potential of autophagy activators in COVID-19 by inhibiting the NLRP3 inflammasome, thereby avoiding the cytokine storm. We hope this review provides enlightenment for the use of autophagy activators targeting the inhibition of the NLRP3 inflammasome, specifically the combinational therapy of autophagy modulators with the inhibitors of the NLRP3 inflammasome, antiviral drugs, or anti-inflammatory drugs in the fight against COVID-19.

Platinum nanoparticles (PtNPs)-based CRISPR/Cas12a platform for detection of nucleic acid and protein in clinical samples.

Early rapid screening diagnostic assay is essential for the identification, prevention, and evaluation of many contagious or refractory diseases. The optical density transducer created by platinum nanoparticles (PtNPs) (OD-CRISPR) is reported in the present research as a cheap and easy-to-execute CRISPR/Cas12a-based diagnostic platform. The OD-CRISPR uses PtNPs, with ultra-high peroxidase-mimicking activity, to increase the detection sensitivity, thereby enabling the reduction of detection time and cost. The OD-CRISPR can be utilized to identify nucleic acid or protein biomarkers within an incubation time of 30-40min in clinical specimens. In the case of taking severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene as an instance, when compared to a quantitative reverse transcription-polymerase chain reaction (RT-qPCR), the OD-CRISPR test attains a sensitivity of 79.17% and a specificity of 100%. In terms of detecting prostate-specific antigen (PSA), aptamer-based OD-CRISPR assay achieves the least discoverable concentration of 0.01 ng mL-1. In general, the OD-CRISPR can detect nucleic acid and protein biomarkers, and is a potential strategy for early rapid screening diagnostic tools.

Application of the amplification-free SERS-based CRISPR/Cas12a platform in the identification of SARS-CoV-2 from clinical samples.

The control of contagious or refractory diseases requires early, rapid diagnostic assays that are simple, fast, and easy-to-use. Here, easy-to-implement CRISPR/Cas12a-based diagnostic platform through Raman transducer generated by Raman enhancement effect, term as SERS-CRISPR (S-CRISPR), are described. The S-CRISPR uses high-activity noble metallic nanoscopic materials to increase the sensitivity in the detection of nucleic acids, without amplification. This amplification-free platform, which can be performed within 30-40 min of incubation time, is then used for detection of SARS-CoV-2 derived nucleic acids in RNA extracts obtained from nasopharyngeal swab specimens (n = 112). Compared with the quantitative reverse transcription polymerase chain reaction (RT-qPCR), the sensitivity and specificity of S-CRISPR reaches 87.50% and 100%, respectively. In general, the S-CRISPR can rapidly identify the RNA of SARS-CoV-2 RNA without amplification and is a potential strategy for nucleic acid point of care test (POCT).

Multidimensional risk spillovers among crude oil, the US and Chinese stock markets: Evidence during the COVID-19 epidemic.

This paper investigates the multidimensional risk spillovers among crude oil, the US and Chinese stock markets during the COVID-19 epidemic through a GARCHSK-Mixed Copula-CoVaR-Network method. Firstly, we find that during the COVID-19 period, the oil-stock risk spillovers are obviously stronger than those during the normal period. And there are significant risk spillovers from the US and Chinese stock markets to the oil markets. It is also discovered that the oil markets are greatly influenced by the second board stock markets, also known as the growth enterprise markets, especially during the COVID-19 outbreak. Furthermore, the bidirectional China-oil risk spillovers during the COVID-19 pandemic have rapidly increased. Besides, it is reported that the relationships across oil futures, main board and second board stock markets in the US and China are stable under different TSI levels and extreme events. Finally, the GARCHSK-Mixed Copula-CoVaR-Network outperforms the control groups in terms of marginal distribution and dependence structure. Our study not only offers new method and insight into the oil-stock relationship, but also has economic implications for investors and policymakers.

A rationale for targeting the P2X7 receptor in Coronavirus disease 19.

Severe pneumonia which shares several of the features of acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid-19) for which there is no effective treatment, so far. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung oedema, inflammatory cell infiltration, and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid-19-associated severe pneumonia. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Predicting the Animal Susceptibility and Therapeutic Drugs to SARS-CoV-2 Based on Spike Glycoprotein Combined With ACE2.

Recently, a few animals have been frequently reported to have been diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether they are SARS-CoV-2 intermediate hosts is worthy of great attention. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from 10 kinds of animals. Results show that chimpanzees, domestic cats and cattles are more susceptible to infection by SARS-CoV-2. Cats in particular, such as pet cats and stray cats, interact very closely with humans, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic. Furthermore, based on ACE2(cats)-SARS-CoV-2-RBD model, through high-throughput screening methods using a pool of 30,000 small molecules, eight compounds were selected for binding free energy calculations. All the eight compounds can effectively interfere with the binding of ACE2 and Spike protein, especially Nelfinavir, providing drug candidates for the treatment and prevention of SARS-CoV-2, suggesting further assessment of the anti-SARS-CoV-2 activity of these compounds in cell culture. Although we only reported the results of the simulation, and more laboratory and epidemiological investigation are required. Like cats are a risk factor, we can further detect SARS-CoV-2 according to the susceptibility of different animals, find the potential host of infection, and completely cut off the living space of the virus. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

EuNPs-mAb fluorescent probe based immunochromatographic strip for rapid and sensitive detection of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea (PED), induced by porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration and high mortality in neonatal piglets, resulting in significant economic losses in the pig industries. In this study, an immunochromatographic assay (ICA) based on a EuNPs-mAb fluorescent probe was developed and optimized for rapid detection of PEDV. The limit of detection (LOD) of the ICA was 0.218 µg/mL (2.725 × 103 TCID50/mL) and its linear detection range was 0.03125-8 µg/mL (3.91 × 102-105 TCID50/mL). The ICA was also validated for the detection of PEDV in swine stool samples. 60 swine stool samples from southern China were analyzed by the ICA and RT-PCR, and the results showed that the coincidence rate of the ICA to RT-PCR was 86.67%, which was significantly higher than that of AuNPs based ICA. The ICA is sensitive and specific and can achieve on-site rapid detection of swine stool samples. Therefore, the ICA has a great potential for PED diagnosis and prevention.