Corrigendum: Prevalence and outcomes of pancreatic enzymes elevation in patients with COVID-19: a meta-analysis and systematic review.

[This corrects the article DOI: 10.3389/fpubh.2022.865855.].

A three-dimensional terbium metal − organic framework fluorescent sensor for efficient detection of chloroquine phosphate in serum

[Display omitted] • Tb-MOF as a potential sensing material for chloroquine phosphate recovered for multiple cycles. • The quenching mechanisms between Tb-MOF and chloroquine phosphate from many aspects investigated. • The sensor used for the visual detection of chloroquine phosphate in serum. A novel three-dimensional (3D) anionic anhydrous metal − organic framework (MOF), {[NH 2 (CH 3) 2 ]·[Tb(pdca) 2 ]} n (Tb-MOF ;H 2 pdca = 2,5-pyridinedicarboxylic acid) has been triumphantly fabricated and structurally characterized. The obtained Tb-MOF displays good stability in some common solvent systems and high temperature environments. The luminescence properties of Tb-MOF are investigated by fluorescence spectra, and the results exhibit superb characteristic emission of Tb3+ ions, which lay a foundation for exploring the fluorescence sensing application of the material. More importantly, based on competitive absorption and dynamic quenching, Tb-MOF can be applied to detect chloroquine phosphate (CQ) used for the treatment of COVID-19 and malaria, showing high sensitivity and fast response speed in the sensing process. Notably, the specific quenching effect between Tb-MOF and CQ in the serum system without interference from other components, demonstrating the practical application potential of Tb-MOF. [ FROM AUTHOR] Copyright of Microchemical Journal is the property of Elsevier B.V. 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.)

RNA extraction-free workflow integrated with a single-tube CRISPR-Cas-based colorimetric assay for rapid SARS-CoV-2 detection in different environmental matrices

On-site environmental surveillance of viruses is increasingly important for infection prevention and pandemic control. Herein, we report a facile single-tube colorimetric assay for detecting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from environmental compartments. Using glycerol as the phase separation additive, reverse transcription recombinase polymerase amplification (RT-RPA), CRISPR-Cas system activation, G-quadruplex (G4) cleavage, and G4-based colorimetric reaction were performed in a single tube. To further simplify the test, viral RNA genomes used for the one-tube assay were obtained via acid/base treatment without further purification. The whole assay from sampling to visual readout was completed within 30 min at a constant temperature without the need for sophisticated instruments. Coupling the RT-RPA to CRISPR-Cas improved the reliability by avoiding false positive results. Non-labeled cost-effective G4-based colorimetric systems are highly sensitive to CRISPR-Cas cleavage events, and the proposed assay reached the limit of detection of 0.84 copies/μL. Moreover, environmental samples from contaminated surfaces and wastewater were analyzed using this facile colorimetric assay. Given its simplicity, sensitivity, specificity, and cost-effectiveness, our proposed colorimetric assay is highly promising for applications in on-site environmental surveillance of viruses. Graphical

Hybridoma-derived neutralizing monoclonal antibodies against Beta and Delta variants of SARS-CoV-2 in vivo.

Neutralizing monoclonal antibodies (mAb) are a major therapeutic strategy for the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The continuous emergence of new SARS-CoV-2 variants worldwide has increased the urgency for the development of new mAbs. In this study, we immunized mice with the receptor-binding domain (RBD) of the SARS-CoV-2 prototypic strain (WIV04) and screened 35 RBD-specific mAbs using hybridoma technology. Results of the plaque reduction neutralization test showed that 25 of the mAbs neutralized authentic WIV04 strain infection. The 25 mAbs were divided into three categories based on the competitive enzyme-linked immunosorbent assay results. A representative mAb was selected from each category (RD4, RD10, and RD14) to determine the binding kinetics and median inhibitory concentration (IC50) of WIV04 and two variants of concern (VOC): B.1.351 (Beta) and B.1.617.2 (Delta). RD4 neutralized the B.1.617.2 variant with an IC50 of 2.67 â€‹ng/mL; however, it completely lost neutralizing activity against the B.1.351 variant. RD10 neutralized both variants with an IC50 exceeding 100 â€‹ng/mL; whereas RD14 neutralized two variants with a higher IC50 (>1 â€‹mg/mL). Animal experiments were performed to evaluate the protective effects of RD4 and RD10 against various VOC infections. RD4 could protect Adv-hACE2 transduced mice from B.1.617.2 infection at an antibody concentration of 25 â€‹mg/kg, while RD10 could protect mice from B.1.351 infection at an antibody concentration of 75 â€‹mg/kg. These results highlight the potential for future modifications of the mAbs for practical use.

Real-world study of the effectiveness of BBIBP-CorV (Sinopharm) COVID-19 vaccine in the Kingdom of Morocco.

BACKGROUND: The Kingdom of Morocco approved BBIBP-CorV (Sinopharm) COVID-19 vaccine for emergency use on 22 January 2021 in a two-dose, three-to-four-week interval schedule. We conducted a retrospective cohort study to determine real-world BBIBP-CorV vaccine effectiveness (VE) against serious or critical hospitalization of individuals RT-PCR-positive for SARS-CoV-2 during the first five months of BBIBP-CorV use in Morocco. METHODS: The study was conducted among adults 18-99 years old who were tested by RT-PCR for SARS-CoV-2 infection between 1 February and 30 June 2021. RT-PCR results were individually linked with outcomes from the COVID-19 severe or critical hospitalization dataset and with vaccination histories from the national vaccination registration system. Individuals with partial vaccination (< 2 weeks after dose two) or in receipt of any other COVID-19 vaccine were excluded. Unadjusted and adjusted VE estimates against hospitalization for serious or critical illness were made by comparing two-dose vaccinated and unvaccinated individuals in logistic regression models, calculated as (1-odds ratio) * 100%. RESULTS: There were 348,190 individuals able to be matched across the three databases. Among these, 140,892 were fully vaccinated, 206,149 were unvaccinated, and 1,149 received homologous BBIBP-CorV booster doses. Unadjusted, full-series, unboosted BBIBP-CorV VE against hospitalization for serious or critical illness was 90.2% (95%CI: 87.8-92.0%). Full-series, unboosted VE, adjusted for age, sex, and calendar day of RT-PCR test, was 88.5% (95%CI: 85.8-90.7%). Calendar day- and sex-adjusted VE was 96.4% (95%CI: 94.6-97.6%) for individuals < 60 years, and was 53.3% (95%CI: 39.6-63.9%) for individuals 60 years and older. There were no serious or critical illnesses among BBIBP-CorV-boosted individuals. CONCLUSIONS: Effectiveness of Sinopharm's BBIBP-CorV was consistent with phase III clinical trial results. Two doses of BBIBP-CorV was highly protective against COVID-19-associated serious or critical hospitalization in working-age adults under real-world conditions and moderately effective in older adults. Booster dose vaccination was associated with complete protection, regardless of age, although only a small proportion of subjects received booster doses.

Prevalence and Outcomes of Pancreatic Enzymes Elevation in Patients With COVID-19: A Meta-Analysis and Systematic Review.

Background: Although coronavirus disease 2019 (COVID-19) is considered to be a disease that mainly involves the respiratory system, an increasing number of studies have reported that COVID-19 patients had pancreatic enzymes (PE) elevation and even pancreatic injury. The study aims to determine the prevalence of PE elevation, and the relationship between elevated PE and prognosis in COVID-19 patients. Methods: A comprehensive literature search was conducted according to the PRISMA guideline in PubMed, Embase, Scopus, Web of Science, and Google Scholar for studies reporting PE elevation in patients with COVID-19 from 1st January 2020 to 24th November 2021. Results: A total of 13 studies (24,353 participants) were included in our review. The pooled prevalence of PE elevation in COVID-19 patients was 24% (18%-31%), the pooled odds ratio (OR) of mortality was 2.5 (1.7-3.6), the pooled OR of ICU admission was 4.4 (2.8-6.8), and the pooled OR of kidney injury, respiratory failure and liver injury were 3.5 (1.6-7.4), 2.0 (0.5-8.7), and 2.3 (1.4-3.9) respectively. In addition, the subgroup analysis revealed that although PE elevated to > 3 × upper normal limit (ULN) was significantly related to the mortality (OR = 4.4, 2.1-9.4), it seemed that mild elevation of PE to 1-3 ULN also had a considerable risk of mortality (OR = 2.3, 1.5-3.5). Conclusions: PE elevation was a common phenomenon in patients with COVID-19, and was associated with poor clinical outcomes. However, due to the limited numbers of included studies, the result of our study still needed to be validated. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=295630, identifier: CRD42021295630.

Variation characteristics and variants identification technique of SARS-CoV-2

The outbreak of COVID-19 caused by SARS-CoV-2 in 2019 has become a major global health crisis. There are multiple variants of SARS-CoV-2 identified, with significant differences in the viral transmission capacity and toxicity.SARS-CoV-2 variation has become one of the major challenges in the prevention and control of the pandemic.The identification of SARS-CoV-2 variants and understanding the variation characteristics may significantly help to curb the spread of SARS-CoV-2, adopt comprehensive and effective disease control measures and choose reasonable treatment plans.In this paper, the variation features of SARS-CoV-2 and the mutation testing techniques were reviewed.

Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti-SARS-CoV-2 Agents.

Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A (1) and oridonin (2) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water-assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone-type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS-CoV-2 replication in HPA EpiC cells with a low EC50 value (19±1 nM) and a high TI value (>1000), both values better than those of remdesivir.

Colorimetric Sensing with Gold Nanoparticles on Electrowetting-Based Digital Microfluidics.

Digital microfluidic (DMF) has been a unique tool for manipulating micro-droplets with high flexibility and accuracy. To extend the application of DMF for automatic and in-site detection, it is promising to introduce colorimetric sensing based on gold nanoparticles (AuNPs), which have advantages including high sensitivity, label-free, biocompatibility, and easy surface modification. However, there is still a lack of studies for investigating the movement and stability of AuNPs for in-site detection on the electrowetting-based digital microfluidics. Herein, to demonstrate the ability of DMF for colorimetric sensing with AuNPs, we investigated the electrowetting property of the AuNPs droplets on the hydrophobic interface of the DMF chip and examined the stability of the AuNPs on DMF as well as the influence of evaporation to the colorimetric sensing. As a result, we found that the electrowetting of AuNPs fits to a modified Young-Lippmann equation, which suggests that a higher voltage is required to actuate AuNPs droplets compared with actuating water droplets. Moreover, the stability of AuNPs was maintained during the processing of electrowetting. We also proved that the evaporation of droplets has a limited influence on the detections that last several minutes. Finally, a model experiment for the detection of Hg2+ was carried out with similar results to the detections in bulk solution. The proposed method can be further extended to a wide range of AuNPs-based detection for label-free, automatic, and low-cost detection of small molecules, biomarkers, and metal ions.

A review of COVID-19: Treatment strategies and CRISPR/Cas9 gene editing technology approaches to the coronavirus disease.

The new coronavirus SARS-CoV-2 pandemic has put the world on lockdown for the first time in decades. This has wreaked havoc on the global economy, put additional burden on local and global public health resources, and, most importantly, jeopardised human health. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, and the CRISPR associated (Cas) protein (CRISPR/Cas) was identified to have structures in E. coli. The most modern of these systems is CRISPR/Cas. Editing the genomes of plants and animals took several years and cost hundreds of thousands of dollars until the CRISPR approach was discovered in 2012. As a result, CRISPR/Cas has piqued the scientific community's attention, particularly for disease diagnosis and treatment, because it is faster, less expensive, and more precise than previous genome editing technologies. Data from gene mutations in specific patients gathered using CRISPR/Cas can aid in the identification of the best treatment strategy for each patient, as well as other research domains such as coronavirus replication in cell culture, such as SARS-CoV2. The implications of the most prevalent driver mutations, on the other hand, are often unknown, making treatment interpretation difficult. For detecting a wide range of target genes, the CRISPR/Cas categories provide highly sensitive and selective tools. Genome-wide association studies are a relatively new strategy to discovering genes involved in human disease when it comes to the next steps in genomic research. Furthermore, CRISPR/Cas provides a method for modifying non-coding portions of the genome, which will help advance whole genome libraries by speeding up the analysis of these poorly defined parts of the genome.

Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients.

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.

ß-sitosterol ameliorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling.

ß-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of ß-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that ß-sitosterol (150-450 µg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of ß-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, ß-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of ß-sitosterol (50, 200 mg·kg-1·d-1, i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of ß-sitosterol protected mice from lethal IAV infection. Our data suggest that ß-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza.

TNFalpha inhibitor may be effective for severe COVID-19: learning from toxic epidermal necrolysis

Increased inflammatory cytokines [such as tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6)] are observed in COVID-19 patients, especially in the severe group. The phenomenon of a cytokine storm may be the central inducer of apoptosis of alveolar epithelial cells, which leads to rapid progression in severe group patients. Given the similarities of clinical features and pathogenesis between toxic epidermal necrolysis (TEN) and COVID-19, we hypothesize that the application of etanercept, an inhibitor of TNFalpha, could attenuate disease progression in severe group COVID-19 patients by suppressing systemic auto-inflammatory responses. The reviews of this paper are available via the supplemental material section.

Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes.

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

A pneumonia outbreak associated with a new coronavirus of probable bat origin.

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats^1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans^5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.