Comparison of postweaning bovine respiratory disease treatment rates between non-vaccinated control beef calves and calves variably primed and boosted using commercially available bovine coronavirus vaccines.

Objective: Bovine respiratory disease (BRD) and overall postweaning treatment rates were compared among 3 groups of calves either differentially primed and boosted with commercially available bovine coronavirus (BCoV) vaccine or not vaccinated against BCoV. Animals: Commercial heifer and steer beef calves born in April and May 2022. Procedure: In June 2022, calves were randomly enrolled into 3 treatment groups. Those in 2 groups [V1 (n = 160) and V2 (n = 160)] were administered a mucosal priming dose of 1 of 2 commercial BCoV vaccines; those in the 3rd group [CTL (n = 151)] were unvaccinated against BCoV. The V1 and V2 groups were boosted by intramuscular injection pre-weaning with the same vaccine used for priming. Weaning occurred 3 wk after the last preweaning processing day. Ranch staff used a BRD case definition provided by their herd veterinarian to identify, treat, and record treatments for 45 d post-weaning. Results: Postweaning BRD treatment rates for V1, V2, and CTL were 7%, 9%, and 14%, respectively. The CTL calves had 2.2× greater odds of receiving treatment for BRD than V1 calves. There were no differences in odds of treatment between CTL and V2 calves or V1 and V2 calves. Conclusion: In a herd with previously diagnosed BCoV BRD cases, prime-boost vaccination of calves is associated with a difference in odds of BRD treatment post-weaning compared to not vaccinating calves against BCoV. Clinical relevance: Prime-boost vaccination with commercial BCoV vaccine may be an important management tool for herds with known BCoV BRD outbreaks.

Comparaison des taux de traitement des maladies respiratoires bovines après le sevrage entre des veaux de boucherie témoins non vaccinés et des veaux vaccinés amorce-rappel de manière variable à l'aide de vaccins contre le coronavirus bovin commercialement disponibles. Objectif: La maladie respiratoire bovine (BRD) et les taux globaux de traitement post-sevrage ont été comparés parmi 3 groupes de veaux soit vaccinés de manière différentielle et avec un rappel avec le vaccin contre le coronavirus bovin (BCoV) disponible commercialement, soit non vaccinés contre le BCoV. Animaux: Génisses et veaux de boucherie commerciaux nés en avril et mai 2022. Procédure: En juin 2022, les veaux ont été randomisés lors du recrutement dans 3 groupes de traitement. Ceux des 2 groupes [V1 (n = 160) et V2 (n = 160)] ont reçu une dose d'amorce par voie muqueuse de l'un des deux vaccins commerciaux BCoV; ceux du 3ème groupe [CTL (n = 151)] n'étaient pas vaccinés contre le BCoV. Les groupes V1 et V2 ont eu un rappel par injection intramusculaire avant le sevrage avec le même vaccin que celui utilisé pour l'amorçage. Le sevrage a eu lieu 3 semaines après le dernier jour de conditionnement pré-sevrage. Le personnel du ranch a utilisé une définition de cas de BRD fournie par le vétérinaire de leur troupeau pour identifier, traiter et enregistrer les traitements pendant 45 jours après le sevrage. Résultats: Les taux de traitement BRD post-sevrage pour V1, V2 et CTL étaient respectivement de 7 %, 9 % et 14 %. Les veaux CTL avaient 2,2 fois plus de chances de recevoir un traitement contre la BRD que les veaux V1. Il n'y avait aucune différence dans les probabilités de traitement entre les veaux CTL et V2 ou entre les veaux V1 et V2. Conclusion: Dans un troupeau avec des cas de BRD causés par le BCoV déjà diagnostiqués, la vaccination amorce-rappel des veaux est associée à une différence de probabilité de traitement par le BRD après le sevrage par rapport à la nonvaccination des veaux contre le BCoV. Pertinence clinique: La vaccination amorce-rappel avec le vaccin commercial BCoV peut être un outil de gestion important pour les troupeaux présentant des foyers connus de BCoV BRD.(Traduit par Dr Serge Messier).

The effectiveness of intervention measures on MERS-CoV transmission by using the contact networks reconstructed from link prediction data.

Introduction: Mitigating the spread of infectious diseases is of paramount concern for societal safety, necessitating the development of effective intervention measures. Epidemic simulation is widely used to evaluate the efficacy of such measures, but realistic simulation environments are crucial for meaningful insights. Despite the common use of contact-tracing data to construct realistic networks, they have inherent limitations. This study explores reconstructing simulation networks using link prediction methods as an alternative approach. Methods: The primary objective of this study is to assess the effectiveness of intervention measures on the reconstructed network, focusing on the 2015 MERS-CoV outbreak in South Korea. Contact-tracing data were acquired, and simulation networks were reconstructed using the graph autoencoder (GAE)-based link prediction method. A scale-free (SF) network was employed for comparison purposes. Epidemic simulations were conducted to evaluate three intervention strategies: Mass Quarantine (MQ), Isolation, and Isolation combined with Acquaintance Quarantine (AQ + Isolation). Results: Simulation results showed that AQ + Isolation was the most effective intervention on the GAE network, resulting in consistent epidemic curves due to high clustering coefficients. Conversely, MQ and AQ + Isolation were highly effective on the SF network, attributed to its low clustering coefficient and intervention sensitivity. Isolation alone exhibited reduced effectiveness. These findings emphasize the significant impact of network structure on intervention outcomes and suggest a potential overestimation of effectiveness in SF networks. Additionally, they highlight the complementary use of link prediction methods. Discussion: This innovative methodology provides inspiration for enhancing simulation environments in future endeavors. It also offers valuable insights for informing public health decision-making processes, emphasizing the importance of realistic simulation environments and the potential of link prediction methods.

High-affinity monoclonal antibodies against the porcine epidemic diarrhea virus S1 protein.

The porcine epidemic diarrhea virus (PEDV) infection inflicted substantial economic losses upon the global pig-breeding industry. This pathogen can infect all pigs and poses a particularly high fatality risk for suckling piglets. The S1 subunit of spike protein is a crucial target protein for inducing the particularly neutralizing antibodies that can intercept the virus-host interaction and neutralize virus infectivity. In the present study, the HEK293F eukaryotic expression system was successfully utilized to express and produce recombinant S1 protein. Through quantitative analysis, five monoclonal antibodies (mAbs) specifically targeting the recombinant S1 protein of PEDV were developed and subsequently evaluated using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and flow cytometry assay (FCA). The results indicate that all five mAbs belong to the IgG1 isotype, and their half-maximal effective concentration (EC50) values measured at 84.77, 7.42, 0.89, 14.64, and 7.86 pM. All these five mAbs can be utilized in ELISA, FCA, and IFA for the detection of PEDV infection. MAb 5-F9 exhibits the highest sensitivity to detect as low as 0.3125 ng/mL of recombinant PEDV-S1 protein in ELISA, while only 0.096 ng/mL of mAb 5-F9 is required to detect PEDV in FCA. The results from antigen epitope analysis indicated that mAb 8-G2 is the sole antibody capable of recognizing linear epitopes. In conclusion, this study has yielded a highly immunogenic S1 protein and five high-affinity mAbs specifically targeting the S1 protein. These findings have significant implications for early detection of PEDV infection and provide a solid foundation for further investigation into studying virus-host interactions.

Research on the global trends of COVID-19 associated acute kidney injury: a bibliometric analysis.

Critically ill COVID-19 patients may exhibit various clinical symptoms of renal dysfunction including severe Acute Kidney Injury (AKI). Currently, there is a lack of bibliometric analyses on COVID-19-related AKI. The aim of this study is to provide an overview of the current research status and hot topics regarding COVID-19 AKI. The literature was retrieved from the Web of Science Core Collection (WoSCC) database. Subsequently, we utilized Microsoft Excel, VOSviewer, Citespace, and Pajek software to revealed the current research status, emerging topics, and developmental trends pertaining to COVID-19 AKI. This study encompassed a total of 1507 studies on COVID-19 AKI. The United States, China, and Italy emerged as the leading three countries in terms of publication numbers, contributing 498 (33.05%), 229 (15.20%), and 140 (9.29%) studies, respectively. The three most active and influential institutions include Huazhong University of Science and Technology, Wuhan University and Harvard Medical School. Ronco C from Italy, holds the record for the highest number of publications, with a total of 15 papers authored. Cheng YC's work from China has garnered the highest number of citations, totaling 470 citations. The co-occurrence analysis of author keywords reveals that 'mortality', 'intensive care units', 'chronic kidney disease', 'nephrology', 'renal transplantation', 'acute respiratory distress syndrome', and 'risk factors' emerge as the primary areas of focus within the realm of COVID-19 AKI. In summary, this study analyzes the research trends in the field of COVID-19 AKI, providing a reference for further exploration and research on COVID-19 AKI mechanisms and treatment.

Inhibition Mechanism of SARS-CoV-2 Infection by a Cholesterol Derivative, Nat-20(S)-yne.

The coronavirus disease 2019 (COVID-19) is caused by the etiological agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19, with the recurrent epidemics of new variants of SARS-CoV-2, remains a global public health problem, and new antivirals are still required. Some cholesterol derivatives, such as 25-hydroxycholesterol, are known to have antiviral activity against a wide range of enveloped and non-enveloped viruses, including SARS-CoV-2. At the entry step of SARS-CoV-2 infection, the viral envelope fuses with the host membrane dependent of viral spike (S) glycoproteins. From the screening of cholesterol derivatives, we found a new compound 26,27-dinorcholest-5-en-24-yne-3ß,20-diol (Nat-20(S)-yne) that inhibited the SARS-CoV-2 S protein-dependent membrane fusion in a syncytium formation assay. Nat-20(S)-yne exhibited the inhibitory activities of SARS-CoV-2 pseudovirus entry and intact SARS-CoV-2 infection in a dose-dependent manner. Among the variants of SARS-CoV-2, inhibition of infection by Nat-20(S)-yne was stronger in delta and Wuhan strains, which predominantly invade into cells via fusion at the plasma membrane, than in omicron strains. The interaction between receptor-binding domain of S proteins and host receptor ACE2 was not affected by Nat-20(S)-yne. Unlike 25-hydroxycholesterol, which regulates various steps of cholesterol metabolism, Nat-20(S)-yne inhibited only de novo cholesterol biosynthesis. As a result, plasma membrane cholesterol content was substantially decreased in Nat-20(S)-yne-treated cells, leading to inhibition of SARS-CoV-2 infection. Nat-20(S)-yne having a new mechanism of action may be a potential therapeutic candidate for COVID-19.

Nucleic acid vaccine candidates encapsulated with mesoporous silica nanoparticles against MERS-CoV.

Middle East respiratory coronavirus (MERS-CoV) is a newly emergent, highly pathogenic coronavirus that is associated with 34% mortality rate. MERS-CoV remains listed as priority pathogen by the WHO. Since its discovery in 2012 and despite the efforts to develop coronaviruses vaccines to fight against SARS-CoV-2, there are currently no MERS-CoV vaccine that has been approved. Therefore, there is high demand to continue on the development of prophylactic vaccines against MERS-CoV. Current advancements in vaccine developments can be adapted for the development of improved MERS-CoV vaccines candidates. Nucleic acid-based vaccines, including pDNA and mRNA, are relatively new class of vaccine platforms. In this work, we developed pDNA and mRNA vaccine candidates expressing S.FL gene of MERS-CoV. Further, we synthesized a silane functionalized hierarchical aluminosilicate to encapsulate each vaccine candidates. We tested the nucleic acid vaccine candidates in mice and evaluated humoral antibodies response. Interestingly, we determined that the non-encapsulated, codon optimized S.FL pDNA vaccine candidate elicited the highest level of antibody responses against S.FL and S1 of MERS-CoV. Encapsulation of mRNA with nanoporous aluminosilicate increased the humoral antibody responses, whereas encapsulation of pDNA did not. These findings suggests that MERS-CoV S.FL pDNA vaccine candidate induced the highest level of humoral responses. This study will enhance further optimization of nanosilica as potential carrier for mRNA vaccines. In conclusion, this study suggests MERS-CoV pDNA vaccine candidate as a suitable vaccine platform for further pivotal preclinical testings.

Lactobacillus rhamnosus GG powder supplementation alleviates intestinal injury in piglets challenged by porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) has become a challenging problem in pig industry worldwide, causing significant profit losses. Lactobacillus rhamnosus GG (LGG) has been regarded as a safe probiotic strain and has been shown to exert protective effects on the intestinal dysfunction caused by PEDV. This study evaluated the effect of LGG on the gut health of lactating piglets challenged with PEDV. Fifteen piglets at 7 days of age were equally assigned into 3 groups (5 piglets per group): 1) control group (basal diet); 2) PEDV group: (basal diet + PEDV challenged); 3) LGG + PEDV group (basal diet + 3×109 CFU/pig/day LGG + PEDV). The trial lasted 11 days including 3 days of adaptation. The treatment with LGG was from D4 to D10. PEDV challenge was carried out on D8. PEDV infection disrupted the cell structure, undermined the integrity of the intestinal tract, and induced oxidative stress, and intestinal damage of piglets. Supplementation of LGG improved intestinal morphology, enhanced intestinal antioxidant capacity, and alleviated jejunal mucosal inflammation and lipid metabolism disorders in PEDV-infected piglets, which may be regulated by LGG by altering the expression of TNF signaling pathway, PPAR signaling pathway, and fat digestion and absorption pathway.

Quantitative assay to analyze neutralization and inhibition of authentic Middle East respiratory syndrome coronavirus.

To date, there is no licensed vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV). Therefore, MERS-CoV is one of the diseases targeted by the Coalition for Epidemic Preparedness Innovations (CEPI) vaccine development programs and has been classified as a priority disease by the World Health Organization (WHO). An important measure of vaccine immunogenicity and antibody functionality is the detection of virus-neutralizing antibodies. We have developed and optimized a microneutralization assay (MNA) using authentic MERS-CoV and standardized automatic counting of virus foci. Compared to our standard virus neutralization assay, the MNA showed improved sensitivity when analyzing 30 human sera with good correlation of results (Spearman's correlation coefficient r = 0.8917, p value < 0.0001). It is important to use standardized materials, such as the WHO international standard (IS) for anti-MERS-CoV immunoglobulin G, to compare the results from clinical trials worldwide. Therefore, in addition to the neutralizing titers (NT50 = 1384, NT80 = 384), we determined the IC50 and IC80 of WHO IS in our MNA to be 0.67 IU/ml and 2.6 IU/ml, respectively. Overall, the established MNA is well suited to reliably quantify vaccine-induced neutralizing antibodies with high sensitivity.

A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus.

The emergence of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has posed a significant global health concern due to its severe respiratory illness and high fatality rate. Currently, despite the potential for resurgence, there are no specific treatments for MERS-CoV, and only supportive care is available. Our study aimed to address this therapeutic gap by developing a potent neutralizing bispecific antibody (bsAb) against MERS-CoV. Initially, we isolated four human monoclonal antibodies (mAbs) that specifically target the MERS-CoV receptor-binding domain (RBD) using phage display technology and an established human antibody library. Among these four selected mAbs, our intensive in vitro functional analyses showed that the MERS-CoV RBD-specific mAb K111.3 exhibited the most potent neutralizing activity against MERS-CoV pseudoviral infection and the molecular interaction between MERS-CoV RBD and human dipeptidyl peptidase 4. Consequently, we engineered a novel bsAb, K207.C, by utilizing K111.3 as the IgG base and fusing it with the single-chain variable fragment of its non-competing pair, K111.1. This engineered bsAb showed significantly enhanced neutralization potential against MERS-CoV compared to its parental mAb. These findings suggest that K207.C may serve as a potential candidate for effective MERS-CoV neutralization, further highlighting the promise of the bsAb dual-targeting approach in MERS-CoV neutralization.

Seasonal human coronavirus NL63 epidemics in children in Guilin, China, reveal the emergence of a new subgenotype of HCoV-NL63.

Introduction: Seasonal human coronavirus NL63 (HCoV-NL63) is a frequently encountered virus linked to mild upper respiratory infections. However, its potential to cause more severe or widespread disease remains an area of concern. This study aimed to investigate a rare localized epidemic of HCoV-NL63-induced respiratory infections among pediatric patients in Guilin, China, and to understand the viral subtype distribution and genetic characteristics. Methods: In this study, 83 pediatric patients hospitalized with acute respiratory infections and positive for HCoV-NL63 were enrolled. Molecular analysis was conducted to identify the viral subgenotypes and to assess genetic variations in the receptor-binding domain of the spiking protein. Results: Among the 83 HCoV-NL63-positive children, three subgenotypes were identified: C4, C3, and B. Notably, 21 cases exhibited a previously unreported subtype, C4. Analysis of the C4 subtype revealed a unique amino acid mutation (I507L) in the receptor-binding domain of the spiking protein, which was also observed in the previously reported C3 genotype. This mutation may suggest potential increases in viral transmissibility and pathogenicity. Discussion: The findings of this study highlight the rapid mutation dynamics of HCoV-NL63 and its potential for increased virulence and epidemic transmission. The presence of a unique mutation in the C4 subtype, shared with the C3 genotype, raises concerns about the virus's evolving nature and its potential public health implications. This research contributes valuable insights into the understanding of HCoV-NL63's epidemiology and pathogenesis, which is crucial for effective disease prevention and control strategies. Future studies are needed to further investigate the biological significance of the observed mutation and its potential impact on the virus's transmissibility and pathogenicity.

Seroprevalence of the novel swine acute diarrhea syndrome coronavirus in China assessed by enzyme-linked immunosorbent assay.

The endemic outbreak of SADS-CoV has resulted in economic losses and potentially threatened the safety of China's pig industry. The molecular epidemiology of SADS-CoV in pig herds has been investigated in many provinces in China. However, there are no data over a long-time span, and there is a lack of extensive serological surveys to assess the prevalence of SADS-CoV in Chinese swine herds since the discovery of SADS-CoV. In this study, an indirect anti-SADS-CoV IgG enzyme-linked immunosorbent assay (ELISA) based on the SADS-CoV S1 protein was established to investigate the seroprevalence of SADS-CoV in Chinese swine herds. Cross-reactivity assays, indirect immunofluorescence, and western blotting assays showed that the developed ELISA had excellent SADS-CoV specificity. In total, 12,978 pig serum samples from 29 provinces/municipalities/autonomous regions in China were tested from 2022 to 2023. The results showed that the general seroprevalence of SADS-CoV in China was 59.97%, with seroprevalence ranging from 16.7% to 77.12% in different provinces and from 42.61% to 68.45% in different months. SADS-CoV is widely prevalent in China, and its seroprevalence was higher in Northeast China, North China, and Central China than in other regions. Among the four seasons, the prevalence of SADS-CoV was the highest in spring and the lowest in autumn. The results of this study provide the general seroprevalence profile of SADS-CoV in China, facilitating the understanding of the prevalence of SADS-CoV in pigs. More importantly, this study is beneficial in formulating preventive and control measures for SADS-CoV and may provide directions for vaccine development.

Lessons learned from the COVID-19 pandemic: The importance of physician leadership in responding to rural community ecosystem disruptions.

INTRODUCTION: The COVID-19 pandemic presented an unprecedented challenge for rural family physicians. The lessons learned over the course of 2 years have potential to help guide responses to future ecosystem disruption. This qualitative study aims to explore the leadership experiences of rural Canadian family physicians during the COVID-19 pandemic as both local care providers and community health leaders and to identify potential supports and barriers to physician leadership. METHODS: Semi-structured, virtual, qualitative interviews were completed with participants from rural communities in Canada from December 2021 to February 2022 inclusive. Participant recruitment involved identifying seed contacts and conducting snowball sampling. Participants were asked about their experiences during the COVID-19 pandemic, including the role of physician leadership in building community resilience. Data collection was completed on theoretical saturation. Data were thematically analysed using NVivo 12. RESULTS: Sixty-four participants took part from 22 rural communities in 4 provinces. Four key factors were identified that supported physician leadership towards rural resilience during ecosystem disruption: (1) continuity of care, (2) team-based care models, (3) physician well-being and (4) openness to innovative care models. CONCLUSION: Healthcare policy and practice transformation should prioritise developing opportunities to strengthen physician leadership, particularly in rural areas that will be adversely affected by ecosystem disruption. INTRODUCTION: La pandémie de COVID-19 a représenté un défi sans précédent pour les médecins de famille en milieu rural. Les leçons tirées au cours des deux années écoulées peuvent aider à orienter les réponses aux futures perturbations de l'écosystème. Cette étude qualitative vise à explorer les expériences de leadership des médecins de famille ruraux canadiens pendant la pandémie de COVID-19, en tant que prestataires de soins locaux et chefs de file de la santé communautaire, et à identifier les soutiens et les obstacles potentiels au leadership des médecins. MTHODES: Des entretiens qualitatifs virtuels semi-structurés ont été réalisés avec des participants issus de communautés rurales du Canada entre décembre 2021 et février 2022 inclus. Le recrutement des participants a consisté à identifier des contacts de base et à procéder à un échantillonnage boule de neige. Les participants ont été interrogés sur leurs expériences durant la pandémie de COVID-19, notamment sur le rôle du leadership des médecins dans le renforcement de la résilience des communautés. La collecte des données s'est achevée après saturation théorique. Les données ont été analysées thématiquement à l'aide de NVivo 12. RSULTATS: Soixante-quatre participants provenant de 22 communautés rurales de quatre provinces ont pris part à l'étude. Quatre facteurs clés ont été identifiés pour soutenir le leadership des médecins en faveur de la résilience rurale en cas de perturbation de l'écosystème: (1) la continuité des soins, (2) les modèles de soins en équipe, (3) le bien-être des médecins et (4) l'ouverture à des modèles de soins novateurs. CONCLUSION: La politique de santé et la transformation des pratiques devraient donner la priorité au développement d'opportunités pour renforcer le leadership des médecins, en particulier dans les zones rurales qui seront négativement affectées par la perturbation de l'écosystème.

A portable transistor immunosensor for fast identification of porcine epidemic diarrhea virus.

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Infectious bronchitis virus: an overview of the "chicken coronavirus".

Infectious bronchitis virus (IBV) is a highly contagious avian Gammacoronavirus that affects mainly chickens (Gallus gallus) but can circulate in other avian species. IBV constitutes a significant threat to the poultry industry, causing reduced egg yield, growth and mortality levels that can vary in impact. The virus can be transmitted horizontally by inhalation or direct/indirect contact with infected birds or contaminated fomites, vehicles, farm personnel and litter (Figure 1). The error-prone viral polymerase and recombination mechanisms mean diverse viral population results, with multiple genotypes, serotypes, pathotypes and protectotypes. This significantly complicates control and mitigation strategies based on vigilance in biosecurity and the deployment of vaccination.

[Expert consensus on the clinical application of oral small-molecule antiviral drugs against COVID-19].

Although COVID-19 no longer constitutes a "public health emergency of international concern", which still has being spreading around the world at a low level. Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China. Although a variety of small-molecule antiviral drugs against COVID-19 have been listed in China, there is no specific drug recommendation for special populations. Society of Bacterial Infection and Resistance of Chinese Medical Association, together with the National Clinical Research Center for Respiratory Disease, and the National Center for Respiratory Medicine, organized domestic experts in various fields such as respiratory, virology, infection, critical care, emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small-Molecule Antiviral Drugs against COVID-19. The main content of this consensus includes the introduction of seven small-molecule antiviral drugs against COVID-19, focusing on the drug recommendations for 14 special groups such as the elderly, patients with complicated chronic diseases, tumor patients, pregnant women, and children, and providing suggestions for clinicians to standardize drug use.

A scoping review of ethics review processes during public health emergencies in Africa.

BACKGROUND: The COVID-19 pandemic forced governments, multilateral public health organisations and research institutions to undertake research quickly to inform their responses to the pandemic. Most COVID-19-related studies required swift approval, creating ethical and practical challenges for regulatory authorities and researchers. In this paper, we examine the landscape of ethics review processes in Africa during public health emergencies (PHEs). METHODS: We searched four electronic databases (Web of Science, PUBMED, MEDLINE Complete, and CINAHL) to identify articles describing ethics review processes during public health emergencies and/or pandemics. We selected and reviewed those articles that were focused on Africa. We charted the data from the retrieved articles including the authors and year of publication, title, country and disease(s) reference, broad areas of (ethical) consideration, paper type, and approach. RESULTS: Of an initial 4536 records retrieved, we screened the titles and abstracts of 1491 articles, and identified 72 articles for full review. Nine articles were selected for inclusion. Of these nine articles, five referenced West African countries including Liberia, Guinea and Sierra Leone, and experiences linked to the Ebola virus disease. Two articles focused on South Africa and Kenya, while the other two articles discussed more general experiences and pitfalls of ethics review during PHEs in Africa more broadly. We found no articles published on ethics review processes in Africa before the 2014 Ebola outbreak, and only a few before the COVID-19 outbreak. Although guidelines on protocol review and approval processes for PHEs were more frequently discussed after the 2014 Ebola outbreak, these did not focus on Africa specifically. CONCLUSIONS: There is a gap in the literature about ethics review processes and preparedness within Africa during PHEs. This paper underscores the importance of these processes to inform practices that facilitate timely, context-relevant research that adequately recognises and reinforces human dignity within the quest to advance scientific knowledge about diseases. This is important to improve fast responses to PHEs, reduce mortality and morbidity, and enhance the quality of care before, during, and after pandemics.

Genetic characterization of bovine coronavirus strain isolated in Inner Mongolia of China.

BACKGROUND: Bovine coronavirus (BCoV) is implicated in severe diarrhea in calves and contributes to the bovine respiratory disease complex; it shares a close relationship with human coronavirus. Similar to other coronaviruses, remarkable variability was found in the genome and biology of the BCoV. In 2022, samples of feces were collected from a cattle farm. A virus was isolated from 7-day-old newborn calves. In this study, we present the genetic characteristics of a new BCoV isolate. The complete genomic, spike protein, and nucleocapsid protein gene sequences of the BCoV strain, along with those of other coronaviruses, were obtained from the GenBank database. Genetic analysis was conducted using MEGA7.0 and the Neighbor-Joining (NJ) method. The reference strains' related genes were retrieved from GenBank for comparison and analysis using DNAMAN. RESULTS: The phylogenetic tree and whole genome consistency analysis showed that it belonged to the GIIb subgroup, which is epidemic in Asia and America, and was quite similar to the Chinese strains in the same cluster. Significantly, the S gene was highly consistent with QH1 (MH810151.1) isolated from yak. This suggests that the strain may have originated from interspecies transmission involving mutations of wild strains. The N gene was conserved and showed high sequence identity with the epidemic strains in China and the USA. CONCLUSIONS: Genetic characterization suggests that the isolated strain could be a new mutant from a wild-type lineage, which is in the same cluster as most Chinese epidemic strains but on a new branch.

SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure.

BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses. METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined. DISCUSSION: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov on 5/31/2023 (NCT05881135). TRIAL STATUS: Currently enrolling.

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal beta-coronavirus that emerged in 2012. The virus is part of the WHO blueprint priority list with a concerning fatality rate of 35%. Scientific efforts are ongoing for the development of vaccines, anti-viral and biotherapeutics, which are majorly directed toward the structural spike protein. However, the ongoing effort is challenging due to conformational instability of the spike protein and the evasion strategy posed by the MERS-CoV. In this study, we have expressed and purified the MERS-CoV pre-fusion spike protein in the Expi293F mammalian expression system. The purified protein was extensively characterized for its biochemical and biophysical properties. Thermal stability analysis showed a melting temperature of 58°C and the protein resisted major structural changes at elevated temperature as revealed by fluorescence spectroscopy and circular dichroism. Immunological assessment of the MERS-CoV spike immunogen in BALB/c mice with AddaVaxTM and Imject alum adjuvants showed elicitation of high titer antibody responses but a more balanced Th1/Th2 response with AddaVaxTM squalene like adjuvant. Together, our results suggest the formation of higher-order trimeric pre-fusion MERS-CoV spike proteins, which were able to induce robust immune responses. The comprehensive characterization of MERS-CoV spike protein warrants a better understanding of MERS spike protein and future vaccine development efforts.

COVID­19 detection from chest X-ray images using transfer learning.

COVID-19 is a kind of coronavirus that appeared in China in the Province of Wuhan in December 2019. The most significant influence of this virus is its very highly contagious characteristic which may lead to death. The standard diagnosis of COVID-19 is based on swabs from the throat and nose, their sensitivity is not high enough and so they are prone to errors. Early diagnosis of COVID-19 disease is important to provide the chance of quick isolation of the suspected cases and to decrease the opportunity of infection in healthy people. In this research, a framework for chest X-ray image classification tasks based on deep learning is proposed to help in early diagnosis of COVID-19. The proposed framework contains two phases which are the pre-processing phase and classification phase which uses pre-trained convolution neural network models based on transfer learning. In the pre-processing phase, different image enhancements have been applied to full and segmented X-ray images to improve the classification performance of the CNN models. Two CNN pre-trained models have been used for classification which are VGG19 and EfficientNetB0. From experimental results, the best model achieved a sensitivity of 0.96, specificity of 0.94, precision of 0.9412, F1 score of 0.9505 and accuracy of 0.95 using enhanced full X-ray images for binary classification of chest X-ray images into COVID-19 or normal with VGG19. The proposed framework is promising and achieved a classification accuracy of 0.935 for 4-class classification.