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1.
Front Cell Infect Microbiol ; 14: 1371916, 2024.
Article En | MEDLINE | ID: mdl-38716199

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.


Coronavirus Infections , Dietary Supplements , Lacticaseibacillus rhamnosus , Porcine epidemic diarrhea virus , Probiotics , Swine Diseases , Animals , Swine , Probiotics/administration & dosage , Swine Diseases/prevention & control , Coronavirus Infections/veterinary , Coronavirus Infections/therapy , Oxidative Stress , Intestines/pathology , Powders , Intestinal Mucosa/pathology
2.
Front Immunol ; 15: 1382655, 2024.
Article En | MEDLINE | ID: mdl-38803494

Introduction: Global microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis, with a growing body of concern surrounding the potential impacts on human health. Methods: Using a mouse model of mild COVID-19, we describe herein the effects of azide-free 1 µm polystyrene MP beads, co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum. The effect of MPs on the host response to SARS-CoV-2 infection was analysed using histopathology and RNA-Seq at 2 and 6 days post-infection (dpi). Results: Although infection reduced clearance of MPs from the lung, virus titres and viral RNA levels were not significantly affected by MPs, and overt MP-associated clinical or histopathological changes were not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 dpi and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the 'cytokine release syndrome' signature observed in some COVID-19 patients. Discussion: The findings are consistent with the recent finding that MPs can inhibit phagocytosis of apoptotic cells via binding of Tim4. They also add to a growing body of literature suggesting that MPs can dysregulate inflammatory processes in specific disease settings.


COVID-19 , Disease Models, Animal , Immunity, Innate , Lung , Microplastics , SARS-CoV-2 , Animals , COVID-19/immunology , COVID-19/virology , Immunity, Innate/drug effects , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Mice , Lung/immunology , Lung/virology , Lung/pathology , Cytokines/metabolism , Humans , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Female , Cytokine Release Syndrome/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Betacoronavirus/immunology , Pandemics
3.
Sci Data ; 11(1): 544, 2024 May 28.
Article En | MEDLINE | ID: mdl-38806489

To examine changes in individuals' psychosocial variables (e.g., psychological distress, social isolation, and alcohol use) during the prolonged COVID-19 pandemic, a two-year longitudinal survey was conducted at approximately one-year intervals between May 2020 and May 2022, after the first COVID-19-related state of emergency was announced in Japan. The online survey was conducted on May 11-12, 2020 (Phase 1), June 14-20, 2021 (Phase 2), and May 13-30, 2022 (Phase 3). The survey in Phase 1 was conducted during the first emergency declaration period, the survey in Phase 2 was conducted during the third emergency declaration period, and the survey in Phase 3 was conducted at a time when there was no state of emergency but many COVID-19 positive cases. Notably, 3,892 participants responded to all three surveys. In addition to psychosocial inventories often used worldwide, survey items included lifestyle and stress management indicators related to COVID-19 and various sociodemographic items including occupation (e.g., healthcare workers) or income, history of medical treatment for mental problems, severe physical illnesses, and COVID-19.


COVID-19 , Pandemics , SARS-CoV-2 , COVID-19/psychology , COVID-19/epidemiology , Humans , Japan/epidemiology , Longitudinal Studies , Surveys and Questionnaires , Stress, Psychological , Social Isolation/psychology , Alcohol Drinking/epidemiology , Psychological Distress , Male , Female , Betacoronavirus , Pneumonia, Viral/psychology , Pneumonia, Viral/epidemiology , Adult , Coronavirus Infections/psychology , Coronavirus Infections/epidemiology
4.
J Med Virol ; 96(6): e29712, 2024 Jun.
Article En | MEDLINE | ID: mdl-38808555

Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused severe intestinal diseases in pigs. It originates from bat coronaviruses HKU2 and has a potential risk of cross-species transmission, raising concerns about its zoonotic potential. Viral entry-related host factors are critical determinants of susceptibility to cells, tissues, or species, and remain to be elucidated for SADS-CoV. Type II transmembrane serine proteases (TTSPs) family is involved in many coronavirus infections and has trypsin-like catalytic activity. Here we examine all 18 members of the TTSPs family through CRISPR-based activation of endogenous protein expression in cells, and find that, in addition to TMPRSS2 and TMPRSS4, TMPRSS13 significantly facilitates SADS-CoV infection. This is confirmed by ectopic expression of TMPRSS13, and specific to trypsin-dependent SADS-CoV. Infection with pseudovirus bearing SADS-CoV spike protein indicates that TMPRSS13 acts at the entry step and is sensitive to serine protease inhibitor Camostat. Moreover, both human and pig TMPRSS13 are able to enhance the cell-cell membrane fusion and cleavage of spike protein. Overall, we demonstrate that TMPRSS13 is another host serine protease promoting the membrane-fusion entry of SADS-CoV, which may expand its host tropism by using diverse TTSPs.


Membrane Proteins , Serine Endopeptidases , Virus Internalization , Animals , Serine Endopeptidases/metabolism , Serine Endopeptidases/genetics , Swine , Humans , Membrane Proteins/metabolism , Membrane Proteins/genetics , Alphacoronavirus/genetics , Alphacoronavirus/physiology , Coronavirus Infections/virology , Coronavirus Infections/metabolism , Gabexate/analogs & derivatives , Gabexate/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/genetics , HEK293 Cells , Cell Line , Chlorocebus aethiops , Swine Diseases/virology , Esters , Guanidines
5.
Sao Paulo Med J ; 142(6): e2022608, 2024.
Article En | MEDLINE | ID: mdl-38808794

BACKGROUND: The cause of oropharyngeal dysphagia in patients with coronavirus disease (COVID-19) can be multifactorial and may underly limitations in swallowing rehabilitation. OBJECTIVE: Analyze the factors related to dysphagia in patients with COVID-19 immediately after orotracheal extubation and the factors that influence swallowing rehabilitation. DESIGN AND SETTING: A retrospective study. METHODS: The presence of dysphagia was evaluated using the American Speech-Language Hearing Association National Outcome Measurement System (ASHA NOMS) scale and variables that influenced swallowing rehabilitation in 140 adult patients who required invasive mechanical ventilation for >48 h. RESULTS: In total, 46.43% of the patients scored 1 or 2 on the ASHA NOMS (severe dysphagia) and 39.29% scored 4 (single consistency delivered orally) or 5 (exclusive oral diet with adaptations). Both the length of mechanical ventilation and the presence of neurological disorders were associated with lower ASHA NOMS scores (odds ratio [OR]: 0.80, 95% confidence interval [CI]: 0.74-0.87 P < 0.05; and OR: 0.13, 95% CI: 0.61-0.29; P < 0.05, respectively). Age and the presence of tracheostomy were negatively associated with speech rehabilitation (OR: 0.92; 95% CI: 0.87--0.96; OR: 0.24; 95% CI: 0.80--0.75), and acute post-COVID-19 kidney injury requiring dialysis and lower scores on the ASHA NOMS were associated with longer time for speech therapy outcomes (ß: 1.62, 95% CI, 0.70-3.17, P < 0.001; ß: -1.24, 95% CI: -1.55--0.92; P < 0.001). CONCLUSION: Prolonged orotracheal intubation and post-COVID-19 neurological alterations increase the probability of dysphagia immediately after extubation. Increased age and tracheostomy limited rehabilitation.


COVID-19 , Deglutition Disorders , Intubation, Intratracheal , Respiration, Artificial , SARS-CoV-2 , Humans , COVID-19/complications , Deglutition Disorders/etiology , Deglutition Disorders/rehabilitation , Retrospective Studies , Male , Female , Middle Aged , Aged , Airway Extubation/adverse effects , Adult , Pandemics , Coronavirus Infections/complications , Coronavirus Infections/rehabilitation , Pneumonia, Viral/complications , Pneumonia, Viral/rehabilitation , Betacoronavirus , Risk Factors , Aged, 80 and over
6.
Sci Transl Med ; 16(748): eadj4504, 2024 May 22.
Article En | MEDLINE | ID: mdl-38776389

Despite the wide availability of several safe and effective vaccines that prevent severe COVID-19, the persistent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that can evade vaccine-elicited immunity remains a global health concern. In addition, the emergence of SARS-CoV-2 VOCs that can evade therapeutic monoclonal antibodies underscores the need for additional, variant-resistant treatment strategies. Here, we characterize the antiviral activity of GS-5245, obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved viral RNA-dependent RNA polymerase (RdRp). We show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, SARS-CoV, SARS-CoV-related bat-CoV RsSHC014, Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant. Moreover, in mouse models of SARS-CoV, SARS-CoV-2 (WA/1 and Omicron B1.1.529), MERS-CoV, and bat-CoV RsSHC014 pathogenesis, we observed a dose-dependent reduction in viral replication, body weight loss, acute lung injury, and pulmonary function with GS-5245 therapy. Last, we demonstrate that a combination of GS-5245 and main protease (Mpro) inhibitor nirmatrelvir improved outcomes in vivo against SARS-CoV-2 compared with the single agents. Together, our data support the clinical evaluation of GS-5245 against coronaviruses that cause or have the potential to cause human disease.


Antiviral Agents , Prodrugs , SARS-CoV-2 , Animals , SARS-CoV-2/drug effects , Prodrugs/pharmacology , Prodrugs/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Mice , Administration, Oral , Chlorocebus aethiops , Vero Cells , COVID-19 Drug Treatment , COVID-19/virology , Virus Replication/drug effects , Nucleosides/pharmacology , Nucleosides/therapeutic use , Nucleosides/chemistry , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Disease Models, Animal
8.
Zhonghua Yi Xue Za Zhi ; 104(20): 1812-1824, 2024 May 28.
Article Zh | MEDLINE | ID: mdl-38782749

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.


Antiviral Agents , COVID-19 , Pandemics , SARS-CoV-2 , Antiviral Agents/therapeutic use , Humans , Pneumonia, Viral/drug therapy , COVID-19 Drug Treatment , Coronavirus Infections/drug therapy , Consensus , Betacoronavirus , Administration, Oral , China , Pregnancy
9.
Sci Rep ; 14(1): 11639, 2024 05 21.
Article En | MEDLINE | ID: mdl-38773161

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.


COVID-19 , Deep Learning , Neural Networks, Computer , SARS-CoV-2 , COVID-19/diagnostic imaging , COVID-19/virology , COVID-19/diagnosis , Humans , SARS-CoV-2/isolation & purification , Radiography, Thoracic/methods , Pandemics , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/virology , Pneumonia, Viral/diagnosis , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Betacoronavirus/isolation & purification , Sensitivity and Specificity , Tomography, X-Ray Computed/methods
10.
BMC Med Ethics ; 25(1): 63, 2024 May 22.
Article En | MEDLINE | ID: mdl-38778293

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.


COVID-19 , Emergencies , Pandemics , Public Health , SARS-CoV-2 , Humans , COVID-19/epidemiology , Public Health/ethics , Africa/epidemiology , Ethical Review , Betacoronavirus , Hemorrhagic Fever, Ebola/epidemiology , Coronavirus Infections/epidemiology , Ethics, Research
11.
Biol Pharm Bull ; 47(5): 930-940, 2024.
Article En | MEDLINE | ID: mdl-38692871

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.


Antiviral Agents , COVID-19 , Cholesterol , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Humans , COVID-19/virology , Cholesterol/metabolism , Vero Cells , Chlorocebus aethiops , Spike Glycoprotein, Coronavirus/metabolism , Animals , Virus Internalization/drug effects , Betacoronavirus/drug effects , Pandemics , COVID-19 Drug Treatment , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Angiotensin-Converting Enzyme 2/metabolism , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology
12.
ACS Nano ; 18(19): 12235-12260, 2024 May 14.
Article En | MEDLINE | ID: mdl-38696217

Variants of coronavirus porcine epidemic diarrhea virus (PEDV) frequently emerge, causing an incomplete match between the vaccine and variant strains, which affects vaccine efficacy. Designing vaccines with rapidly replaceable antigens and high efficacy is a promising strategy for the prevention of infection with PEDV variant strains. In our study, three different types of self-assembled nanoparticles (nps) targeting receptor-binding N-terminal domain (NTD) and C-terminal domain (CTD) of S1 protein, named NTDnps, CTDnps, and NTD/CTDnps, were constructed and evaluated as vaccine candidates against PEDV. NTDnps and CTDnps vaccines mediated significantly higher neutralizing antibody (NAb) titers than NTD and CTD recombinant proteins in mice. The NTD/CTDnps in varying ratios elicited significantly higher NAb titers when compared with NTDnps and CTDnps alone. The NTD/CTDnps (3:1) elicited NAb with titers up to 92.92% of those induced by the commercial vaccine. Piglets immunized with NTD/CTDnps (3:1) achieved a passive immune protection rate of 83.33% of that induced by the commercial vaccine. NTD/CTDnps (3:1) enhanced the capacity of mononuclear macrophages and dendritic cells to take up and present antigens by activating major histocompatibility complex I and II molecules to stimulate humoral and cellular immunity. These data reveal that a combination of S1-NTD and S1-CTD antigens targeting double receptor-binding domains strengthens the protective immunity of nanoparticle vaccines against PEDV. Our findings will provide a promising vaccine candidate against PEDV.


Nanoparticles , Porcine epidemic diarrhea virus , Viral Vaccines , Porcine epidemic diarrhea virus/immunology , Animals , Nanoparticles/chemistry , Swine , Mice , Viral Vaccines/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Mice, Inbred BALB C , Antigens, Viral/immunology , Antigens, Viral/chemistry , Antibodies, Neutralizing/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Protein Domains/immunology , Female , Nanovaccines
13.
Anal Chem ; 96(19): 7360-7366, 2024 May 14.
Article En | MEDLINE | ID: mdl-38697955

During the coronavirus disease 2019 (COVID-19) pandemic, which has witnessed over 772 million confirmed cases and over 6 million deaths globally, the outbreak of COVID-19 has emerged as a significant medical challenge affecting both affluent and impoverished nations. Therefore, there is an urgent need to explore the disease mechanism and to implement rapid detection methods. To address this, we employed the desorption separation ionization (DSI) device in conjunction with a mass spectrometer for the efficient detection and screening of COVID-19 urine samples. The study encompassed patients with COVID-19, healthy controls (HC), and patients with other types of pneumonia (OP) to evaluate their urine metabolomic profiles. Subsequently, we identified the differentially expressed metabolites in the COVID-19 patients and recognized amino acid metabolism as the predominant metabolic pathway involved. Furthermore, multiple established machine learning algorithms validated the exceptional performance of the metabolites in discriminating the COVID-19 group from healthy subjects, with an area under the curve of 0.932 in the blind test set. This study collectively suggests that the small-molecule metabolites detected from urine using the DSI device allow for rapid screening of COVID-19, taking just three minutes per sample. This approach has the potential to expand our understanding of the pathophysiological mechanisms of COVID-19 and offers a way to rapidly screen patients with COVID-19 through the utilization of machine learning algorithms.


COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnosis , COVID-19/urine , COVID-19/virology , SARS-CoV-2/isolation & purification , Pandemics , Male , Pneumonia, Viral/diagnosis , Pneumonia, Viral/urine , Pneumonia, Viral/virology , Middle Aged , Coronavirus Infections/diagnosis , Coronavirus Infections/urine , Female , Betacoronavirus/isolation & purification , Mass Spectrometry/methods , Adult , Metabolomics/methods , Aged , Machine Learning
14.
Vet Microbiol ; 293: 110101, 2024 Jun.
Article En | MEDLINE | ID: mdl-38718529

Cross-species transmission of coronaviruses has been continuously posing a major challenge to public health. Pigs, as the major animal reservoirs for many zoonotic viruses, frequently mediate viral transmission to humans. This study comprehensively mapped the relationship between human and porcine coronaviruses through in-depth bioinformatics analysis. We found that human coronavirus OC43 and porcine coronavirus PHEV share a close phylogenetic relationship, evidenced by high genomic homology, similar codon usage patterns and comparable tertiary structure in spike proteins. Inoculation of infectious OC43 viruses in organoids derived from porcine small and large intestine demonstrated that porcine intestinal organoids (pIOs) are highly susceptible to human coronavirus OC43 infection and support infectious virus production. Using transmission electron microscopy, we visualized OC43 viral particles in both intracellular and extracellular compartments, and observed abnormalities of multiple organelles in infected organoid cells. Robust OC43 infections in pIOs result in a significant reduction of organoids viability and widespread cell death. This study bears essential implications for better understanding the evolutionary origin of human coronavirus OC43, and provides a proof-of-concept for using pIOs as a model to investigate cross-species transmission of human coronavirus.


Computational Biology , Coronavirus Infections , Coronavirus OC43, Human , Intestines , Organoids , Phylogeny , Animals , Organoids/virology , Swine , Humans , Coronavirus Infections/virology , Coronavirus Infections/transmission , Coronavirus Infections/veterinary , Coronavirus OC43, Human/physiology , Coronavirus OC43, Human/genetics , Intestines/virology , Swine Diseases/virology , Swine Diseases/transmission , Genome, Viral
15.
Vet Microbiol ; 293: 110100, 2024 Jun.
Article En | MEDLINE | ID: mdl-38718527

Recent epidemiological studies have discovered that a lot of cases of porcine epidemic diarrhea virus (PEDV) infection are frequently accompanied by porcine kobuvirus (PKV) infection, suggesting a potential relationship between the two viruses in the development of diarrhea. To investigate the impact of PKV on PEDV pathogenicity and the number of intestinal lymphocytes, piglets were infected with PKV or PEDV or co-infected with both viruses. Our findings demonstrate that co-infected piglets exhibit more severe symptoms, acute gastroenteritis, and higher PEDV replication compared to those infected with PEDV alone. Notably, PKV alone does not cause significant intestinal damage but enhances PEDV's pathogenicity and alters the number of intestinal lymphocytes. These results underscore the complexity of viral interactions in swine diseases and highlight the need for comprehensive diagnostic and treatment strategies addressing co-infections.


Coinfection , Coronavirus Infections , Intestines , Kobuvirus , Lymphocytes , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Porcine epidemic diarrhea virus/pathogenicity , Porcine epidemic diarrhea virus/physiology , Swine , Swine Diseases/virology , Coinfection/virology , Coinfection/veterinary , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Lymphocytes/virology , Kobuvirus/pathogenicity , Kobuvirus/genetics , Intestines/virology , Diarrhea/virology , Diarrhea/veterinary , Virus Replication , Gastroenteritis/virology , Gastroenteritis/veterinary , Picornaviridae Infections/veterinary , Picornaviridae Infections/virology
16.
Front Cell Infect Microbiol ; 14: 1378804, 2024.
Article En | MEDLINE | ID: mdl-38736749

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.


Coronavirus Infections , Coronavirus NL63, Human , Epidemics , Genotype , Phylogeny , Respiratory Tract Infections , Humans , Coronavirus NL63, Human/genetics , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Coronavirus Infections/transmission , Child , Female , Male , Child, Preschool , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Infant , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Seasons , Mutation , Adolescent
17.
Front Cell Infect Microbiol ; 14: 1367975, 2024.
Article En | MEDLINE | ID: mdl-38736750

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.


Antibodies, Viral , Coronavirus Infections , Enzyme-Linked Immunosorbent Assay , Swine Diseases , Animals , China/epidemiology , Seroepidemiologic Studies , Swine , Enzyme-Linked Immunosorbent Assay/methods , Antibodies, Viral/blood , Swine Diseases/epidemiology , Swine Diseases/virology , Coronavirus Infections/veterinary , Coronavirus Infections/epidemiology , Coronavirus Infections/diagnosis , Immunoglobulin G/blood , Alphacoronavirus/immunology , Alphacoronavirus/genetics , Cross Reactions , Sensitivity and Specificity
18.
Neurosciences (Riyadh) ; 29(2): 133-138, 2024 May.
Article En | MEDLINE | ID: mdl-38740405

Bilateral femoral neuropathy is rare, especially that caused by bilateral compressive iliopsoas, psoas, or iliacus muscle hematomas. We present a case of bilateral femoral neuropathy due to spontaneous psoas hematomas developed during COVID-19 critical illness. A 41-year-old patient developed COVID-19 pneumonia, and his condition deteriorated rapidly. A decrease in the hemoglobin level prompted imaging studies during his intensive care unit (ICU) stay. Bilateral psoas hematomas were identified as the source of bleeding. Thereafter, the patient complained of weakness in both upper and lower limbs and numbness in the lower limb. He was considered to have critical illness neuropathy and was referred to rehabilitation. Electrodiagnostic testing suggested bilateral femoral neuropathy because of compression due to hematomas developed during the course of his ICU stay. The consequences of iliopsoas hematomas occurring in the critically ill can be catastrophic, ranging from hemorrhagic shock to severe weakness, highlighting the importance of recognizing this entity.


COVID-19 , Femoral Neuropathy , Hematoma , Psoas Muscles , SARS-CoV-2 , Humans , COVID-19/complications , Hematoma/diagnostic imaging , Hematoma/etiology , Hematoma/complications , Male , Adult , Femoral Neuropathy/etiology , Psoas Muscles/diagnostic imaging , Critical Illness , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Pandemics , Betacoronavirus
19.
Can J Rural Med ; 29(2): 71-79, 2024 Apr 01.
Article En, Fr | MEDLINE | ID: mdl-38709017

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.


COVID-19 , Leadership , Pandemics , Qualitative Research , Rural Health Services , SARS-CoV-2 , Humans , COVID-19/epidemiology , Canada , Rural Health Services/organization & administration , Pneumonia, Viral/epidemiology , Physicians, Family , Female , Coronavirus Infections/epidemiology , Betacoronavirus , Ecosystem , Male , Rural Population
20.
J Nanobiotechnology ; 22(1): 239, 2024 May 12.
Article En | MEDLINE | ID: mdl-38735951

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.


Biosensing Techniques , Nanotubes, Carbon , Porcine epidemic diarrhea virus , Porcine epidemic diarrhea virus/isolation & purification , Animals , Swine , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Nanotubes, Carbon/chemistry , Limit of Detection , Immunoassay/methods , Immunoassay/instrumentation , Antibodies, Monoclonal/immunology , Transistors, Electronic , Swine Diseases/diagnosis , Swine Diseases/virology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/analysis , Coronavirus Infections/diagnosis , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Antibodies, Viral/immunology , Equipment Design
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