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1.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3691844.v1

ABSTRACT

The escalation of antibiotic resistance, pandemics, and nosocomial infections underscores the importance of research in both animal and human infectious diseases. Recent advancements in three-dimensional tissue cultures, or "organoids," have revolutionized the development of in vitro models for infectious diseases. Our study conducts a bibliometric analysis on the use of organoids in modeling infectious diseases, offering an in-depth overview of this field's current landscape. We examined scientific contributions from 2009 onward that focused on organoids in host‒pathogen interactions using the Web of Science Core Collection. Our analysis included temporal trends, reference aging, author and institutional productivity, collaborative networks, citation metrics, and keyword cluster dynamics. VOSviewer and CiteSpace facilitated this analytical assessment. The findings reveal significant growth and advancements in organoid-based infectious disease research. Analysis of keywords and impactful publications identified three distinct developmental phases in this area that were significantly influenced by outbreaks of Zika virus and SARS-CoV-2. Hans Clevers and his team are prominent within the author and institutional collaboration networks. The research also highlights the synergistic efforts between academia and publishers in tackling global pandemic challenges. Organoids are proving to be a promising tool in infectious disease research. Their integration into the field necessitates methodological refinements for better physiological emulation and the establishment of extensive organoid biobanks. These improvements are crucial for fully harnessing the potential of organoids in understanding infectious diseases and advancing the development of targeted treatments and vaccines.


Subject(s)
Cross Infection , Communicable Diseases
2.
Vaccines (Basel) ; 11(5)2023 May 04.
Article in English | MEDLINE | ID: covidwho-20245130

ABSTRACT

Lipid nanoparticles (LNPs) are widely used as delivery systems for mRNA vaccines. The stability and bilayer fluidity of LNPs are determined by the properties and contents of the various lipids used in the formulation system, and the delivery efficiency of LNPs largely depends on the lipid composition. For the quality control of such vaccines, here we developed and validated an HPLC-CAD method to identify and determine the contents of four lipids in an LNP-encapsulated COVID-19 mRNA vaccine to support lipid analysis for the development of new drugs and vaccines.

3.
Medicine (Baltimore) ; 102(23): e33912, 2023 Jun 09.
Article in English | MEDLINE | ID: covidwho-20234985

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is considered a risk factor for severe COVID-19, but the mechanism remains unknown. This study used bioinformatics to help define the relationship between these diseases. The GSE147507 (COVID-19), GSE126848 (NAFLD), and GSE63067 (NAFLD-2) datasets were screened using the Gene Expression Omnibus. Common differentially expressed genes were then identified using a Venn diagram. Gene ontology analysis and KEGG pathway enrichment were performed on the differentially expressed genes. A protein-protein interaction network was also constructed using the STRING platform, and key genes were identified using the Cytoscape plugin. GES63067 was selected for validation of the results. Analysis of ferroptosis gene expression during the development of the 2 diseases and prediction of their upstream miRNAs and lncRNAs. In addition, transcription factors (TFs) and miRNAs related to key genes were identified. Effective drugs that act on target genes were found in the DSigDB. The GSE147507 and GSE126848 datasets were crossed to obtain 28 co-regulated genes, 22 gene ontology terms, 3 KEGG pathways, and 10 key genes. NAFLD may affect COVID-19 progression through immune function and inflammatory signaling pathways. CYBB was predicted to be a differential ferroptosis gene associated with 2 diseases, and the CYBB-hsa-miR-196a/b-5p-TUG1 regulatory axis was identified. TF-gene interactions and TF-miRNA coregulatory network were constructed successfully. A total of 10 drugs, (such as Eckol, sulfinpyrazone, and phenylbutazone) were considered as target drugs for Patients with COVID-19 and NAFLD. This study identified key gene and defined molecular mechanisms associated with the progression of COVID-19 and NAFLD. COVID-19 and NAFLD progression may regulate ferroptosis through the CYBB-hsa-miR-196a/b-5p-TUG1 axis. This study provides additional drug options for the treatment of COVID-19 combined with NAFLD disease.


Subject(s)
COVID-19 , MicroRNAs , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Systems Biology , Gene Expression Profiling/methods , COVID-19/genetics , MicroRNAs/genetics , Computational Biology/methods , Gene Regulatory Networks
4.
Mol Genet Genomics ; 298(4): 823-836, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2297231

ABSTRACT

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.


Subject(s)
COVID-19 , Cell-Free Nucleic Acids , Humans , COVID-19/diagnosis , Cell-Free Nucleic Acids/genetics
5.
Ann Hematol ; 102(6): 1589-1598, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2293303

ABSTRACT

COVID-19 is characterized by a predominantly prothrombotic state, which underlies severe disease and poor outcomes. Imbalances of the gut microbiome have been linked with abnormal hemostatic processes. Understanding the relationship between the gut microbiome and abnormal coagulation parameters in COVID-19 could provide a novel framework for the diagnosis and management of COVID-related coagulopathies (CRC). This cross-sectional study used shotgun metagenomic sequencing to examine the gut microbiota of patients with CRC (n = 66) and compared it to COVID control (CCs) (n = 27) and non-COVID control (NCs) (n = 22) groups. Three, 1, and 3 taxa were found enriched in CRCs, CCs, and NCs. Next, random forest models using 7 microbial biomarkers and differential clinical characteristics were constructed and achieved strong diagnostic potential in distinguishing CRC. Specifically, the most promising biomarker species for CRC were Streptococcus thermophilus, Enterococcus faecium, and Citrobacter portucalensis. Conversely, Enterobacteriaceae family and Fusicatenibacter genus are potentially protective against CRC in COVID patients. We further identified 4 species contributing to 20 MetaCyc pathways that were differentially abundant among groups, with S. thermophilus as the main coding species in CRCs. Our findings suggest that the alterations of gut microbiota compositional and functional profiles may influence the pathogenesis of CRC and that microbiota-based diagnosis and treatment could potentially benefit COVID patients in preventing and alleviating thrombosis-related clinical outcomes.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Gastrointestinal Microbiome , Microbiota , Humans , Cross-Sectional Studies , COVID-19/complications , Blood Coagulation Disorders/etiology
6.
Int J Rheum Dis ; 26(5): 957-959, 2023 May.
Article in English | MEDLINE | ID: covidwho-2293286

ABSTRACT

BACKGROUND: In the first half 2022, SARS-CoV-2 variant omicron rapidly spread in Shanghai. CASE PRESENTATION: A 74-year-old woman, diagnosed as having rheumatoid arthritis for almost 30 years and treated with prednisone and cyclophosphamide, went through nasopharyngeal swab RNA test for SARS-CoV-2 for routine screening and was positive. She was then sent to the designated hospital. After negative RNA test, the patient returned to the former hospital for the treatment of basic disease. Unfortunately, the RNA test of this patient became positive again. And in this period, the clinical manifestations and computed tomography scans were more progressive. Finally, the patient passed away. CONCLUSION: There is a long way to go for us to study expression characteristics of SARS-CoV-2.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Female , Humans , Aged , SARS-CoV-2 , RNA, Viral , China
7.
Front Public Health ; 10: 978237, 2022.
Article in English | MEDLINE | ID: covidwho-2285969

ABSTRACT

Objective: This study aimed to analyze the association between the activity of daily living (ADL), coronavirus disease (COVID-19), and the value of the Barthel Index in predicting the prognosis of patients. Methods: This study included 398 patients with COVID-19, whose ADL at admission to hospital were assessed with the Barthel Index. The relationship between the index and the mortality risk of the patients was analyzed. Several regression models and a decision tree were established to evaluate the prognostic value of the index in COVID-19 patients. Results: The Barthel Index scores of deceased patients were significantly lower than that of discharged patients (median: 65 vs. 90, P < 0.001), and its decrease indicated an increased risk of mortality in patients (P < 0.001). After adjusting models for age, gender, temperature, pulse, respiratory rate, mean arterial pressure, oxygen saturation, etc., the Barthel Index could still independently predict prognosis (OR = 0.809; 95% CI: 0.750-0.872). The decision tree showed that patients with a Barthel Index of below 70 had a higher mortality rate (33.3-40.0%), while those above 90 were usually discharged (mortality: 2.7-7.2%). Conclusion: The Barthel Index is of prognostic value for mortality in COVID-19 patients. According to their Barthel Index, COVID-19 patients can be divided into emergency, observation, and normal groups (0-70; 70-90; 90-100), with different treatment strategies.


Subject(s)
COVID-19 , Humans , Prognosis , Cross-Sectional Studies , Activities of Daily Living , Hospitalization
8.
Frontiers in public health ; 10, 2022.
Article in English | EuropePMC | ID: covidwho-2236779

ABSTRACT

Objective This study aimed to analyze the association between the activity of daily living (ADL), coronavirus disease (COVID-19), and the value of the Barthel Index in predicting the prognosis of patients. Methods This study included 398 patients with COVID-19, whose ADL at admission to hospital were assessed with the Barthel Index. The relationship between the index and the mortality risk of the patients was analyzed. Several regression models and a decision tree were established to evaluate the prognostic value of the index in COVID-19 patients. Results The Barthel Index scores of deceased patients were significantly lower than that of discharged patients (median: 65 vs. 90, P < 0.001), and its decrease indicated an increased risk of mortality in patients (P < 0.001). After adjusting models for age, gender, temperature, pulse, respiratory rate, mean arterial pressure, oxygen saturation, etc., the Barthel Index could still independently predict prognosis (OR = 0.809;95% CI: 0.750–0.872). The decision tree showed that patients with a Barthel Index of below 70 had a higher mortality rate (33.3–40.0%), while those above 90 were usually discharged (mortality: 2.7–7.2%). Conclusion The Barthel Index is of prognostic value for mortality in COVID-19 patients. According to their Barthel Index, COVID-19 patients can be divided into emergency, observation, and normal groups (0–70;70–90;90–100), with different treatment strategies.

9.
J Med Virol ; 2022 Sep 02.
Article in English | MEDLINE | ID: covidwho-2236823

ABSTRACT

Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from humans to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, to evaluate the impact of S mutations, we tested 27 pseudoviruses of SARS-CoV-2 carrying different spike mutants by infecting Hela cells expressing different angiotensin-converting enzyme 2 (ACE2) orthologs from 20 animals. Of these 27 pseudoviruses, 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429), and Mu (B.1.621). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammal ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations.

10.
Health Commun ; : 1-15, 2022 Dec 28.
Article in English | MEDLINE | ID: covidwho-2187257

ABSTRACT

Public health messages disseminated by trusted government authorities are likely to have more influence over individuals' intentions and behaviors. However, individuals worldwide have different levels of trust in government authorities, which leads to varying levels of compliance intentions. Additionally, these trust levels may vary during major public crises, such as pandemics. Based on a COVID-19 pandemic communication survey (N = 3,065) disseminated throughout six countries (Australia, Finland, Italy, South Korea, Sweden, and the United States), this study examined the association among trust in distinct government sources, cultural orientations, and health behavioral intentions. Findings indicated that trust in official health communication sources at four governmental levels (i.e. national government, the head of the national government, the national health authority, and the chief representative of the national health authority) was related to vaccination intentions and other behavioral compliance intentions (i.e. willingness to prevent COVID-19 infection in other ways). Meanwhile, these direct associations were mediated by the cultural orientations of power distance and uncertainty avoidance. Findings also revealed that the direct association of trust in government sources and the indirect relationship through the above cultural orientations varied by country. This study offers insight into the important role of credible sources and individuals' cultural orientations in the domain of health communication aimed at influencing behavioral intentions.

11.
ACS Appl Mater Interfaces ; 15(1): 354-363, 2023 Jan 11.
Article in English | MEDLINE | ID: covidwho-2185494

ABSTRACT

Supramolecules have been drawing increasing attention recently in addressing healthcare challenges caused by infectious pathogens. We herein report a novel class of guanidinium-perfunctionalized polyhedral oligomeric silsesquioxane (Gua-POSS) supramolecules with highly potent antimicrobial activities. The modular structure of Gua-POSS Tm-Cn consists of an inorganic T10 or T8 core (m = 10 or 8), flexible linear linkers of varying lengths (n = 1 or 3), and peripherally aligned cationic guanidinium groups as the membrane-binding units. Such Gua-POSS supramolecules with spherically arrayed guanidinium cations display high antimicrobial potency against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, as well as fungus (Candida albicans), with the best showing excellently low minimal inhibitory concentrations (MICs) of 1.7-6.8 µM in media, yet with negligible hemolytic activity and low in vitro cytotoxicity to mammalian cells. More significantly, they can inhibit biofilm formation at around their MICs and near-completely break down preestablished difficult-to-break biofilms at 250 µg mL-1 (∼50 µM). Their strong antiviral efficacy was also experimentally demonstrated against the enveloped murine hepatitis coronavirus as a surrogate of the SARS-CoV species. Overall, this study provides a new design approach to novel classes of sphere-shaped organic-inorganic hybrid supramolecular materials, especially for potent antimicrobial, anti-biofilm, and antiviral applications.


Subject(s)
Anti-Infective Agents , Coronavirus , Mice , Animals , Guanidine/pharmacology , Plankton , Anti-Infective Agents/pharmacology , Biofilms , Antiviral Agents/pharmacology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Mammals
13.
Ann Transl Med ; 10(21): 1154, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2124167

ABSTRACT

Background: The number of Chinese clinical trials has continued to grow throughout the coronavirus disease 2019 (COVID-19) pandemic, but we know little about clinical trial team members' perceptions and attitudes toward the impacts of the pandemic. This study aimed to assess the impact of the COVID-19 pandemic on clinical trials in China from the perspective of research staff to provide a deeper understanding and some recommendations for the ongoing and upcoming clinical trials during the pandemic. Methods: A nationwide cross-sectional questionnaire was distributed to respondents throughout mainland China between September 2021 and October 2021. The participants assessed the impact of the COVID-19 pandemic on clinical trials based on a 5-point Likert-type scale, and exploratory factor analysis (EFA) was used to confirm the factor structure. Descriptive statistical analysis and the Mann-Whitney test were used to discover the differences between different groups. Results: A total of 2,393 questionnaires from 272 hospitals were collected in mainland China. Factor analysis resulted in 4 factors, with a cumulative explained variance of 64.93%, as follows: subject enrollment, patient care, study supplies and data management, and research milestones and quality management. The research team members, predominantly represented by clinical research coordinators (CRCs), basically agreed with all but 3 preset scenarios of the impact of COVID-19 on clinical trials. Most respondents did not agree that the pandemic was associated with more serious adverse events (SAEs), missed reports of safety events, or any increase of unscheduled unblinding. In addition, significant differences were revealed in different age, gender, and role groups of respondents based on their views on the impact of the pandemic. Conclusions: The current pandemic situation has had a negative impact on clinical trials, especially in terms of subject recruitment and protocol compliance, yet research team members feel confident that some of the effective measures proposed in the study can moderate the negative impact.

14.
World J Clin Cases ; 10(31): 11411-11418, 2022 Nov 06.
Article in English | MEDLINE | ID: covidwho-2119549

ABSTRACT

BACKGROUND: The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced a global pandemic of coronavirus disease 2019 (COVID-19), resulting in modifications to public health policies on a universal scale. SARS-CoV-2 vaccine has evolved as the most effective and secure way for protecting healthy individuals against COVID-19. Patients with cancer were excluded from clinical trials due to their increased COVID-19 risk and current immunosuppressing therapy. Safety and effectiveness evidence is insufficient for SARS-CoV-2 vaccination in cancer patients. AIM: To assess the efficacy and safety of two-dose SARS-CoV-2 vaccines in cancer patients. METHODS: A multicenter observational study was performed at ten Chinese hospitals between January 1, 2021 and December 31, 2021. Each participant in the research received two doses of vaccination. A total of 215 healthy people were screened and 132 eligible patients with cancer were recruited. In order to verify the safety of the second dose of the vaccine, a side-effect report was compiled. Two weeks following the second vaccination dose, subjects underwent an analogous questionnaire survey. Utilizing a magnetic particle-based chemiluminescence immunoassay, serum levels of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were measured to determine the effectiveness of vaccination. IgG levels ≥ 10 AU/mL were considered seropositive. RESULTS: All the 347 eligible patients completed the follow-up, and anti-SARS-CoV-2 IgG antibodies were detected. Local pain at the injection location was the most common side effect mentioned by all responders, with an increased incidence in cancer patients than the healthy people after the second dose vaccine (17.2% vs 9.1%; P = 0.035). There was no significant difference in headache, urticaria, or other adverse reactions between patients with cancer and healthy people. In the group of cancer patients, the seropositivity incidence was 83.3%, while it was 96.3% in the group of healthy people. In the group of cancer patients, the seropositivity incidence and antibody levels were significantly lower (P < 0.001). This analysis showed a poorer response rate in patients on active immunosuppressive treatment and elderly cancer patients. CONCLUSION: Two-dose Chinese vaccines are effective and safe in cancer patients. However, further research is required on the efficacy in elderly cancer patients and those on active immunosuppressive treatment.

15.
Epidemiol Infect ; 150: e131, 2022 06 21.
Article in English | MEDLINE | ID: covidwho-2000836

ABSTRACT

Severe fever with thrombocytopenia syndrome (SFTS) virus has caused a large number of human infections since discovered in 2009. This study elucidated epidemiological features and fatal risk factors of SFTS cases accumulated up to ten years in Taizhou, a coastal prefecture of Zhejiang Province in Eastern China. A total of 188 hospitalised SFTS cases (including 40 deaths) reported to Taizhou Center for Disease Control and Prevention (CDC) during 2011-2020 were enrolled in the study. In the past decade, the annual incidence of SFTS increased over the years (P < 0.001) along with an expanding epidemic area, and the case fatality of hospitalised cases has remained high (21.3%). Although most cases occurred in hilly areas, a coastal island had the highest incidence and case fatality. The majority of cases were over the age of 60 years (72.3%), and both incidence and case fatality of SFTS increased with age. Multivariate logistic regression analysis showed that age (OR 7.47, 95% CI 1.32-42.33; P = 0.023), and haemorrhagic manifestations including petechiae (OR 7.76, 95% CI 1.17-51.50; P = 0.034), gingival haemorrhage (OR 5.38, 95% CI 1.25-23.15; P = 0.024) and melena (OR 5.75, 95% CI 1.18-28.07; P = 0.031) were significantly associated with the death of SFTS cases. Five family clusters identified were farmers, among four of which the index patients were female with a history of hypertension. Based on the study, age is a critical risk factor for incidence and case fatality of SFTS. With an increased annual incidence over the last ten years, SFTS remains a public health threat that should not be ignored. Further study is needed to look at the natural foci in the coastal islands.


Subject(s)
Bunyaviridae Infections , Phlebovirus , Severe Fever with Thrombocytopenia Syndrome , Thrombocytopenia , China/epidemiology , Female , Fever/epidemiology , Humans , Male , Middle Aged , Risk Factors , Thrombocytopenia/epidemiology
16.
Front Cell Infect Microbiol ; 12: 888582, 2022.
Article in English | MEDLINE | ID: covidwho-1963405

ABSTRACT

Host genetic factors have been shown to play an important role in SARS-CoV-2 infection and the course of Covid-19 disease. The genetic contributions of common variants influencing Covid-19 susceptibility and severity have been extensively studied in diverse populations. However, the studies of rare genetic defects arising from inborn errors of immunity (IEI) are relatively few, especially in the Chinese population. To fill this gap, we used a deeply sequenced dataset of nearly 500 patients, all of Chinese descent, to investigate putative functional rare variants. Specifically, we annotated rare variants in our call set and selected likely deleterious missense (LDM) and high-confidence predicted loss-of-function (HC-pLoF) variants. Further, we analyzed LDM and HC-pLoF variants between non-severe and severe Covid-19 patients by (a) performing gene- and pathway-level association analyses, (b) testing the number of mutations in previously reported genes mapped from LDM and HC-pLoF variants, and (c) uncovering candidate genes via protein-protein interaction (PPI) network analysis of Covid-19-related genes and genes defined from LDM and HC-pLoF variants. From our analyses, we found that (a) pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164) showed significant enrichment in severe patients compared to the non-severe ones, (b) HC-pLoF mutations were enriched in Covid-19-related genes in severe patients, and (c) several candidate genes, such as IL12RB1, TBK1, TLR3, and IFNGR2, are uncovered by PPI network analysis and worth further investigation. These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that our identified candidate genes/pathways can be potentially used as Covid-19 diagnostic markers and help distinguish patients at higher risk.


Subject(s)
COVID-19 , Alleles , Asian People , COVID-19/genetics , Genetic Predisposition to Disease , Humans , SARS-CoV-2/genetics
18.
PLoS Pathog ; 18(6): e1010620, 2022 06.
Article in English | MEDLINE | ID: covidwho-1892334

ABSTRACT

Intestinal microbial metabolites have been increasingly recognized as important regulators of enteric viral infection. However, very little information is available about which specific microbiota-derived metabolites are crucial for swine enteric coronavirus (SECoV) infection in vivo. Using swine acute diarrhea syndrome (SADS)-CoV as a model, we were able to identify a greatly altered bile acid (BA) profile in the small intestine of infected piglets by untargeted metabolomic analysis. Using a newly established ex vivo model-the stem cell-derived porcine intestinal enteroid (PIE) culture-we demonstrated that certain BAs, cholic acid (CA) in particular, enhance SADS-CoV replication by acting on PIEs at the early phase of infection. We ruled out the possibility that CA exerts an augmenting effect on viral replication through classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling, innate immune suppression or viral attachment. BA induced multiple cellular responses including rapid changes in caveolae-mediated endocytosis, endosomal acidification and dynamics of the endosomal/lysosomal system that are critical for SADS-CoV replication. Thus, our findings shed light on how SECoVs exploit microbiome-derived metabolite BAs to swiftly establish viral infection and accelerate replication within the intestinal microenvironment.


Subject(s)
Alphacoronavirus , Coronavirus Infections , Swine Diseases , Alphacoronavirus/physiology , Animals , Bile Acids and Salts , Caveolae , Diarrhea , Swine
19.
Frontiers in cellular and infection microbiology ; 12, 2022.
Article in English | EuropePMC | ID: covidwho-1887967

ABSTRACT

Host genetic factors have been shown to play an important role in SARS-CoV-2 infection and the course of Covid-19 disease. The genetic contributions of common variants influencing Covid-19 susceptibility and severity have been extensively studied in diverse populations. However, the studies of rare genetic defects arising from inborn errors of immunity (IEI) are relatively few, especially in the Chinese population. To fill this gap, we used a deeply sequenced dataset of nearly 500 patients, all of Chinese descent, to investigate putative functional rare variants. Specifically, we annotated rare variants in our call set and selected likely deleterious missense (LDM) and high-confidence predicted loss-of-function (HC-pLoF) variants. Further, we analyzed LDM and HC-pLoF variants between non-severe and severe Covid-19 patients by (a) performing gene- and pathway-level association analyses, (b) testing the number of mutations in previously reported genes mapped from LDM and HC-pLoF variants, and (c) uncovering candidate genes via protein-protein interaction (PPI) network analysis of Covid-19-related genes and genes defined from LDM and HC-pLoF variants. From our analyses, we found that (a) pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164) showed significant enrichment in severe patients compared to the non-severe ones, (b) HC-pLoF mutations were enriched in Covid-19-related genes in severe patients, and (c) several candidate genes, such as IL12RB1, TBK1, TLR3, and IFNGR2, are uncovered by PPI network analysis and worth further investigation. These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that our identified candidate genes/pathways can be potentially used as Covid-19 diagnostic markers and help distinguish patients at higher risk.

20.
Front Nutr ; 9: 853565, 2022.
Article in English | MEDLINE | ID: covidwho-1817991

ABSTRACT

Background: Between January and April 2020, China implemented differentiated prevention and control strategies across the country, based on the severity of the COVID-19 epidemic/pandemic in different regions. These strategies included lockdowns, social distancing, and the closure of public places. These measures may have affected dietary intake to varying degrees. This study aimed to assess variations in food intake and diet quality among pregnant women according to regional severity and related control measures during the most severe period of COVID-19 restrictions in 2020. Methods: A total of 3,678 pregnant women from 19 provinces/municipalities in mainland China were analyzed in this nationwide, multi-center study. Food intake data were obtained and assessed using a validated food frequency questionnaire (FFQ). Diet quality was quantified using the Diet Balance Index for Pregnancy (DBI-P), which included high bound score (HBS, excessive dietary intake), low bound score (LBS, insufficient dietary intake), and diet quality distance (DQD, dietary imbalance). Linear trend tests and multivariable regression analyses were performed to examine the association between food intake, DBI-P and the severity of pandemic. Results: The median daily intake of vegetables, fruit, livestock/poultry meat, dairy, and nuts decreased (p < 0.05) according to low, moderate, and high severity of the pandemic, while no significant differences in cereals/potatoes, eggs, and fish/shrimp intake. The median daily intake of cereals/potatoes exceeded the recommended ranges, and the daily intake of eggs and fish/shrimp was below recommended ranges regardless of the pandemic severity (p < 0.05). Regarding diet quality, HBS decreased (lower excessive consumption) (p = 0.047) and LBS increased (greater insufficient consumption) (p = 0.046) with increased severity of the pandemic. On multivariable analyses, moderate and high pandemic severity were related to lower HBS risk (OR = 0.687, OR = 0.537) and higher LBS risk (ß = 1.517, ß = 3.020) when compared to low pandemic severity. Conclusions: Under more severe COVID-19 pandemic conditions, pregnant women consumed less quality food, characterized by reduced consumption of vegetables, fruit, livestock/poultry meat, dairy and nuts, while the quality of the foods that pregnant women consumed in excess tended to improve, but the overconsumption of cereals/potatoes was a problem.

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