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1.
arxiv; 2024.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2403.01513v1

ABSTRACT

Accurate segmentation of COVID-19 CT images is crucial for reducing the severity and mortality rates associated with COVID-19 infections. In response to blurred boundaries and high variability characteristic of lesion areas in COVID-19 CT images, we introduce CDSE-UNet: a novel UNet-based segmentation model that integrates Canny operator edge detection and a dual-path SENet feature fusion mechanism. This model enhances the standard UNet architecture by employing the Canny operator for edge detection in sample images, paralleling this with a similar network structure for semantic feature extraction. A key innovation is the Double SENet Feature Fusion Block, applied across corresponding network layers to effectively combine features from both image paths. Moreover, we have developed a Multiscale Convolution approach, replacing the standard Convolution in UNet, to adapt to the varied lesion sizes and shapes. This addition not only aids in accurately classifying lesion edge pixels but also significantly improves channel differentiation and expands the capacity of the model. Our evaluations on public datasets demonstrate CDSE-UNet's superior performance over other leading models, particularly in segmenting large and small lesion areas, accurately delineating lesion edges, and effectively suppressing noise


Subject(s)
COVID-19
2.
EMBO Rep ; 24(4): e55747, 2023 04 05.
Article in English | MEDLINE | ID: covidwho-2308515

ABSTRACT

Metabolic processes play a critical role in immune regulation. Metabolomics is the systematic analysis of small molecules (metabolites) in organisms or biological samples, providing an opportunity to comprehensively study interactions between metabolism and immunity in physiology and disease. Integrating metabolomics into systems immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. Here, we provide an overview on recent technological developments of metabolomic applications in immunological research. To begin, two widely used metabolomics approaches are compared: targeted and untargeted metabolomics. Then, we provide a comprehensive overview of the analysis workflow and the computational tools available, including sample preparation, raw spectra data preprocessing, data processing, statistical analysis, and interpretation. Third, we describe how to integrate metabolomics with other omics approaches in immunological studies using available tools. Finally, we discuss new developments in metabolomics and its prospects for immunology research. This review provides guidance to researchers using metabolomics and multiomics in immunity research, thus facilitating the application of systems immunology to disease research.


Subject(s)
Metabolomics , Multiomics , Research Design
3.
Antibiotics (Basel) ; 12(4)2023 Apr 16.
Article in English | MEDLINE | ID: covidwho-2298064

ABSTRACT

BACKGROUND: Antibiotic prescription practices in primary care in Singapore have received little scholarly attention. In this study, we ascertained prescription prevalence and identified care gaps and predisposing factors. METHODS: A retrospective study was conducted on adults (>21 years old) at six public primary care clinics in Singapore. Prescriptions >14 days were excluded. Descriptive statistics were used to showcase the prevalence data. We used chi-square and logistic regression analyses to identify the factors affecting care gaps. RESULTS: A total of 141,944 (4.33%) oral and 108,357 (3.31%) topical antibiotics were prescribed for 3,278,562 visits from 2018 to 2021. There was a significant reduction in prescriptions (p < 0.01) before and after the pandemic, which was attributed to the 84% reduction in prescriptions for respiratory conditions. In 2020 to 2021, oral antibiotics were most prescribed for skin (37.7%), genitourinary (20.2%), and respiratory conditions (10.8%). Antibiotic use in the "Access" group (WHO AWaRe classification) improved from 85.6% (2018) to 92.1% (2021). Areas of improvement included a lack of documentation of reasons for antibiotic use, as well as inappropriate antibiotic prescription for skin conditions. CONCLUSION: There was a marked reduction in antibiotic prescriptions associated with the onset of the COVID-19 pandemic. Further studies could address the gaps identified here and evaluate private-sector primary care to inform antibiotic guidelines and the local development of stewardship programs.

4.
ACS Sens ; 8(5): 1960-1970, 2023 05 26.
Article in English | MEDLINE | ID: covidwho-2306620

ABSTRACT

Rapid and accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the most effective measures to control the coronavirus disease 2019 (COVID-19) pandemic. However, there is still lack of an ideal detection platform capable of high sample throughput, portability, and multiplicity. Herein, by combining Hive-Chip (capillary microarray) and reverse transcriptional loop-mediated isothermal amplification (RT-LAMP), we developed an iPad-controlled, high-throughput (48 samples at one run), portable (smaller than a backpack), multiplex (monitoring 8 gene fragments in one reaction), and real-time detection platform for SARS-CoV-2 detection. This platform is composed of a portable Hive-Chip device (HiCube; 32.7 × 29.7 × 20 cm, 5 kg), custom-designed software, and optimized Hive-Chips. RT-LAMP primers targeting seven SARS-CoV-2 genes (S, E, M, N, ORF1ab, ORF3a, and ORF7a) and one positive control (human RNase P) were designed and prefixed in the Hive-Chip. On-chip RT-LAMP showed that the limit of detection (LOD) of SARS-CoV-2 synthetic RNAs is 1 copy/µL, and there is no cross-reaction among different target genes. The platform was validated by 100 clinical samples of SARS-CoV-2, and the results were highly consistent with those of the traditional real-time PCR assay. In addition, on-chip detection of 6 other respiratory pathogens showed no cross-reactivity. Overall, our platform has great potential for fast, accurate, and on-site detection of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19 Testing , Limit of Detection , RNA, Viral/genetics , RNA, Viral/analysis
5.
Antimicrobial Stewardship and Healthcare Epidemiology ; 3(S1):s24, 2023.
Article in English | ProQuest Central | ID: covidwho-2255005

ABSTRACT

Objectives: Over the past 2 years, many infection prevention and control (IPC) resources have been diverted to manage the COVID-19 pandemic. Its impact on the incidence of antimicrobial-resistant organisms has not been adequately studied. We investigated the impact of the pandemic on the incidence of carbapenem-resistant Enterobacterales (CRE) in Singapore. Methods: We extracted data on unique CRE isolates (clinical and/or surveillance cultures) and patient days for 6 public hospitals in Singapore from the carbapenemase-producing Enterobacteriaceae (CaPES) study group database, and we calculated the monthly incidence of CRE (per 10,000 patient days). Interrupted time-series (ITS) analysis was conducted with the pre–COVID-19 period defined as before February 2020, and the COVID-19 period defined as after February 2020. Statistical analyses were performed using Stata version 15 software. Results: From January 2017 to March 2021, 6,770 CRE isolates and 9,126,704 patient days were documented. The trend in CRE monthly incidence increased significantly during the pre–COVID-19 period (0.060;95% CI, 0.033–0.094;P < .001) but decreased during the COVID-19 period (−0.183;95% CI, −0.390 to 0.023;P = .080) without stepwise change in the incidence (−1.496;95% CI, −3.477 to 0.485;P = .135). The trend in monthly incidence rate of CRE clinical cultures increased significantly during the pre–COVID-19 period (0.046;95% CI, 0.028–0.064;P < .001) and decreased significantly during COVID-19 period (−0.148;95% CI, −0.249 to −0.048;P = .048) with no stepwise change in the incidence (−0.063;95% CI, −0.803 to 0.677;P = .864). The trend in monthly incidence rate of CRE surveillance cultures decreased during the pre–COVID-19 period (−0.020;95% CI, −0.062 to 0.022;P = .341) and the COVID-19 period (−0.067;95% CI, −0.291to 0.158;P = .552) without stepwise change in the incidence (−1.327;95% CI, −3.535 to 0.881;P = .233). Conclusions: The rate of CRE in clinical cultures decreased during COVID-19 but not the rate in surveillance cultures. Further studies are warranted to study the impact of COVID-19 on CREs.(DUPLICATE DELETED)

6.
Comput Struct Biotechnol J ; 19: 1694-1700, 2021.
Article in English | MEDLINE | ID: covidwho-2254505

ABSTRACT

BACKGROUND: To investigate and select the useful prognostic parameters to develop and validate a model to predict the mortality risk for severely and critically ill patients with the coronavirus disease 2019 (COVID-19). METHODS: We established a retrospective cohort of patients with laboratory-confirmed COVID-19 (≥18 years old) from two tertiary hospitals: the People's Hospital of Wuhan University and Leishenshan Hospital between February 16, 2020, and April 14, 2020. The diagnosis of the cases was confirmed according to the WHO interim guidance. The data of consecutive severely and critically ill patients with COVID-19 admitted to these hospitals were analyzed. A total of 566 patients from the People's Hospital of Wuhan University were included in the training cohort and 436 patients from Leishenshan Hospital were included in the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression were used to select the variables and build the mortality risk prediction model. RESULTS: The prediction model was presented as a nomograph and developed based on identified predictors, including age, chronic lung disease, C-reactive protein (CRP), D-dimer levels, neutrophil-to-lymphocyte ratio (NLR), creatinine, and total bilirubin. In the training cohort, the model displayed good discrimination with an AUC of 0.912 [95% confidence interval (CI): 0.884-0.940] and good calibration (intercept = 0; slope = 1). In the validation cohort, the model had an AUC of 0.922 [95% confidence interval (CI): 0.891-0.953] and a good calibration (intercept = 0.056; slope = 1.161). The decision curve analysis (DCA) demonstrated that the nomogram was clinically useful. CONCLUSION: A risk score for severely and critically ill COVID-19 patients' mortality was developed and externally validated. This model can help clinicians to identify individual patients at a high mortality risk.

7.
J Ginseng Res ; 47(2): 183-192, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2288719

ABSTRACT

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

8.
Anal Methods ; 15(15): 1915-1922, 2023 04 13.
Article in English | MEDLINE | ID: covidwho-2288598

ABSTRACT

RNA has been recognized as an important biomarker of many infectious pathogens; thus, sensitive, simple and rapid detection of RNA is urgently required for the control of epidemics. Herein, we report an ultrafast ligation-dependent RNA transcription amplification assay with high sensitivity and specificity for real-time detection of SARS-CoV-2 in real clinical samples, termed splint-based cascade transcription amplification (SCAN). Target RNA is first recognized by two DNA probes, which are then ligated together by SplintR, followed by the binding of the T7 promotor and T7 RNA polymerase to the ligated probe and the start of the transcription process. By introducing a vesicular stomatitis virus (VSV) terminator in the ligated probe, large amounts of RNA transcripts are rapidly produced within 10 min, which then directly hybridize with molecular beacons (MBs) and trigger the conformational switch of the MBs to generate a fluorescence signal that can be monitored in real time. The SCAN assay, which can be completed within 30-50 min, has a limit of detection of 104 copies per mL, while exhibiting high specificity to distinguish the target pathogen from those causing similar syndromes. More importantly, the results of SCAN for SARS-CoV-2 detection in clinical samples display great agreement with the most used qRT-PCR and qRT-LAMP, indicating great potential in the diagnosis of pathogens in clinical practice.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Molecular Diagnostic Techniques/methods , Sensitivity and Specificity , Real-Time Polymerase Chain Reaction , RNA
9.
Int J Mol Sci ; 24(4)2023 Feb 17.
Article in English | MEDLINE | ID: covidwho-2287597

ABSTRACT

Plastic pollution is a significant problem worldwide because of the risks it poses to the equilibrium and health of the environment as well as to human beings. Discarded plastic released into the environment can degrade into microplastics (MPs) due to various factors, such as sunlight, seawater flow, and temperature. MP surfaces can act as solid scaffolds for microorganisms, viruses, and various biomolecules (such as LPS, allergens, and antibiotics), depending on the MP characteristics of size/surface area, chemical composition, and surface charge. The immune system has efficient recognition and elimination mechanisms for pathogens, foreign agents, and anomalous molecules, including pattern recognition receptors and phagocytosis. However, associations with MPs can modify the physical, structural, and functional characteristics of microbes and biomolecules, thereby changing their interactions with the host immune system (in particular with innate immune cells) and, most likely, the features of the subsequent innate/inflammatory response. Thus, exploring differences in the immune response to microbial agents that have been modified by interactions with MPs is meaningful in terms of identifying new possible risks to human health posed by anomalous stimulation of immune reactivities.


Subject(s)
Microplastics , Water Pollutants, Chemical , Humans , Plastics , Seawater/chemistry , Host-Pathogen Interactions , Immunity , Water Pollutants, Chemical/analysis , Environmental Monitoring
10.
BMJ Open ; 13(3): e067879, 2023 03 30.
Article in English | MEDLINE | ID: covidwho-2268913

ABSTRACT

OBJECTIVE: This study aimed to investigate the effect of high-flow nasal cannula therapy (HFNC) versus conventional oxygen therapy (COT) on intubation rate, 28-day intensive care unit (ICU) mortality, 28-day ventilator-free days (VFDs) and ICU length of stay (ICU LOS) in adult patients with acute respiratory failure (ARF) associated with COVID-19. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Library and Embase up to June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Only randomised controlled trials or cohort studies comparing HFNC with COT in patients with COVID-19 were included up to June 2022. Studies conducted on children or pregnant women, and those not published in English were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the titles, abstracts and full texts. Relevant information was extracted and curated in the tables. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to assess the quality of randomised controlled trials or cohort studies. Meta-analysis was conducted using RevMan V.5.4 computer software using a random effects model with a 95% CI. Heterogeneity was assessed using Cochran's Q test (χ2) and Higgins I2 statistics, with subgroup analyses to account for sources of heterogeneity. RESULTS: Nine studies involving 3370 (1480 received HFNC) were included. HFNC reduced the intubation rate compared with COT (OR 0.44, 95% CI 0.28 to 0.71, p=0.0007), decreased 28-day ICU mortality (OR 0.54, 95% CI 0.30 to 0.97, p=0.04) and improved 28-day VFDs (mean difference (MD) 2.58, 95% CI 1.70 to 3.45, p<0.00001). However, HFNC had no effect on ICU LOS versus COT (MD 0.52, 95% CI -1.01 to 2.06, p=0.50). CONCLUSIONS: Our study indicates that HFNC may reduce intubation rate and 28-day ICU mortality, and improve 28-day VFDs in patients with ARF due to COVID-19 compared with COT. Large-scale randomised controlled trials are necessary to validate our findings. PROSPERO REGISTRATION NUMBER: CRD42022345713.


Subject(s)
COVID-19 , Noninvasive Ventilation , Respiratory Distress Syndrome , Respiratory Insufficiency , Pregnancy , Adult , Child , Humans , Female , Cannula , COVID-19/therapy , Oxygen , Oxygen Inhalation Therapy , Respiratory Distress Syndrome/therapy , Intubation, Intratracheal , Respiratory Insufficiency/therapy
11.
12.
J Psychosoc Nurs Ment Health Serv ; : 1-7, 2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-2268928

ABSTRACT

The current study aimed to investigate Chinese immigrants' sleep quality and associations between the coronavirus disease 2019 pandemic's impact and racism and sleep disruption using a cross-sectional online survey. A total of 507 Chinese immigrants were recruited via social network sites. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. The pandemic's impact and racism were measured using questions developed for this study. More than 42% of participants reported poor sleep quality. Those who reported having been affected by the pandemic had poorer subjective sleep quality, longer sleep latency, and greater daytime dysfunction. Those who experienced racist incidents were more likely to use sleep medication and exhibit poor subjective sleep quality, long sleep latency, short sleep duration, and daytime dysfunction. Chinese immigrants' sleep health warrants particular consideration by health care professionals. Timely, effective interventions, such as relaxation techniques and online psychoeducation, need to be delivered in the Chinese community. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].

13.
J Biophotonics ; : e202200277, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2252174

ABSTRACT

Infrared spectroscopy is a non-destructive and rapid characterization tool that can distinguish different viral proteins by spectral details. However, traditional infrared spectroscopy has insufficient absorption signal intensity contrast when measuring low-concentration samples. In this work, surface enhanced infrared absorption (SEIRA) spectroscopy is proposed by deploying a novel nanostructure array as SEIRA substrates. An array of gold dendric nanostructures are designed and fabricated with a precision resonance control to achieve surface enhancement covering a broadband molecular "finger-print" region. The spectral positions of the multiple resonances accurately correspond to the characteristic absorption peaks of the SARS-CoV-2 proteins. An approach for SARS-CoV-2 protein detection based on SEIRA spectroscopy is then proposed. A low concentration detection of 40 µg/ml diluted SARS-CoV-2 nucleocapsid protein is experimentally demonstrated and the enhancement factor (EF) achieved is in good agreement with simulation results. The SEIRA methodology based on broadband resonance nanostructure design provides a systematic approach for sensitive, non-destructive and rapid protein molecular detection, which could be extended to various kind of molecular characterization and biomedical diagnostics.

14.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2853386.v1

ABSTRACT

Background The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses SARS-CoV-2, SARS-CoV, and MARS-CoV have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. Results In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8), suggesting that the polymerase activity and stability of SARS-CoV-2 RdRp were affected by them to varying degrees. Furthermore, the entry efficacy of SARS-CoV-2 pseudovirus considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. In addition, NSP12 and its homologues from SARS-CoV and MARS-CoV suppressed thealternative splicing (AS) of cellular genes, which were influenced by the three splicing factors. Conclusions Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.


Subject(s)
Severe Acute Respiratory Syndrome
15.
Mol Biotechnol ; 2023 Feb 13.
Article in English | MEDLINE | ID: covidwho-2246707

ABSTRACT

In this study, Skullcapflavone I and Skullcapflavone II molecules showed good inhibitory activities against α-glucosidase and sorbitol dehydrogenase enzymes with IC50 values of 102.66 ± 8.43 and 95.04 ± 11.52 nM for α-glucosidase and 38.42 ± 3.82 and 28.81 ± 3.26 µM for sorbitol dehydrogenase. The chemical activities of Skullcapflavone I and Skullcapflavone II against α-glucosidase and sorbitol dehydrogenase were assessed by conducting the molecular docking study. The anticancer activities of the compounds were examined against SW-626, SK-OV-3, OVCAR3, and Caov-3 cell lines. The chemical activities of Skullcapflavone I and Skullcapflavone II against some of the expressed surface receptor proteins (estrogen receptor, EGFR, androgen receptor, and GnRH receptor) in the mentioned cell lines were investigated using in silico calculations. Moreover, the activity of the compounds against RNA polymerase of SARS-COVE-2 was also assessed using the molecular modeling study. These compounds created strong contacts with the enzymes and receptors. The considerable binding affinity of the compounds to the enzymes and proteins showed their ability as inhibitors. Furthermore, even at modest dosages, these substances markedly reduced the viability of ovarian cancer cells. Additionally, the viability of ovarian cancer cells was significantly decreased by a 300 µM dosage of all compounds. Antiovarian cancer results of Skullcapflavone I on SK-OV-3, SW-626, OVCAR3, and Caov-3 were 63.14, 1.55, 19.42, and 52.04 µM, respectively. Also, cytotoxicity results of Skullcapflavone II on SK-OV-3, SW-626, OVCAR3, and Caov-3 were 5.18, 21.44, 33.87, and 72.66 µM, respectively.

16.
Virus Genes ; 59(3): 479-483, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2241389

ABSTRACT

Highly pathogenic (HP) avian influenza A H7N9 virus has emerged in China since 2016. In recent years, it has been most prevalent in northern China. However, several strains of HP H7N9 reappeared in southwestern China (Yunnan Province) in 2021. As a result, we are wondering if these viruses have re-emerged in situ or been reintroduced. Here, we present phylogenetic evidence that the HP H7N9 viruses isolated in Yunnan emigrated from northern to southwestern China in 2020. The northern subregion of China has become a novel epicenter in HP H7N9 dissemination. Meanwhile, a cleavage motif re-emerged due to the T341I mutation, implying a parallel evolution. This cross-region transmission, which originated in non-adjacent provinces and traveled a great geographic distance in an unknown way, indicates that HP H7N9 dissemination did not halt in 2020, even under the shadow of the COVID-19 pandemic. Additional surveillance studies in poultry are required to determine the HP H7N9 virus's geographic distribution and spread.


Subject(s)
COVID-19 , Influenza A Virus, H7N9 Subtype , Influenza in Birds , Influenza, Human , Animals , Humans , Influenza A Virus, H7N9 Subtype/genetics , Phylogeny , Pandemics , China/epidemiology , COVID-19/epidemiology
17.
Microbiol Spectr ; : e0023123, 2023 Feb 13.
Article in English | MEDLINE | ID: covidwho-2240915

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, large differences in susceptibility and mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including Mycobacterium bovis BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10 to 12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon stimulation. The chromatin accessibility of genes important for adaptive immunity was higher in the Indians than in the Europeans, while the latter had more accessible chromatin regions in genes of the innate immune system. At the transcriptional level, we observed that the Indian volunteers displayed a more tolerant immune response to stimulation, in contrast to a more exaggerated response in the Europeans. BCG vaccination strengthened the tolerance program in the Indians but not in the Europeans. These differences may partly explain the different impact of COVID-19 on the two populations. IMPORTANCE In this study, we assessed the differences in immune responses in individuals from India and Europe. This aspect is of great relevance, because of the described differences in morbidity and mortality between India and Europe during the pandemic. We found a significant difference in chromatin accessibility in immune cells from the two populations, followed by a more balanced and effective response in individuals from India. These exciting findings represent a very important piece of the puzzle for understanding the COVID-19 pandemic at a global level.

18.
Cell ; 186(4): 850-863.e16, 2023 02 16.
Article in English | MEDLINE | ID: covidwho-2239711

ABSTRACT

It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.


Subject(s)
Coronavirus Infections , Coronavirus , Dipeptidyl Peptidase 4 , Pangolins , Animals , Humans , Mice , Chiroptera , Coronavirus Infections/veterinary , Coronavirus Infections/virology , Dipeptidyl Peptidase 4/genetics , Dipeptidyl Peptidase 4/metabolism , Endopeptidases/metabolism , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/metabolism , Peptide Hydrolases/metabolism , Receptors, Virus/metabolism , Virus Internalization , Coronavirus/physiology
19.
Emerg Microbes Infect ; : 1-30, 2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2246462

ABSTRACT

BACKGROUND: : It is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. METHODS: . This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. RESULTS: . A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1029, mild disease: 1858, pneumonia: 108, severe disease: 21) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. CONCLUSION: . The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.

20.
Proteomics ; : e2200306, 2022 Oct 07.
Article in English | MEDLINE | ID: covidwho-2242447

ABSTRACT

The majority of people in China have been immunized with the inactivated viral vaccine BBIBP-CorV. The emergence of the Omicron variant raised the concerns about protection efficacy of the inactivated viral vaccine in China. However, longitudinal neutralization data describing protection efficacy against Omicron variant is still lacking. Here we present one-year longitudinal neutralization data of BBIBP-CorV on authentic Omicron, Delta, and wild-type strains using 224 sera collected from 14 volunteers who have finished three doses BBIBP-CorV. The sera were also subjected for monitoring the SARS-CoV-2 specific IgG, IgA, and IgM responses on protein and peptide microarrays. The neutralization titers showed different protection efficacies against the three strains. By incorporating IgG and IgA signals of proteins and Spike protein derived peptide on microarray, panels as potential surrogate biomarkers for rapid estimation of neutralization titers were established. These data support the necessity of the 3rd dose of BBIBP-CorV vaccination. After further validation and assay development, the panels could be used for reliable, convenient and fast evaluation of the efficacy of vaccination.

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