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1.
Pharmaceuticals (Basel) ; 16(5)2023 May 19.
Article in English | MEDLINE | ID: covidwho-20234038

ABSTRACT

Drugs that cure COVID-19 have been marketed; however, this disease continues to ravage the world without becoming extinct, and thus, drug discoveries are still relevant. Since Mpro has known advantages as a drug target, such as the conserved nature of the active site and the absence of homologous proteins in the body, it receives the attention of many researchers. Meanwhile, the role of traditional Chinese medicine (TCM) in the control of epidemics in China has also led to a focus on natural products, with the hope of finding some promising lead molecules through screening. In this study, we selected a commercial library of 2526 natural products from plants, animals and microorganisms with known biological activity for drug discovery, which had previously been reported for compound screening of the SARS CoV-2 S protein, but had not been tested on Mpro. This library contains compounds from a variety of Chinese herbs, including Lonicerae Japonicae Flos, Forsythiae Fructus and Scutellariae Radix, which are derived from traditional Chinese medicine prescriptions that have been shown to be effective against COVID-19. We used the conventional FRET method for the initial screening. After two rounds of selection, the remaining 86 compounds were divided into flavonoids, lipids, phenylpropanoids, phenols, quinones, alkaloids, terpenoids and steroids according to the skeleton structures, with inhibition rates greater than 70%. The top compounds in each group were selected to test the effective concentration ranges; the IC50 values were as follows: (-)-gallocatechin gallate (1.522 ± 0.126 µM), ginkgolic acid C15:1 (9.352 ± 0.531 µM), hematoxylin (1.025 ± 0.042 µM), fraxetin (2.486 ± 0.178 µM), wedelolactone (1.003 ± 0.238 µM), hydroxytyrosol acetate (3.850 ± 0.576 µM), vanitiolide (2.837 ± 0.225 µM), ß,ß-dimethylacrylalkannin (2.731 ± 0.308 µM), melanin (7.373 ± 0.368 µM) and cholesteryl sodium sulfate (2.741 ± 0.234µM). In the next step, we employed two biophysical techniques, SPR and nanoDSF, to obtain KD/Kobs values: hematoxylin (0.7 µM), (-)-gallocatechin gallate (126 µM), ginkgolic acid C15:1 (227 µM), wedelolactone (0.9770 µM), ß,ß-dimethylacrylalkannin (1.9004 µM,), cholesteryl sodium sulfate (7.5950 µM) and melanin (11.5667 µM), which allowed better assessments of the binding levels. Here, seven compounds were the winners. Then, molecular docking experiments were specially performed by AutoDock Vina to analyze the mode of interactions within Mpro and ligands. We finally formulated the present in silico study to predict pharmacokinetic parameters as well as drug-like properties, which is presumably the step that tells humans whether the compounds are drug-like or not. Moreover, hematoxylin, melanin, wedelolactone, ß,ß-dimethylacrylalkannin and cholesteryl sodium sulfate are in full compliance with the "Lipinski" principle and possess reasonable ADME/T properties, they have a greater potential of being lead compounds. The proposed five compounds are also the first to be found to have potential inhibitory effects on SARS CoV-2 Mpro. We hope that the results in this manuscript may serve as benchmarks for the above potentials.

2.
Vaccine ; 41(22): 3461-3466, 2023 05 22.
Article in English | MEDLINE | ID: covidwho-2316953

ABSTRACT

PREVENT-19, the pivotal phase 3 trial of the Novavax adjuvanted, recombinant spike protein COVID-19 vaccine (NVX-CoV2373), demonstrated that the vaccine was well tolerated and efficacious (vaccine efficacy, VE = 90%) for the prevention of symptomatic COVID-19. In the trial, participants were randomly assigned in a 2:1 ratio to receive 2 doses of NVX-CoV2373 or placebo 21 days apart. Throughout the study, the predominant SARS-CoV-2 variant was alpha, but additional variants were in circulation (i.e., beta, gamma, epsilon, and iota). VE among the per-protocol efficacy analysis population was calculated according to pre-specified disease severity (mild, moderate, or severe) criteria, but the impact on the risk of COVID-19-associated hospitalization was not specifically investigated. During this analysis period (January 25, 2021, to April 30, 2021 [95 days]), 4 hospitalizations occurred among the 77 events analyzed for the primary endpoint using the per-protocol population, 0 among vaccine recipients and 4 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 28.8, 100). Among an expanded efficacy population, also identified post hoc, which included COVID-19-associated hospitalizations without a requirement for diagnostic polymerase chain reaction testing performed at the study central laboratory, 12 total hospitalizations were identified, 0 among vaccine recipients and 12 among placebo recipients, yielding a post hoc VE against hospitalization of 100% (95% CI: 83.1, 100). These additional data from the PREVENT-19 trial provide relevant public health information concerning the attributes of NVX-CoV2373.


Subject(s)
COVID-19 , Vaccines , Humans , SARS-CoV-2 , COVID-19 Vaccines , COVID-19/prevention & control , Vaccine Efficacy
3.
Microbes Infect ; 25(4): 105082, 2023 05.
Article in English | MEDLINE | ID: covidwho-2308846

ABSTRACT

Available COVID-19 vaccine only provide protection for a limited time due in part to the rapid emergence of viral variants with spike protein mutations, necessitating the generation of new vaccines to combat SARS-CoV-2. Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing early SARS-CoV-2 isolate spike (S) or nucleocapsid (N) proteins, the latter expressed as a fusion protein within herpes simplex virus glycoprotein D (gD), were tested individually or as a mixture in a hamster COVID-19 SARS-CoV-2 challenge model. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gD N fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable than the S protein may potentiate and prolong protection achieved by the currently used S protein based genetic COVID-19 vaccines.


Subject(s)
COVID-19 , Animals , Cricetinae , Humans , COVID-19/prevention & control , SARS-CoV-2/genetics , COVID-19 Vaccines/genetics , Pan troglodytes , Adenoviridae/genetics , Nucleocapsid , Immunization , Antibodies, Viral , Antibodies, Neutralizing
4.
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
5.
Fam Process ; 2022 Feb 14.
Article in English | MEDLINE | ID: covidwho-2288980

ABSTRACT

Children and their families have been significantly impacted by the unfolding of the COVID-19 syndemic. We sought to identify (1) groups of families with distinct profiles of joint trajectories of parental anxiety and child emotional distress and (2) protective and risk factors associated with these dual-trajectory profiles. A sample of 488 parents (65% White; 77% mothers) with 3- to 8-year-old children (MAge  = 5.04, SDAge  = 1.59) was followed from late March to early July in 2020. Survey data on parent (i.e., anxiety symptoms) and child (i.e., emotional distress) adjustment were collected at three time points. Using multivariate growth mixture modeling, we identified one group with low parental anxiety and child emotional distress (42.7%) and three other distinct groups with varying risk levels among parents and/or children. We also identified protective (e.g., positive parenting) and risk (e.g., child negative affect, negative parenting, perceived stress with racism) factors in predicting parent and child adjustment. It can be concluded that, overall, our sample (mostly middle- and high-socioeconomic status families) demonstrated family resilience amid COVID-19, consistent with prior disaster coping literature. At the same time, our findings also indicated the need to identify at-risk families and modifiable factors for post-disaster public health interventions.

6.
Foods ; 12(3)2023 Jan 31.
Article in English | MEDLINE | ID: covidwho-2286172

ABSTRACT

Adulteration of meat with carnivorous animals (such as cats, dogs, foxes, and minks) can cause ethical problems and lead to disease transmission; however, DNA quantitative methods for four carnivorous species in one tube reaction are still rare. In this study, a carnivore-specific nuclear DNA sequence that is conserved in carnivorous animals but has base differences within the sequence was used to design universal primers for its conserved region and corresponding species-specific probes for the hypervariable region. A novel universal primer multiplex real-time PCR (UP-M-rtPCR) approach was developed for the specific identification and quantitation of cat, dog, fox, and mink fractions in a single reaction, with a 0.05 ng absolute limit of detection (LOD) and 0.05% relative LOD. This approach simplifies the PCR system and improves the efficiency of simultaneous identification of multiple animal-derived ingredients in meat. UP-M-rtPCR showed good accuracy (0.48-7.04% relative deviation) and precision (1.42-13.78% relative standard deviation) for quantitative analysis of cat, dog, fox, and mink DNA as well as excellent applicability for the evaluation of meat samples.

7.
Adv Sci (Weinh) ; 10(10): e2206433, 2023 04.
Article in English | MEDLINE | ID: covidwho-2263412

ABSTRACT

Conditional control of RNA structure and function has emerged as an effective toolkit. Here, a strategy based on a one-step introduction of diacylation linkers and azide groups on the 2'-OH of RNA is advance. Selected from eight phosphine reagents, it is found that 2-(diphenylphosphino)ethylamine has excellent performance in reducing azides via a Staudinger reduction to obtain the original RNA. It is demonstrated that the enzymatic activities of Cas13 and Cas9 can be regulated by chemically modified guide RNAs, and further achieved ligand-induced gene editing in living cells by a controllable CRISPR/Cas9 system.


Subject(s)
CRISPR-Cas Systems , Gene Editing , CRISPR-Cas Systems/genetics , RNA, Guide, Kinetoplastida/genetics
8.
Emerg Microbes Infect ; 12(1): 2178238, 2023 Dec.
Article in English | MEDLINE | ID: covidwho-2236789

ABSTRACT

5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, negatively regulates type I interferon responses during various viral infections, including SARS-CoV-2. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-ß production. Knockout or knockdown of NSUN2 enhanced type I interferon and downstream ISGs during various viral infection in vitro. And in vivo, the antiviral innate response is more dramatically enhanced in Nsun2+/- mice than in Nsun2+/+ mice. The highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation enhanced cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), or Zika virus (ZIKV) resulted in a reduction of endogenous NSUN2 levels. Especially, SARS-CoV-2 infection (WT strain and BA.1 omicron variant) also decreased endogenous levels of NSUN2 in COVID-19 patients and K18-hACE2 KI mice, further increasing type I interferon and downstream ISGs. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease during SARS-CoV-2 and various viral infections to boost antiviral responses for effective elimination of viruses.


Subject(s)
COVID-19 , Interferon Type I , Virus Diseases , Zika Virus Infection , Zika Virus , Animals , Mice , Interferon Type I/genetics , Interferon Type I/metabolism , Interferon-beta/genetics , Interferon-beta/metabolism , Methylation , Zika Virus/metabolism , Mice, Knockout , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Antiviral Agents , Immunity, Innate , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism
9.
Front Psychol ; 13: 1026712, 2022.
Article in English | MEDLINE | ID: covidwho-2199202

ABSTRACT

COVID-19, as a crucial public health crisis, has affected our lives in nearly every aspect. Besides its major health threats, COVID-19 brings severe secondary impacts, one of which is the rise of social stigma. Although numerous studies have examined the antecedents and outcomes of COVID-19-related stigma, we still lack a systematic understanding of who is being stigmatized during the COVID-19 pandemic, what exacerbates COVID-19-related stigma, and what impacts COVID-19-related stigma has on victims. Therefore, this review aims to provide a systematic overview of COVID-19-related stigma. With 93 papers conducted with 126,371 individuals in more than 150 countries and territories spanning five continents, we identify three targets that have received the most research: Chinese/Asian people, (suspected) patients and survivors, and healthcare workers. Furthermore, we find that for each stigma target, characteristics of the stigmatized, stigmatizer, and context contribute to COVID-19-related stigma and that this stigma negatively influences victims' health and non-health outcomes. We call for future research to provide a more integrative, balanced, and rigorous picture of COVID-19-related stigma via conducting research on neglected topics (e.g., contextual factors that contribute to stigma toward HCWs) and stigma interventions and using a longitudinal design. In practice, we urge governments and institutions (e.g., ministries of public health, hospitals) to pay close attention to stigma issues and to promote safe and inclusive societies.

10.
Int J Mol Sci ; 23(22)2022 Nov 13.
Article in English | MEDLINE | ID: covidwho-2143225

ABSTRACT

Target-based drug design, a high-efficiency strategy used to guide the development of novel pesticide candidates, has attracted widespread attention. Herein, various natural-derived ferulic acid derivatives incorporating substituted isopropanolamine moieties were designed to target the tobacco mosaic virus (TMV) helicase. Bioassays demonstrating the optimized A19, A20, A29, and A31 displayed excellent in vivo antiviral curative abilities, affording corresponding EC50 values of 251.1, 336.2, 347.1, and 385.5 µg/mL, which visibly surpassed those of commercial ribavirin (655.0 µg/mL). Moreover, configurational analysis shows that the R-forms of target compounds were more beneficial to aggrandize antiviral profiles. Mechanism studies indicate that R-A19 had a strong affinity (Kd = 5.4 µM) to the TMV helicase and inhibited its ability to hydrolyze ATP (50.61% at 200 µM). Meanwhile, A19 could down-regulate the expression of the TMV helicase gene in the host to attenuate viral replication. These results illustrate the excellent inhibitory activity of A19 towards the TMV helicase. Additionally, docking simulations uncovered that R-A19 formed more hydrogen bonds with the TMV helicase in the binding pocket. Recent studies have unambiguously manifested that these designed derivatives could be considered as promising potential helicase-based inhibitors for plant disease control.


Subject(s)
Tobacco Mosaic Virus , Structure-Activity Relationship , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , DNA Helicases
11.
Comput Biol Med ; 152: 106385, 2023 01.
Article in English | MEDLINE | ID: covidwho-2130528

ABSTRACT

BACKGROUND: Numerous traditional filtering approaches and deep learning-based methods have been proposed to improve the quality of ultrasound (US) image data. However, their results tend to suffer from over-smoothing and loss of texture and fine details. Moreover, they perform poorly on images with different degradation levels and mainly focus on speckle reduction, even though texture and fine detail enhancement are of crucial importance in clinical diagnosis. METHODS: We propose an end-to-end framework termed US-Net for simultaneous speckle suppression and texture enhancement in US images. The architecture of US-Net is inspired by U-Net, whereby a feature refinement attention block (FRAB) is introduced to enable an effective learning of multi-level and multi-contextual representative features. Specifically, FRAB aims to emphasize high-frequency image information, which helps boost the restoration and preservation of fine-grained and textural details. Furthermore, our proposed US-Net is trained essentially with real US image data, whereby real US images embedded with simulated multi-level speckle noise are used as an auxiliary training set. RESULTS: Extensive quantitative and qualitative experiments indicate that although trained with only one US image data type, our proposed US-Net is capable of restoring images acquired from different body parts and scanning settings with different degradation levels, while exhibiting favorable performance against state-of-the-art image enhancement approaches. Furthermore, utilizing our proposed US-Net as a pre-processing stage for COVID-19 diagnosis results in a gain of 3.6% in diagnostic accuracy. CONCLUSIONS: The proposed framework can help improve the accuracy of ultrasound diagnosis.


Subject(s)
COVID-19 Testing , COVID-19 , Humans , Ultrasonography/methods , Image Enhancement/methods , Image Processing, Computer-Assisted , Algorithms
12.
Front Immunol ; 13: 960709, 2022.
Article in English | MEDLINE | ID: covidwho-2109764

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious disease that affects the global pig industry. To understand mechanisms of susceptibility/resistance to PRRSV, this study profiled the time-serial white blood cells transcriptomic and serum metabolomic responses to PRRSV in piglets from a crossbred population of PRRSV-resistant Tongcheng pigs and PRRSV-susceptible Large White pigs. Gene set enrichment analysis (GSEA) illustrated that PRRSV infection up-regulated the expression levels of marker genes of dendritic cells, monocytes and neutrophils and inflammatory response, but down-regulated T cells, B cells and NK cells markers. CIBERSORT analysis confirmed the higher T cells proportion in resistant pigs during PRRSV infection. Resistant pigs showed a significantly higher level of T cell activation and lower expression levels of monocyte surface signatures post infection than susceptible pigs, corresponding to more severe suppression of T cell immunity and inflammatory response in susceptible pigs. Differentially expressed genes between resistant/susceptible pigs during the course of infection were significantly enriched in oxidative stress, innate immunity and humoral immunity, cell cycle, biotic stimulated cellular response, wounding response and behavior related pathways. Fourteen of these genes were distributed in 5 different QTL regions associated with PRRSV-related traits. Chemokine CXCL10 levels post PRRSV infection were differentially expressed between resistant pigs and susceptible pigs and can be a promising marker for susceptibility/resistance to PRRSV. Furthermore, the metabolomics dataset indicated differences in amino acid pathways and lipid metabolism between pre-infection/post-infection and resistant/susceptible pigs. The majority of metabolites levels were also down-regulated after PRRSV infection and were significantly positively correlated to the expression levels of marker genes in adaptive immune response. The integration of transcriptome and metabolome revealed concerted molecular events triggered by the infection, notably involving inflammatory response, adaptive immunity and G protein-coupled receptor downstream signaling. This study has increased our knowledge of the immune response differences induced by PRRSV infection and susceptibility differences at the transcriptomic and metabolomic levels, providing the basis for the PRRSV resistance mechanism and effective PRRS control.


Subject(s)
Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Animals , Swine , Porcine respiratory and reproductive syndrome virus/genetics , Porcine Reproductive and Respiratory Syndrome/genetics , Transcriptome , Immunity, Humoral , Adaptive Immunity/genetics
13.
researchsquare; 2022.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2325932.v1

ABSTRACT

Background The safety and efficacy of several vaccine candidates have been tested and found to be effective and safe against COVID-19. But, little is known about the actual level of people with lung cancer willing to accept a COVID-19 vaccine and the impact factors that affect acceptability. The survey aimed to determine the prevalence of vaccine hesitancy in lung cancer patients after surgery and characterize underlying factors contributing to reluctance.Methods An clinical survey was inducted from May 1, 2021, to August 20, 2021. Eligible participants were 18 years or older, were diagnosed with lung cancer, and received lung cancer surgery, including lobectomy, sublobectomy, and pneumonectomy. Data were collected on a self-administered questionnaire from 294 lung cancer patients after surgery.Results Among the final included 281 participants, 54.1% were female, and 93.6% were of Han ethnicity. 48.0% were in pathologic stage I, 36.3% in stage II, 10.3% in stage III, and 5.3% in stage IV. The vaccination hesitancy/refusal rate was 41.6%. In multivariable regression analysis, age over 60 years old, low educational level, duration of cancer (< 1 year), subjective health status, current cancer treatments use, presence of postoperative pain, and report of the items “ever hesitated or refused to get a vaccination,” “get negative information about getting the COVID-19 vaccine”, “worried about vaccine adverse reactions,” and “worried about the COVID vaccine interferes with cancer treatments” were independently associated with hesitant of the COVID-19 vaccine.Conclusions Vaccine hesitancy is common among lung cancer patients after surgery, related mainly to health status and concerns about side effects, worsens cancer prognosis, and interferes with cancer treatments. These results suggest that vaccination programs may need tailoring to specific populations’ hesitancy.

14.
Int J Mol Sci ; 23(16)2022 Aug 14.
Article in English | MEDLINE | ID: covidwho-1981428

ABSTRACT

The emergence of phytopathogenic bacteria resistant to antibacterial agents has rendered previously manageable plant diseases intractable, highlighting the need for safe and environmentally responsible agrochemicals. Inhibition of bacterial cell division by targeting bacterial cell division protein FtsZ has been proposed as a promising strategy for developing novel antibacterial agents. We previously identified 4'-demethylepipodophyllotoxin (DMEP), a naturally occurring substance isolated from the barberry species Dysosma versipellis, as a novel chemical scaffold for the development of inhibitors of FtsZ from the rice blight pathogen Xanthomonas oryzae pv. oryzae (Xoo). Therefore, constructing structure-activity relationship (SAR) studies of DMEP is indispensable for new agrochemical discovery. In this study, we performed a structure-activity relationship (SAR) study of DMEP derivatives as potential XooFtsZ inhibitors through introducing the structure-based virtual screening (SBVS) approach and various biochemical methods. Notably, prepared compound B2, a 4'-acyloxy DMEP analog, had a 50% inhibitory concentration of 159.4 µM for inhibition of recombinant XooFtsZ GTPase, which was lower than that of the parent DMEP (278.0 µM). Compound B2 potently inhibited Xoo growth in vitro (minimum inhibitory concentration 153 mg L-1) and had 54.9% and 48.4% curative and protective control efficiencies against rice blight in vivo. Moreover, compound B2 also showed low toxicity for non-target organisms, including rice plant and mammalian cell. Given these interesting results, we provide a novel strategy to discover and optimize promising bactericidal compounds for the management of plant bacterial diseases.


Subject(s)
Oryza , Xanthomonas , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Cell Division , Plant Diseases/microbiology , Plant Diseases/prevention & control , Podophyllotoxin/metabolism , Podophyllotoxin/pharmacology , Structure-Activity Relationship
15.
Curr Trends Microbiol ; 15: 1-28, 2021.
Article in English | MEDLINE | ID: covidwho-1970504

ABSTRACT

SARS-CoV-2 vaccines aim to protect against COVID-19 through neutralizing antibodies against the viral spike protein. Mutations within the spike's receptor-binding domain may eventually reduce vaccine efficacy, necessitating periodic updates. Vaccine-induced immunity could be broadened by adding T cell-inducing antigens such as SARS-CoV-2's nucleoprotein (N). Here we describe two replication-defective chimpanzee adenovirus (AdC) vectors from different serotypes expressing SARS-CoV-2 N either in its wild-type form or fused into herpes simplex virus glycoprotein D (gD), an inhibitor of an early T cell checkpoint. The vaccines induce potent and sustained CD8+ T cell responses that are broadened upon inclusion of gD. Depending on the vaccine regimen booster immunizations increase magnitude and breadth of T cell responses. Epitopes that are recognized by the vaccine-induced T cells are highly conserved among global SARS-CoV-2 isolates indicating that addition of N to COVID-19 vaccines may lessen the risk of loss of vaccine-induced protection due to variants.

17.
Chin Med J (Engl) ; 135(9): 1064-1075, 2022 May 05.
Article in English | MEDLINE | ID: covidwho-1922352

ABSTRACT

BACKGROUND: It is crucial to improve the quality of care provided to ICU patient, therefore a national survey of the medical quality of intensive care units (ICUs) was conducted to analyze adherence to quality metrics and outcomes among critically ill patients in China from 2015 to 2019. METHODS: This was an ICU-level study based on a 15-indicator online survey conducted in China. Considering that ICU care quality may vary between secondary and tertiary hospitals, direct standardization was adopted to compare the rates of ICU quality indicators among provinces/regions. Multivariate analysis was performed to identify potential factors for in-hospital mortality and factors related to ventilator-associated pneumonia (VAP), catheter-related bloodstream infections (CRBSIs), and catheter-associated urinary tract infections (CAUTIs). RESULTS: From the survey, the proportions of structural indicators were 1.83% for the number of ICU inpatients relative to the total number of inpatients, 1.44% for ICU bed occupancy relative to the total inpatient bed occupancy, and 51.08% for inpatients with Acute Physiology and Chronic Health Evaluation II scores ≥15. The proportions of procedural indicators were 74.37% and 76.60% for 3-hour and 6-hour surviving sepsis campaign bundle compliance, respectively, 62.93% for microbiology detection, 58.24% for deep vein thrombosis prophylaxis, 1.49% for unplanned endotracheal extubations, 1.99% for extubated inpatients reintubated within 48 hours, 6.38% for unplanned transfer to the ICU, and 1.20% for 48-hour ICU readmission. The proportions of outcome indicators were 1.28‰ for VAP, 3.06‰ for CRBSI, 3.65‰ for CAUTI, and 10.19% for in-hospital mortality. Although the indicators varied greatly across provinces and regions, the treatment level of ICUs in China has been stable and improved based on various quality control indicators in the past 5 years. The overall mortality rate has dropped from 10.19% to approximately 8%. CONCLUSIONS: The quality indicators of medical care in China's ICUs are heterogeneous, which is reflected in geographic disparities and grades of hospitals. This study is of great significance for improving the homogeneity of ICUs in China.


Subject(s)
Critical Illness , Pneumonia, Ventilator-Associated , Benchmarking , Critical Care , Humans , Intensive Care Units , Quality Control
18.
PLoS One ; 17(6): e0269882, 2022.
Article in English | MEDLINE | ID: covidwho-1892328

ABSTRACT

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) has made a serious public health threat worldwide. Recent evidence has indicated that COVID-19 patients in convalescence frequently experience insomnia, which reduces their quality of life and causes unknown risks. The positive effect of cognitive behavior on insomnia has been well addressed in previous studies. Given the high infectivity and epidemicity of COVID-19, Internet-delivered intervention may be safer than face-to-face treatment. However, whether Internet-delivered cognitive behavioral therapy can effectively improve the insomnia of COVID-19 patients in convalescence has not been completely determined yet. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of Internet-delivered cognitive behavioral therapy on insomnia in COVID-19 patients in convalescence, with the aim to confer some guidance for its clinical application. METHODS AND ANALYSIS: This systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). Two researchers will retrieve the relevant literature on Internet-delivered cognitive behavioral therapy for insomnia in convalescent patients with COVID-19 in PubMed, Web of Science, Embase, MEDLINE, Cochrane Library, Clinical Trials gov, Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge Infrastructure (CNKI) from inception to 11th of December. In addition, we will review the relevant trials and references of the included literature and manually searched the grey literature. The two researchers will independently extracted data and information and evaluated the quality of the included literature. The Review Manager software (version 5.3) and Stata software (version 14.0) will be used for data analysis. The mean difference or the standardized mean difference of 95% CI will be used to calculate continuous variables to synthesize the data. In addition, I2 and Cochrane will be used for heterogeneity assessment. TRIAL REGISTRATION: PROSPERO registration number CRD42021271278.


Subject(s)
COVID-19 , Cognitive Behavioral Therapy , Sleep Initiation and Maintenance Disorders , COVID-19/complications , COVID-19/therapy , Convalescence , Humans , Internet , Meta-Analysis as Topic , Quality of Life , Research Design , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/therapy , Systematic Reviews as Topic
19.
Front Psychol ; 13: 879312, 2022.
Article in English | MEDLINE | ID: covidwho-1883952

ABSTRACT

This study examined the relationship between psychological capital (PsyCap) and teacher enjoyment in the context of online teaching and investigated whether the emotion regulation (ER) strategy of reappraisal mediated their relationship. 221 Chinese university teachers were selected as the research sample through snowball sampling in an online survey. After controlling for age, gender, teaching experience, education level, time and energy input during online teaching and online teaching experience, the results showed that PsyCap and reappraisal positively influence the teachers' online teaching enjoyment (OTE), and reappraisal significantly mediated the relationship between teachers' PsyCap and OTE, suggesting that optimistic and resilient teachers with more self-efficacy and hope are more likely to find enjoyment during online teaching, and high PsyCap combined with the use of reappraisal leads to greater OTE. The study not only confirms the positive role of reappraisal as an emotion regulation strategy in online teaching, but also provides practical implications for the realization of enjoyable online teaching experience.

20.
Behav Med ; 48(2): 85-94, 2022.
Article in English | MEDLINE | ID: covidwho-1751936

ABSTRACT

The COVID-19 syndemic, with a disproportionately higher adverse impact on communities of color (i.e., COVID-19 infection and death), will likely exacerbate the existing health disparities in trauma-related symptoms between people of color (POC) and White Americans. However, no studies have examined the racial disparity in posttraumatic stress symptoms (PTSS) during COVID-19. Grounded in ecological theory and racial trauma framework, we investigated racial disparity in PTSS and three possible mechanisms, 1) COVID stress, 2) direct racism, and 3) indirect racism, for these disparities using a large U.S. national sample. Results indicated that POC reported higher levels of PTSS than White Americans. The PTSS racial disparity was accounted more by direct and indirect racism than by the COVID-19-specific stressors, after controlling for age, gender, education, income, parent status, adverse childhood experiences (ACEs), and intimate partner violence (IPV). Additional fine-grained analyses for Hispanic/Latinx Americans, Black/African Americans, and Asian American and Pacific Islanders by and large corroborated the above findings. Our findings highlighted the deleterious impact of the ongoing racism pandemic on the POC community as a public health crisis in addition to the COVID-19 pandemic.Supplemental data for this article is available online at at http://doi:10.1080/08964289.2021.2006131.


Subject(s)
COVID-19 , Racism , Stress Disorders, Post-Traumatic , Humans , Pandemics , Stress Disorders, Post-Traumatic/diagnosis , Syndemic
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