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2.
Frontiers in public health ; 11, 2023.
Article in English | EuropePMC | ID: covidwho-2276100

ABSTRACT

Introduction With the COVID-19 pandemic in China, a large number of mild or ordinary confirmed cases have been sent to Fangcang shelter hospitals for treatment. We aimed to investigate the mental health condition of Fangcang patients 2 years after the pandemic when patients knew more about COVID-19 and the virus was less virulent. We focused on the effect of dysfunctional beliefs and attitudes about sleep on depression, anxiety, and insomnia. Methods A total of 1,014 patients from two large Fangcang shelter hospitals in Shanghai between 22 April and 8 May 2022 completed a set of questionnaires comprising: the Dysfunctional Beliefs and Attitudes about Sleep scale, the Generalized Anxiety Disorder scale, the Patient Health Questionnaire, and the Insomnia Severity Index scale. Results Results show that the positive screening rates for anxiety, depression, and insomnia among tested patients were 55.3, 27.0, and 47.8%, respectively. Patients were more likely to report higher anxiety, depression, and insomnia, and to endorse affective and sleep disorders if they were: female, aged 18–40 years, with undergraduate course or above, white-collar employees, or those who thought the pandemic would have severe economic effects. About 51.4% of the participants had dysfunctional beliefs about sleep to varying degrees. Compared with patients who had accurate beliefs about sleep, the ratios of insomnia, anxiety, and depression were significantly higher among patients with dysfunctional beliefs about sleep. Discussion Attention should be paid to the mental health problems of patients in Fangcang shelter hospitals. The results indicate that dysfunctional beliefs about sleep significantly increased anxiety, depression, and insomnia of Fangcang patients.

3.
Psychol Med ; : 1-10, 2020 Dec 10.
Article in English | MEDLINE | ID: covidwho-2277703

ABSTRACT

BACKGROUND: This study aimed to explore the impacts of COVID-19 outbreak on mental health status in general population in different affected areas in China. METHODS: This was a comparative study including two groups of participants: (1) general population in an online survey in Ya'an and Jingzhou cities during the COVID-19 outbreak from 10-20 February 2020; and (2) matching general population selected from the mental health survey in Ya'an in 2019 (from January to May 2019). General Health Questionnaire (GHQ-12), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used. RESULTS: There were 1775 participants (Ya'an in 2019 and 2020: 537 respectively; Jingzhou in 2020: 701). Participants in Ya'an had a significantly higher rate of general health problems (GHQ scores ⩾3) in 2020 (14.7%) than in 2019 (5.2%) (p < 0.001). Compared with Ya'an (8.0%), participants in Jingzhou in 2020 had a significantly higher rate of anxiety (SAS scores ⩾50, 24.1%) (p < 0.001). Participants in Ya'an in 2020 had a significantly higher rate of depression (SDS scores ⩾53, 55.3%) than in Jingzhou (16.3%) (p < 0.001). The risk factors of anxiety symptoms included female, number of family members (⩾6 persons), and frequent outdoor activities. The risk factors of depression symptoms included participants in Ya'an and uptake self-protective measures. CONCLUSIONS: The prevalence of psychological symptoms has increased sharply in general population during the COVID-19 outbreak. People in COVID-19 severely affected areas may have higher scores of GHQ and anxiety symptoms. Culture-specific and individual-based psychosocial interventions should be developed for those in need during the COVID-19 outbreak.

4.
Cell Mol Immunol ; 20(4): 351-364, 2023 04.
Article in English | MEDLINE | ID: covidwho-2287148

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.


Subject(s)
COVID-19 , Receptors, Chimeric Antigen , Humans , SARS-CoV-2/metabolism , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Caspofungin , Felodipine , Cytokine Release Syndrome/drug therapy , Inflammation , Cytokines/metabolism
5.
BMC Psychol ; 11(1): 66, 2023 Mar 10.
Article in English | MEDLINE | ID: covidwho-2287052

ABSTRACT

Self-compassion is negatively associated with aggressive behaviors. However, the association between self-compassion and cyber aggression toward stigmatized people (e.g., people infected with COVID-19) has not been investigated in the COVID-19 context and the mechanism underlying this association remains underexplored. On the basis of emotion regulation theory and attribution theory, this study examined the indirect effects of self-compassion on cyber aggression toward people infected with COVID-19 through attribution and public stigma of COVID-19. Data were collected from 1162 Chinese college students (415 male, mean age = 21.61 years). Participants completed an online questionnaire including measurement of the key variables and basic demographic information. Results indicated that self-compassion was negatively associated with cyber aggression through the lower attribution of COVID-19 and lower public stigma of COVID-19. A sequential pathway from the attribution of COVID-19 to public stigma of COVID-19 was identified in the relationship between self-compassion and cyber aggression. Our findings are consistent with emotion regulation theory and attribution theory, which posit that emotion regulation strategies are associated with interpersonal mistreatment through cognitive pathways. These findings suggest that emotional self-regulation strategies can be used to reduce cyber aggression toward stigmatized people by reducing attribution and public stigma in the COVID-19 context. Self-compassion improvement could be target for the interventions aiming at alleviating public stigma and interpersonal mistreatment toward stigmatized people.


Subject(s)
COVID-19 , Self-Compassion , Humans , Male , Young Adult , Adult , Aggression/psychology , Social Stigma , Social Perception
6.
Front Public Health ; 11: 1129322, 2023.
Article in English | MEDLINE | ID: covidwho-2276101

ABSTRACT

Introduction: With the COVID-19 pandemic in China, a large number of mild or ordinary confirmed cases have been sent to Fangcang shelter hospitals for treatment. We aimed to investigate the mental health condition of Fangcang patients 2 years after the pandemic when patients knew more about COVID-19 and the virus was less virulent. We focused on the effect of dysfunctional beliefs and attitudes about sleep on depression, anxiety, and insomnia. Methods: A total of 1,014 patients from two large Fangcang shelter hospitals in Shanghai between 22 April and 8 May 2022 completed a set of questionnaires comprising: the Dysfunctional Beliefs and Attitudes about Sleep scale, the Generalized Anxiety Disorder scale, the Patient Health Questionnaire, and the Insomnia Severity Index scale. Results: Results show that the positive screening rates for anxiety, depression, and insomnia among tested patients were 55.3, 27.0, and 47.8%, respectively. Patients were more likely to report higher anxiety, depression, and insomnia, and to endorse affective and sleep disorders if they were: female, aged 18-40 years, with undergraduate course or above, white-collar employees, or those who thought the pandemic would have severe economic effects. About 51.4% of the participants had dysfunctional beliefs about sleep to varying degrees. Compared with patients who had accurate beliefs about sleep, the ratios of insomnia, anxiety, and depression were significantly higher among patients with dysfunctional beliefs about sleep. Discussion: Attention should be paid to the mental health problems of patients in Fangcang shelter hospitals. The results indicate that dysfunctional beliefs about sleep significantly increased anxiety, depression, and insomnia of Fangcang patients.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Humans , Female , Mental Health , Sleep Quality , Pandemics , Hospitals, Special , Depression/psychology , Mobile Health Units , China , Sleep
7.
Electronics ; 12(1):80, 2023.
Article in English | MDPI | ID: covidwho-2166348

ABSTRACT

In recent years, chest X-ray (CXR) imaging has become one of the significant tools to assist in the diagnosis and treatment of novel coronavirus pneumonia. However, CXR images have complex-shaped and changing lesion areas, which makes it difficult to identify novel coronavirus pneumonia from the images. To address this problem, a new deep learning network model (BoT-ViTNet) for automatic classification is designed in this study, which is constructed on the basis of ResNet50. First, we introduce multi-headed self-attention (MSA) to the last Bottleneck block of the first three stages in the ResNet50 to enhance the ability to model global information. Then, to further enhance the feature expression performance and the correlation between features, the TRT-ViT blocks, consisting of Transformer and Bottleneck, are used in the final stage of ResNet50, which improves the recognition of complex lesion regions in CXR images. Finally, the extracted features are delivered to the global average pooling layer for global spatial information integration in a concatenated way and used for classification. Experiments conducted on the COVID-19 Radiography database show that the classification accuracy, precision, sensitivity, specificity, and F1-score of the BoT-ViTNet model is 98.91%, 97.80%, 98.76%, 99.13%, and 98.27%, respectively, which outperforms other classification models. The experimental results show that our model can classify CXR images better.

8.
Frontiers in immunology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-2046063

ABSTRACT

Background The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global crisis. Although many people recover from COVID-19 infection, they are likely to develop persistent symptoms similar to those of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after discharge. Those constellations of symptoms persist for months after infection, called Long COVID, which may lead to considerable financial burden and healthcare challenges. However, the mechanisms underlying Long COVID and ME/CFS remain unclear. Methods We collected the genes associated with Long COVID and ME/CFS in databases by restricted screening conditions and clinical sample datasets with limited filters. The common genes for Long COVID and ME/CFS were finally obtained by taking the intersection. We performed several advanced bioinformatics analyses based on common genes, including gene ontology and pathway enrichment analyses, protein–protein interaction (PPI) analysis, transcription factor (TF)–gene interaction network analysis, transcription factor–miRNA co-regulatory network analysis, and candidate drug analysis prediction. Results We found nine common genes between Long COVID and ME/CFS and gained a piece of detailed information on their biological functions and signaling pathways through enrichment analysis. Five hub proteins (IL-6, IL-1B, CD8A, TP53, and CXCL8) were collected by the PPI network. The TF–gene and TF–miRNA coregulatory networks were demonstrated by NetworkAnalyst. In the end, 10 potential chemical compounds were predicted. Conclusion This study revealed common gene interaction networks of Long COVID and ME/CFS and predicted potential therapeutic drugs for clinical practice. Our findings help to identify the potential biological mechanism between Long COVID and ME/CFS. However, more laboratory and multicenter evidence is required to explore greater mechanistic insight before clinical application in the future.

9.
Mol Ther Nucleic Acids ; 29: 923-940, 2022 Sep 13.
Article in English | MEDLINE | ID: covidwho-1996465

ABSTRACT

The current coronavirus disease 2019 (COVID-19) pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand, 5'-C; antisense strand, 3'-GGG) that mediates end-to-end dimer self-assembly. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases did not affect their ability to induce IFN. Unlike previously described immunostimulatory small interfering RNAs (siRNAs), their activity is independent of Toll-like receptor (TLR) 7/8, but requires the RIG-I/IRF3 pathway that induces a more restricted antiviral response with a lower proinflammatory signature compared with immunostimulant poly(I:C). Immune stimulation mediated by these duplex RNAs results in broad-spectrum inhibition of infections by many respiratory viruses with pandemic potential, including severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus (HCoV)-NL63, and influenza A virus in cell lines, human lung chips that mimic organ-level lung pathophysiology, and a mouse SARS-CoV-2 infection model. These short double-stranded RNAs (dsRNAs) can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics.

10.
Genet Res (Camb) ; 2021: 9952620, 2021.
Article in English | MEDLINE | ID: covidwho-1775004

ABSTRACT

Purpose: Herbal medicine is one of crucial symbols of Chinese national medicine. Investigation on molecular responses of different herbal strategies against viral myocarditis is immeasurably conducive to targeting drug development in the current international absence of miracle treatment. Methods: Literature retrieval platforms were applied in the collection of existing empirical evidences for viral myocarditis-related single-herbal strategies. SwissTargetPrediction, Metascape, and Discovery Studio coordinating with multidatabases investigated underlying target genes, interactive proteins, and docking molecules in turn. Results: Six single-herbal medicines consisting of Huangqi (Hedysarum Multijugum Maxim), Yuganzi (Phyllanthi Fructus), Kushen (Sophorae Flavescentis Radix), Jianghuang (Curcumaelongae Rhizoma), Chaihu (Radix Bupleuri), and Jixueteng (Spatholobus Suberectus Dunn) meet the requirement. There were 11 overlapped and 73 unique natural components detected in these herbs. SLC6A2, SLC6A4, NOS2, PPARA, PPARG, ACHE, CYP2C19, CYP51A1, and CHRM2 were equally targeted by six herbs and identified as viral myocarditis-associated symbols. MCODE algorithm exposed the hub role of SRC and EGFR in strategies without Jianghuang. Subsequently, we learned intermolecular interactions of herbal components and their targeting heart-tissue-specific CHRM2, FABP3, TNNC1, TNNI3, TNNT2, and SCN5A and cardiac-myocytes-specific IL6, MMP1, and PLAT coupled with viral myocarditis. Ten interactive characteristics such as π-alkyl and van der Waals were modeled in which ARG111, LYS253, ILE114, and VAL11 on cardiac troponin (TNNC1-TNNI3-TNNT2) and ARG208, ASN106, and ALA258 on MMP1 fulfilled potential communicating anchor with ellagic acid, 5α, 9α-dihydroxymatrine, and leachianone g via hydrogen bond and hydrophobic interaction, respectively. Conclusions: The comprehensive outcomes uncover differences and linkages between six herbs against viral myocarditis through component and target analysis, fostering development of drugs.


Subject(s)
Cardiovascular Infections , Drugs, Chinese Herbal , Myocarditis , Plants, Medicinal , Virus Diseases , Drugs, Chinese Herbal/therapeutic use , Humans , Myocarditis/drug therapy , Phytotherapy , Serotonin Plasma Membrane Transport Proteins , Virus Diseases/drug therapy
11.
Prostate Cancer Prostatic Dis ; 25(4): 762-769, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1747251

ABSTRACT

BACKGROUND: Men with progressive neuroendocrine or aggressive-variant metastatic prostate cancer (NEPC/AVPC) have a poor prognosis and limited treatment options, and immunotherapy has not been tested in such patients. METHODS: We conducted an open label single center phase 2 trial (NCT03179410) of men with progressive NEPC/AVPC either defined by histology or AVPC criteria. Avelumab (10 mg/kg every 2 weeks) was administered until progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Secondary endpoints included ORR, radiographic progression-free survival (rPFS), overall survival, and safety. Correlative studies included longitudinal peripheral blood immune phenotyping. The study was limited by the small number of patients enrolled and by the early termination due to COVID-19. RESULTS: A total of 15 men with AVPC/NEPC were enrolled. The median age was 71 (range 51-85 years), and men had received a median of two prior therapies (range 1-3). Median PSA was 54 ng/dl (range 0-393), and 73% of men had liver metastasis. The ORR with avelumab in this setting by iRECIST or RECIST 1.1 was 6.7%, including one patient (6.7%) with a complete remission (CR), 20% with stable disease, and 67% with progressive disease. The patient with the CR had an MSH2 somatic mutation and MSI-high NEPC with central nervous system metastases, and his CR remains durable off all therapy for 2 years. The median rPFS was 1.8 months (95% CI 1.6-3.6 months), and median overall survival was 7.4 months (85% CI 2.8-12.6 months). Safety was consistent with the known profile of avelumab. Phenotyping of peripheral immune subsets suggest enhanced CXCR2-dependent myeloid and T-cell responses in this extraordinary responder. CONCLUSIONS: While the study was terminated early due to slow enrollment at the onset of the COVID-19 pandemic and lower than anticipated objective response rate, PD-L1 inhibition with avelumab monotherapy showed poor efficacy in patients with microsatellite stable NEPC/AVPC. Immune profiling revealed enhanced CXCR2 positive immune cell activation in the one extraordinary responder, suggesting potential mechanisms for further immunotherapy development in this population.


Subject(s)
COVID-19 , Carcinoma, Neuroendocrine , Prostatic Neoplasms , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Pandemics , Antibodies, Monoclonal, Humanized/adverse effects , Carcinoma, Neuroendocrine/pathology
12.
Front Mol Neurosci ; 15: 812479, 2022.
Article in English | MEDLINE | ID: covidwho-1686515

ABSTRACT

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

13.
JAMA Netw Open ; 4(11): e2134330, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1513769

ABSTRACT

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.


Subject(s)
Androgen Antagonists/adverse effects , COVID-19/complications , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/mortality , Aged , Aged, 80 and over , Androgen Antagonists/therapeutic use , COVID-19/epidemiology , COVID-19/mortality , Cohort Studies , Humans , Male , Middle Aged , Prostatic Neoplasms/epidemiology , Risk Factors , Tennessee/epidemiology
14.
Int J Environ Res Public Health ; 18(21)2021 11 08.
Article in English | MEDLINE | ID: covidwho-1512321

ABSTRACT

This study aimed to examine the profile of COVID-19-related public stigma and its correlates in the general population of China. A cross-sectional online survey was conducted in China from 7 May to 25 May in 2020. A total of 1212 participants from the general population completed the survey measuring their stigmatizing attitudes towards COVID-19, as well as knowledge and causal attributions of COVID-19. Univariate and multivariate analyses were performed to examine the correlates of COVID-19-related public stigma. A total of 31.8% of participants endorsed stigmatization towards people with COVID-19. Those who were of older age (t = -3.97, p < 0.001), married (F = 3.04, p < 0.05), had a lower level of education (F = 8.11, p < 0.001), and a serious psychological response (F = 3.76, p < 0.05) reported significantly higher scores of public stigma. Dangerousness (B = 0.047, p < 0.001), fear (B = 0.059, p < 0.001), anger (B = 0.038, p < 0.01), and responsibility (B = 0.041, p < 0.001) were positively associated with public stigma. This study shows that public stigma related to COVID-19 is prevalent in the general population of China. Actions against public stigma need to contain the spread of misinformation about COVID-19, alter inappropriate attributions, alleviate unfavorable reactions, and provide psychosocial support for the public.


Subject(s)
COVID-19 , Aged , China , Cross-Sectional Studies , Humans , SARS-CoV-2 , Social Stigma , Surveys and Questionnaires
15.
Chem Biol Interact ; 351: 109744, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1509623

ABSTRACT

Remdesivir, an intravenous nucleotide prodrug, has been approved for treating COVID-19 in hospitalized adults and pediatric patients. Upon administration, remdesivir can be readily hydrolyzed to form its active form GS-441524, while the cleavage of the carboxylic ester into GS-704277 is the first step for remdesivir activation. This study aims to assign the key enzymes responsible for remdesivir hydrolysis in humans, as well as to investigate the kinetics of remdesivir hydrolysis in various enzyme sources. The results showed that remdesivir could be hydrolyzed to form GS-704277 in human plasma and the microsomes from human liver (HLMs), lung (HLuMs) and kidney (HKMs), while the hydrolytic rate of remdesivir in HLMs was the fastest. Chemical inhibition and reaction phenotyping assays suggested that human carboxylesterase 1 (hCES1A) played a predominant role in remdesivir hydrolysis, while cathepsin A (CTSA), acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) contributed to a lesser extent. Enzymatic kinetic analyses demonstrated that remdesivir hydrolysis in hCES1A (SHUTCM) and HLMs showed similar kinetic plots and much closed Km values to each other. Meanwhile, GS-704277 formation rates were strongly correlated with the CES1A activities in HLM samples from different individual donors. Further investigation revealed that simvastatin (a therapeutic agent for adjuvant treating COVID-19) strongly inhibited remdesivir hydrolysis in both recombinant hCES1A and HLMs. Collectively, our findings reveal that hCES1A plays a predominant role in remdesivir hydrolysis in humans, which are very helpful for predicting inter-individual variability in response to remdesivir and for guiding the rational use of this anti-COVID-19 agent in clinical settings.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Carboxylesterase/metabolism , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Adenosine Monophosphate/chemistry , Adenosine Monophosphate/metabolism , Alanine/chemistry , Alanine/metabolism , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Carboxylesterase/chemistry , Cathepsin A/chemistry , Cathepsin A/metabolism , Humans , Hydrolysis/drug effects , Kinetics , Liver/metabolism , Microsomes, Liver/metabolism , Simvastatin/pharmacology
16.
Journal for Immunotherapy of Cancer ; 9(Suppl 2):A655, 2021.
Article in English | ProQuest Central | ID: covidwho-1511496

ABSTRACT

625 Table 1Baseline characteristics of ICI and control populations

17.
Emerg Microbes Infect ; 10(1): 365-375, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1490458

ABSTRACT

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.


Subject(s)
Hepatitis E/immunology , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Papillomavirus Infections/immunology , Papillomavirus Vaccines/immunology , Vaccines, Synthetic/immunology , Viral Hepatitis Vaccines/immunology , Adolescent , Adult , Aged , Antibodies, Viral/immunology , Female , Hepatitis E/prevention & control , Hepatitis E/virology , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Immunity , Immunoglobulin G/immunology , Male , Middle Aged , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/adverse effects , Papillomavirus Vaccines/genetics , Vaccination/adverse effects , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Viral Hepatitis Vaccines/administration & dosage , Viral Hepatitis Vaccines/adverse effects , Viral Hepatitis Vaccines/genetics , Young Adult
18.
Obesity (Silver Spring) ; 29(11): 1907-1915, 2021 11.
Article in English | MEDLINE | ID: covidwho-1439707

ABSTRACT

OBJECTIVE: The Chinese government decisively imposed nationwide confinement in response to the COVID-19 outbreak. This study aimed to evaluate the impact of the COVID-19 pandemic on the progression of obesity in children and adolescents in Changshu, China. METHODS: Based on the Health Promotion Program for Children and Adolescents (HPPCA), which is a prospective cross-sectional and school-based study, BMI assessed in seven consecutive years (2014 to 2020) among children and adolescents aged 6 to 17 years in Changshu city was extracted. The standardized BMI z scores (zBMI) and prevalence of obesity between 2020 (after COVID-19 home confinement) and the previous 6 years were compared among age-specific subgroups and between sexes. RESULTS: The mean number of participants per year was 29,648. The overall mean zBMI drastically increased from 0.29 in 2019 to 0.45 in 2020, resulting in a rise of 0.16 (95% CI: 0.14-0.18); the prevalence of obesity substantially elevated to 12.77% in 2020 (versus 10.38% in 2017), with an acceleration of 2.39% (95% CI: 1.88%-2.90%). Of note, these increases were more likely to be observed in boys and those 6 to 11 years old. CONCLUSIONS: The COVID-19 pandemic seemed to exacerbate the obesity epidemic among pediatric populations in Changshu, China.


Subject(s)
COVID-19 , Pandemics , Pediatric Obesity , Adolescent , COVID-19/epidemiology , Child , China/epidemiology , Cross-Sectional Studies , Female , Health Surveys , Humans , Male , Pediatric Obesity/epidemiology , Prevalence , Prospective Studies , Schools
19.
Mol Psychiatry ; 27(1): 19-33, 2022 01.
Article in English | MEDLINE | ID: covidwho-1440466

ABSTRACT

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.


Subject(s)
COVID-19 , Communicable Diseases , Influenza A Virus, H1N1 Subtype , Zika Virus Infection , Zika Virus , Humans , Prevalence
20.
Acta Pharm Sin B ; 11(9): 2850-2858, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1415197

ABSTRACT

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

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