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1.
J Allergy Clin Immunol Pract ; 2022.
Article in English | PubMed | ID: covidwho-2028163

ABSTRACT

BACKGROUND: Although immediate potentially allergic reactions have been reported after dose one of mRNA COVID-19 vaccines, comprehensively defined subtypes have not been clearly distinguished. OBJECTIVE: To define distinct clinical phenotypes of immediate reactions after dose one of mRNA COVID-19 vaccination, and to assess the relation of clinical phenotype to mRNA COVID-19 vaccine second dose tolerance. METHODS: This retrospective study included patients with ≥1 potentially allergic symptom or sign within 4 hours of receiving dose one of a mRNA COVID-19 vaccine and assessed by Allergy/Immunology specialists from 5 US academic medical centers (January-June 2021). We used latent class analysis - an unbiased, machine-learning modeling method - to define novel clinical phenotypes. We assessed demographic, clinical, and reaction characteristics associated with phenotype membership. Using log-binomial regression, we assessed the relation between phenotype membership and second dose tolerance, defined as either no symptoms or mild, self-limited symptoms resolving with antihistamines alone. A sensitivity analysis considered second dose tolerance as 'objective signs only.' RESULTS: We identified 265 patients with dose one immediate reactions with 3 phenotype clusters: 1) Limited/Predominantly Cutaneous, 2) Sensory and 3) Systemic. A total of 223 patients (84%) received a second dose and 200 (90%) tolerated their second dose. Sensory cluster (all patients had the symptom of numbness or tingling) was associated with a higher likelihood of second dose intolerance, but this finding did not persist when accounting for objective signs. CONCLUSIONS: Three novel clinical phenotypes of immediate-onset reactions after dose one of mRNA COVID-19 vaccines were identified using latent class analysis: 1) Limited/Predominantly Cutaneous, 2) Sensory and 3) Systemic. While these clinical phenotypes may indicate differential mechanistic etiologies or associations with subsequent dose tolerance, most individuals proceeding to their second dose tolerated it.

2.
JAMA Network Open ; 5(9):e2231790, 2022.
Article in English | MEDLINE | ID: covidwho-2027281

ABSTRACT

Importance: Relatively little is known about the persistence of symptoms in patients with COVID-19 for more than 1 year after their acute illness. Objective: To assess the health outcomes among hospitalized COVID-19 survivors over 2 years and to identify factors associated with increased risk of persistent symptoms. Design, Setting, and Participants: This was a longitudinal cohort study of patients who survived COVID-19 at 2 COVID-19-designated hospitals in Wuhan, China, from February 12 to April 10, 2020. All patients were interviewed via telephone at 1 year and 2 years after discharge. The 2-year follow-up study was conducted from March 1 to April 6, 2022. Statistical analysis was conducted from April 20 to May 5, 2022. The severity of disease was defined by World Health Organization guideline for COVID-19. Exposures: COVID-19. Main Outcomes and Measures: The main outcome was symptom changes over 2 years after hospital discharge. All patients completed a symptom questionnaire for evaluation of symptoms, along with a chronic obstructive pulmonary disease assessment test (CAT) at 1-year and 2-year follow-up visits. Results: Of 3988 COVID-19 survivors, a total of 1864 patients (median [IQR] age, 58.5 [49.0-68.0] years;926 male patients [49.7%]) were available for both 1-year and 2-year follow-up visits. The median (IQR) time from discharge to follow-up at 2 years was 730 (719-743) days. At 2 years after hospital discharge, 370 patients (19.8%) still had symptoms, including 224 (12.0%) with persisting symptoms and 146 (7.8%) with new-onset or worsening of symptoms. The most common symptoms were fatigue, chest tightness, anxiety, dyspnea, and myalgia. Most symptoms resolved over time, but the incidence of dyspnea showed no significant change (1-year vs 2-year, 2.6% [49 patients] vs 2.0% [37 patients]). A total of 116 patients (6.2%) had CAT total scores of at least 10 at 2 years after discharge. Patients who had been admitted to the intensive care unit had higher risks of persistent symptoms (odds ratio, 2.69;95% CI, 1.02-7.06;P = .04) and CAT scores of 10 or higher (odds ratio, 2.83;95% CI, 1.21-6.66;P = .02). Conclusions and Relevance: In this cohort study, 2 years after hospital discharge, COVID-19 survivors had a progressive decrease in their symptom burden, but those with severe disease during hospitalization, especially those who required intensive care unit admission, had higher risks of persistent symptoms. These results are related to the original strain of the virus, and their relevance to infections with the Omicron variant is not known.

3.
Journal of Traditional Chinese Medicine ; 42(5):803-809, 2022.
Article in English | MEDLINE | ID: covidwho-2026022

ABSTRACT

OBJECTIVE: To evaluate the efficacy of the Shugan Jieyu capsule on improving sleep and emotional disorder during Coronavirus disease 2019 (COVID-19) convalescence. METHODS: We conducted a randomized, double-blind, placebo-controlled trial, and recruit 200 COVID-19 convalescence patients and then divide the subjects into two groups respectively: the experimental group ( 100) and the control group ( 100). Patients in the control group were given doses as a placebo, while those in the experimental group were given Shugan Jieyu capsule. The investigators mainly observed the differences between the two groups before and after treatment in terms of the rate of reduction and the rate of efficiency in Hamilton Depression Scale (HAMD-17) total scores from baseline, and recorded the scores of Hamilton Anxiety Scale (HAMA), Patient Health Questionnaire-15 (PHQ-15), Insomnia Severity Index (ISI) and Treatment Emergent Symptom Scale at 2 week, the 4 week and the 6 week respectively after treatment, and compared the differences between the groups. And the occurrence of adverse events was recorded. RESULTS: After 6-week treatment, there were statistically significant differences in the rate of reduction as well as efficiency in HAMD-17 scores, HAMA Total Scores, PHQ-15 Score, ISI Score from baseline in the experimental group and control group (< 0.05). There were 4 adverse events in the experimental group and 1 in the control group. CONCLUSION: Shugan Jieyu capsule could significantly improve sleep and emotional disorder in patients during COVID-19 convalescence.

4.
Int J Public Health ; 67:1604979, 2022.
Article in English | PubMed | ID: covidwho-2023043

ABSTRACT

Objectives: The study aimed at analyzing the prevalence of five psychological outcomes (depression, anxiety, stress, post-traumatic stress disorder (PTSD), and suicidal ideation) among Chinese healthcare workers (HCWs), and measured the total possible negative psychological impact 1 year after the COVID-19 initial outbreak. Methods: A cross-sectional nationwide multi-center study was performed between November 2020 and March 2021 in China. A self-report questionnaire was applied, and three psychological scales were used. Binary logistic regression was performed to analyze the risk factors associated with each psychological outcome. Results: The findings demonstrated that the COVID-19 pandemic had a negative psychological impact on HCWs, which was still evident 1 year after the initial outbreak. Nurses showed higher depression and anxiety than other HCWs. Female gender, passive coping, long working hours, having a chronic disease, and experiencing violence, among other factors, were all risk factors for psychological impairment. Conclusion: Developing and promoting programs to improve mental health among HCWs, and identifying those who might need psychological support is still relevant 1 year after the initial outbreak.

5.
Frontiers in Physics ; 10, 2022.
Article in English | Scopus | ID: covidwho-2022845

ABSTRACT

Non-pharmaceutical interventions (NPIs) are essential for the effective prevention and control of the COVID-19 pandemic. However, the scenarios for disease transmission are complicated and varied, and it remains unclear how real-world networks respond to the changes in NPIs. Here, we propose a multi-layer network combining structurally fixed social contact networks with a time-varying mobility network, select the COVID-19 outbreak in two metropolitans in China as case studies, and assess the effectiveness of NPIs. Human mobility, both in relatively fixed places and in urban commuting, is considered. Enclosed places are simulated by three different types of social contact networks, while urban commuting is represented by a time-varying commute network. We provide a composite framework that captures the heterogeneity and time variation of the real world and enables us to simulate large populations with low computational costs. We give out a thorough evaluation of the effectiveness of NPIs (i.e., work from home, school closure, close-off management, public transit limitation, quarantine, and mask use) under certain vaccine coverage varying with implementation timing and intensity. Our results highlight the strong correlation between the NPI pattern and the epidemic mitigation effect and suggest important operational strategies for epidemic control. Copyright © 2022 Chen, Guo, Jiao, Liang, Li, Yan, Huang, Liu and Fan.

6.
Frontiers in Pharmacology ; 13, 2022.
Article in English | Web of Science | ID: covidwho-2022844

ABSTRACT

Patients with breast cancer are prone to SARS-CoV-2 infection [the causative virus of coronavirus disease (COVID-19)] due to their lack of immunity. In the current study, we examined the mechanism of action of Diosmetin, a flavonoid with anti-inflammatory properties, in patients with BRCA infected with SARS-CoV-2.We used bioinformatics technology to analyze the binding ability, biological function, and other biological characteristics of Diosmetin in vivo and examine the core target and potential mechanism of action of Diosmetin in patients with patients with breast cancer infected with SARS-CoV-2. A prognostic model of SARS-COV-2-infected breast cancer patients was constructed, and the core genes were screened out, revealing the correlation between these core genes and clinicopathological characteristics, survival rate, and high-risk and low-risk populations. The docking results revealed that Diosmetin binds well to the core genes of patients with breast cancer with COVID-19. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that Diosmetin inhibited inflammation, enhanced immune function, and regulated the cellular microenvironment in patients with BRCA/COVID-19. For the first time, we reveal the molecular functions and potential targets of Diosmetin in patients with breast cancer infected with SARS-CoV-2, improving the reliability of the new drug and laying the foundation for further research and development.

7.
Canadian Respiratory Journal ; 2022:5460400, 2022.
Article in English | MEDLINE | ID: covidwho-2020512

ABSTRACT

Objectives: Viral load is important when evaluating viral transmission potential, involving the use of a polymerase chain reaction (PCR) cycle threshold (Ct) value. We aimed to analyze the PCR Ct values of respiratory tract samples taken from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant strains to evaluate these strains' viral dynamics. Methods: This study comprised 361 patients. The Ct values of SARS-CoV-2-related respiratory samples were compared between symptomatic and asymptomatic patients. Results: The median (25th percentile and 75th percentile) nasopharynx and oropharynx SARS-CoV-2 Ct values were 30.5 (24.5-35.0) and 34.5 (30.0-37.0) in the symptomatic group, respectively, and 27.8 (23.4-34.5) and 33.5 (26.0-35.0) in the asymptomatic group, respectively, without significance. In the symptomatic group, subgroup analyses according to age showed the mean nasal Ct value for patients aged >18 years was 29.0 (23.5-34.5), which was significantly lower than that of patients aged 0-4 years and 5-13 years (36.0 (30.5-38.0) and 34.5 (31.0-39.0), respectively). The nasal Ct value for asymptomatic patients aged >18 years was 25.5 (20.9-28.4), which was significantly lower than of patients aged 5-13 years (34.5 (25.6-36.4)). Conclusion: Our findings suggest that the viral loads of asymptomatic and symptomatic patients did not differ significantly. However, adults infected with SARS-CoV-2 had higher nasal viral loads that those of young children.

8.
IEEE Journal of Biomedical & Health Informatics. PP ; 08:08, 2022.
Article in English | MEDLINE | ID: covidwho-2018932

ABSTRACT

Chest X-ray (CXR) is commonly performed as an initial investigation in COVID-19, whose fast and accurate diagnosis is critical. Recently, deep learning has a great potential in detecting people who are suspected to be infected with COVID-19. However, deep learning resulting with black-box models, which often breaks down when forced to make predictions about data for which limited supervised information is available and lack inter-pretability, still is a major barrier for clinical integration. In this work, we hereby propose a semantic-powered explainable model-free few-shot learning scheme to quickly and precisely diagnose COVID-19 with higher reliability and transparency. Specifically, we design a Report Image Explanation Cell (RIEC) to exploit clinically indicators derived from radiology reports as interpretable driver to introduce prior knowledge at training. Meanwhile, multi-task colla-borative diagnosis strategy (MCDS) is developed to construct [Formula: see text]-way [Formula: see text]-shot tasks, which adopts a cyclic and collaborative training approach for producing better generalization performance on new tasks. Extensive experiments demonstrate that the proposed scheme achieves competitive results (accuracy of 98.91%, precision of 98.95%, recall of 97.94% and F1-score of 98.57%) to diagnose COVID-19 and other pneumonia infected categories, even with only 200 paired CXR images and radiology reports for training. Furthermore, statistical results of comparative experiments show that our scheme provides an interpretable window into the COVID-19 diagnosis to improve the performance of the small sample size, the reliability and transparency of black-box deep learning mod-els. Our source codes will be released on https://github.com/AI-medical-diagnosis-team-of-JNU/SPEMFSL-Diagnosis-COVID-19.

9.
Briefings in Bioinformatics ; 06:06, 2022.
Article in English | MEDLINE | ID: covidwho-2017729

ABSTRACT

Drug-drug interactions (DDIs) prediction is a challenging task in drug development and clinical application. Due to the extremely large complete set of all possible DDIs, computer-aided DDIs prediction methods are getting lots of attention in the pharmaceutical industry and academia. However, most existing computational methods only use single perspective information and few of them conduct the task based on the biomedical knowledge graph (BKG), which can provide more detailed and comprehensive drug lateral side information flow. To this end, a deep learning framework, namely DeepLGF, is proposed to fully exploit BKG fusing local-global information to improve the performance of DDIs prediction. More specifically, DeepLGF first obtains chemical local information on drug sequence semantics through a natural language processing algorithm. Then a model of BFGNN based on graph neural network is proposed to extract biological local information on drug through learning embedding vector from different biological functional spaces. The global feature information is extracted from the BKG by our knowledge graph embedding method. In DeepLGF, for fusing local-global features well, we designed four aggregating methods to explore the most suitable ones. Finally, the advanced fusing feature vectors are fed into deep neural network to train and predict. To evaluate the prediction performance of DeepLGF, we tested our method in three prediction tasks and compared it with state-of-the-art models. In addition, case studies of three cancer-related and COVID-19-related drugs further demonstrated DeepLGF's superior ability for potential DDIs prediction. The webserver of the DeepLGF predictor is freely available at http://120.77.11.78/DeepLGF/.

10.
Nano Letters ; 02:02, 2022.
Article in English | MEDLINE | ID: covidwho-2016526

ABSTRACT

The ongoing coronavirus (COVID-19) pandemic requires enormous production of facemasks and related personal protection materials, thereby increasing the amount of nondegradable plastic waste. The core material for facemasks is melt-blown polypropylene (PP) fiber. Each disposable facemask consumes ~0.7 g of PP fibers, resulting in annual global consumption and disposal of more than 1150000 tons of PP fibers annually. Herein, we developed a laser-assisted melt-blown (LAMB) technique to manufacture PP nanofibers with a quality factor of 0.17 Pa-1 and significantly reduced the filter's weight. We demonstrated that a standard surgical facemask could be made with only 0.13 g of PP nanofibers, saving approximately 80% of the PP materials used in commercial facemasks. Theoretical analysis and modeling were also conducted to understand the LAMB process. Importantly, nanofibers can be easily scaled up for mass production by upgrading traditional melt blown line with scanning laser-assisted melt-blown (SLAMB).

11.
Jama ; 26:26, 2022.
Article in English | MEDLINE | ID: covidwho-2013218

ABSTRACT

Importance: Despite the expansion of SARS-CoV-2 testing, available tests have not received Emergency Use Authorization for performance with self-collected anterior nares (nasal) swabs from children younger than 14 years because the effect of pediatric self-swabbing on SARS-CoV-2 test sensitivity is unknown. Objective: To characterize the ability of school-aged children to self-collect nasal swabs for SARS-CoV-2 testing compared with collection by health care workers. Design, Setting, and Participants: Cross-sectional study of 197 symptomatic children and adolescents aged 4 to 14 years old. Individuals were recruited based on results of testing in the Children's Healthcare of Atlanta system from July to August 2021. Exposures: Children and adolescents were given instructional material consisting of a short instructional video and a handout with written and visual steps for self-swab collection. Participants first provided a self-collected nasal swab. Health care workers then collected a second specimen. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 detection and relative quantitation by cycle threshold (Ct) in self- vs health care worker-collected nasal swabs when tested with a real-time reverse transcriptase-polymerase chain reaction test with Emergency Use Authorization. Results: Among the study participants, 108 of 194 (55.7%) were male and the median age was 9 years (IQR, 6-11). Of the 196 participants, 87 (44.4%) tested positive for SARS-CoV-2 and 105 (53.6%) tested negative by both self- and health care worker-collected swabs. Two children tested positive by self- or health care worker-collected swab alone;1 child had an invalid health care worker swab. Compared with health care worker-collected swabs, self-collected swabs had 97.8% (95% CI, 94.7%-100.0%) and 98.1% (95% CI, 95.6%-100.0%) positive and negative percent agreement, respectively, and SARS-CoV-2 Ct values did not differ significantly between groups (mean [SD] Ct, self-swab: 26.7 [5.4] vs health care worker swab: 26.3 [6.0];P = .65). Conclusions and Relevance: After hearing and seeing simple instructional materials, children and adolescents aged 4 to 14 years self-collected nasal swabs that closely agreed on SARS-CoV-2 detection with swabs collected by health care workers.

12.
Innovation in Aging ; 5:38-38, 2021.
Article in English | Web of Science | ID: covidwho-2011845
13.
Innovation in Aging ; 5:39-39, 2021.
Article in English | Web of Science | ID: covidwho-2011844
14.
Journal of Xi'an Jiaotong University (Medical Sciences) ; 43(5):646-652, 2022.
Article in Chinese | EMBASE | ID: covidwho-2010479

ABSTRACT

Since the outbreak of a new round of COVID-19 in Xi'an on December 9, 2021, the response capability of the city's and even the province's health system to major public health emergencies has been severely tested and challenged. Faced with the rapid spread of the Delta strain and its multiple hidden transmission chains, The First Affiliated Hospital of Xi'an Jiaotong University, as the largest comprehensive tertiary hospital in Northwest China, has successfully applied the 4R crisis management theory to prevent the pandemic spread and continue the clinic work as well. Balancing of epidemic prevention and medical service with scientific, orderly and standardized procedures has been achieved. Hence, we have contributed to the "The First Affiliated Hospital of Xi'an Jiaotong University model" for controlling the epidemic and restoring normal production and life as soon as possible under the guidance and command of the National Health Commission and provincial and municipal health administrative institutions at all levels. The First Affiliated Hospital of Xi'an Jiaotong University has improved the present management system and enhanced its management level amid epidemic prevention and control. This paper aims to provide new epidemic prevention experience under the changeable environment by explaining and summarizing our theoretical basis, operation mode and practical effects of our management system.

16.
Journal of Laryngology and Otology ; 2022.
Article in English | EMBASE | ID: covidwho-2008232

ABSTRACT

Introduction This study aimed to investigate the use of HaNC-RC v.2 in a primary care setting and to evaluate the impact of the risk calculator on the number of referrals stratified by urgency and cancer yield. Methods Referrals between 04/19-08/19 and 04/20-07/20 (pre-risk calculator) and 08/20-06/21 (post-risk calculator) were analysed. Referral urgency, HaNC-RC v.2 score, cancer diagnosis, cancer type and further investigations were recorded. Results 2023 patient encounters were analysed;1110 (55%) referrals pre-and 913 (45%) post-HaNC-RC v.2. A higher proportion of older (p<0.001) and male (p<0.013) patients were seen post-HaNC-RC v.2. All cancer cases were seen on the USOC pathway post-HaNC-RC v.2, however a higher proportion of patients were seen as USOC (51.1%vs83.5%,p<0.001). Overall, the cancer diagnosis rate increased from 2.7% to 4.1%. Conclusions The HaNC-RC v.2 had high sensitivity in cancer diagnosis. More studies are required to optimise the predicted vs. actual cancer probability gap. (Word count: 267).

17.
Journal of medical virology ; 2022.
Article in English | MEDLINE | ID: covidwho-2007104

ABSTRACT

In 2019, an outbreak of pharyngoconjunctival fever (PCF) occurred at a swimming center in Zhejiang Province, China. A total of 97 (13.55%) of the 716 amateur swimmers had illnesses, with 24 patients (24.74%) hospitalized in the pediatric ward. Human adenovirus serotype 7 (HAdV-7) was isolated from one concentrated water from the swimming pool, and 20 of 97 positive cases without liver damage. This outbreak led to a nosocomial outbreak in the pediatric ward, in which one nurse had a fever and was confirmed to be adenovirus positive. The hexon, fiber, and penton genes from 20 outbreak cases, one water sample, and one nurse had 100% homology. Furthermore, two cases admitted to the pediatric ward, two parents, and one doctor were confirmed to be human coronaviruses (HCoV-229E) positive. Finally, all outbreak cases had fully recovered, regardless of a single infection (adenovirus or HCoV-229E) or co-infection of these two viruses simultaneously. Thus, PCF and acute respiratory disease outbreaks in Zhejiang were caused by the completely homologous type 7 adenovirus and HCoV-229E, respectively. The swimming pool water contaminated with HAdV-7 was most likely the source of the PCF outbreak, whereas nosocomial transmission might be the source of HCoV-229E outbreak. This article is protected by copyright. All rights reserved.

18.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2005664

ABSTRACT

Background: GC012F is a B cell maturation antigen (BCMA)/CD19 dual-targeting CAR-T developed on the novel FasT CAR-T platform with overnight manufacturing and designed to improve depth of response and efficacy. Data was presented at ASCO and EHA 2021 for initial 19 pts. We present updated data for study (NCT04236011;NCT04182581) with longer follow up and 9 additional pts treated (n = 28) in 3 different dose levels. Methods: From October 2019 to November 2021, 28 heavily pretreated RRMM pts (age 27-76) median of 5 prior lines (range 2-9) were treated on a single-arm, open label, multicenter Investigator Initiated Trial receiving a single infusion of GC012F. 89.3% (25/ 28) were high risk (HR- mSMART), 8 pts had EM disease, 3 had never achieved a CR including after transplant, 1 pts presented with plasma cell leukemia, 24/28 pts were refractory to last therapy, 3 pts primary refractory. 9/28 pts had received prior anti-CD38, 27/28 pts prior IMiDs. 26/28 pts were refractory to PI, 26/28 pts to IMiDs. After lymphodepletion over 2-3 days (30 mg/m2/d, 300mg/ m2/d Flu/Cy) GC012F was administered as single infusion at 3 dose levels: 1x105/kg (DL1) n = 2, 2x105/kg (DL2) n = 10 and 3x105/kg (DL3) n = 16. Results: As of Jan 26th 2022, 28 pts - median follow-up (f/ u) 6.3 mths (1.8-29.9) - had been evaluated for response. Overall response rate (ORR) in DL1 was 100% (2/2)- DL 2 -80% (8/10) DL 3 -93.8% (15/16) with 27 pts MRD negative by flow cytometry (sensitivity 10-4-10-6). 100% of MRD assessable pts (27/27) achieved MRD negativity. One patient out of 28 could not get assessed. At d28, 21/24 assessable patients were MRD negative (81.5%), 4/ 28 pts could not get d28 MRD assessment f/u due to COVID-19 restrictions however were assessed at a later timepoint. To date best response is MRD- sCR in 21/28 patients(75.0%) across all dose levels. Some pts after short f/u show responses that are still deepening. Cytokine Release Syndrome (CRS) was mostly low grade: gr 0 n = 3 (10.7%), gr 1-2 n = 23 (82.1%), gr 3 n = 2 (7.1%) - no gr 4/5 CRS and no ICANs were observed (Graded by ASBMT criteria). Median duration of CRS was 3 d (1-8 d). PK results showed no difference amongst dose levels DL1 to DL3. Overall, CAR-T median Tmax was 10 d (range 8-14 d), median peak copy number (Cmax) was 97009 (16,011-374,346) copies /μg DNA with long duration of persistence of up to d793 (data cut-off). CAR-T geometric mean AUC0-28 for DL1, DL2 and DL3 were 468863, 631540 and 581620 copies/μg DNA×day, respectively. Pts continue to be monitored for safety and efficacy including DOR. Conclusions: BCMA-CD19 dual FasT CAR-T GC012F continues to provide deep and durable responses with a favorable safety profile in additional RRMM pts across all dose levels demonstrating a very high MRD negativity rate including in pts refractory to anti-CD38, PI and IMIDs. GC012F is currently being studied in earlier lines of therapy as well as additional indications.

19.
International Social Work ; 2022.
Article in English | Web of Science | ID: covidwho-2005553

ABSTRACT

As the first review to systematically explore the scope and application of Chinese social work research ethics, this study incorporated web-crawling technology in the scoping review process and identified 18 eligible studies from 1168 publications from January 2020 to July 2021. Findings suggest that social work scholars are aware of research ethics when conducting human subjects research in the Chinese population. Yet, many failed to fully demonstrate practical considerations of internationally accepted ethical principles (e.g. respect for persons). We discuss education on research ethics, new challenges of the digital age, and considerations of Chinese culture in developing ethical protocols for social work research in China.

20.
Journal of Virology ; : e0090722, 2022.
Article in English | MEDLINE | ID: covidwho-2001774

ABSTRACT

The rapid global emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused serious health problems, highlighting the urgent need for antiviral drugs. The viral main protease (Mpro) plays an important role in viral replication and thus remains the target of choice for the prevention or treatment of several viral diseases due to high sequence and structural conservation. Prolonged use of viral protease inhibitors can lead to the development of mutants resistant to those inhibitors and to many of the available antiviral drugs. Here, we used feline infectious peritonitis virus (FIPV) as a model to investigate its development of resistance under pressure from the Mpro inhibitor GC376. Passage of wild-type (WT) FIPV in the presence of GC376 selected for a mutation in the nsp12 region where Mpro cleaves the substrate between nsp12 and nsp13. This mutation confers up to 3-fold resistance to GC376 and nirmatrelvir, as determined by EC50 assay. In vitro biochemical and cellular experiments confirmed that FIPV adapts to the stress of GC376 by mutating the nsp12 and nsp13 hydrolysis site to facilitate cleavage by Mpro and release to mediate replication and transcription. Finally, we demonstrate that GC376 cannot treat FIP-resistant mutants that cause FIP in animals. Taken together, these results suggest that Mpro affects the replication of coronaviruses (CoVs) and the drug resistance to GC376 by regulating the amount of RdRp from a distant site. These findings provide further support for the use of an antiviral drug combination as a broad-spectrum therapy to protect against contemporary and emerging CoVs. IMPORTANCE CoVs cause serious human infections, and antiviral drugs are currently approved to treat these infections. The development of protease-targeting therapeutics for CoV infection is hindered by resistance mutations. Therefore, we should pay attention to its resistance to antiviral drugs. Here, we identified possible mutations that lead to relapse after clinical treatment of FIP. One amino acid substitution in the nsp12 polymerase at the Mpro cleavage site provided low-level resistance to GC376 after selection exposure to the GC376 parental nucleoside. Resistance mutations enhanced FIPV viral fitness in vitro and attenuated the therapeutic effect of GC376 in an animal model of FIPV infection. Our research explains the evolutionary characteristics of coronaviruses under antiviral drugs, which is helpful for a more comprehensive understanding of the molecular basis of virus resistance and provides important basic data for the effective prevention and control of CoVs.

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