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1.
J Virol ; : e0040022, 2022.
Article in English | PubMed | ID: covidwho-1807320

ABSTRACT

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic enteric coronavirus that causes high mortality in piglets. Interferon (IFN) responses are the primary defense mechanism against viral infection;however, viruses always evolve elaborate strategies to antagonize the antiviral action of IFN. Previous study showed that PEDV nonstructural protein 7 (nsp7), a component of the viral replicase polyprotein, can antagonize ploy(I:C)-induced type I IFN production. Here, we found that PEDV nsp7 also antagonized IFN-α-induced JAK-STAT signaling and the production of IFN-stimulated genes. PEDV nsp7 did not affect the protein and phosphorylation levels of JAK1, Tyk2, STAT1, and STAT2 or the formation of the interferon-stimulated gene factor 3 (ISGF3) complex. However, PEDV nsp7 prevented the nuclear translocation of STAT1 and STAT2. Mechanistically, PEDV nsp7 interacted with the DNA binding domain of STAT1/STAT2, which sequestered the interaction between karyopherin α1 (KPNA1) and STAT1, thereby blocking the nuclear transport of ISGF3. Collectively, these data reveal a new mechanism developed by PEDV to inhibit type I IFN signaling pathway. IMPORTANCE In recent years, an emerging porcine epidemic diarrhea virus (PEDV) variant has gained attention because of serious outbreaks of piglet diarrhea in China and the United States. Coronavirus nonstructural protein 7 (nsp7) has been proposed to act with nsp8 as part of an RNA primase to generate RNA primers for viral RNA synthesis. However, accumulating evidence indicates that coronavirus nsp7 can also antagonize type I IFN production. Our present study extends previous findings and demonstrates that PEDV nsp7 also antagonizes IFN-α-induced IFN signaling by competing with KPNA1 for binding to STAT1, thereby enriching the immune regulation function of coronavirus nsp7.

2.
PubMed; 2022.
Preprint in English | PubMed | ID: ppcovidwho-333410

ABSTRACT

We describe Bioformer team's participation in the multi-label topic classification task for COVID-19 literature (track 5 of BioCreative VII). Topic classification is performed using different BERT models (BioBERT, PubMedBERT, and Bioformer). We formulate the topic classification task as a sentence pair classification problem, where the title is the first sentence, and the abstract is the second sentence. Our results show that Bioformer outperforms BioBERT and PubMedBERT in this task. Compared to the baseline results, our best model increased micro, macro, and instance-based F1 score by 8.8%, 15.5%, 7.4%, respectively. Bioformer achieved the highest micro F1 and macro F1 scores in this challenge. In post-challenge experiments, we found that pretraining of Bioformer on COVID-19 articles further improves the performance.

3.
Virology ; 571:12-20, 2022.
Article in English | EMBASE | ID: covidwho-1799672

ABSTRACT

An epidemic owing to Norovirus (NoV) has recently been occurring worldwide. Severe cases of NoV can lead to patient death, resulting in significant public health problems. In the early stages of infection, antagonizing the production of host interferon (IFN) is an important strategy for viruses to establish infection. However, the relationship between NoV and interferon and its mechanism remains unclear. In this study, the 3C-like protease encoded by NoV was found to effectively suppress Sendai virus (SEV)-mediated IFN-β production by cleaving the NF-κB essential modulator (NEMO). Glutamine 205 is the site of NoV3CLpro-mediated cleavage of NEMO and this cleavage suppresses the ability of NEMO to activate downstream IFN production. These findings demonstrate that NoV3CLpro-induced cleavage limits NEMO to the activation of type I IFN signaling. In summary, our findings indicate that NoV3CLpro is a new interferon antagonist, and enhances our understanding of the escape of innate immunity mediated by NoV3CLpro.

4.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-329391

ABSTRACT

Background: Easily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 ( ClinicalTrials.gov NCT04405570 ). Methods: Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. Results: Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. Conclusions: Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

5.
European Respiratory Journal ; 58:2, 2021.
Article in English | Web of Science | ID: covidwho-1706837
6.
American Journal of Translational Research ; 14(1):501-510, 2022.
Article in English | EMBASE | ID: covidwho-1688163

ABSTRACT

Objectives: Traditional Chinese medicine has been reported to be effective in the treatment of epidemic diseases. Here, we aimed to investigate the effects of combined therapy of Chinese and western medicine on coronavirus disease 2019 (COVID-19). Methods: A total of 60 patients diagnosed with COVID-19 were enrolled. Both the ordinary and severely affected patients were randomly divided into Groups A-C each with 10 cases each. The patients in Group A-C received Western medicine, Western medicine + traditional Chinese medicine, and Western medicine + traditional Chinese medicine + high dose of vitamin C, respectively. The time of disease recovery, symptoms disappearance, chest CT improvement, and tongue amelioration was recorded. Leukocyte, neutrophil and lymphocyte were monitored, as well as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalitonin (PCT), inflammatory factors, partial pressure of oxygen and carbon dioxide (PaCO2) and oxygenation index (PaO2). Urinary tract stones, liver function, and other side-effects such as gastrointestinal dysfunction were also investigated. Results: Traditional Chinese medicine enhanced the effect of Western medicine, including the reduction of CRP, ESR, PCT, and inflammatory factors, and the increase of leukocyte, neutrophil, and lymphocyte counts, and the improvement of respiratory rate, PaO2, PaCO2, and oxygenation index. Traditional Chinese medicine combined with high-dose Vitamin C therapy more effectively shortened the time of disease recovery, symptom disappearance, chest CT improvement, and tongue amelioration. Conclusions: a combined therapy of Western medicine, traditional Chinese medicine, and high dose of Vitamin C results in a most effective outcome in the treatment of COVID-19.

7.
European Heart Journal ; 42(SUPPL 1):876, 2021.
Article in English | EMBASE | ID: covidwho-1554146

ABSTRACT

Introduction: Presence of heart failure is associated with a poor prognosis in patients with COVID-19. The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of pre-clinical heart failure, is associated with survival in patients hospitalised with COVID-19. Methods: A retrospective outcome study was performed in patients hospitalised with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King's Health Partners in South London UK. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar co-morbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic. Results: In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory and echocardiographic characteristics including age, co-morbidities and biochemical markers (figure 1). A cut-off value of 25% for EF1 gave a hazard ratio of 5.23 (95% CI: 2.85-9.60, p<0.001) unadjusted and 4.83 (95% CI: 2.35-9.95, p<0.001) when adjusted for demographics, co-morbidities, hs-cTnI and CRP (figure 2). EF1 was similar in patients with and without COVID-19 (23.2±7.3 vs 22.0±7.6%, p=0.092, adjusted for prevalence of risk factors and co-morbidities). Conclusion: Impaired first-phase ejection fraction is strongly associated with mortality in COVID-19 and probably reflects pre-existing, pre-clinical heart failure.

8.
Lancet Infectious Diseases ; 21(5):617-628, 2021.
Article in English | Web of Science | ID: covidwho-1510470

ABSTRACT

Methods This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect. Findings 27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15middot6% (95% CI 15middot2-16middot0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0-1 years were significantly more likely to be infected than children aged 2-5 years (odds ratio [OR] 2middot20, 95% CI 1middot40-3middot44) and children aged 6-12 years (1middot53, 1middot01-2middot34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1middot58, 1middot28-1middot95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0middot21, 0middot14-0middot31). Symptomatic cases were more likely to infect others before symptom onset than after (1middot42, 1middot30-1middot55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0middot25 [95% CI 0middot24-0middot26] to 0middot12 [0middot10-0middot13]) and by 63% among secondary cases (from 0middot17 [0middot16-0middot18] to 0middot063 [0middot057-0middot070]). Interpretation Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available.

9.
Acta Medica Mediterranea ; 37(4):2187-2189, 2021.
Article in English | EMBASE | ID: covidwho-1326087

ABSTRACT

Objective: This study was designed to analyze the characteristics of the novel coronavirus disease 2019 (COVID-19) epidemic in seven clusters in the city of Chenzhou, China, to act as a reference for the prevention and control of the COVID-19 epidemic. Methods: The data of confirmed COVID-19 cases reported between January 23 and February 24, 2020, were obtained from the Chenzhou infectious disease surveillance system. In line with the diagnostic criteria of the Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Sixth Edition, Trial Implementation), 33 patients in seven clusters were selected as the research subjects, and epidemiological data were collected for descriptive analysis. Results: Between January 23 and February 24, 2020, 46 patients with COVID-19 were diagnosed in the city of Chenzhou, comprising 24 male patients and 22 female patients. The age of these patients ranged from seven months to 72 years old. The average age was 35.88 ± 17.98 and included 13 individual patients and 33 patients in seven clusters. Six clusters were exposed to the virus in Wuhan (the Wuhan group), and the other cluster was exposed to it in Shenzhen (the Shenzhen group). In the Wuhan group, the disease was spread in clusters of one family. The incubation period was 1-9 days, and the average length of hospital stay was 13.25 ± 2.67 days. Only close contacts were infected. In the Shenzhen group, three different families were infected in the same cluster. The incubation period was 11-14 days, the time of positive-to-negative conversion in the nucleic acid test was longer, and the average hospitalization time was 17.33 ± 5.87 days. Contacts who were not in close contact were infected. Conclusion: Patients are infectious in the incubation period, and asymptomatic patients are also infectious. The infectivity of the Shenzhen group was stronger than that of the Wuhan group. In the Shenzhen group, the time of positive-to-negative conversion of COVID-19 nucleic acid was longer, and the length of hospital stay was longer.

10.
Developmental Medicine and Child Neurology ; 63(SUPPL 2):76, 2021.
Article in English | EMBASE | ID: covidwho-1276620

ABSTRACT

Introduction: During the Covid-19 outbreak, everything was locked down early in February 2020 in China. The Chinese Association of Rehabilitation Medicine Pediatric Rehabilitation Committee (CARMPRC) quickly responded to the challenges and created a plan to provide rehabilitation services of afflicted children and support for the front line staff treating the infected . Patients and Methods: (1) Working closely with front line medical staff in Wuhan and providing early intervention programs for children who had been infected with COVID-19. The Rehabilitation Department of Wuhan Children's Hospital is the only designated hospital for the treatment of children with COVID-19 in Wuhan. Our members formulated the rehabilitation project for early intervention of children who were infected with COVID-19. (2) The dissemination of virus prevention information in common languages, via every channel of media which helped inform children and families at home. (3) The set up of online therapy and conferences: more than 20 rehabilitation institutions held more than 40 free online consultation courses with over 48,000 participants. Results: More than 2000 families with children with disabilities had 'home service' during the lock-down and more than 7700 people utilized the online services and lectures. The infection rate among these children and staff was zero. Conclusion: The pandemic caused a dramatic change to the life and work of the people in China. CARMPRC managed the situation in a way that was suitable and feasible to meet the needs of these children and families. Through our professionals quick and effective response to the virus, these actions resulted in a successful campaign against COVID-19 in China.

11.
Topics in Antiviral Medicine ; 29(1):304-305, 2021.
Article in English | EMBASE | ID: covidwho-1250563

ABSTRACT

Background: The emergence of SARS-CoV-2 viral variants threatens current anti-viral and preventative strategies, including monoclonal antibodies and vaccines. Critically, the limited supply of vaccines and the complex logistics surrounding the delivery of infusion-based therapies herald the need for an easily produced, distributed, and specific direct-acting antiviral for COVID-19 that limits progression of illness and ideally prevents transmission. Methods: The efficacy of molnupiravir was evaluated in a double-blind, randomized, placebo-controlled, Phase 2 dose-range finding study using realtime polymerase chain reaction (RT-PCR) and virus isolation was conducted at 11 study sites in the U.S. Participants were randomized if they had signs or symptoms of COVID-19 within 7 days, and a positive SARS-CoV-2 RT-PCR within 4 days of enrollment. Initially, participants were randomized in a 1:1 ratio to receive 200 mg molnupiravir or placebo twice daily for 5 days. Subsequently, in the dose-range finding portion of the study, participants were randomized in a 3:1 ratio to receive 200, 400, or 800 mg molnupiravir or placebo twice daily for 5 days. Nasopharyngeal swabs were analyzed from 175 subjects at enrollment, Day 3, and Day 5 for SARS-CoV-2 infectivity. Samples were stored at 4°C for up to 72 hours, shipped refrigerated, aliquoted, and stored at -80°C until testing. Vero E6 cell monolayers were infected with the sample for 1 hour. Culture medium was analyzed for viral load at 2 and 5 days post-infection by RT-PCR. Results: Seventy-eight (45%) participants, median 4.62 days (min. 1.40, max. 7.54) from symptom onset, had a positive SARS-CoV-2 culture at enrollment (52 on active and 26 on placebo). The percentage of participants with a positive viral culture at enrollment who were positive on Day 3 was 20.4% on active and 28% on placebo (p = 0.56). At day 5, 24% of placebo participants were culturethe positive compared to none treated with molnupiravir (p = 0.001). Between treatment, comparisons were performed using Fisher's exact test. Conclusion: This is the first demonstration of reduced infectiousness by antiviral therapy in people with SARS-2 infection. This simple, short-course oral therapy may benefit individuals and public health and is unlikely to be impacted by spike-protein variants.

12.
Chinese Journal of General Practitioners ; 19(4):273-276, 2020.
Article in Chinese | Scopus | ID: covidwho-1143634

ABSTRACT

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has rapidly swept across the country, posing great challenges to the public health in China. In the epidemic prevention and control, primary care practitioners play a very important role in patient triage, home-based visit, follow-up as well as screening at the checkpoints. However, due to the lack of necessary protective equipment and heavy workload, primary care practitioners are facing great challenges in containing the epidemic outbreak. Based on the relevant guidelines and practice in primary care, this article summarizes the challenges primary care practitioners encountered and coping strategies for containing the epidemic outbreak in primary care settings to provide reference for improvement of their working quality. © 2020 Chinese Medical Association

13.
Chinese Journal of General Practitioners ; 19(7):598-602, 2020.
Article in Chinese | Scopus | ID: covidwho-1143631

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19), in order to relieve the pressure of outpatient services, especially fever clinic service in hospital, and to avoid the cross-infection among patients, the general practice team of Sir Run Run Shaw Hospital has opened free online counseling service. This article introduces the workflow and related contents of the online counseling mode of general practice under the COVID-19 epidemic situation, so as to provide reference for medical institutions to implement "internet+general practice" mode of counseling service. © 2020 Chinese Medical Association

14.
15.
Proceedings - 2020 IEEE 19th International Conference on Trust, Security and Privacy in Computing and Communications, TrustCom 2020 ; : 277-284, 2020.
Article | Scopus | ID: covidwho-1112167

ABSTRACT

Over the years, public health has faced a large number of challenges like COVID-19. Medical cloud computing is a promising method since it can make healthcare costs lower. The computation of health data is outsourced to the cloud server. If the encrypted medical data is not decrypted, it is difficult to search for those data. Many researchers have worked on searchable encryption schemes that allow executing searches on encrypted data. However, many existing works support single-keyword search. In this article, we propose a patient-centered fine-grained attribute-based encryption scheme with multi-keyword search (CP-ABEMKS) for medical cloud computing. First, we leverage the ciphertext-policy attribute-based technique to construct trapdoors. Then, we give a security analysis. Besides, we provide a performance evaluation, and the experiments demonstrate the efficiency and practicality of the proposed CP-ABEMKS. © 2020 IEEE.

18.
Chinese Journal of Laboratory Medicine ; 43(9):889-893, 2020.
Article in Chinese | EMBASE | ID: covidwho-984934

ABSTRACT

Objective: To investigate the interference factors causing false-positive result of novel coronavirus IgM antibody detected by gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA). Methods: A total of 71 serum from different pathogen infections and related chronic diseases patients were collected from the Affiliated Hospital of North Sichuan Medical College from January 22, 2020 to February 15, 2020. GICA and ELISA were used to detect 2019-nCoV IgM in 71 serum, including 5 influenza A virus (Flu A) IgM positive serum, 5 influenza B virus (Flu B) IgM positive serum, 5 Mycoplasma pneumonia (MP) IgM positive serum, 5 Legionella pneumophila (LP) IgM positive serum, 29 rheumatoid factor (RF) IgM positive serum, 5 hypertension patients serum, 5 diabetes mellitus patients serum, 6 human immunodeficiency virus (HIV) infection patients serum and 6 COVID-19 patients serum. The interference factors causing false positive results of the two methods were analyzed, and urea dissociation test was employed to dissociate the 2019-nCoV IgM positive serum using the best dissociation concentration. Statistical analyses were performed by SPSS, version 19.0. Results: 2019-nCoV IgM was positive in 18 cases of middle-high level RF-IgM positive serum and 6 cases of 2019-nCoV-infected serum detected by two methods, and the other 47 serum were negative. When the dissociation concentration of urea was 6 mol/L, 2019-nCoV IgM was negative in 17 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by GICA. When the urea dissociation concentration was 4 mol/L, dissociation time was 10 min and the avidity index<0.46 was set as negative, 2019-nCoV IgM was negative in 15 cases of middle-high level RF-IgM positive serum and positive in 6 cases of 2019-nCoV-infected serum detected by ELISA. Conclusion: The middle-high level of RF-IgM could cause false positive results of 2019-nCoV IgM detected by GICA and ELISA, and the urea dissociation test would be helpful for reducing the probability of false-positive results of 2019-nCoV IgM test.

19.
Chinese Journal of Clinical Pharmacology and Therapeutics ; 25(8):895-902, 2020.
Article in Chinese | EMBASE | ID: covidwho-846922

ABSTRACT

AIM: To analyze the adverse events (AE) of tocilizumab by using the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports related to tocilizumab were extracted from the FAERS database. Disproportionality analysis of reporting odds ratio (ROR) and Medicines and Healthcare Products Regulatory Agency (MHRA) methods were performed for safety signal detection. RESULTS: A total of 19 773 reports associated with tocilizumab as the primary or secondary suspected drugs were extracted from the FAERS database between July 2014 to March 2019. AEs of drug ineffective, pain, drug intolerance, fatigue and rash were commonly reported. There were 13 642 serious AE reports, and 602 reports of death outcome. The proportion of serious and death outcome AEs of male patients was significantly higher than female, and these proportions were significantly higher in children and elderly compared with others. Respectively 602 and 490 of tocilizumab signals were detected by ROR method and MHRA method, including common AEs such as infection, drug hypersensitivity, leukopenia, and hepatic enzyme increased, and signals not indicated in label, for instance, pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, were also detected. CONCLUSION: The commonly reported AEs of tocilizumab include drug inefficiency, pain, drug intolerance, fatigue and rash. Pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, which not indicated in label, should be further assessed and be cautious in COVID-19 treatment.

20.
Sn Comprehensive Clinical Medicine ; (2523-8973 (Electronic))2020.
Article in English | PMC | ID: covidwho-841862

ABSTRACT

Russia has been currently in the “hard-hit” area of the COVID-19 outbreak, with more than 396,000 confirmed cases as of May 30. It is necessary to analyze and predict its epidemic situation to help formulate effective public health policies. Autoregressive integrated moving average (ARIMA) models were developed to predict the cumulative confirmed, dead, and recovered cases, respectively. R 3.6.2 software was used to fit the data from January 31 to May 20, 2020, and predict the data for the next 30 days. The COVID-19 epidemic in Russia was divided into two stages and reached its peak in May. The epidemic began to stabilize on May 19. The case fatality rate has been at an extremely low level. ARIMA (2,2,1), ARIMA (3,2,0), and ARIMA (0,2,1) were the models of cumulative confirmed, dead, and recovered cases, respectively. After testing, the mean absolute percentage error (MAPE) of three models were 0.6, 3.9, and 2.4, respectively. This paper indicates that Russia’s health system capacity can effectively respond to the COVID-19 pandemic. Three ARIMA models have a good fitting effect and can be used for short-term prediction of the COVID-19 trend, providing a theoretical basis for Russia to formulate new intervention policies. FAU - Fang, Lanlan

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