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1.
Antimicrob Agents Chemother ; 65(7): e0009721, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1486469

ABSTRACT

Efforts to mitigate the coronavirus disease 2019 (COVID-19) pandemic include the screening of existing antiviral molecules that could be repurposed to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although SARS-CoV-2 replicates and propagates efficiently in African green monkey kidney (Vero) cells, antivirals such as nucleos(t)ide analogs (NUCs) often show decreased activity in these cells due to inefficient metabolization. SARS-CoV-2 exhibits low viability in human cells in culture. Here, serial passages of a SARS-CoV-2 isolate (original-SARS2) in the human hepatoma cell clone Huh7.5 led to the selection of a variant (adapted-SARS2) with significantly improved infectivity in human liver (Huh7 and Huh7.5) and lung cancer (unmodified Calu-1 and A549) cells. The adapted virus exhibited mutations in the spike protein, including a 9-amino-acid deletion and 3 amino acid changes (E484D, P812R, and Q954H). E484D also emerged in Vero E6-cultured viruses that became viable in A549 cells. Original and adapted viruses were susceptible to scavenger receptor class B type 1 (SR-B1) receptor blocking, and adapted-SARS2 exhibited significantly less dependence on ACE2. Both variants were similarly neutralized by COVID-19 convalescent-phase plasma, but adapted-SARS2 exhibited increased susceptibility to exogenous type I interferon. Remdesivir inhibited original- and adapted-SARS2 similarly, demonstrating the utility of the system for the screening of NUCs. Among the tested NUCs, only remdesivir, molnupiravir, and, to a limited extent, galidesivir showed antiviral effects across human cell lines, whereas sofosbuvir, ribavirin, and favipiravir had no apparent activity. Analogously to the emergence of spike mutations in vivo, the spike protein is under intense adaptive selection pressure in cell culture. Our results indicate that the emergence of spike mutations will most likely not affect the activity of remdesivir.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Chlorocebus aethiops , Humans , Pandemics , Spike Glycoprotein, Coronavirus , Virus Replication
2.
J Speech Lang Hear Res ; 64(3): 1008-1022, 2021 03 17.
Article in English | MEDLINE | ID: covidwho-1454832

ABSTRACT

Aim The aim of this scoping review is to identify the eye tracking paradigms and eye movement measures used to investigate auditory and reading comprehension deficits in persons with aphasia (PWA). Method MEDLINE via PubMed, Cochrane, CINAHL, Embase, PsycINFO, OTseeker, Scopus, Google Scholar, Grey Literature Database, and ProQuest Search (Dissertations & Theses) were searched for relevant studies. The Covidence software was used to manage the initial and full-text screening process for the search. Results and Discussion From a total of 1,803 studies, 68 studies were included for full-text screening. In addition, 418 records from gray literature were also screened. After full-text screening, 16 studies were included for this review-12 studies for auditory comprehension in PWA and four studies for reading comprehension in PWA. The review highlights the use of common eye tracking paradigms used to study language comprehension in PWA. We also discusse eye movement measures and how they help in assessing auditory and reading comprehension. Methodological challenges of using eye tracking are discussed. Conclusion The studies summarized in this scoping review provide evidence that the eye tracking methods are beneficial for studying auditory and reading comprehension in PWA.


Subject(s)
Aphasia , Comprehension , Eye Movements , Eye-Tracking Technology , Humans
3.
Obstet Gynecol ; 135(5): 1070-1083, 2020 05.
Article in English | MEDLINE | ID: covidwho-1455363

ABSTRACT

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the efficacy of adjuvant human papillomavirus (HPV) vaccination in preventing recurrent cervical intraepithelial neoplasia (CIN) 2 or greater after surgical excision. DATA SOURCES: Electronic databases (Cochrane, PubMed, EMBASE, MEDLINE, Scopus, and ClinicalTrials.gov) were searched for studies comparing surgical excision alone to surgical excision with adjuvant HPV vaccination for CIN 2 or greater. Studies published from January 1990 to January 2019 were included. METHODS: A total of 5,901 studies were reviewed. The primary outcomes evaluated included: recurrence of CIN 2 or greater, CIN 1 or greater, and HPV 16,18 associated CIN within 6-48 months. We used Covidence software to assist with screening, and meta-analysis was performed using Review Manager. TABULATION, INTEGRATION, AND RESULTS: Six studies met inclusion criteria and were included in the final analysis. In total 2,984 women were included; 1,360 (45.6%) received adjuvant HPV vaccination after surgical excision, and 1,624 (54.4%) received either placebo or surgical management alone for CIN 2 or greater. Recurrence of CIN 2 or greater occurred within 6-48 months in 115 women (3.9%) overall; however, recurrence was significantly lower for vaccinated women: 26 of 1,360 women (1.9%) vs 89 of 1,624 unvaccinated women (5.9%) (relative risk [RR] 0.36 95% CI 0.23-0.55). The risk of CIN 1 or greater was also significantly lower with adjuvant HPV vaccination, occurring in 86 of 1,360 vaccinated women (6.3%) vs 157 of 1,624 unvaccinated women (9.7%) (RR 0.67 95% CI 0.52-0.85). Thirty-five women developed recurrent CIN 2 or greater lesions specific to HPV 16,18; nine received adjuvant vaccination (0.9%) vs 26 who were unvaccinated (2.0%) (RR 0.41 95% CI 0.20-0.85). CONCLUSION: Adjuvant HPV vaccination in the setting of surgical excision for CIN 2 or greater is associated with a reduced risk of recurrent cervical dysplasia overall and a reduction in the risk of recurrent lesions caused by the most oncogenic strains (HPV 16,18). Human papillomavirus vaccination should therefore be considered for adjuvant treatment in patients undergoing surgical excision for CIN 2 or greater. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019123786.


Subject(s)
Cervical Intraepithelial Neoplasia/drug therapy , Neoplasm Recurrence, Local/prevention & control , Papillomavirus Infections/complications , Papillomavirus Vaccines/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Adult , Cervical Intraepithelial Neoplasia/surgery , Cervical Intraepithelial Neoplasia/virology , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/virology , Papillomavirus Infections/virology , Treatment Outcome , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/virology , Young Adult
4.
Cell Mol Immunol ; 18(8): 1847-1860, 2021 08.
Article in English | MEDLINE | ID: covidwho-1387308

ABSTRACT

CD4+ T cells orchestrate adaptive immune responses via binding of antigens to their receptors through specific peptide/MHC-II complexes. To study these responses, it is essential to identify protein-derived MHC-II peptide ligands that constitute epitopes for T cell recognition. However, generating cells expressing single MHC-II alleles and isolating these proteins for use in peptide elution or binding studies is time consuming. Here, we express human MHC alleles (HLA-DR4 and HLA-DQ6) as native, noncovalent αß dimers on yeast cells for direct flow cytometry-based screening of peptide ligands from selected antigens. We demonstrate rapid, accurate identification of DQ6 ligands from pre-pro-hypocretin, a narcolepsy-related immunogenic target. We also identify 20 DR4-binding SARS-CoV-2 spike peptides homologous to SARS-CoV-1 epitopes, and one spike peptide overlapping with the reported SARS-CoV-2 epitope recognized by CD4+ T cells from unexposed individuals carrying DR4 subtypes. Our method is optimized for immediate application upon the emergence of novel pathogens.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , COVID-19/metabolism , Epitopes, T-Lymphocyte/metabolism , HLA-DQ Antigens/metabolism , HLA-DR4 Antigen/metabolism , Saccharomyces cerevisiae/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Two-Hybrid System Techniques , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/virology , COVID-19/genetics , COVID-19/immunology , Epitopes, T-Lymphocyte/genetics , Epitopes, T-Lymphocyte/immunology , Flow Cytometry , HLA-DQ Antigens/genetics , HLA-DQ Antigens/immunology , HLA-DR4 Antigen/genetics , HLA-DR4 Antigen/immunology , Ligands , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
5.
Med (N Y) ; 2(2): 149-163.e4, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1386269

ABSTRACT

BACKGROUND: Antibody responses to virus reflect exposure and potential protection. METHODS: We developed a highly specific and sensitive approach to measuring antibodies against SARS-CoV-2 for population-scale immune surveillance. Antibody positivity was defined as a dual-positive response against both the receptor-binding domain and nucleocapsid proteins of SARS-CoV-2. Antibodies were measured by immunoprecipitation assays in capillary blood from 15,771 children aged 1 to 18 years living in Bavaria, Germany, and participating in a public health type 1 diabetes screening program (ClinicalTrials.gov: NCT04039945), in 1,916 dried blood spots from neonates in a Bavarian screening study (ClinicalTrials.gov: NCT03316261), and in 75 SARS-CoV-2-positive individuals. Virus positive incidence was obtained from the Bavarian health authority data. FINDINGS: Dual-antibody positivity was detected in none of the 3,887 children in 2019 (100% specificity) and 73 of 75 SARS-CoV-2-positive individuals (97.3% sensitivity). Antibody surveillance in children during 2020 resulted in frequencies of 0.08% in January to March, 0.61% in April, 0.74% in May, 1.13% in June, and 0.91% in July. Antibody prevalence from April 2020 was 6-fold higher than the incidence of authority-reported cases (156 per 100,000 children), showed marked variation between the seven Bavarian regions (p < 0.0001), and was not associated with age or sex. Transmission in children with virus-positive family members was 35%. 47% of positive children were asymptomatic. No association with type 1 diabetes autoimmunity was observed. Antibody frequency in newborns was 0.47%. CONCLUSIONS: We demonstrate the value of population-based screening programs for pandemic monitoring. FUNDING: The work was supported by funding from the BMBF (FKZ01KX1818).


Subject(s)
COVID-19 , Diabetes Mellitus, Type 1 , Antibodies, Viral , COVID-19/diagnosis , Child , Diabetes Mellitus, Type 1/diagnosis , Humans , Infant, Newborn , Public Health , SARS-CoV-2
7.
IEEE/ACM Trans Comput Biol Bioinform ; 18(4): 1290-1298, 2021.
Article in English | MEDLINE | ID: covidwho-1349906

ABSTRACT

An outbreak of COVID-19 that began in late 2019 was caused by a novel coronavirus(SARS-CoV-2). It has become a global pandemic. As of June 9, 2020, it has infected nearly 7 million people and killed more than 400,000, but there is no specific drug. Therefore, there is an urgent need to find or develop more drugs to suppress the virus. Here, we propose a new nonlinear end-to-end model called LUNAR. It uses graph convolutional neural networks to automatically learn the neighborhood information of complex heterogeneous relational networks and combines the attention mechanism to reflect the importance of the sum of different types of neighborhood information to obtain the representation characteristics of each node. Finally, through the topology reconstruction process, the feature representations of drugs and targets are forcibly extracted to match the observed network as much as possible. Through this reconstruction process, we obtain the strength of the relationship between different nodes and predict drug candidates that may affect the treatment of COVID-19 based on the known targets of COVID-19. These selected candidate drugs can be used as a reference for experimental scientists and accelerate the speed of drug development. LUNAR can well integrate various topological structure information in heterogeneous networks, and skillfully combine attention mechanisms to reflect the importance of neighborhood information of different types of nodes, improving the interpretability of the model. The area under the curve(AUC) of the model is 0.949 and the accurate recall curve (AUPR) is 0.866 using 10-fold cross-validation. These two performance indexes show that the model has superior predictive performance. Besides, some of the drugs screened out by our model have appeared in some clinical studies to further illustrate the effectiveness of the model.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/virology , Drug Evaluation, Preclinical/methods , Neural Networks, Computer , SARS-CoV-2/drug effects , COVID-19/epidemiology , Computational Biology , Databases, Pharmaceutical/statistics & numerical data , Drug Development/methods , Drug Development/statistics & numerical data , Drug Evaluation, Preclinical/statistics & numerical data , Drug Repositioning/methods , Drug Repositioning/statistics & numerical data , Host Microbial Interactions/drug effects , Humans , Nonlinear Dynamics , Pandemics
8.
JAMA ; 325(24): 2448-2456, 2021 06 22.
Article in English | MEDLINE | ID: covidwho-1318650

ABSTRACT

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures: Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.


Subject(s)
COVID-19 Vaccines/adverse effects , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/etiology , Adolescent , Adult , Critical Care , Fatal Outcome , Female , Headache/etiology , Humans , Middle Aged , Platelet Count , Sinus Thrombosis, Intracranial/therapy , Thrombocytopenia/therapy
9.
JAMA ; 325(24): 2457-2465, 2021 Jun 22.
Article in English | MEDLINE | ID: covidwho-1318647

ABSTRACT

IMPORTANCE: Randomized clinical trials have provided estimates of the effectiveness of the BNT162b2 vaccine against symptomatic SARS-CoV-2 infection, but its effect on asymptomatic infections remains unclear. OBJECTIVE: To estimate the association of vaccination with the Pfizer-BioNTech BNT162b2 vaccine with symptomatic and asymptomatic SARS-CoV-2 infections among health care workers. DESIGN, SETTING, AND PARTICIPANTS: This was a single-center, retrospective cohort study conducted at a tertiary medical center in Tel Aviv, Israel. Data were collected on symptomatic and asymptomatic SARS-CoV-2 infections confirmed via polymerase chain reaction (PCR) tests in health care workers undergoing regular screening with nasopharyngeal swabs between December 20, 2020, and February 25, 2021. Logistic regression was used to calculate incidence rate ratios (IRRs) comparing the incidence of infection between fully vaccinated and unvaccinated participants, controlling for demographics and the number of PCR tests performed. EXPOSURES: Vaccination with the BNT162b2 vaccine vs unvaccinated status was ascertained from the employee health database. Full vaccination was defined as more than 7 days after receipt of the second vaccine dose. MAIN OUTCOMES AND MEASURES: The primary outcome was the regression-adjusted IRR for symptomatic and asymptomatic SARS-CoV-2 infection of fully vaccinated vs unvaccinated health care workers. The secondary outcomes included IRRs for partially vaccinated health care workers (days 7-28 after first dose) and for those considered as late fully vaccinated (>21 days after second dose). RESULTS: A total of 6710 health care workers (mean [SD] age, 44.3 [12.5] years; 4465 [66.5%] women) were followed up for a median period of 63 days; 5953 health care workers (88.7%) received at least 1 dose of the BNT162b2 vaccine, 5517 (82.2%) received 2 doses, and 757 (11.3%) were not vaccinated. Vaccination was associated with older age compared with those who were not vaccinated (mean age, 44.8 vs 40.7 years, respectively) and male sex (31.4% vs 17.7%). Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated health care workers and 38 unvaccinated health care workers (incidence rate, 4.7 vs 149.8 per 100 000 person-days, respectively, adjusted IRR, 0.03 [95% CI, 0.01-0.06]). Asymptomatic SARS-CoV-2 infection occurred in 19 fully vaccinated health care workers and 17 unvaccinated health care workers (incidence rate, 11.3 vs 67.0 per 100 000 person-days, respectively, adjusted IRR, 0.14 [95% CI, 0.07-0.31]). The results were qualitatively unchanged by the propensity score sensitivity analysis. CONCLUSIONS AND RELEVANCE: Among health care workers at a single center in Tel Aviv, Israel, receipt of the BNT162b2 vaccine compared with no vaccine was associated with a significantly lower incidence of symptomatic and asymptomatic SARS-CoV-2 infection more than 7 days after the second dose. Findings are limited by the observational design.


Subject(s)
COVID-19 Vaccines , COVID-19/epidemiology , Health Personnel , Adult , Asymptomatic Infections/epidemiology , COVID-19/diagnosis , COVID-19/prevention & control , Female , Humans , Incidence , Israel , Male , Middle Aged , Polymerase Chain Reaction , Propensity Score , Retrospective Studies , SARS-CoV-2/isolation & purification , Tertiary Care Centers
10.
Int J Mol Sci ; 22(8)2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1298161

ABSTRACT

The use of the new psychoactive substances is continuously growing and the implementation of accurate and sensible analysis in biological matrices of users is relevant and fundamental for clinical and forensic purposes. Two different analytical technologies, high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) were used for a screening analysis of classic drugs and new psychoactive substances and their metabolites in urine of formed heroin addicts under methadone maintenance therapy. Sample preparation involved a liquid-liquid extraction. The UHPLC-HRMS method included Accucore™ phenyl Hexyl (100 × 2.1 mm, 2.6 µm, Thermo, USA) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2 mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2 mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode for substances identification (mass range 100-1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m, 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40-550 m/z). Urine samples from 296 patients with a history of opioid use disorder were examined. Around 80 different psychoactive substances and/or metabolites were identified, being methadone and metabolites the most prevalent ones. The possibility to screen for a huge number of psychotropic substances can be useful in suspected drug related fatalities or acute intoxication/exposure occurring in emergency departments and drug addiction services.


Subject(s)
Gas Chromatography-Mass Spectrometry , Psychotropic Drugs/urine , Analgesics, Opioid/urine , Chromatography, High Pressure Liquid , Humans , Methadone/urine , Substance-Related Disorders/urine
12.
Biomed Khim ; 67(3): 259-267, 2021 May.
Article in Russian | MEDLINE | ID: covidwho-1278813

ABSTRACT

Docking and quantum-chemical methods have been used for screening of drug-like compounds from the own database of the Voronezh State University to find inhibitors the SARS-CoV-2 main protease, an important enzyme of the coronavirus responsible for the COVID-19 pandemic. Using the SOL program more than 42000 3D molecular structures were docked into the active site of the main protease, and more than 1000 ligands with most negative values of the SOL score were selected for further processing. For all these top ligands, the protein-ligand binding enthalpy has been calculated using the PM7 semiempirical quantum-chemical method with the COSMO implicit solvent model. 20 ligands with the most negative SOL scores and the most negative binding enthalpies have been selected for further experimental testing. The latter has been made by measurements of the inhibitory activity against the main protease and suppression of SARS-CoV-2 replication in a cell culture. The inhibitory activity \of the compounds was determined using a synthetic fluorescently labeled peptide substrate including the proteolysis site of the main protease. The antiviral activity was tested against SARS-CoV-2 virus in the Vero cell culture. Eight compounds showed inhibitory activity against the main protease of SARS-CoV-2 in the submicromolar and micromolar ranges of the IC50 values. Three compounds suppressed coronavirus replication in the cell culture at the micromolar range of EC50 values and had low cytotoxicity. The found chemically diverse inhibitors can be used for optimization in order to obtain a leader compound, the basis of new direct-acting antiviral drugs against the SARS-CoV-2 coronavirus.


Subject(s)
COVID-19 , Hepatitis C, Chronic , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Pandemics , Peptide Hydrolases , Protease Inhibitors/pharmacology , SARS-CoV-2 , Viral Nonstructural Proteins
13.
Sci Prog ; 104(2): 368504211026152, 2021.
Article in English | MEDLINE | ID: covidwho-1277845

ABSTRACT

The most common method for SARS-CoV-2 testing is throat or nasal swabbing by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. In South Korea, drive-through swab test is used for screening system and community treatment centers (CTCs), which admit and treat confirmed COVID-19 patients with mild symptoms, are being used. This retrospective study was conducted on patients admitted to a CTC on March 6, 2020. A total of 313 patients were admitted. The nasal and throat swabs were collected from the upper respiratory tract, and a sputum test was performed to obtain lower respiratory samples. The positive rate of the first set of test, sputum test was higher than that of the swab test (p = 0.011). In the second set of test, 1 week after the first ones, the rate of positive swab tests was relatively high (p = 0.026). In the first set of test, 66 of 152 (43.4%) patients showed 24-h consecutive negative swab test results, when the sputum test results were considered together, that number fell to 29 patients (19.1%) (p < 0.001). Also, in the second set of test, 63 of 164 (38.4%) patients met the discharge criteria only when the swab test was considered; that number fell to 30 (18.3%) when the sputum test results were also considered (p < 0.001). Using the swab test alone is insufficient for screening test and discharge decision. Patients who may have positive result in the sputum test can be missed.


Subject(s)
COVID-19 Nucleic Acid Testing/standards , COVID-19/diagnosis , Patient Discharge/statistics & numerical data , SARS-CoV-2/genetics , Specimen Handling/methods , Adult , Asymptomatic Diseases , COVID-19/epidemiology , COVID-19/virology , Community Health Centers/organization & administration , Female , Humans , Male , Mass Screening/methods , Nasopharynx/virology , Pharynx/virology , Quarantine/methods , Republic of Korea/epidemiology , Retrospective Studies , Severity of Illness Index , Sputum/virology
14.
Transfusion ; 60(9): 2038-2046, 2020 09.
Article in English | MEDLINE | ID: covidwho-1263879

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA could be detected in the blood of infected cases. From February 9, all blood establishments in Hubei province, China, implemented nucleic acid testing (NAT) for SARS-CoV-2 RNA among blood donors to ensure blood safety. STUDY DESIGN AND METHODS: Nucleic acid test screening individually (ID) or by minipool (MP) testing was performed according to the manufacturer's instructions. Inactivated culture supernatant of SARS-CoV-2-infected Vero cells was quantified by droplet digital polymerase chain reaction (ddPCR) and series diluted with negative plasma to evaluate the assay's performance. RESULTS: The limit of detection of the kit for MP testing was 62.94 and 33.14 copies/mL for N and ORF1ab region, respectively. ID testing could achieve 3.87 and 4.85 copies/mL for two regions using 1600 µL of plasma. Coefficients of variations of two different concentrations of reference samples were all less than 5% in MP testing. As of April 30, 2020, a total of 98,342 blood donations including 87,095 whole blood donations and 11,247 platelet donations were tested by ID or MP testing, and no RNAemia was found. In addition, Hubei province suffered precipitously decreased blood supply, especially in February: 86% reduction compared with the same period of 2019. CONCLUSION: Nucleic acid test screening of SARS-CoV-2 on blood donations is suitable in blood establishments using the commercial real-time PCR detection kit based on available instruments. The negative result indicated that SARS-CoV-2 appears to be no direct threat to blood safety but raises some serious issues for general blood supply.


Subject(s)
Blood Donors , COVID-19 Nucleic Acid Testing , COVID-19/epidemiology , RNA, Viral/blood , SARS-CoV-2/isolation & purification , Viremia/diagnosis , Animals , Blood Banks , Blood Donors/supply & distribution , COVID-19/diagnosis , China/epidemiology , Chlorocebus aethiops , Humans , Limit of Detection , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction/methods , SARS-CoV-2/physiology , Vero Cells , Viral Load , Virus Cultivation
15.
BMC Psychiatry ; 21(1): 284, 2021 06 02.
Article in English | MEDLINE | ID: covidwho-1255911

ABSTRACT

BACKGROUND: The onset of COVID-19 required rapid organisational changes in the mental health domain. Most mental health-care departments appear to have set up infection control measures and also organised planning, coordination and measures that enabled them to provide psychiatric care in a restrictive environment. Our objective was to assess the organisation by psychiatric facilities in France of their response to COVID-19, during the first wave. METHODS: In June 2020, a cross-sectional study was performed by an audit with 48 items which was proposed to 331 hospitals in metropolitan France with a capacity for full-time, that is, inpatient psychiatric hospitalisation of adults. RESULTS: Of the 331 establishments contacted, 94 (28.4%) agreed to respond to the survey questionnaire. Full-time inpatient hospitalisation was completely or partially maintained by 94.7% (n = 89) of facilities. Specific measures concerning respect for patients' rights were reported by 58% (n = 55) of establishments. Overall, 74.5% (n = 70) had set up a dedicated channel of care for patients at risk of severe COVID-19, and 52.1% (n = 49) a system for routine screening at admission for these risk factors. Nearly half the establishments (48.9%, n = 46) reported they had set up specific training programmes for patients about barrier measures and social distancing. CONCLUSIONS: French psychiatric establishments on the whole were able to provide a necessary reorganisation of their management of patients and their families, regardless of facility status. Patients' rights nonetheless seem to have not received the attention they merited during the early pandemic period. Somatic management of patients with mental illness must absolutely be improved.


Subject(s)
COVID-19 , Adult , Cross-Sectional Studies , France/epidemiology , Humans , Pandemics , SARS-CoV-2
16.
Biomed Signal Process Control ; 69: 102814, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1252535

ABSTRACT

BACKGROUND AND OBJECTIVE: SARS-CoV-2, a novel strain of coronavirus' also called coronavirus disease 19 (COVID-19), a highly contagious pathogenic respiratory viral infection emerged in December 2019 in Wuhan, a city in China's Hubei province without an obvious cause. Very rapidly it spread across the globe (over 200 countries and territories) and finally on 11 March 2020 World Health Organisation characterized it as a "pandemic". Although it has low mortality of around 3% as of 18 May 2021 it has already infected 164,316,270 humans with 3,406,027 unfortunate deaths. Undoubtedly the world was rocked by the COVID-19 pandemic, but researchers rose to all manner of challenges to tackle this pandemic by adopting the shreds of evidence of ML and AI in previous epidemics to develop novel models, methods, and strategies. We aim to provide a deeper insight into the convolutional neural network which is the most notable and extensively adopted technique on radiographic visual imagery to help expert medical practitioners and researchers to design and finetune their state-of-the-art models for their applicability in the arena of COVID-19. METHOD: In this study, a deep convolutional neural network, its layers, activation and loss functions, regularization techniques, tools, methods, variants, and recent developments were explored to find its applications for COVID-19 prognosis. The pipeline of a general architecture for COVID-19 prognosis has also been proposed. RESULT: This paper highlights recent studies of deep CNN and its applications for better prognosis, detection, classification, and screening of COVID-19 to help researchers and expert medical community in multiple directions. It also addresses a few challenges, limitations, and outlooks while using such methods for COVID-19 prognosis. CONCLUSION: The recent and ongoing developments in AI, MI, and deep learning (Deep CNN) has shown promising results and significantly improved performance metrics for screening, prediction, detection, classification, forecasting, medication, treatment, contact tracing, etc. to curtail the manual intervention in medical practice. However, the research community of medical experts is yet to recognize and label the benchmark of the deep learning framework for effective detection of COVID-19 positive cases from radiology imagery.

17.
Future Gener Comput Syst ; 124: 119-132, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1242986

ABSTRACT

Internet of Things (IoT) has recently brought an influential research and analysis platform in a broad diversity of academic and industrial disciplines, particularly in healthcare. The IoT revolution is reshaping current healthcare practices by consolidating technological, economic, and social views. Since December 2019, the spreading of COVID-19 across the world has impacted the world's economy. IoT technology integrated with Artificial Intelligence (AI) can help to address COVID-19. UAVs equipped with IoT devices can collect raw data that demands computing and analysis to make intelligent decision without human intervention. To mitigate the effect of COVID-19, in this paper, we propose an IoT-UAV-based scheme to collect raw data using onboard thermal sensors. The thermal image captured from the thermal camera is used to determine the potential people in the image (of the massive crowd in a city), which may have COVID-19, based on the temperature recorded. An efficient hybrid approach for a face recognition system is proposed to detect the people in the image having high body temperature from infrared images captured in a real-time scenario. Also, a face mask detection scheme is introduced, which detects whether a person has a mask on the face or not. The schemes' performance evaluation is done using various machine learning and deep learning classifiers. We use the edge computing infrastructure (onboard sensors and actuators) for data processing to reduce the response time for real-time analytics and prediction. The proposed scheme has an average accuracy of  99.5% using various performance evaluation metrics indicating its practical applicability in real-time scenarios.

18.
Womens Health (Lond) ; 17: 17455065211017070, 2021.
Article in English | MEDLINE | ID: covidwho-1242233

ABSTRACT

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented upheaval within global healthcare systems and resulted in the temporary pausing of the National Health Service (NHS) Scotland Cervical Screening Programme. With several months of backlogs in appointments, there has not only been a reduction in primary samples being taken for human papilloma virus (HPV) testing but there have also been fewer women referred to colposcopy for investigation and treatment of precancerous or cancerous changes as a result. Encouraging uptake for cervical screening was always a priority before the pandemic, but it is even more important now, considering that the fears and barriers to screening that women may have are now exacerbated by COVID-19. OBJECTIVES: This article explores the impact of the pandemic on the uptake of cervical screening within NHS Ayrshire & Arran and evaluates potential strategies to improve uptake now and in future such as self-sampling and telemedicine. METHODS: This article presents evidence-based literature and local health board data relating to cervical screening during the pandemic. RESULTS: Human papilloma virus self-sampling carried out by the woman in her home has been shown to improve uptake, especially in non-attenders, whilst maintaining a high sensitivity and, crucially, reducing the need for face-to-face contact. Increased education is key to overcoming barriers women have to screening and telemedicine can strengthen engagement with women during this time. CONCLUSION: There are lessons to be learned from the pandemic, and we must use this opportunity to improve cervical screening uptake for the future.


Subject(s)
Early Detection of Cancer/methods , Mass Screening/methods , Mass Screening/statistics & numerical data , Papillomaviridae , Self Care , Uterine Cervical Neoplasms/prevention & control , Adult , Appointments and Schedules , COVID-19/epidemiology , Cervical Intraepithelial Neoplasia/prevention & control , Colposcopy , Female , Humans , Middle Aged , Papanicolaou Test , Scotland/epidemiology , Vaginal Smears
19.
J Pediatr Health Care ; 36(1): 64-70, 2022.
Article in English | MEDLINE | ID: covidwho-1240543

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has disrupted outpatient pediatrics, postponing well-child care to address immediate patient safety concerns. Screening for lead toxicity is a critical component of this care. Children may be at increased risk for lead exposure at home because of social restrictions. We present data on how COVID-19 restrictions have impacted lead screening in a primary care practice. METHOD: Lead testing data on 658 children in a primary care practice were analyzed to determine the effect of COVID-19 restrictions on lead screening rates, levels, and deficiencies. RESULTS: Lead screening significantly decreased during peak restrictions, leading to increased screening deficiencies. Despite this decrease, screening lead levels increased during peak restrictions. DISCUSSION: These data show how COVID-19 restrictions have disrupted routine care and highlight the importance of continued lead screening in at-risk populations. The electronic medical record can be leveraged to identify deficiencies to be targeted by quality improvement initiatives.


Subject(s)
COVID-19 , Lead , Child , Humans , Pandemics , Primary Health Care , SARS-CoV-2
20.
Lancet Microbe ; 2(8): e397-e404, 2021 08.
Article in English | MEDLINE | ID: covidwho-1233658

ABSTRACT

BACKGROUND: Quantitative RT-PCR (RT-qPCR) of nasopharyngeal swab (NPS) samples for SARS-CoV-2 detection requires medical personnel and is time consuming, and thus is poorly suited to mass screening. In June, 2020, a chemiluminescent enzyme immunoassay (CLEIA; Lumipulse G SARS-CoV-2 Ag kit, Fujirebio, Tokyo, Japan) was developed that can detect SARS-CoV-2 nucleoproteins in NPS or saliva samples within 35 min. In this study, we assessed the utility of CLEIA in mass SARS-CoV-2 screening. METHODS: We did a diagnostic accuracy study to develop a mass-screening strategy for salivary detection of SARS-CoV-2 by CLEIA, enrolling hospitalised patients with clinically confirmed COVID-19, close contacts identified at community health centres, and asymptomatic international arrivals at two airports, all based in Japan. All test participants were enrolled consecutively. We assessed the diagnostic accuracy of CLEIA compared with RT-qPCR, estimated according to concordance (Kendall's coefficient of concordance, W), and sensitivity (probability of CLEIA positivity given RT-qPCR positivity) and specificity (probability of CLEIA negativity given RT-qPCR negativity) for different antigen concentration cutoffs (0·19 pg/mL, 0·67 pg/mL, and 4·00 pg/mL; with samples considered positive if the antigen concentration was equal to or more than the cutoff and negative if it was less than the cutoff). We also assessed a two-step testing strategy post hoc with CLEIA as an initial test, using separate antigen cutoff values for test negativity and positivity from the predefined cutoff values. The proportion of intermediate results requiring secondary RT-qPCR was then quantified assuming prevalence values of RT-qPCR positivity in the overall tested population of 10%, 30%, and 50%. FINDINGS: Self-collected saliva was obtained from 2056 participants between June 12 and Aug 6, 2020. Results of CLEIA and RT-qPCR were concordant in 2020 (98·2%) samples (Kendall's W=0·99). Test sensitivity was 85·4% (76 of 89 positive samples; 90% credible interval [CrI] 78·0-90·3) at the cutoff of 0·19 pg/mL; 76·4% (68 of 89; 68·2-82·8) at the cutoff of 0·67 pg/mL; and 52·8% (47 of 89; 44·1-61·3) at the cutoff of 4·0 pg/mL. Test specificity was 91·3% (1796 of 1967 negative samples; 90% CrI 90·2-92·3) at the cutoff of 0·19 pg/mL, 99·2% (1952 of 1967; 98·8-99·5) at the cutoff of 0·67 pg/mL, and 100·0% (1967 of 1967; 99·8-100·0) at the cutoff of 4·00 pg/mL. Using a two-step testing strategy with a CLEIA negativity cutoff of 0·19 pg/mL (to maximise sensitivity) and a CLEIA positivity cutoff of 4·00 pg/mL (to maximise specificity), the proportions of indeterminate results (ie, samples requiring secondary RT-qPCR) would be approximately 11% assuming a prevalence of RT-qPCR positivity of 10%, 16% assuming a prevalence of RT-qPCR positivity of 30%, and 21% assuming a prevalence of RT-qPCR positivity of 50%. INTERPRETATION: CLEIA testing of self-collected saliva is simple and provides results quickly, and is thus suitable for mass testing. To improve accuracy, we propose a two-step screening strategy with an initial CLEIA test followed by confirmatory RT-qPCR for intermediate concentrations, varying positive and negative thresholds depending on local prevalence. Implementation of this strategy has expedited sample processing at Japanese airports since July, 2020, and might apply to other large-scale mass screening initiatives. FUNDING: Ministry of Health, Labour and Welfare, Japan.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Humans , Mass Screening/methods , SARS-CoV-2/genetics , Saliva , Sensitivity and Specificity
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