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1.
Klin Lab Diagn ; 66(4): 210-212, 2021 Apr 17.
Article in English | MEDLINE | ID: covidwho-1780502

ABSTRACT

To study the diagnostic characteristics of test systems for detecting antibodies to SARS-Cov-2. We studied the diagnostic characteristics of two test systems for detecting antibodies to SARS-Cov-2, registered in the Russian Federation. The first test system is a kit for detecting total antibodies to SARS-Cov-2 using immunochemiluminescence analysis on the «Cobas e 411¼ analyzer («Roche Diagnostics¼, Germany). The second test system is a kit for detecting IgM and IgG to SARS-Cov-2 («Core Technology Co., Ltd¼, China) by immunochromatographic analysis. The biological material for the study was blood serum. We assessed: diagnostic sensitivity, diagnostic specificity, and predictive value of positive and negative results. In the test system for detecting total antibodies to SARS-CoV-2, using an IHLA, the diagnostic sensitivity and specificity were 100%; the predictive value of positive and negative results was 100%. In the test system for the detection of IgM and IgG to Sars-CoV-2, using IHA, diagnostic sensitivity for IgM and IgG were 100%; diagnostic specificity for IgM - 60%, for IgG - 72%; predictive value of a positive result for IgM - 60%, IgG - 68,18%; predictive value of negative results for IgM and IgG - 100%. The best diagnostic characteristics were found in the test system for the detection of total antibodies to SARS-Cov-2, which must be taken into account when deciding whether to purchase test systems for the detection of antibodies to SARS-Cov-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Immunoglobulin G , Immunoglobulin M , Russia , Sensitivity and Specificity , Serologic Tests
2.
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
3.
Jpn J Infect Dis ; 74(5): 421-423, 2021 Sep 22.
Article in English | MEDLINE | ID: covidwho-1436359

ABSTRACT

Green tea extracts effectively inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro in a dose-dependent manner. Ten-fold serially diluted solutions of catechin mixture reagent from green tea were mixed with the viral culture fluid at a volume ratio of 9:1, respectively, and incubated at room temperature for 5 min. The solution of 10 mg/mL catechin reagent reduced the viral titer by 4.2 log and 1.0 mg/mL solution by one log. Pre-infection treatment of cells with the reagent alone did not affect viral growth. In addition, cells treated with only the reagent were assayed for host cell viability using the WST-8 system, and almost no host cell damage by the treatment was observed. These findings suggested that the direct treatment of virus with the reagent before inoculation decreased the viral activity and that catechins might have the potential to suppress SARSCoV-2 infection.


Subject(s)
Antiviral Agents/pharmacology , Catechin/pharmacology , SARS-CoV-2/drug effects , Tea/chemistry , Animals , COVID-19/virology , Cell Survival/drug effects , Chlorocebus aethiops , Dose-Response Relationship, Drug , Humans , Vero Cells , Viral Load/drug effects
4.
Materials (Basel) ; 14(9)2021 Apr 29.
Article in English | MEDLINE | ID: covidwho-1389429

ABSTRACT

We report on the design, characterization and validation of a spherical irradiation system for inactivating SARS-CoV-2, based on UV-C 275 nm LEDs. The system is designed to maximize irradiation intensity and uniformity and can be used for irradiating a volume of 18 L. To this aim: (i) several commercially available LEDs have been acquired and analyzed; (ii) a complete optical study has been carried out in order to optimize the efficacy of the system; (iii) the resulting prototype has been characterized optically and tested for the inactivation of SARS-CoV-2 for different exposure times, doses and surface types; (iv) the result achieved and the efficacy of the prototype have been compared with similar devices based on different technologies. Results indicate that a 99.9% inactivation can be reached after 1 min of treatment with a dose of 83.1 J/m2.

5.
Sensors (Basel) ; 20(20)2020 Oct 14.
Article in English | MEDLINE | ID: covidwho-1308405

ABSTRACT

The present paper describes a system for older people to self-administer the 30-s chair stand test (CST) at home without supervision. The system comprises a low-cost sensor to count sit-to-stand (SiSt) transitions, and an Android application to guide older people through the procedure. Two observational studies were conducted to test (i) the sensor in a supervised environment (n = 7; m = 83.29 years old, sd = 4.19; 5 female), and (ii) the complete system in an unsupervised one (n = 7; age 64-74 years old; 3 female). The participants in the supervised test were asked to perform a 30-s CST with the sensor, while a member of the research team manually counted valid transitions. Automatic and manual counts were perfectly correlated (Pearson's r = 1, p = 0.00). Even though the sample was small, none of the signals around the critical score were affected by harmful noise; p (harmless noise) = 1, 95% CI = (0.98, 1). The participants in the unsupervised test used the system in their homes for a month. None of them dropped out, and they reported it to be easy to use, comfortable, and easy to understand. Thus, the system is suitable to be used by older adults in their homes without professional supervision.


Subject(s)
Exercise Test , Geriatric Assessment/methods , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Sitting Position , Standing Position
6.
J Med Internet Res ; 23(6): e26143, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1289819

ABSTRACT

BACKGROUND: The use of technology has the potential to support the patient´s active participation regarding treatment of hypertension. This might lead to changes in the roles of the patient and health care professional and affect the partnership between them. OBJECTIVE: The aim of this qualitative study was to explore the partnership between patients and health care professionals and the roles of patients and professionals in hypertension management when using an interactive web-based system for self-management of hypertension via the patient's own mobile phone. METHODS: Focus group interviews were conducted with 22 patients and 15 professionals participating in a randomized controlled trial in Sweden aimed at lowering blood pressure (BP) using an interactive web-based system via mobile phones. The interviews were audiorecorded and transcribed and analyzed using thematic analysis. RESULTS: Three themes were identified: the technology, the patient, and the professional. The technology enabled documentation of BP treatment, mainly for sharing knowledge between the patient and the professional. The patients gained increased knowledge of BP values and their relation to daily activities and treatment. They were able to narrate about their BP treatment and take a greater responsibility, inspired by new insights and motivation for lifestyle changes. Based on the patient's understanding of hypertension, professionals could use the system as an educational tool and some found new ways of communicating BP treatment with patients. Some reservations were raised about using the system, that it might be too time-consuming to function in clinical practice and that too much measuring could result in stress for the patient and an increased workload for the professionals. In addition, not all professionals and patients had adopted the instructions regarding the use of the system, resulting in less realization of its potential. CONCLUSIONS: The use of the system led to the patients taking on a more active role in their BP treatment, becoming more of an expert of their BP. When using the system as intended, the professionals experienced it as a useful resource for communication regarding BP and lifestyle. Patients and professionals described a consultation on more equal grounds. The use of technology in hypertension management can promote a constructive and person-centered partnership between patient and professional. However, implementation of a new way of working should bring benefits and not be considered a burden for the professionals. To establish a successful partnership, both the patient and the professional need to be motivated toward a new way of working. TRIAL REGISTRATION: ClinicalTrials.gov NCT03554382; https://clinicaltrials.gov/ct2/show/NCT03554382.


Subject(s)
Cell Phone , Hypertension , Self-Management , Communication , Humans , Hypertension/therapy , Internet
7.
Appl Energy ; 292: 116848, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1279532

ABSTRACT

Radiant cooling-assisted natural ventilation is an innovative technical approach that combines new radiant cooling technology with natural ventilation to increase fresh air delivery into buildings year-round with minimal energy cost and improvment of air quality. Currently, the standard paradigm for HVAC (heating, ventilation and air conditioning) is based on central air systems that tie the delivery of heating and cooling to the delivery of fresh air. To prevent heat loss, the delivery of fresh air must be tightly controlled and is often limited through recirculation of already heated or cooled air. Buildings are designed with airtight envelopes, which do not allow for natural ventilation, and depend on energy-intensive central-air systems. As closed environments, buildings have become sites of rapid COVID-19 transmission. In this research, we demonstrate the energy cost of increasing outdoor air supply with standard systems per COVID-19 recommendations and introduce an alternative HVAC paradigm that maximizes the decoupling of ventilation and thermal control. We first consider a novel analysis of the energy costs of increasing the amount of conditioned fresh air using standard HVAC systems to address COVID-19 concerns. We then present an alternative that includes a novel membrane-assisted radiant system we have studied for cooling in humid climates, in place of an air conditioning system. The proposed system can work in conjunction with natural ventilation and thus decreases the risk of indoor spread of infectious diseases and significantly lowers energy consumption in buildings. Our results for modeling HVAC energy in different climates show that increasing outdoor air in standard systems can double cooling costs, while increasing natural ventilation with radiant systems can halve costs. More specifically, it is possible to add up to 100 days' worth of natural ventilation while saving energy when coupling natural ventilation and radiant systems. This combination decreases energy costs by 10-45% in 60 major cities globally, while increasing fresh air intake.

8.
Clin Appl Thromb Hemost ; 27: 10760296211022847, 2021.
Article in English | MEDLINE | ID: covidwho-1277871

ABSTRACT

Pediatric cerebral venous sinus thrombosis (CVST) is rare but a potentially fatal disease requiring its understanding in local setting. In this study, we observed the clinical course, management, and outcome of pediatric patients with sinus thrombosis in a tertiary care center at Pakistan. Patients between age 0 to 18 years of both genders diagnosed with sinus thrombosis during 2011 to 2020 were included. Data was collected through in-house computerized system and SPSS version 19 was used for analysis. Of 143492 pediatric admissions, 32 (21 males and 11 females) patients with a median (IQR) age of 4.5 years (0-16) had CVST. This is equivalent to 18.5 CVST events per million pediatric admissions. Adolescents were mostly affected, and the overall mortality was 7%. Primary underlying disorders were infections (59%), hematological neoplasms (12.5%), thrombotic thrombocytopenic purpura (3%) and antiphospholipid syndrome (3%). Activated protein C resistance (44%) was the most common inherited thrombophilia. Twenty-one (66%) patients were anemic with a mean (±SD) hemoglobin of 9.0 g/dL (±2.3). Regression analysis showed a positive association of anemia with multiple sinus involvement (P-value 0.009) but not with duration of symptoms (P-value 0.344), hospital stay (P-value 0.466), age (P-value 0.863) or gender (P-value 0.542) of the patients. SARS-COV2 was negative in patients during 2020. Adolescents were primarily affected by sinus thrombosis and infections was the predominant risk factor for all age groups, with a low all-cause mortality. A high index of clinical suspicion is required for prompt diagnosis and intervention.


Subject(s)
Sinus Thrombosis, Intracranial/epidemiology , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Poverty , Risk Factors
9.
J Clin Lab Anal ; 35(8): e23876, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1270480

ABSTRACT

BACKGROUND: Pooling of samples for SARS-CoV-2 testing in low-prevalence settings has been used as an effective strategy to expand testing capacity and mitigate challenges with the shortage of supplies. We evaluated two automated molecular test systems for the detection of SARS-CoV-2 RNA in pooled specimens. METHODS: Pooled nasopharyngeal and saliva specimens were tested by Qiagen QIAstat-Dx Respiratory SARS-CoV-2 Panel (QIAstat) or Cepheid Xpert Xpress SARS-CoV-2 (Xpert), and the results were compared to that of standard RT-qPCR tests without pooling. RESULTS: In nasopharyngeal specimens, the sensitivity/specificity of the pool testing approach, with 5 and 10 specimens per pool, were 77%/100% (n = 105) and 74.1%/100% (n = 260) by QIAstat, and 97.1%/100% (n = 250) and 100%/99.5% (n = 200) by Xpert, respectively. Pool testing of saliva (10 specimens per pool; n = 150) by Xpert resulted in 87.5% sensitivity and 99.3% specificity compared to individual tests. Pool size of 5 or 10 specimens did not significantly affect the difference of RT-qPCR cycle threshold (CT ) from standard testing. RT-qPCR CT values obtained with pool testing by both QIAstat and Xpert were positively correlated with that of individual testing (Pearson's correlation coefficient r = 0.85 to 0.99, p < 0.05). However, the CT values from Xpert were significantly stronger (p < 0.01, paired t test) than that of QIAstat in a subset of SARS-CoV-2 positive specimens, with mean differences of -4.3 ± 2.43 and -4.6 ± 2 for individual and pooled tests, respectively. CONCLUSION: Our results suggest that Xpert SARS-CoV-2 can be utilized for pooled sample testing for COVID-19 screening in low-prevalence settings providing significant cost savings and improving throughput without affecting test quality.


Subject(s)
COVID-19 Testing/methods , Nasopharynx/virology , Saliva/virology , Automation, Laboratory , COVID-19 Nucleic Acid Testing/methods , Humans , Molecular Diagnostic Techniques/methods , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity
10.
Biomed Res Int ; 2021: 9940010, 2021.
Article in English | MEDLINE | ID: covidwho-1259034

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment. METHODS: In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Our framework involves data accession, antigenicity and subcellular localization analysis, T cell epitope prediction, proteasomal and conservancy evaluation, host-pathogen-protein interactions, pathway studies, and in silico binding affinity analysis. RESULTS: We found glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH) of RSV as potential vaccine candidates. Of these proteins (G, F, and SH), we found 9 epitopes for multiple alleles of MHC classes I and II bear significant binding affinity. These potential epitopes were linked to form a polyvalent construct using AAY, GPGPG linkers, and cholera toxin B adjuvant at N-terminal with a 23.9 kDa molecular weight of 224 amino acid residues. The final construct was a stable, immunogenic, and nonallergenic protein containing cleavage sites, TAP transport efficiency, posttranslation shifts, and CTL epitopes. The molecular docking indicated the optimum binding affinity of RSV polyvalent construct with MHC molecules (-12.49 and -10.48 kcal/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. CONCLUSION: Our vaccinomics and system-level investigation could be appropriate to trigger the host immune system to prevent RSV infection.


Subject(s)
Computational Biology/methods , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus, Human , Vaccines, Combined/therapeutic use , Alleles , Antigens , Codon , Computer Simulation , Epitopes , Epitopes, T-Lymphocyte , Glycoproteins/chemistry , Histocompatibility Antigens Class I , Histocompatibility Antigens Class II , Hospitalization , Humans , Immune System , Molecular Docking Simulation , Proteasome Endopeptidase Complex , Protein Interaction Mapping , Proteomics , T-Lymphocytes/immunology , Vaccines , Viral Fusion Proteins/chemistry
11.
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
12.
JMIR Form Res ; 5(5): e25713, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1249616

ABSTRACT

BACKGROUND: Italy was the first country to largely experience the COVID-19 epidemic among other Western countries during the so-called first wave of the COVID-19 pandemic. Proper management of an increasing number of home-quarantined individuals created a significant challenge for health care authorities and professionals. This was especially true when considering the importance of remote surveillance to detect signs of disease progression and consequently regulate access to hospitals and intensive care units on a priority basis. OBJECTIVE: In this paper, we report on an initiative promoted to cope with the first wave of the COVID-19 epidemic in the Spring/Summer of 2020, in the Autonomous Province of Trento, Italy. A purposefully built app named TreCovid19 was designed to provide dedicated health care staff with a ready-to-use tool for remotely monitoring patients with progressive symptoms of COVID-19, who were home-quarantined during the first wave of the epidemic, and to focus on those patients who, based on their self-reported clinical data, required a quick response from health care professionals. METHODS: TreCovid19 was rapidly developed to facilitate the monitoring of a selected number of home-quarantined patients with COVID-19 during the very first epidemic wave. The app was built on top of an existing eHealth platform, already in use by the local health authority to provide home care, with the following functionalities: (1) to securely collect and link demographic and clinical information related to the patients and (2) to provide a two-way communication between a multidisciplinary health care team and home-quarantined patients. The system supported patients to self-assess their condition and update the multidisciplinary team on their health status. The system was used between March and June 2020 in the province of Trento. RESULTS: A dedicated multidisciplinary group of health care professionals adopted the platform over a period of approximately 3 months (from March-end to June 2020) to monitor a total of 170 patients with confirmed COVID-19 during home quarantine. All patients used the system until the end of the initiative. The TreCovid19 system has provided useful insights of possible viability and impact of a technological-organizational asset to manage a potentially critical workload for the health care staff involved in the periodic monitoring of a relevant number of quarantined patients, notwithstanding its limitations given the rapid implementation of the whole initiative. CONCLUSIONS: The technological and organizational model adopted in response to the COVID-19 pandemic was developed and finalized in a relatively short period during the initial few weeks of the epidemic. The system successfully supported the health care staff involved in the periodic monitoring of an increasing number of home-quarantined patients and provided valuable data in terms of disease surveillance.

13.
Pharmaceuticals (Basel) ; 14(5)2021 May 06.
Article in English | MEDLINE | ID: covidwho-1244096

ABSTRACT

Obesity and overweight are associated with lethal diseases. In this context, obese and overweight individuals infected by COVID-19 are at greater risk of dying. Obesity is treated by three main pharmaceutical approaches, namely suppressing appetite, reducing energy intake by impairing absorption, and increasing energy expenditure. Most compounds used for the latter were first envisaged for other medical uses. However, several candidates are now being developed explicitly for targeting obesity by increasing energy expenditure. This review analyzes the compounds that show anti-obesity activity exerted through the energy expenditure pathway. They are classified on the basis of their development status: FDA-approved, Withdrawn, Clinical Trials, and Under Development. The chemical nature, target, mechanisms of action, and description of the current stage of development are described for each one.

14.
Brief Bioinform ; 22(6)2021 11 05.
Article in English | MEDLINE | ID: covidwho-1243456

ABSTRACT

Despite the volume of experiments performed and data available, the complex biology of coronavirus SARS-COV-2 is not yet fully understood. Existing molecular profiling studies have focused on analysing functional omics data of a single type, which captures changes in a small subset of the molecular perturbations caused by the virus. As the logical next step, results from multiple such omics analysis may be aggregated to comprehensively interpret the molecular mechanisms of SARS-CoV-2. An alternative approach is to integrate data simultaneously in a parallel fashion to highlight the inter-relationships of disease-driving biomolecules, in contrast to comparing processed information from each omics level separately. We demonstrate that valuable information may be masked by using the former fragmented views in analysis, and biomarkers resulting from such an approach cannot provide a systematic understanding of the disease aetiology. Hence, we present a generic, reproducible and flexible open-access data harmonisation framework that can be scaled out to future multi-omics analysis to study a phenotype in a holistic manner. The pipeline source code, detailed documentation and automated version as a R package are accessible. To demonstrate the effectiveness of our pipeline, we applied it to a drug screening task. We integrated multi-omics data to find the lowest level of statistical associations between data features in two case studies. Strongly correlated features within each of these two datasets were used for drug-target analysis, resulting in a list of 84 drug-target candidates. Further computational docking and toxicity analyses revealed seven high-confidence targets, amsacrine, bosutinib, ceritinib, crizotinib, nintedanib and sunitinib as potential starting points for drug therapy and development.


Subject(s)
COVID-19/drug therapy , Genomics , Molecular Targeted Therapy , SARS-CoV-2/drug effects , Algorithms , Biomarkers/chemistry , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Computational Biology , Databases, Genetic , Humans , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Software
15.
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.

16.
J Diet Suppl ; : 1-35, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1225581

ABSTRACT

Overall mental health depends in part on the blood-brain barrier, which regulates nutrient transfer in-and-out of the brain and its central nervous system. Lactoferrin, an innate metal-transport protein, synthesized in the substantia nigra, particularly in dopaminergic neurons and activated microglia is vital for brain physiology. Lactoferrin rapidly crosses the blood-brain barrier via receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Lactoferrin receptors are additionally present on glioma cells, brain micro-vessels, and neurons. As a regulator of neuro-redox, microglial lactoferrin is critical for protection/repair of neurons and healthy brain function. Iron imbalance and oxidative stress are common among patients with neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, dementia, depression, and multiple sclerosis. As an endogenous iron-chelator, lactoferrin prevents iron accumulation and dopamine depletion in Parkinson's disease patients. Oral lactoferrin supplementation could modulate the p-Akt/PTEN pathway, reduce Aß deposition, and ameliorate cognitive decline in Alzheimer's disease. Novel lactoferrin-based nano-therapeutics have emerged as effective drug-delivery systems for clinical management of neurodegenerative disorders. Recent emergence of the Coronavirus disease-2019 (COVID-19) pandemic, initially considered a respiratory illness, demonstrated a broader virulence spectrum with the ability to cross the blood-brain barrier and inflict a plethora of neuropathological manifestations in the brain - the Neuro-COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are widely reported in Parkinson's disease, Alzheimer's disease, dementia, and multiple sclerosis patients with aggravated clinical outcomes. Lactoferrin, credited with several neuroprotective benefits in the brain could serve as a potential adjuvant in the clinical management of Neuro-COVID-19.

17.
J Med Virol ; 93(5): 2962-2970, 2021 05.
Article in English | MEDLINE | ID: covidwho-1206825

ABSTRACT

Tracing the globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogenetic clades by high-throughput sequencing is costly, time-consuming, and labor-intensive. We here propose a rapid, simple, and cost-effective amplification refractory mutation system (ARMS)-based multiplex reverse-transcription polymerase chain reaction (PCR) assay to identify six distinct phylogenetic clades: S, L, V, G, GH, and GR. Our multiplex PCR is designed in a mutually exclusive way to identify V-S and G-GH-GR clade variants separately. The pentaplex assay included all five variants and the quadruplex comprised of the triplex variants alongside either V or S clade mutations that created two separate subsets. The procedure was optimized with 0.2-0.6 µM primer concentration, 56-60°C annealing temperature, and 3-5 ng/µl complementary DNA to validate on 24 COVID-19-positive samples. Targeted Sanger sequencing further confirmed the presence of the clade-featured mutations with another set of primers. This multiplex ARMS-PCR assay is a fast, low-cost alternative and convenient to discriminate the circulating phylogenetic clades of SARS-CoV-2.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , COVID-19/virology , COVID-19 Nucleic Acid Testing/economics , Cost-Benefit Analysis , Genotype , Humans , Multiplex Polymerase Chain Reaction , Mutation , Phylogeny , Reproducibility of Results , SARS-CoV-2/classification
18.
Antimicrob Agents Chemother ; 65(7): e0009721, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1203931

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
19.
Expert Rev Mol Diagn ; 21(7): 723-732, 2021 07.
Article in English | MEDLINE | ID: covidwho-1201082

ABSTRACT

INTRODUCTION: Rapid and accurate diagnostic approaches are essential for impeding the spread of infectious diseases. This review aims to summarize current progress of clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) systems in the applications for diagnostics of infectious diseases including the ongoing COVID-19 epidemic. AREAS COVERED: In this review, we discuss class 2 CRISPR-Cas biosensing systems-based diagnostics in various emerging and reemerging infectious diseases, CRISPR-Cas systems have created a new era for early diagnostics of infectious diseases, especially with the discovery of the collateral cleavage activity of Cas12 and Cas13. We mainly focus on different CRISPR-Cas effectors for the detection of pathogenic microorganisms as well as provide a detailed explanation of the pros and cons of CRISPR-Cas biosensing systems. In addition, we also introduce future research perspectives. EXPERT COMMENTARY: However, further improvement of newly discovered systems and engineering existing ones should be developed to increase the specificity, sensitivity or stability of the diagnostic tools. It may be a long journey to finish the clinical transition from research use. CRISPR-Cas approaches will emerge as more promising and robust tools for infectious disease diagnosis in the future.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19 , CRISPR-Cas Systems , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/genetics , Humans
20.
Hum Gene Ther ; 32(19-20): 997-1003, 2021 10.
Article in English | MEDLINE | ID: covidwho-1177257

ABSTRACT

Advanced therapy medicinal products (ATMPs), such as gene therapies that consist of or contain genetically modified organisms (GMOs) need to comply with the European Union (EU) GMO legislation, as implemented in each EU Member State, before a clinical trial can commence. Complying with GMO requirements is complex, varies significantly across EU Member States and is leading to delays to clinical trials with ATMPs. Such delays and varying implementation of the GMO legislation makes the EU less attractive as a region to conduct clinical trials with investigational gene therapies. This is detrimental to EU patients, since their timely access to these transformative potentially curative medicines is delayed. Despite recent initiatives coordinated by the European Commission (EC) to facilitate and reduce discrepancies across the EU regarding the application of the GMO requirements, it remains particularly difficult to conduct multicenter clinical trials with ATMPs containing or consisting of GMOs involving several EU Member States. The recent decision for the EC to temporarily derogate potential coronavirus disease 2019 treatments and vaccines from some provisions of the GMO requirements was made on the basis of a clear recognition of such complexities and resulting delays to clinical development. The Alliance for Regenerative Medicine, the European Federation of Pharmaceutical Industries and Associations, and the European Association for Bioindustries call upon the EC, together with national competent authorities, to exempt ATMPs containing or consisting of GMOs from the GMO legislation. Such a simplification will eliminate the delays currently reported to occur when submitting environmental risk assessments and GMO applications to the national competent authorities. An exemption from GMO requirements will make the EU a more attractive region for clinical development of gene therapies and could accelerate European patients' access to these potentially life-saving medicines. Maintaining a system for GMO assessment that is different across countries may also prevent ATMPs from realizing the full benefits of a harmonized clinical trial approval process under the Clinical Trials Regulation. The undersigned organizations to this publication urge the EC to use its right of initiative to put forward a legislative proposal to exempt ATMPs in clinical development from the EU GMO legislation, within the timeframe proposed in the 2020 EU Pharmaceutical Strategy (by 2022). Implementation of a GMO exemption scheme before the end of the transition period for the Clinical Trial Regulation (the end of 2023) is important to avoid new Clinical Trial Application submissions for ATMPs under the Clinical Trial Regulation having to conduct the whole GMO assessment process in parallel. It is considered that ATMPs pose negligible risk to the environment. Such ATMPs include the following: human somatic cells modified ex vivo; recombinant virus-based vectors, including those containing genome editing nucleic acid sequences (which may also be delivered nonvirally); and bacterial vectors. Outside of controlled storage conditions, gene therapies cannot survive for any appreciable length of time. Upon clinical administration, any recombinant gene therapy viral vector particles that do not enter host cells are diluted within the body and if excreted are in such low multiplicity to no longer be viable or considered infectious to persons, animals, or living organisms within the environment. Any nucleic acids released into the environment are rapidly degraded.


Subject(s)
COVID-19 , Food, Genetically Modified , Legislation, Medical , Multicenter Studies as Topic/legislation & jurisprudence , Organisms, Genetically Modified , SARS-CoV-2 , European Union , Humans
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