A Multivent System for Non-invasive Ventilation: Solving the Problem of Ventilator Shortage during the COVID-19 Pandemic

The COVID-19 pandemic has caused a severe global problem of ventilator shortage. Placing multiple patients on a single ventilator (ventilator sharing) or dual patient ventilation has been proposed and conducted to increase the cure efficiency for ventilated patients. However, the ventilator-sharing method needs to use the same ventilator settings for all the patients, which cannot meet the ventilation needs of different patients. Therefore, a novel multivent system for non-invasive ventilation has been proposed in this study. The close loop system consists of the proportional valve and the flow-pressure sensor can regulate the airway pressure and flow for each patient. Multiple ventilation circuits can be combined in parallel to meet patients’ventilation demands simultaneously. Meanwhile, the mathematical model of the multivent system is established and validated through experiments. The experiments for different inspired positive airway pressure (IPAP), expired positive airway pressure (EPAP), inspiratory expiratory ratio (I:E), and breath per minute (BPM) have been conducted and analyzed to test the performance of the multivent system. The results show that the multivent system can realize the biphasic positive airway pressure (BIPAP) ventilation mode in non-invasive ventilation without interfering among the three ventilation circuits, no matter the change of IPAP, EPAP, I:E, and BPM. However, pressure fluctuation exists during the ventilation process because of the exhaust valve effect, especially in EPAP control. The control accuracy and stability need to be improved. Nevertheless, the novel designed multivent system can theoretically solve the problem of ventilator shortage during the COVID-19 pandemic and may bring innovation to the current mechanical ventilation system. Author

Mobile Malaysian Sign Language Application

Due to the Covid-19 plague, children with hearing misfortune have experienced challenges in learning and practicing sign language due to need of educational services and learning assets. The next considerations for creating an educational mobile learning application to help deaf kids learn Malaysian Sign Language (MSL). The investigation was conducted through gatherings based on inquire about and interviews with subject matter experts. Instructors recommend that within the current circumstance, versatile learning application are the foremost reasonable stage for understudies to memorize or as an extra learning strategy in arrange to educate them well. This research was conducted through research-based and interview sessions with subject matter experts and followed the Multimedia Mobile Content Development (MMCD) methodology as it was shown to help accelerate development activities and ensure that the application would work and execute as planned. Once the application is developed, students from Sekolah Kebangsaan Silabukan in Lahad Datu, Sabah, will participate in beta testing. Based on the results of user acceptance tests, the application has received positive reviews from its target users. As such, the project's goals are said to have been achieved. At the conclusion of the study, the advantages, limitations and future work of Pocket Sign Language were also identified. © 2022 IEEE.

Resistance Analyses of Patient Viral Samples from the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1)

Background. Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in non-hospitalized and hospitalized adult as well as pediatric patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 ACTT-1 placebo-controlled clinical trial in hospitalized adults. Methods. Oro- or nasopharyngeal swab samples in ACTT-1 study were collected on Day 1, 3, 5, 8, 11, 15, and 29. All participants with >80th and 50% of participants with < 20th percentile of cumulative viral shedding underwent resistance analysis in both the RDV and placebo arm. The SARS-CoV-2 genome was sequenced using next generation sequencing. Phenotyping was conducted using virus isolation from clinical samples or generation of select site-directed mutants (SDMs) in a SARS-CoV-2 replicon system. Results. The majority of the sequencing data were obtained from participants with 80th percentile of cumulative viral shedding from the RDV and placebo arms as shown in Table 1. Among participants with both baseline and postbaseline sequencing data, emergent substitutions in nsp12 were observed in 12 of 31 participants (38.7%) treated with RDV and 12 of 30 participants (40.0%) in the placebo arm. The nsp12 substitutions that emerged in the RDV arm were only observed in one participant each, and the majority were present as mixtures with wildtype sequence. The following nsp12 mutations emerged in the RDV treatment group and were successfully phenotyped as clinical isolates or SDMs with low to no fold change in RDV susceptibility: A16V (0.8-fold), P323L+V792I (2.2-fold), C799F (2.5-fold), K59N (1.0-fold), and K59N+V792I (3.4-fold). V792I and C799F were identified previously in vitro in resistance selection experiments (Stevens Sci Transl Med 2022). In addition, for D684N and V764L identified in the RDV arm, the recovery of neither clinical isolates nor SDMs for phenotypic analysis were successful. Conclusion. The similar rate of emerging nsp12 substitutions in participants treated with RDV compared to placebo and the minimal to no change in RDV susceptibility among the treatment-emergent nsp12 substitutions support a high barrier to RDV resistance development in COVID-19 patients.

Diagnostic Test Kinetics, Infectivity, and Immunological Responses Among Unvaccinated Adults During Acute SARS-CoV-2 Infection

Background. Appropriate diagnostic testing can be used to inform infection control measures and reduce SARS-CoV-2 transmission, yet the test kinetics, infectivity, and immunological responses during acute, non-severe SARS-CoV-2 infection need clarity. Methods. We conducted a prospective cohort study between Nov 2020-July 2021 in Seattle, Washington of 95 unvaccinated, immunocompetent adults with no prior SARS-CoV-2 infection. Nasal swabs (nasopharyngeal and anterior) and blood serum samples were serially collected at six visits over two months. Viral RNA, N and S antigen concentrations, and viral growth/infectivity were measured from nasal samples. Anti-S total antibody and IgG assays were performed on serum. We fit loess curves to quantitative data corresponding to each testing modality by days since symptom onset (DSSO) and compared qualitative test results across time points to demonstrate timedependent agreement of PCR, N antigen, and culture results. Generalized estimating equations were used to approximate relative risk of culture positivity (a proxy for infectiousness) for positive vs. negative test results (antigen and PCR), stratified by presence/ absence of symptoms and DSSO. Sampling Schema Nasal swabs and venous blood were collected at visits 1-4;venous blood only at visits 5-6. All participants were enrolled within 14 days of symptom onset (median: 6) and 7 days of a positive test (median: 4). Results. Infections in this cohort (median age: 29y) were mild (no hospitalization). Median (IQR) time to negative result was 11 (4), 13 (6), and 20 (7) DSSO for culture growth, N antigen, and PCR tests, respectively. Viral RNA quantities declined more slowly than antigen and culturable virus;antibody titers rose rapidly 5-15 DSSO and plateaued 20-30 DSSO. All culture-positive samples collected 0-5 DSSO were positive by PCR, but relative risk of culture positivity (infectiousness) for positive vs. negative PCR results declined 6-10 DSSO. Relative risk of culture positivity for positive vs. negative antigen results was consistently high 0-10 DSSO, with similar results when stratified by presence of symptoms. Diagnostic test kinetics and immunological responses Diagnostic test kinetics and immunological responses measured in adults with non-severe, symptomatic SARS-CoV-2 infection: loess trendlines and 95% confidence intervals are given for SARS-CoV-2 viral load (calculated from PCR Ct value using a calibration curve), TCID50 from viral culture, mean concentrations of nucleocapsid and spike antigen proteins, and anti-S total and IgG antibody concentrations. Conclusion. The results reinforce the importance of molecular PCR testing as a highly sensitive diagnostic tool but with limited utility as an indicator of viral culturability and likely infectiousness. N antigen testing may be a preferable diagnostic test within two weeks of symptom onset, especially 6-10 DSSO, because it more closely correlates with culture growth over the course of infection.

A Remotely Controlled Oropharyngeal Swab Sampling Robot and its Application in COVID-19 Prevention

Oropharyngeal swab sampling is the major viral nucleic acid detection method to diagnose COVID-19. Medical staff exposes themselves to the respiratory secretions of patients, which makes them vulnerable to infection. To protect medical staff, we summarize the clinical requirements for robot into five considerations (standardization, ergonomics, safety, isolation, and task allocation) and developed a remotely operated oropharyngeal swab sampling robot. With robot assistance, spatial isolation between medical staff and the patients can be achieved. We designed a hybrid force/position control scheme for the sampling robot to achieve intuitive operation and stable contact force. The experiment results on phantom tissue show that the sampling robot can achieve intuitive operation and stable contact on the soft posterior pharyngeal. Clinical trials for 20 volunteers and 2 patients diagnosed with COVID-19 are carried out. The results of the clinical trial indicated that the sampling robot can collect samples stably and effectively, and the contact force is gentler and more uniform. For two patients diagnosed with COVID-19, the robot sampling results are consistent with manual sampling. IEEE

A comprehensive genome report for COVID-19 patients: GENCOV Study Canada

Background: Severe acute respiratory syndrome coronavirus (SARSCoV- 2) is a novel virus that causes Coronavirus Disease 2019 (COVID- 19). High-throughput sequencing technologies such as whole genome sequencing (WGS) and sequencing of viral genome DNA are being implemented to identify and report on genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. Genome sequencing has been useful for clinical diagnostic purposes, and can reveal other useful information such as disease risk factors that might lead to disease prevention or patient management strategies. UsingWGS and bioinformatics software tools, we describe a novel pipeline for the analysis of medically relevant genetic results and other findings identified in COVID-19 positive individuals, and the generation of a genome report that can effectively communicate these results to patients and their physicians. Study design: Enrollment will include up to 1500 patients with a positive COVID-19 nasopharyngeal swab. Blood samples will be collected at baseline, 1 month, 6 months, and 1 year after diagnosis. Antibody isotype (IgG, IgA, and IgM), titers, and viral neutralization will be analyzed. DNA will be isolated from blood lymphocytes and host genomes will be sequenced. Whole genomes will be assessed using ACMG criteria for the interpretation of pathogenic sequence variation using in-house and third-party software tools, and publicly available disease and control databases. Comprehensive gene panels will be implemented to allow for patients to receive clinically significant findings, including risk factor and carrier status, from multiple categories of potential genetic conditions including blood and immunology, endocrine, metabolic/mitochondrial, musculoskeletal, hearing loss, neurology, cardiology, ophthalmology, renal, skin, and gastrointestinal disorders. Common disease risk will be assessed using polygenic risk scores calculated for 6 diseases (atrial fibrillation, coronary artery disease, type 2 diabetes, prostate cancer, colorectal cancer, breast cancer). Pharmacogenomic gene variants that alter metabolizer phenotype and drug response in individuals will be reported, in addition to patient HLA-type. The genomic predictions fromABO and Rh blood types will be summarized and reported. Largescale continental ancestry estimation will be performed using publicly available reference populations. Finally, using viral genome DNA sequencing, the SARS-CoV-2 viral lineage will be identified and reported. An appointment with the study genetic counsellor will be scheduled to discuss results identified in the genome report and manage appropriate clinical referrals if necessary. Serology results will be reported. Regression models will examine associations between antibody response (titer, antigen target, viral neutralization ability), physiological response (biochemical, hematological and clinical characteristics), patient outcomes, viral lineage and genomic results. Significance: This study will link clinically relevant genomic results, in addition to other biological and serological characteristics, to potential factors that contribute to variability in SARS-CoV-2 outcomes. Results will be shared with family physicians for clinical follow up. This study will establish an efficient workflow using highthroughput genomic sequencing technology coupled with emerging bioinformatics platforms for the generation of comprehensive genome reports to aid in COVID-19 patient management and follow-up.

Design of Face Recognition Temperature Detector Based on YoloV2 Strategy

Because of the new champions league epidemic raged in the whole world, a variety of inconvenience to people's production, life, at present, although the effective control of domestic outbreak, but the epidemic still cannot relax, requires a lot of manpower, material resources, financial resources, in particular schools, hospitals, shopping malls and other crowded places, as the main representation of the new champions league patients body fever, Temperature detection is needed for initial screening of COVID-19 patients. Based on the above reasons, a non-contact, long-distance body temperature detector was designed to detect the temperature of candidates to avoid problems such as temperature misdetection, false alarm, and omission. The method of manual verification by invigilators was changed, and the YoloV2 algorithm was used to obtain identity in real time and automatically. Validation results. This article first analyzes the existing problems of the current body temperature detector and the market demand for epidemic prevention and control, and then designs the non-contact, remote body temperature measurement and face recognition functions of the body temperature detector. Finally, it has been actually verified to meet the design requirements, especially for the success rate of face recognition of blurred images is over 74%. With the continuous improvement and upgrade of functions, it will have high engineering application value. © 2021 IEEE.

Open design and 3D printing of face shields: The case study of a UK-China initiative

At the start of the COVID-19 outbreak, many countries lacked personal protective equipment (PPE) to protect healthcare workers. To address this problem, open design and 3D printing technologies were adopted to provide much-in-need PPEs for key workers. This paper reports an initiative by designers and engineers in the UK and China. The case study approach and content analysis method were used to study the stakeholders, the design process, and other relevant issues such as regulation. Good practice and lessons were summarised, and suggestions for using distributed 3D printing to supply PPEs were made. It concludes that 3D printing has played an important role in producing PPEs when there was a shortage of supply, and distributed manufacturing has the potential to quickly respond to local small-bench production needs. In the future, clearer specification, better match of demands and supply, and quicker evaluation against relevant regulations will provide efficiency and quality assurance for 3D printed PPE supplies. © 2020 Universidade do Vale do Rio dos Sinos. All rights reserved.