Empowering the scholarship of teaching and learning (SoTL) towards society 5.0

The Scholarship of Teaching and Learning (SoTL) is often viewed as a secondary tier of research which consequently contributes to its undervalued status amongst many academicians. However, Higher Education (HE) aims to empower students with the ability to comprehend, analyze, solve problems, apply theories relevant practices, as well as being imbued with a greater appreciation of the knowledge gained from the teaching and learning (T&L) sessions, all as a means of preparing for their integration as a part of Society 5.0. The recent Covid-19 pandemic has accelerated the migration from face-to-face learning to online and hybrid learning across all institutions of HE, even including those which are typically skills and practice-based. The current situation has effectively catalyzed the importance of SoTL in ensuring the process of teaching and learning at institutions of HE can still be effectively conducted, even during the enforcement of lockdown measures. This study aims to describe the fundamentals and methods for conducting SoTL. Additionally, several case studies of SoTL conducted during the Covid-19 pandemic are reviewed and discussed, mainly to exemplify SoTL practices in institutions of HE. These findings are expected to provide new ideas, strategies, as well as guidelines for conducting SoTL at HE level in the present uncertain conditions. Scholars from SoTL-focus disciplines are strongly recommended to collaborate with those from other disciplines to overcome the tidal wave of uncertainty and complexity of T&L in a post-Covid-19 reality. © 2023 Author(s).

Containing an Island: Coronavirus (Covid-19) Outbreak in Perhentian Islands, Terengganu State of Malaysia, in 2021

Background: The spread of COVID-19 was inevitable and has not spared small and isolated communities, including the community on Perhentian Island in Besut District, Terengganu. Managing clusters in small islands can be difficult, given the limited resources. This study explores the characteristics of COVID-19 cases and the experience of outbreak containment at Perhentian Island. Methodology: A retrospective study involving record review of COVID-19 cases and at-risk individuals registered under the Perhentian Cluster were retrieved from the Besut District Health Office COVID-19 online registry from the 16th August 2021 until 6th October 2021. All notified cases and close contacts who fulfilled the inclusion criteria were extracted and analysed using descriptive statistics. Result(s): A total of 1,093 out of 2,500 community members of Perhentian Island were screened of which 170 (15.5%) tested positive for COVID-19, while 923 (84.5%) tested negative. Among individuals who tested positive, the majority were adults (52.4%), males (51.8%), Malays (98.8%), and villagers (96.5%). Clinical characteristics were categorized into: asymptomatic (55.9%), had no known medical comorbidities (90.6%), low-risk groups (87.1%), vaccinated (57.6%), and admitted to PKRC (97.1%) for treatment. Multiple agencies were involved in the outbreak containment of the Perhentian Cluster, working collectively and in good coordination. Conclusion(s): The outbreak was attributed to community gatherings and close interactions among villagers. Prompt actions, targeted planning, and inter-agency collaboration were the key factors in successful containment of further spread of COVID-19 in Perhentian Island.Copyright © 2023, Faculty of Medicine, University of Malaya. All rights reserved.

Utilizing Deep Learning in Arabic Text Classification Sentiment Analysis of Twitter

The number of social media users has increased. These users share and reshare their ideas in posts and this information can be mined and used by decision-makers in different domains, who analyse and study user opinions on social media networks to improve the quality of products or study specific phenomena. During the COVID-19 pandemic, social media was used to make decisions to limit the spread of the disease using sentiment analysis. Substantial research on this topic has been done;however, there are limited Arabic textual resources on social media. This has resulted in fewer quality sentiment analyses on Arabic texts. This study proposes a model for Arabic sentiment analysis using a Twitter dataset and deep learning models with Arabic word embedding. It uses the supervised deep learning algorithms on the proposed dataset. The dataset contains 51,000 tweets, of which 8,820 are classified as positive, 37,360 neutral, and 8,820 as negative. After cleaning it will contain 31,413. The experiment has been carried out by applying the deep learning models, Convolutional Neural Network and Long Short-Term Memory while comparing the results of different machine learning techniques such as Naive Bayes and Support Vector Machine. The accuracy of the AraBERT model is 0.92% when applying the test on 3,505 tweets.

Nutritional Intervention for the Treatment and Prevention Against Novel Coronavirus-19

Introduction: The ongoing pandemic of Severe Acute Respiratory Syndrome coronavirus-2 (SARS COV-2) has jeopardized people's health and the global economy. The infection caused by these viruses inflicts immunosuppression and an unprecedented range of symptoms leading to mortality. At this stage, there are no countermeasures or medicines to overcome rapid disease proliferation and aberrant immunological response. Objective(s): The study aims to determine different immunomodulatory therapeutics that could be potential agents to alleviate viral and other lethal infections and possibly rejuvenate immunological and tissue repair response against this disease. Method(s): A review of the literature was performed by screening different scientific databases to procure various immunomodulatory therapies for the treatment of SAR COV-2. Result(s): A comprehensive literature review indicated that different foods rich in vitamins (A-D), selenium and iron can enhance immunological response against various deleterious infections, whereas different nutritious drinks that include hydrogen-enriched water and green tea alleviate inflammation and elicit wound healing properties. Black cumin seeds and Garlic have a myriad of biological activities due to abundant bioactive phytochemicals that play an important role in the elimination of various bacterial and viral infections. Conclusion(s): These foods/supplements are relatively safe to consume and possess high toxicity profile and could be a potential nutritional intervention in order to create adequate immunity within a population to fight against this prevailing infection.Copyright © 2021 Bentham Science Publishers.

Assessment Model for Information Visualization of Human-Computer Interface in the COVID-19 Pandemic

The purpose of this study is to investigate and describe an example of COVID-19 pandemic information visualization in human-computer interface to serve as a reference for future pandemic information visualization performance improvements. The relevant local and international literature was investigated and studied, as well as the visualization projects of pandemic information from each stage released by major media outlets in the mid-term outbreak of COVID-19. Thereby, the assessment model of information charts, color evaluation, and interaction model for pandemic information visualization of human-computer interface design was obtained. To make the assessment model more effective, an evaluation system was introduced which contributes to the popularization of information, narrows the gap between truth and public cognition, and arouses public attention and vigilance. In the future, pandemic prevention and control will be supported by the assessment model for the design of information visualization of human-computer interface in different scenarios by systematization, standardization and real-time. © 2022, Success Culture Press. All rights reserved.

Nanoarchitectonics: role of nanomaterials in vaccination strategies for curbing SARs-CoV-2/COVID-19

With the exponential rise in infections by CoV-2 and the scarcity of antiviral therapeutics, the development of an effective vaccine for the SARS CoV-2 is critical. The emerging pandemic has prompted the international science community to seek answers in therapeutic agents, including vaccines, to battle the SARS CoV-2. The various scientific literature on SARS CoV, to a lesser degree, MERS (Middle East Respiratory Syndrome), has mentored vaccine techniques for the unique Coronavirus. This disease, COVID-19, is triggered by SARS-CoV-2 virus that causes COVID-19 that needs vaccine protection. Vaccines producing significant amounts of virus-neutralizing antibodies with high affinity may be the only way to combat infection while avoiding negative consequences. There is a summary of numerous vaccine contenders in the review, including nucleotide, vector-based vaccines, & subunit, and attenuated & killed types. That has previously shown preventive effects against the MERS-CoV & SARS-CoV, while suggesting that these candidates may yield a safe and efficient vaccine for SARS-CoV-2. Vector-based vaccines, monoclonal antibodies, genetic vaccines, and protein subunit types for passive immunization are among the vaccination platforms currently being evaluated for the CoV-2 virus;each has its own set of benefits and drawbacks. The clinical safety and effectiveness evidence is the main challenging research task for this possible vaccine developed in the lab. The most challenging aspect of production is constructing and validating distribution platforms worthy of mass-producing the vaccine on a larger scale. Since target vaccine groups include high-risk people above the age of 60, including severe co-morbid diseases, the healthcare staff, and those engaged in vital industries, an effective COVID-19 vaccine would need a careful confirmation of effectiveness and detrimental reactivity. The study summarises efforts devoted to developing an efficient vaccine for the new Coronavirus that devastated the global economy, people's health, and even their lives.

Radiological Finding of Crazy-Paving Pattern in COVID-19 Pneumonia

The recent global pandemic of coronavirus disease 2019 (COVID-19) has brought many radiographic findings in other respiratory disease processes. One of these radiological findings is crazy paving. This paper discusses crazy paving in a 75-year-old female with dyspnea, nonproductive cough, pleuritic chest pain, and a polymerase chain reaction (PCR) positive test for COVID-19 infection. Chest CT showed ground-glass opacities and interlobular septal thickening consistent with a crazy-paving appearance. As part of the common CT findings of patients with active COVID-19 infection, crazy paving should prompt the interpreting radiologist to consider COVID-19 pneumonia as part of the differential.

A Review on Machine Learning Approaches in COVID-19 Pandemic Prediction and Forecasting

Novel COVID-19 Coronavirus disease, namely SARS-CoV-2, is a global pandemic and has spread to more than 200 countries. The sudden rise in the number of cases is causing a tremendous effect on healthcare services worldwide. To assist strategies in containing its spread, machine learning (ML) has been employed to effectively track the daily infected and mortality cases as well as to predict the peak growth among the states or/and country-wise. The evidence of ML in tackling previous epidemics has encouraged researchers to reciprocate with this outbreak. In this paper, recent studies that apply various ML models in predicting and forecasting COVID-19 trends have been reviewed. The development in ML has significantly supported health experts with improved prediction and forecasting. By developing prediction models, the world can prepare and mitigate the spread and impact against COVID-19. © 2022 UPM Press. All rights reserved.

CRISPR-cas13 enzymology rapidly detects SARS-CoV-2 fragments in a clinical setting.

BACKGROUND: The well-recognized genome editing ability of the CRISPR-Cas system has triggered significant advances in CRISPR diagnostics. This has prompted an interest in developing new biosensing applications for nucleic acid detection. Recently, such applications have been engineered for detection of SARS-CoV-2. Increased demand for testing and consumables of RT-PCR assays has led to the use of alternate testing options. Here we evaluate the accuracy and performance of a novel fluorescence-based assay that received EUA authorization for detecting SARS-CoV-2 in clinical samples. METHODS: The Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) technology forms the basis of the Sherlock CRISPR SARS-CoV-2 kit using the CRISPR-Cas13a system. Our experimental strategy included selection of COVID-19 patient samples from previously validated RT-PCR assays. Positive samples were selected based on a broad range of cycle thresholds. RESULTS: A total of 60 COVID-19 patient samples were correctly diagnosed with 100% detection accuracy (relative fluorescence ratios: N gene 95% CI 29.9-43.8, ORF1ab gene 95% CI 30.1-46.3). All controls, including RNase P, showed expected findings. Overall ratios were robustly distinct between positive and negative cases relative to the pre-established 5-fold change in fluorescence. CONCLUSIONS: We have evaluated the accuracy of detecting conserved targets of SARS-CoV-2 across a range of viral loads, including low titers, using SHERLOCK CRISPR collateral detection in a clinical setting. These findings demonstrate encouraging results, at a time when COVID-19 clinical diagnosis and screening protocols remain in demand; especially as new variants emerge and vaccine mandates evolve. This approach highlights new thinking in infectious disease identification and can be expanded to measure nucleic acids in other clinical isolates.

Does thromboelastography predict clinical outcomes in COVID-19?

Background : COVID-19 infection is associated with thrombosis and death, but the role of global coagulation assays such as thromboelastography (TEG) in predicting clinical outcomes is unclear. Aims : To assess TEG patterns in patients with COVID-19 and to determine association with mortality and thrombosis. Methods : TEGs were performed prospectively as part of a multicenter randomized controlled trial comparing standard vs intermediate dosing of prophylactic anticoagulation in hospitalized patients with severe COVID-19 (NCT04360824). All enrolled patients had a modified ISTH DIC score>3 and/or were admitted to an intensive care unit. TEG and baseline coagulation labs were obtained at study entry. TEG parameters and baseline labs and patient demographics were analyzed and correlated with the primary outcome (30-day mortality) and secondary outcomes (arterial and venous thrombosis, acute kidney injury, and major and minor bleeding). Results : The baseline characteristics for 131 patients for which TEG results were available are shown in Table 1. Thrombotic events occurred in 9.9% of patients ( N = 13), acute kidney injury in 13% ( N = 18) and the 30-day mortality rate was 16 % ( N = 21). No significant associations were noted between baseline TEG results and patient outcomes based on standard reference ranges. When comparing the continuous TEG data against relevant outcomes, only LY30 was associated with any outcome (30-day mortality). White blood cell count, D-dimer, and creatinine were better predictors of major patient outcomes. A multivariable model including categorical representations of age, LY30, and D-dimer values showed good performance in predicting 30-day mortality (Table 2). Conclusions : Hypercoagulability and thrombotic events occur frequently in hospitalized COVID-19 patients and are associated with adverse outcomes. TEG data independently was not predictive of major outcomes, but the addition of TEG results to a multivariate model improved prognostic implications for mortality.

High-Throughput CRISPR-Cas13 SARS-CoV-2 Test.

BACKGROUND: The ability to control the spread of COVID-19 continues to be hampered by a lack of rapid, scalable, and easily deployable diagnostic solutions. METHODS: We developed a diagnostic method based on CRISPR (clustered regularly interspaced short palindromic repeats) that can deliver sensitive, specific, and high-throughput detection of Sudden Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The assay utilizes SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the qualitative detection of SARS-CoV-2 RNA and may be performed directly on a swab or saliva sample without nucleic acid extraction. The assay uses a 384-well format and provides results in <1 hour. RESULTS: Assay performance was evaluated with 105 (55 negative, 50 positive) remnant SARS-CoV-2 specimens previously tested using Food and Drug Administration emergency use authorized assays and retested with a modified version of the Centers for Disease Control and Prevention (CDC) quantitative PCR with reverse transcription (RT-qPCR) assay. When combined with magnetic bead-based extraction, the high-throughput SHERLOCK SARS-CoV-2 assay was 100% concordant (n = 60) with the CDC RT-qPCR. When used with direct sample addition the high-throughput assay was also 100% concordant with the CDC RT-qPCR direct method (n = 45). With direct saliva sample addition, the negative and positive percentage agreements were 100% (15/15, 95% CI: 81.8-100%) and 88% (15/17, 95% CI: 63.6-98.5%), respectively, compared with results from a collaborating clinical laboratory. CONCLUSIONS: This high-throughput assay identifies SARS-CoV-2 from patient samples with or without nucleic acid extraction with high concordance to RT-qPCR methods. This test enables high complexity laboratories to rapidly increase their testing capacities with simple equipment.

Bispecific CART cells in the treatment of relapsed and refractory multiple myeloma: A review of literature

Background: Chimeric antigen receptor T cells (CART) have shown promising results in the treatment of relapsed and refractory multiple myeloma (RRMM). Recently, bispecific-CART cells targeting 2 antigens are being evaluated in various clinical trials. Methods: A comprehensive literature search was done of Pubmed, Embase, and Cochrane. Data presented at annual hematology and oncology conferences were also included. Results: We included 4 phase I clinical trials with a total of 77 RRMM patients between the ages of 18 to 71 years. The median follow-up duration ranged from 1 month to 27.5 months. All were lymphodepleted with Cyclophosphamide and Fludarabine before receiving CAR-T cell therapy. The CAR-T cell targets include BCMA and CD38 (dose range 0.5 x 10∧6 - 4 x 10∧6 cells/kg), BCMA and TACI (dose range 15 - 900 x 10e6 CAR-T cells), BCMA and CD19 (1 x 10e5/kg - 3 x 10e5 CAR-T cells/kg), and BCMA and CD19 (dose 1 x 10e6 cells/kg). Overall response rate (ORR) was reported by 4 trials (87.5%, 43%, 93.8%, 95%). Complete response (CR) was also reported in 4 trials as 50%, 64%, 56.3% and 14% and partial response (PR) reported as 25%, 28%, 16.6%, 14%, 18% in 5 trials (table). The most common grade 3-4 adverse effects that were reported include cytokine release syndrome, neurotoxicity, neutropenia, lymphopenia, anemia, thrombocytopenia, diarrhea, increased LDH, lower respiratory tract infections (LRTI), dehydration, renal failure (table). Yan et al. reported one death due to cerebral hemorrhage which was considered unrelated to treatment. Jiang et al. reported one death from unknown cause of a patient who presented with fever during the COVID- 19 pandemic.Conclusions: Bispecific CART cells have shown promising results in the treatment of RRMM. However, the clinical trials are ongoing, and a longer follow-up is needed.

Physical Distancing and Temperature Sensing Bracelet

The world is enduring difficulties in numerous fields because of this Coronavirus pandemic flare-up. All government had played it safe to forestall the infection transmission, for example, rehearsing social distancing and temperature checking before entering any preface just as declaring a lockdown. Notwithstanding, the 1-meter distance is not straightforward to estimate by unaided eyes, and it is difficult to carry along a meter rule regularly. Subsequently, inadvertently connect with others. Therefore, this would build our danger of getting contaminated by the COVID-19 infection. Moreover, the thermometer put at each person’s passageway has the threat of causing disease since numerous individuals share it. Regardless of whether a specialist is appointed to quantify guests’ temperature, the person does not have the option to keep up the guest’s social distance when taking temperature. In this research, a sensing bracelet proposed to determine physical distancing and temperature. The bracelet has two fundamental capacities. It can continually screen distance among client and others utilising a sensor. It will warn the client to keep up social distancing and avoid swarmed places when it distinguishes individuals under 1 meter. Second, it has a temperature sensor to determine the client’s internal heat level and will ring to caution the client if the internal heat level is more than 37.5°C. The experiment conducted able to achieve the requirement for a physical distancing.

Novel Coronavirus: A Review from Origin to Current Status of Therapeutic Strategies

Coronaviruses (CoVs) are continuously emerging, highly transmissible, and pathogenic agents that primarily target the human respiratory system. Previous outbreaks of severe acute respiratory syndrome-CoV and Middle East respiratory syndrome-CoV remain life-threatening and global public health concerns. A novel CoV outbreak that occurred in December 2019 in Wuhan, China was declared a pandemic outbreak that has since killed millions of individuals worldwide. Rapid transmission, genetic variations, and unavailability of specific therapeutic drugs are major factors that led to this alarming and deadly situation. Currently, > 200 clinical vaccine trials are underway to combat infection. This review summarizes reports related to CoV origin, genetic variations, drug options, status of nine vaccines that were in phase III trials, and novel therapies including convalescent plasma and stem cell treatment.

Clinical description of the broad range of neurological presentations of COVID-19: A retrospective case series.

BACKGROUND: Neurological disorders associated with SARS-CoV-2 infection represent a clinical challenge because they encompass a broad neurological spectrum and may occur before the diagnosis of COVID-19. METHODS: In this monocentric retrospective case series, medical records from patients with acute neurological disorders associated with SARS-CoV-2 infection from medicine departments of an academic center in Paris area were collected between March 15th and May 15th 2020. Diagnosis of SARS-CoV-2 was ascertained through specific RT-PCR in nasopharyngeal swabs or based on circulating serum IgG antibodies. RESULTS: Twenty-six patients diagnosed with SARS-CoV-2 infection presented with neurological disorders: encephalitis (N=8), encephalopathy (N=6), cerebrovascular events (ischemic strokes N=4 and vein thromboses N=2), other central nervous system (CNS) disorders (N=4), and Guillain-Barré syndrome (N=2). The diagnosis of SARS-CoV-2 was delayed on average 1.6 days after the onset of neurological disorder, especially in case of encephalitis 3.9 days, encephalopathy 1.0 day, and cerebrovascular event 2.7 days. CONCLUSIONS: Our study confirms that COVID-19 can yield a broad spectrum of neurological disorders. Because neurological presentations of COVID-19 often occur a few days before the diagnosis of SARS-COV-2 infection, clinicians should take preventive measures such as patient isolation and masks for any new admission to avoid nosocomial infections. Anti-SARS-CoV2 antibody detection in RT-PCR SARS CoV-2 negative suspected cases is useful to confirm a posteriori the diagnosis of atypical COVID-19 presentations.

Analysis and design of emergency field isolation hospital building using innovative rapidly construction prefabricated units to treat patients infected with COVID-19

Coronavirus pandemic is the most catastrophic phenomena of nature. In a major disaster which affected substantially to human lifecycle and property loss. Instant rehabilitation for the people affected with coronavirus was essential. As an immediate measure, it led to the application of light-gauge steel within Saudi Arabia for quick construction, in addition for the safety purposes during disaster in the forthcoming. Several hospital buildings with changeable categories of earthquake and seismic performance design needs are present. Broadly, the earthquake performance is categorized into two types: structural and non-structural, either under unsatisfactory conditions can be dangerous to occupants in the building once damage occurs. The deprivation in structural support of hospital building’s systems (i.e. lateral and vertical force resisting systems) like frames and walls in the hospital building comes under structural damage, whereas the non-structural damage means the damage which doesn’t affect the structural support system reliability such as pipes damage and pumps disruption, window breaking, breakdown of chimney viz. Furthermore, the non-structural damage is life intimidating also uneconomical. © 2021, Springer Nature Switzerland AG.

Outcomes of Coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders

Background: Outcomes of coronavirus disease 2019 (COVID- 19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibodyassociated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. Objectives: The objective was to describe the clinical characteristics and outcomes of COVID-19 in patients with neuromyelitis optica and associated disorders and to identify the factors associated with COVID-19 severity. Methods: We conducted a multi-center, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and June 30th, 2020. Main outcome was COVID-19 severity score assessed on a 7-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). Results: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower EDSS score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). Conclusions: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19, however we recommend to maintain preventive measures to limit the risk of contamination with SARS-CoV-2 in this immunocompromised population.

Clinical characteristics and outcomes in patients with coronavirus disease 2019 and multiple sclerosis

Background: Risk factors associated with the severity of COVID- 19 in patients with multiple sclerosis (MS) begin to be identified from several cohort studies. Disease modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objectives: The objective was to describe the clinical characteristics and outcomes in patients with COVID-19 and to identify the factors associated with COVID-19 severity. Methods: This multicenter, retrospective, observational cohort study (COVISEP registry, NCT04355611) included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020 and July 14, 2020. The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1: not hospitalized, no limitations on activities, to 7: death;cutoff at 3: hospitalized, not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Score (EDSS), comorbidities, COVID-19 characteristics and outcome. Univariate and multivariate logistic regression models were used to estimate the influence of collected variables on COVID-19 outcome. Results: A total of 405 patients (mean age: 44.7 years, female/male: 293/112, mean disease duration: 13.4 years) were analyzed. Seventy-eight patients (19.3%) had a COVID-19 severity score ≥ 3, and 12 patients (3.0%) died from COVID-19. Median EDSS was 2.0 (range: 0-9.5), 326 patients (80.5%) were on DMT. There was a higher proportion of patients with COVID-19 severity score ≥ 3 among patients with no DMT relative to patients on DMTs (39.2% versus 14.4%, p<0.001). Multivariate logistic regression models determined that age (OR for 10 years: 1.8, 95% CI: 1.4-2.4), EDSS (OR for EDSS ≥ 6: 4.5, 95% CI: 2.0-10.0) were independent risk factors for COVID-19 severity score ≥ 3 (hospitalization or higher severity) while immunomodulatory treatment (interferon or glatiramer acetate) was associated with lower risk of COVID-19 severity score ≥ 3 (OR: 0.2, 95% CI: 0.05-0.8). EDSS was associated with the highest variability of COVID-19 severe outcome (R2= 0.18), followed by age (R2= 0.06) and immunomodulatory treatment (R2= 0.02). Conclusions: EDSS and age were independent risk factors of severe COVID-19, while exposure to immunomodulatory DMTs (interferon and glatiramer acetate) were independently associated with lower COVID-19 severity. We did not find an association between other DMTs exposure (including immunosuppressive therapies) and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of MS patients during the COVID- 19 pandemic.

CRISPR-cas13 enzymology rapidly detects SARS-CoV-2 fragments in a clinical setting (preprint)

The well-recognized genome editing ability of the CRISPR-Cas system has triggered significant advances in CRISPR diagnostics. This has prompted an interest in developing new biosensing applications for nucleic acid detection. Recently, such applications have been engineered for detection of SARS-CoV-2. Increased demand for testing and consumables of RT-qPCR assays has led to the use of alternate testing options in some cases. Here we evaluate the accuracy and performance of a novel fluorescence based assay that received EUA authorization from the FDA for detecting SARS-CoV-2 in clinical samples. The Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) technology forms the basis of the Sherlock CRISPR SARS-CoV-2 kit using the CRISPR-Cas13a system. Our experimental strategy included selection of COVID-19 patient samples from previously validated RT-qPCR assays. Positive samples were selected based on a broad range of cycle thresholds. A total of 50 COVID-19 patient samples were correctly diagnosed with 100% accuracy (relative fluorescence ratios: N gene 95% CI 23.2-36.3, ORF1ab gene 95% CI 27.6-45.4). All controls, including RNase P, showed expected findings. Overall ratios were robustly distinct between positive and negative cases relative to the pre-established 5-fold change in fluorescence read output. We have evaluated the accuracy of detecting conserved targets of SARS-CoV-2 across a range of viral loads using the SHERLOCK CRISPR collateral detection reaction in a clinical setting. These findings demonstrate encouraging results, especially at a time when COVID-19 clinical diagnosis is in high demand; often with limited resources. This approach highlights new thinking in infectious disease identification and can be expanded to measure nucleic acids in other clinical isolates.