COVID Seq as Laboratory Developed Test (LDT) for diagnosis of SARS-CoV-2 Variants of Concern (VOC) (preprint)

Rapid classification and detection of SARS-CoV-2 variants have been critical in comprehending the virus's transmission dynamics. Clinical manifestation of the infection is influenced by comorbidities such as age, immune status, diabetes, and the infecting variant. Thus, clinical management may differ for new variants. For example, some monoclonal antibody treatments are variant-specific. Yet, an FDA-approved test for detecting the SARS-CoV-2 variant is unavailable. A laboratory-developed test (LDT) remains a viable option for reporting the infecting variant for clinical intervention or epidemiological purposes. Accordingly, we have validated the Illumina COVID-Seq assay as an LDT according to the guidelines prescribed by the College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). The limit of detection (LOD) of this test is Ct<30 (~15 viral copies) and >200X genomic coverage, and the test is 100% specific in the detection of existing variants. The test demonstrated 100% precision in inter-day, intra-day, and intra-laboratory reproducibility studies. It is also 100% accurate, defined by reference strain testing and split sample testing with other CLIA laboratories. Advanta Genetics LDT COVID Seq has been reviewed by CAP inspectors and is under review by FDA for Emergency Use Authorization.

44 Palliative simulation for internal medicine trainees (PALL-SIM-IM): a nationally adopted education initiative in response to shape of training

BackgroundShape of Training represents a significant change in postgraduate-medical-education. Internal Medicine trainees (IMT) must prove competency in 8 Clinical Capabilities in Practice (CiPs). CiP 8 Managing End-of-Life and Applying Palliative Care Skills represents an opportunity to improve palliative medicine education for generalists, however, the provision of the required education and training is also a significant challenge requiring consideration and innovation. Simulation has been recognised by the Joint Royal College of Physicians Training Board (JRCPTB) as a holistic teaching and assessment method.AimTo produce a simulation training package for IMTs covering all components/descriptors of CiP 8 which can be effectively delivered by a combination of Palliative Medicine Trainees (PMTs), consultants, simulation technicians and teaching fellows. To enable IMTs to learn/practice required skills whilst PMTs address teaching and management curriculum competencies.MethodsThe North East Palliative Registrars Research Alliance (NEPRRA) (a unique initiative ensuring all North East PMTs are involved in teaching/research projects) received simulation training and designed Palliative Simulation for Internal Medicine Trainees (PALL-SIM-IM) a package comprising scenarios mapped to IMT curriculum descriptors. Modification occurred based on feedback and new scenarios incorporated requirements unique to the COVID-19 pandemic.ResultsPALL-SIM-IM has been effectively piloted in 6 sessions throughout the North-East, training 25 IMTs/equivalent. It has received excellent qualitative feedback. Quantitative data demonstrates significant improvement in competence in all curriculum descriptors following training. PALL-SIM-IM has been presented (on request) to IM Specialist Trainee Committees, Health Education England and the JRCPTB. PALL-SIM-IM has been requested by, distributed to and is to be adopted by 7 Health Education England training regions, Scotland and Northern Ireland.ConclusionsThis educational initiative has successfully produced a nationally adopted simulation-based training package for IMTs to aid competency development in CiP 8, reducing duplication of work whilst allowing reciprocal development of PMTs’ leadership and teaching skills.

Characterization of Critical Determinants of ACE2-RBD Interaction (preprint)

Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. Utilizing our recently developed NanoBiT technology-based biosensor, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, before and after the addition of competitive inhibitors, as well as neutralizing antibody activity. These critical determinants of virus-host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.

O19 SBE, SOPs and COVID-19: Using simulation-based education (SBE) to facilitate the development of paediatric COVID-19 standard operating procedures (SOP)

IntroductionSARS-CoV-2 is highly infectious, spread through respiratory droplets and fomites. COVID-19 has, thus, resulted in a worldwide change in medical practice, in particular when performing aerosol generating procedures (AGPs), to ensure reduction of viral spread, and safety to our staff and patients.The University Hospitals Bristol and Weston Simulation Services (UHBW SS) paediatric team used high-fidelity systems test simulations to deliver multi-professional COVID-19-relevant education in collaboration with Bristol Royal Hospital for Children (BRHC) to aid the development of COVID-19 standard operating procedures (SOPs).MethodsWe liaised with the BRHC Anaesthetic, Paediatric Intensive Care (PIC) and Children’s Emergency Department (CED), Resuscitation Services, paediatric Critical Care Outreach and HDU teams to identify high risk areas, procedures and SOPs that required reviewing and amending in light of COVID-19.Primary topics identifiedRapid sequence induction (RSI) and intubationResuscitation and cardiac arrestInitiation of non–invasive ventilationMulti–professionals from four key areas were educated:Anaesthetic DepartmentPICCEDCOVID–19 ‘hot’ wardWe designed and delivered high-fidelity multi-professional simulation based-education (SBE) and system tests, addressing latent safety threats and modified procedures when managing patients with suspected COVID-19, using new, drafted COVID-19 SOPs. To ensure the safety of our staff and patients, rapid introduction of the amended SOPs and dissemination of education and information was required, therefore, we delivered 7 large-scale systems test simulation over a 4-week period.ResultsAs a result of our simulations over 70 multi-professional staff from four key areas were educated in COVID-19 latent safety threats and modified procedures, including appropriate use, and donning and doffing of personal protective equipment. Feedback from all simulations was positive;all participants felt ‘confident’ or ‘very confident’ about managing the case presented, and using the relevant SOP, following participation.Four amended SOPs and protocols were tested, amended and retested as required:COVID–19 Paediatric Intubation Emergency ChecklistModified Paediatric Medical Emergency Call management at BRHC during COVID–19 PandemicCOVID–19 in Children: Use Of Non–Invasive Respiratory Support (HFNC And NIV)COVID–19 Paediatric Cardiac Arrest AlgorithmDiscussionCombining SBE with system testing new, or amended, SOPs is a safe and effective way to educate MDT colleagues on new practices, safety risks, and system changes. The positive outcomes and reflections from our sessions has encouraged our team and BRHC colleagues to continue to work closely to deliver combined SBE and system testing of new SOPs.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma: a prospective study (preprint)

Background Effective antiviral therapy against the severe acute respiratory syndrome virus 2 (SARS-CoV-2) remains elusive. Convalescent plasma is an anti-viral approach currently under investigation. We aimed to assess the laboratory and clinical parameters of patients with COVID-19 pneumonia treated with convalescent plasma containing high levels of neutralizing anti-SARS-CoV-2 antibodies.