e-REC Capturing The Occurrence and Burden Of COVID-19 Infections In People With Rare Genetic Obesity Disorders

Introduction: Following the onset of the COVID-19 pandemic in spring 2020, the European Registries For Rare Endocrine Conditions (EuRRECa), which is a collaboration between Endo- ERN, ESPE and ESE provided the possibility for registration of cases. Obesity is a risk factor for severe COVID-19 disease course in adults. In children and adolescents, COVID-19 disease course is much milder, but has also been identified as risk factor. As rare genetic obesity disorders often present with extreme obesity early in life, it might be postulated that they are at increased risk for severe course of COVID-19 infection. The aim was to study the clinical course of COVID-19 infection in these patients. Method(s): The RareEndoERN COVID-19 taskforce, formed in April 2020, set up the monthly e-REC reporting of new clinical encounters of confirmed or suspected COVID-19 cases in rare genetic obesity disorders. Thirteen centres committed to reporting. Case specific data were collected by an additional digital survey. Result(s): Seventeen patients with rare genetic obesity disorders and COVID-19 infection were reported by two centers between April 2020 and December 2021. Median age was 16 years (range min 2 - max 22), 11/17 were female, median BMI was 28kg/m2 (min 17-max 73). Diagnosis was: rare genetic obesity- syndromal form in 13/17 cases (of which 8 Prader-Willi Syndrome (PWS) and 5 other forms of syndromal obesity);non-syndromal form in 2/17;and 'other' in 2/17 patients. The following co-morbidities were present: type2 DM in 3/17, dyslipidemia 2/17, NAFLD 2/17, sleep apnoea 1/17;COVID-19 was confirmed in all cases. Symptoms were Fever (5/17);Cough (3/17);Tiredness or exhaustion (2/17);Loss of appetite (1/17);Loss of taste or smell (0/17);Muscle pain (0/17);Runny nose (3/17);Headache (4/17);Sore throat (4/17);Stomach symptoms (1/17);Diarrhoea (0/17);None (/17)2;Other (3/17) like change of behavior or seizure. One patient with PWS was admitted to the emergency room due to a seizure and was dismissed after a few hours of observation. None of the patients needed admission to the hospital, IC unit care, or oxygen treatment;18/17 patients fully recovered, 1 PWS patient had persistent complaints of tiredness. Conclusion(s): In patients with rare genetic obesity disorders and confirmed COVID-19 infection reported number of cases are low, even in large centers of expertise. The clinical course seems mild for these patients, in the age range 2-22 years, even in the presence of extreme obesity and type 2 diabetes.

Development, testing and validation of a SARS-CoV-2 multiplex panel for detection of the five major variants of concern on a portable PCR platform.

Many SARS-CoV-2 variants have emerged during the course of the COVID-19 pandemic. These variants have acquired mutations conferring phenotypes such as increased transmissibility or virulence, or causing diagnostic, therapeutic, or immune escape. Detection of Alpha and the majority of Omicron sublineages by PCR relied on the so-called S gene target failure due to the deletion of six nucleotides coding for amino acids 69-70 in the spike (S) protein. Detection of hallmark mutations in other variants present in samples relied on whole genome sequencing. However, whole genome sequencing as a diagnostic tool is still in its infancy due to geographic inequities in sequencing capabilities, higher cost compared to other molecular assays, longer turnaround time from sample to result, and technical challenges associated with producing complete genome sequences from samples that have low viral load and/or high background. Hence, there is a need for rapid genotyping assays. In order to rapidly generate information on the presence of a variant in a given sample, we have created a panel of four triplex RT-qPCR assays targeting 12 mutations to detect and differentiate all five variants of concern: Alpha, Beta, Gamma, Delta, and Omicron. We also developed an expanded pentaplex assay that can reliably distinguish among the major sublineages (BA.1-BA.5) of Omicron. In silico, analytical and clinical testing of the variant panel indicate that the assays exhibit high sensitivity and specificity. This panel can help fulfill the need for rapid identification of variants in samples, leading to quick decision making with respect to public health measures, as well as treatment options for individuals. Compared to sequencing, these genotyping PCR assays allow much faster turn-around time from sample to results-just a couple hours instead of days or weeks.

Development, testing and validation of a SARS-CoV-2 multiplex panel for detection of the five major variants of concern on a portable PCR platform (preprint)

Many SARS-CoV-2 variants have emerged during the course of the COVID-19 pandemic. These variants have acquired mutations conferring phenotypes such as increased transmissibility or virulence, or causing diagnostic, therapeutic, or immune escape. Detection of Alpha and the majority of Omicron sublineages by PCR relied on the so-called S gene target failure due to the deletion of six nucleotides coding for amino acids 69-70 in the spike (S) protein. Detection of hallmark mutations in other variants present in samples relied on whole genome sequencing. However, whole genome sequencing as a diagnostic tool is still in its infancy due to geographic inequities in sequencing capabilities, higher cost compared to other molecular assays, longer turnaround time from sample to result, and technical challenges associated with producing complete genome sequences from samples that have low viral load and/or high background. Hence, there is a need for rapid genotyping assays. In order to rapidly generate information on the presence of a variant in a given sample, we have created a panel of four triplex RT-qPCR assays targeting 12 mutations to detect and differentiate all five variants of concern: Alpha, Beta, Gamma, Delta and Omicron. We also developed an expanded pentaplex assay that can reliably distinguish among the major sublineages (BA.1-BA.5) of Omicron. In silico, analytical and clinical testing of the variant panel indicate the assays have a sensitivity and specificity of >95%. This variant panel can be used as a Research Use Only screening tool for triaging SARS-CoV-2 positive samples prior to whole genome sequencing.

Medical students' perceptions of learning and working on the COVID-19 frontlines: ' a confirmation that I am in the right place professionally'.

The COVID-19 pandemic caused complex and enduring challenges for healthcare providers and medical educators. The rapid changes to the medical education landscape forced universities across the world to pause traditional medical training. In Basel, Switzerland, however, medical students had the opportunity to work on the COVID-19 frontlines. Our purpose was to understand how they perceived both learning and professional identity development in this novel context. We conducted semi-structured interviews with 21 medical students who worked in a COVID-19 testing facility at the University Hospital of Basel. Using constructivist grounded theory methodology, we collected and analyzed data iteratively using the constant comparative approach to develop codes and theoretical themes. Most participants perceived working on the pandemic frontlines as a positive learning experience, that was useful for improving their technical and communication skills. Participants particularly valued the comradery amongst all team members, perceiving that the hierarchy between faculty and students was less evident in comparison to their usual learning environments. Since medical students reported that their work on the pandemic frontlines positively affected their learning, the need to create more hands-on learning opportunities for medical students challenges curriculum developers. Medical students wish to feel like full-fledged care team members rather than observing sideliners. Performing simple clinical tasks and collaborative moments in a supportive learning environment may promote learning and professional development and should be encouraged in the post-pandemic era.

A phenomenological exploration of the impact of COVID-19 on the medical education community.

INTRODUCTION: The COVID-19 pandemic has caused unprecedented stress to the medical education community, potentially worsening problems like burnout and work-life imbalance that its members have long been grappling with. However, the collective struggle sparked by the pandemic could generate the critical reflection necessary for transforming professional values and practices for the better. In this hermeneutic phenomenological study, we explore how the community is adapting-and even reconceptualising-their personal and professional roles amidst the COVID-19 crisis. METHOD: Between April and October 2020, we conducted 27 (17F, 10M) semi-structured interviews with medical trainees (8), physicians (8), graduate students (3) and PhD scientists (8) working in medical education in Canada, the United States and Switzerland. Data analysis involved a variety of strategies, including coding for van Manen's four lifeworld existentials, reflexive writing and multiple team meetings. RESULTS: Participants experienced grief related to the loss of long-established personal and professional structures and boundaries, relationships and plans for the future. However, experiences of grief were often conflicting. Some participants also experienced moments of relief, perceiving some losses as metaphorical permissions slips to slow down and focus on their well-being. In turn, many reflected on the opportunity they were being offered to re-imagine the nature of their work. DISCUSSION: Participants' experiences with grief, relief and opportunity resonate with Ratcliffe's account of grief as a process of relearning the world after a significant loss. The dismantling of prior life structures and possibilities incited in participants critical reflection on the nature of the medical education community's professional practices. Participants demonstrated their desire for more flexibility and autonomy in the workplace and a re-adjustment of the values and expectations inherent to their profession. On both individual and systems levels, the community must ensure that long-standing calls for wellness and work-life integration are realised-and persist-after the pandemic is over.

Overview Of The Canadian Clinician Investigator Trainees' Research Presented At The 2020 CSCI-CITAC Joint Meeting.

The 2020 Annual General Meeting (AGM) and Young Investigators' Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherches Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was the first meeting to be hosted virtually. The theme was "Navigating Uncertainty, Embracing Change and Empowering the Next Generation of Clinician-Scientists", and the meeting featured lectures and workshops that were designed to provide knowledge and skills for professional development of clinician investigator trainees. The opening remarks were given by Jason Berman (President of CSCI/SCRC), Tina Marvasti (President of CITAC/ACCFC) and Nicola Jones (University of Toronto Clinician Investigator Program Symposium Chair). Dr. Michael Strong, President of the Canadian Institutes of Health Research, delivered the keynote presentation titled "CIHR's COVID-19 Response and Strategic Planning". Dr. John Bell (University of Ottawa) received the CSCI Distinguished Scientist Award, Dr. Stanley Nattel (Université de Montréal) received the CSCI-RCPSC Henry Friesen Award (RCPSC; Royal College of Physicians and Surgeons of Canada) and Dr. Meghan Azad (University of Manitoba) received the CSCI Joe Doupe Young Investigator Award. Each scientist delivered talks on their award-winning research. The interactive workshops were "Developing Strategies to Maintain Wellness", "Understanding the Hidden Curriculum: Power and Privilege in Science and Medicine", "Hiring a Clinician Scientist Trainee: What Leaders Are Looking For" and "COVID-19: A Case Study for Pivoting Your Research". The AGM included presentations from clinician investigator trainees nationwide. Over 70 abstracts were showcased, most are summarized in this review, and six were selected for oral presentations.

OVERVIEW OF THE CANADIAN CLINICIAN INVESTIGATOR TRAINEES' RESEARCH PRESENTED AT THE 2020 CSCI-CITAC JOINT MEETING

The 2020 Annual General Meeting (AGM) and Young Investigators' Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherches Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was the first meeting to be hosted virtually. The theme was Navigating Uncertainty, Embracing Change and Empowering the Next Generation of Clinician-Scientists, and the meeting featured lectures and workshops that were designed to provide knowledge and skills for professional development of clinician investigator trainees. The opening remarks were given by Jason Berman (President of CSCI/SCRC), Tina Marvasti (President of CITAC/ ACCFC) and Nicola Jones (University of Toronto Clinician Investigator Program Symposium Chair). Dr. Michael Strong, President of the Canadian Institutes of Health Research, delivered the keynote presentation titled CIHR's COVID-19 Response and Strategic Planning. Dr. John Bell (University of Ottawa) received the CSCI Distinguished Scientist Award, Dr. Stanley Nattel (Université de Montréal) received the CSCI-RCPSC Henry Friesen Award (RCPSC;Royal College of Physicians and Surgeons of Canada) and Dr. Meghan Azad (University of Manitoba) received the CSCI Joe Doupe Young Investigator Award. Each scientist delivered talks on their award-winning research. The interactive workshops were Developing Strategies to Maintain Wellness, Understanding the Hidden Curriculum: Power and Privilege in Science and Medicine, Hiring a Clinician Scientist Trainee: What Leaders Are Looking For and COVID-19: A Case Study for Pivoting Your Research. The AGM included presentations from clinician investigator trainees nationwide. Over 70 abstracts were showcased, most are summarized in this review, and six were selected for oral presentations.

The European Registry for Rare Bone and Mineral Conditions (EuRR-Bone): First year experience of the use of an e-reporting tool

Background/Introduction: The European Registry for Rare Bone and Mineral Conditions (EuRR-Bone) was founded in April 2020 and is the affiliated registry of the European Reference Network for Rare Bone Diseases (ERN BOND). Purpose: As bone and mineral conditions are seen by a variety of specialists there is a close connection with the European Registries for Rare Endocrine Conditions (EuRRECa) and its affiliated ERN Rare Endocrine Diseases (Endo-ERN). EuRR-Bone is open not only to centres within these ERNs but also to others and consists of a core registry for all cases and an e-reporting registry for new cases. Methods: The latter is accomplished via an electronic reporting platform, e-REC (e-Reporting of Rare Conditions), a light touch approach that does not collect personally identifiable information. Unique IDs for reported cases are generated instantaneously and emailed to users to be stored locally at reporting centres. Data are available to all collaborators following approval by the joint Data Access Committee of EuRRECa and EuRR-Bone. Results: Until July 2020, 12 centres from 9 different countries joined, of which 5 are ERN BOND members and 10 are Endo-ERN members. A total of 23 adults and 20 children were newly diagnosed with a Bone and Mineral condition. Amongst adults, the most frequently reported conditions were fibrous dysplasia and PTH independent hypercalcemia, while in children pseudohypoparathyroidism and osteogenesis imperfecta were the most reported. Since April 2020, the e-REC platform is also being used to capture the occurrence of a new COVID19 infection in a patient with an existing bone or mineral condition. Conclusion(s): e-REC is a promising tool enabling clinical networks to objectively map conditions and related activity, providing a better understanding of the occurrence of the rare bone and mineral conditions.