ABSTRACT
Background: First-year resident physicians began training in July 2020 in an environment of decreased clinical case exposure and increased feelings of discomfort because of the COVID-19 pandemic. To improve specialty learning, the University of Toronto Department of Otolaryngology - Head and Neck Surgery piloted a novel virtual case-based teaching intervention for first-year residents. Methods: A weekly virtual resident-led casebased discussion series was designed. Six residents and 4 staff otolaryngologists participated. A Likert-type survey administered retrospectively evaluated the effect on resident confidence. The survey rated participant comfort level on a scale of 1 to 5, from "not well prepared or comfortable" to "very well prepared or comfortable," in 7 different areas at the beginning of postgraduate year (PGY) 1 in July 2020, and in April 2021. Qualitative data collected assessed strengths and weaknesses of the intervention. Results: Residents reported increased comfort level in all areas assessed, including overall emergency department consults, inpatient consults, and specific epistaxis consults by 28%;triaging consults and addressing peritonsillar abscess consults by 24%;addressing pediatric otolaryngologic and airway concerns by 20% each;and addressing otologic concerns by 32%. All respondents agreed the intervention would benefit residents of other programs. Conclusion: The studied intervention can potentially improve both resident education and patient care. It facilitated real-time discussion of topics relevant to self-perceived knowledge deficits and timely advice on management of a new and changing population of patients with COVID-19. The intervention described could be applied to benefit residents in otolaryngology and other surgical specialty programs nationwide during and after the pandemic.
ABSTRACT
We have previously reported that the SARS-CoV-2 neutralizing antibody, STI-2020, potently inhibits cytopathic effects of infection by genetically diverse clinical SARS-CoV-2 pandemic isolates in vitro, and has demonstrated efficacy in a hamster model of COVID-19 when administered by the intravenous route immediately following infection. We now have extended our in vivo studies of STI-2020 to include disease treatment efficacy, profiling of biodistribution of STI-2020 in mice when antibody is delivered intranasally (IN) or intravenously (IV), as well as pharmacokinetics in mice following IN antibody administration. Importantly, SARS-CoV-2-infected hamsters were treated with STI-2020 using these routes, and treatment effects on severity and duration of COVID-19-like disease in this model were evaluated. In SARS-CoV-2 infected hamsters, treatment with STI-2020 12 hours post-infection using the IN route led to a decrease in severity of clinical disease signs and a more robust recovery during 9 days of infection as compared to animals treated with an isotype control antibody. Treatment via the IV route using the same dose and timing regimen resulted in a decrease in the average number of consecutive days that infected animals experienced weight loss, shortening the duration of disease and allowing recovery to begin more rapidly in STI-2020 treated animals. Following IN administration in mice, STI-2020 was detected within 10 minutes in both lung tissue and lung lavage. The half-life of STI-2020 in lung tissue is approximately 25 hours. We are currently investigating the minimum effective dose of IN-delivered STI-2020 in the hamster model as well as establishing the relative benefit of delivering neutralizing antibodies by both IV and IN routes.
Subject(s)
COVID-19 , Weight Loss , Severe Acute Respiratory Syndrome , Behcet SyndromeABSTRACT
Current transmission rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still increasing and many countries are facing second waves of infections. Rapid SARS-CoV-2 whole genome sequencing (WGS) is often unavailable but could support public health organizations and hospitals in monitoring and determining transmission links. Here we report a novel reverse complement polymerase chain reaction (RC-PCR) technology for WGS of SARS-CoV-2. This technique is unique as it enables library preparation in a single PCR saving time, resources and enables high throughput screening. A total of 173 samples tested positive for SARS-CoV-2 between March and September 2020 were included. RC-PCR WGS applicability for outbreak analysis in public health service and hospital settings was tested on six predefined clusters containing samples of healthcare workers and patients. RC-PCR resulted in WGS data for 146 samples. It showed a genome coverage of up to 98,2% for samples with a maximum Ct value of 32. Three out of six suspected clusters were fully confirmed, while in other clusters four healthcare workers were not associated. Importantly, a previously unknown chain of transmission was confirmed in the public health service samples. These findings confirm the reliability and applicability of the RC-PCR technology for SARS-CoV-2 sequencing in outbreak analysis and surveillance.
Subject(s)
Genomic InstabilityABSTRACT
While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and auto-directed antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense. One Sentence SummaryIn severe COVID-19 patients, the immune system fails to generate cells that define mild disease; antibodies in their serum actively prevents the successful production of those cells.
Subject(s)
COVID-19ABSTRACT
While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a wholeblood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferonstimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and autodirected antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense.