Clinical Performance Characteristics of the Swift Normalase Amplicon Panel for Sensitive Recovery of Severe Acute Respiratory Syndrome Coronavirus 2 Genomes.

Amplicon-based sequencing methods are central in characterizing the diversity, transmission, and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but need to be rigorously assessed for clinical utility. Herein, we validated the Swift Biosciences' SARS-CoV-2 Swift Normalase Amplicon Panels using remnant clinical specimens. High-quality genomes meeting our established library and sequence quality criteria were recovered from positive specimens, with 95% limit of detection of 40.08 SARS-CoV-2 copies/PCR. Breadth of genome recovery was evaluated across a range of CT values (11.3 to 36.7; median, 21.6). Of 428 positive samples, 413 (96.5%) generated genomes with <10% unknown bases, with a mean genome coverage of 13,545× ± SD 8382×. No genomes were recovered from PCR-negative specimens (n = 30) or from specimens positive for non-SARS-CoV-2 respiratory viruses (n = 20). Compared with whole-genome shotgun metagenomic sequencing (n = 14) or Sanger sequencing for the spike gene (n = 11), pairwise identity between consensus sequences was 100% in all cases, with highly concordant allele frequencies (R2 = 0.99) between Swift and shotgun libraries. When samples from different clades were mixed at varying ratios, expected variants were detected even in 1:99 mixtures. When deployed as a clinical test, 268 tests were performed in the first 23 weeks, with a median turnaround time of 11 days, ordered primarily for outbreak investigations and infection control.

Racial and Ethnic Disparities in Hospitalization and Clinical Outcomes Among Patients with COVID-19.

INTRODUCTION: The recent spread of coronavirus disease 2019 (COVID-19) has disproportionately impacted racial and ethnic minority groups; however, the impact of healthcare utilization on outcome disparities remains unexplored. Our study examines racial and ethnic disparities in hospitalization, medication usage, intensive care unit (ICU) admission and in-hospital mortality for COVID-19 patients. METHODS: In this retrospective cohort study, we analyzed data for adult patients within an integrated healthcare system in New York City between February 28-August 28, 2020, who had a lab-confirmed COVID-19 diagnosis. Primary outcome was likelihood of inpatient admission. Secondary outcomes were differences in medication administration, ICU admission, and in-hospital mortality. RESULTS: Of 4717 adult patients evaluated in the emergency department (ED), 3219 (68.2%) were admitted to an inpatient setting. Black patients were the largest group (29.1%), followed by Hispanic/Latinx (29.0%), White (22.9%), Asian (3.86%), and patients who reported "other" race-ethnicity (19.0%). After adjusting for demographic, clinical factors, time, and hospital site, Hispanic/Latinx patients had a significantly lower adjusted rate of admission compared to White patients (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.34-0.76). Black (OR 0.60; 95% CI 0.43-0.84) and Asian patients (OR 0.47; 95% CI 0.25 - 0.89) were less likely to be admitted to the ICU. We observed higher rates of ICU admission (OR 2.96; 95% CI 1.43-6.15, and OR 1.83; 95% CI 1.26-2.65) and in-hospital mortality (OR 4.38; 95% CI 2.66-7.24; and OR 2.96; 95% CI 2.12-4.14) at two community-based academic affiliate sites relative to the primary academic site. CONCLUSION: Non-White patients accounted for a disproportionate share of COVID-19 patients seeking care in the ED but were less likely to be admitted. Hospitals serving the highest proportion of minority patients experienced the worst outcomes, even within an integrated health system with shared resources. Limited capacity during the COVID-19 pandemic likely exacerbated pre-existing health disparities across racial and ethnic minority groups.

De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report.

SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but have not been reported in patients receiving treatment with the antiviral agent. We present a case of an immunocompromised patient with acquired B-cell deficiency who developed an indolent, protracted course of SARS-CoV-2 infection. Remdesivir therapy alleviated symptoms and produced a transient virologic response, but her course was complicated by recrudescence of high-grade viral shedding. Whole genome sequencing identified a mutation, E802D, in the nsp12 RNA-dependent RNA polymerase, which was not present in pre-treatment specimens. In vitro experiments demonstrated that the mutation conferred a ~6-fold increase in remdesivir IC50 but resulted in a fitness cost in the absence of remdesivir. Sustained clinical and virologic response was achieved after treatment with casirivimab-imdevimab. Although the fitness cost observed in vitro may limit the risk posed by E802D, this case illustrates the importance of monitoring for remdesivir resistance and the potential benefit of combinatorial therapies in immunocompromised patients with SARS-CoV-2 infection.

Perspectives on Telehealth for older adults during the COVID-19 pandemic using the quadruple aim: interviews with 48 physicians.

BACKGROUND: Telehealth delivery expanded quickly during the COVID-19 pandemic after the reduction of payment and regulatory barriers, but older adults are the least likely to benefit from this expansion. Little is known about physician experiences initiating telehealth and factors that fostered or discouraged adoption during the COVID-19 pandemic with older adult patients. Therefore, our objective was to understand experiences of frontline physicians caring for older adults via telehealth during the COVID-19 pandemic. METHODS: We conducted semi-structured interviews from September 2020 to November 2020 with 48 physicians. We recruited a diverse sample of geriatricians (n = 18), primary care (n = 15), and emergency (n = 15) physicians from all United Stated (US) regions, rural-urban settings, and academic-community practices who cared for older adult patients during the pandemic using purposive sampling methods. We completed framework analysis of the transcribed interviews to identify emerging themes and used the Quadruple Aim to organize themes. RESULTS: Frontline physicians described telehealth as a more flexible, value-based, and patient-centered mode of health care delivery. Benefits of using telehealth to treat older adults included reducing deferred care and increasing timely care, improving efficiency for physicians, enhancing communication with caregivers and patients, reducing patient travel burdens, and facilitating health outreach and education. Challenges included unequal access for rural, older, or cognitively impaired patients. Physicians noted that payment parity with in-person visits, between video and telephone visits, and relaxation of restrictive regulations would enhance their ability to continue to offer telehealth. CONCLUSIONS: Frontline physicians who treated older adults during the COVID-19 pandemic were largely in favor of continuing telehealth use beyond the pandemic; however, they noted that sustainability would depend on enacting policies that address access inequities and reimbursement concerns. Our data provide policy insights that if placed into action could facilitate the long-term success of telehealth and encourage a more flexible healthcare delivery system in the US.

Retrospective Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Symptomatic Patients Prior to Widespread Diagnostic Testing in Southern California.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused one of the worst pandemics in recent history. Few reports have revealed that SARS-CoV-2 was spreading in the United States as early as the end of January. In this study, we aimed to determine if SARS-CoV-2 had been circulating in the Los Angeles (LA) area at a time when access to diagnostic testing for coronavirus disease 2019 (COVID-19) was severely limited. METHODS: We used a pooling strategy to look for SARS-CoV-2 in remnant respiratory samples submitted for regular respiratory pathogen testing from symptomatic patients from November 2019 to early March 2020. We then performed sequencing on the positive samples. RESULTS: We detected SARS-CoV-2 in 7 specimens from 6 patients, dating back to mid-January. The earliest positive patient, with a sample collected on January 13, 2020 had no relevant travel history but did have a sibling with similar symptoms. Sequencing of these SARS-CoV-2 genomes revealed that the virus was introduced into the LA area from both domestic and international sources as early as January. CONCLUSIONS: We present strong evidence of community spread of SARS-CoV-2 in the LA area well before widespread diagnostic testing was being performed in early 2020. These genomic data demonstrate that SARS-CoV-2 was being introduced into Los Angeles County from both international and domestic sources in January 2020.

Executive summary of the 2021 SAEM consensus conference: From bedside to policy: Advancing social emergency medicine and population health through research, collaboration, and education.

BACKGROUND: Social emergency medicine (social EM) examines the intersection of emergency care and the social factors that influence health outcomes. In 2021, the SAEM consensus conference focused on social EM and population health, with the goal of prioritizing research topics, creating collaborations, and advancing the field of social EM. METHODS: Organization of the conference began in 2019 within SAEM. Cochairs were identified and a planning committee created the framework for the conference. Leaders for subgroups were identified, and subgroups performed literature reviews and identified additional stakeholders within EM and community organizations. As a result of the COVID-19 pandemic, the conference format was modified. RESULTS: A total of 246 participants registered for the conference and participated in some capacity at three distinct online sessions. Research prioritization subgroups were as follows-group 1: ED screening and referral for social and access needs; group 2: structural competency; and group 3: race, racism, and antiracism. Thirty-two "projects in progress" were presented within five domains-identity and health: people and places; health care systems; training and education; material needs; and individual and structural violence. CONCLUSIONS: Despite ongoing challenges posed by the COVID-19 pandemic, the 2021 SAEM consensus conference brought together hundreds of stakeholders to define research priorities and create collaborations to push the field forward.

Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets.

Remdesivir is an antiviral approved for COVID-19 treatment, but its wider use is limited by intravenous delivery. An orally bioavailable remdesivir analog may boost therapeutic benefit by facilitating early administration to non-hospitalized patients. This study characterizes the anti-SARS-CoV-2 efficacy of GS-621763, an oral prodrug of remdesivir parent nucleoside GS-441524. Both GS-621763 and GS-441524 inhibit SARS-CoV-2, including variants of concern (VOC) in cell culture and human airway epithelium organoids. Oral GS-621763 is efficiently converted to plasma metabolite GS-441524, and in lungs to the triphosphate metabolite identical to that generated by remdesivir, demonstrating a consistent mechanism of activity. Twice-daily oral administration of 10 mg/kg GS-621763 reduces SARS-CoV-2 burden to near-undetectable levels in ferrets. When dosed therapeutically against VOC P.1 gamma γ, oral GS-621763 blocks virus replication and prevents transmission to untreated contact animals. These results demonstrate therapeutic efficacy of a much-needed orally bioavailable analog of remdesivir in a relevant animal model of SARS-CoV-2 infection.

Analysis of SARS-CoV-2 infection dynamic in vivo using reporter-expressing viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, is one of the biggest threats to public health. However, the dynamic of SARS-CoV-2 infection remains poorly understood. Replication-competent recombinant viruses expressing reporter genes provide valuable tools to investigate viral infection. Low levels of reporter gene expressed from previous reporter-expressing recombinant (r)SARS-CoV-2 in the locus of the open reading frame (ORF)7a protein have jeopardized their use to monitor the dynamic of SARS-CoV-2 infection in vitro or in vivo. Here, we report an alternative strategy where reporter genes were placed upstream of the highly expressed viral nucleocapsid (N) gene followed by a porcine tescherovirus (PTV-1) 2A proteolytic cleavage site. The higher levels of reporter expression using this strategy resulted in efficient visualization of rSARS-CoV-2 in infected cultured cells and excised lungs or whole organism of infected K18 human angiotensin converting enzyme 2 (hACE2) transgenic mice. Importantly, real-time viral infection was readily tracked using a noninvasive in vivo imaging system and allowed us to rapidly identify antibodies which are able to neutralize SARS-CoV-2 infection in vivo. Notably, these reporter-expressing rSARS-CoV-2, in which a viral gene was not deleted, not only retained wild-type (WT) virus-like pathogenicity in vivo but also exhibited high stability in vitro and in vivo, supporting their use to investigate viral infection, dissemination, pathogenesis, and therapeutic interventions for the treatment of SARS-CoV-2 in vivo.

Specific allelic discrimination of N501Y and other SARS-CoV-2 mutations by ddPCR detects B.1.1.7 lineage in Washington State.

Real-time epidemiological tracking of variants of concern (VOCs) can help limit the spread of more contagious forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as those containing the N501Y mutation. Typically, genetic sequencing is required to be able to track VOCs in real-time. However, sequencing can take time and may not be accessible in all laboratories. Genotyping by RT-ddPCR offers an alternative to rapidly detect VOCs through discrimination of specific alleles such as N501Y, which is associated with increased transmissibility and virulence. Here we describe the first cases of the B.1.1.7 lineage of SARS-CoV-2 detected in Washington State by using a combination of reverse-transcription polymerase chain reaction (RT-PCR), RT-ddPCR, and next-generation sequencing. We initially screened 1035 samples positive for SARS-CoV-2 by our CDC-based laboratory-developed assay using ThermoFisher's multiplex RT-PCR COVID-19 assay over four weeks from late December 2020 to early January 2021. S gene target failures (SGTF) were subsequently assayed by RT-ddPCR to confirm four mutations within the S gene associated with the B.1.1.7 lineage: a deletion at amino acid (AA) 69-70 (ACATGT), deletion at AA 145, (TTA), N501Y mutation (TAT), and S982A mutation (GCA). All four targets were detected in two specimens; follow-up sequencing revealed a total of 9 mutations in the S gene and phylogenetic clustering within the B.1.1.7 lineage. Next, we continued screening samples for SGTF detecting 23 additional B.1.1.7 variants by RT-ddPCR and confirmed by sequencing. As VOCs become increasingly prevalent, molecular diagnostic tools like RT-ddPCR can be utilized to quickly, accurately, and sensitively distinguish more contagious lineages of SARS-CoV-2.

A Bifluorescent-Based Assay for the Identification of Neutralizing Antibodies against SARS-CoV-2 Variants of Concern In Vitro and In Vivo.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and has been responsible for the still ongoing coronavirus disease 2019 (COVID-19) pandemic. Prophylactic vaccines have been authorized by the U.S. Food and Drug Administration (FDA) for the prevention of COVID-19. Identification of SARS-CoV-2-neutralizing antibodies (NAbs) is important to assess vaccine protection efficacy, including their ability to protect against emerging SARS-CoV-2 variants of concern (VoC). Here, we report the generation and use of a recombinant (r)SARS-CoV-2 USA/WA1/2020 (WA-1) strain expressing Venus and an rSARS-CoV-2 strain expressing mCherry and containing mutations K417N, E484K, and N501Y found in the receptor binding domain (RBD) of the spike (S) glycoprotein of the South African (SA) B.1.351 (beta [ß]) VoC in bifluorescent-based assays to rapidly and accurately identify human monoclonal antibodies (hMAbs) able to neutralize both viral infections in vitro and in vivo. Importantly, our bifluorescent-based system accurately recapitulated findings observed using individual viruses. Moreover, fluorescent-expressing rSARS-CoV-2 strain and the parental wild-type (WT) rSARS-CoV-2 WA-1 strain had similar viral fitness in vitro, as well as similar virulence and pathogenicity in vivo in the K18 human angiotensin-converting enzyme 2 (hACE2) transgenic mouse model of SARS-CoV-2 infection. We demonstrate that these new fluorescent-expressing rSARS-CoV-2 can be used in vitro and in vivo to easily identify hMAbs that simultaneously neutralize different SARS-CoV-2 strains, including VoC, for the rapid assessment of vaccine efficacy or the identification of prophylactic and/or therapeutic broadly NAbs for the treatment of SARS-CoV-2 infection. IMPORTANCE SARS-CoV-2 is responsible of the COVID-19 pandemic that has warped daily routines and socioeconomics. There is still an urgent need for prophylactics and therapeutics to treat SARS-CoV-2 infections. In this study, we demonstrate the feasibility of using bifluorescent-based assays for the rapid identification of hMAbs with neutralizing activity against SARS-CoV-2, including VoC in vitro and in vivo. Importantly, results obtained with these bifluorescent-based assays recapitulate those observed with individual viruses, demonstrating their feasibility to rapidly advance our understanding of vaccine efficacy and to identify broadly protective human NAbs for the therapeutic treatment of SARS-CoV-2.

Professional development during a pandemic: a live virtual conference for emergency medicine chief residents.

Limited professional development training exists for chief residents. The available training uses in-person lectures and workshops at annual national conferences. The COVID-19 pandemic prevented most in-person gatherings in 2020, including pivotal onboarding and training events for new chief residents. However, for the last five years, Academic Life in Emergency Medicine's Chief Resident Incubator conducted year-long remote training programs, creating virtual communities of practice for chief residents in emergency medicine (EM). As prior leaders and alumni from the Incubator, we sought to respond to the limitations presented by the pandemic and create an onboarding event to provide foundational knowledge for incoming chief residents. We developed a half-day virtual conference, whereupon 219 EM chief residents enrolled. An effective professional development experience is feasible and scalable using online videoconferencing technologies, especially if constructed with content expertise, psychological safety, and production design in mind.

RéSUMé: Il existe une formation de développement professionnel limitée pour les résidents en chef. La formation disponible utilise des conférences et des ateliers en personne lors de conférences nationales annuelles. La pandémie de COVID-19 a empêché la plupart des rassemblements en personne en 2020, y compris des activités d'intégration et de formation essentielles pour les nouveaux résidents en chef. Cependant, au cours des cinq dernières années, l'incubateur des résidents en chef de Academic Life in Emergency Medicine a organisé des programmes de formation à distance d'un an, créant ainsi des communautés de pratique virtuelles pour les résidents en chef en médecine d'urgence (MU). En tant qu'anciens dirigeants et anciens de l'incubateur, nous avons cherché à répondre aux limites présentées par la pandémie et à créer un événement d'intégration pour fournir des connaissances fondamentales aux nouveaux résidents en chef. Nous avons mis au point une conférence virtuelle d'une demi-journée, à laquelle 219 résidents en chef de MU se sont inscrits. Une expérience de développement professionnel efficace est réalisable et évolutive grâce aux technologies de vidéoconférence en ligne, surtout si elle est construite en tenant compte de l'expertise du contenu, de la sécurité psychologique et de la conception de la production.

A SARS-CoV-2 Nucleocapsid Variant that Affects Antigen Test Performance.

More than one year into a global pandemic, SARS-CoV-2 is now defined by a variety of rapidly evolving variant lineages. Several FDA authorized molecular diagnostic tests have been impacted by viral variation, while no reports of viral variation affecting antigen test performance have occurred to date. While determining the analytical sensitivity of the Quidel Sofia SARS Antigen FIA test (Sofia 2), we uncovered a high viral load specimen that repeatedly tested negative by this antigen test. Whole genome sequencing of the specimen uncovered two mutations, T205I and D399N, present in the nucleocapsid protein of the isolate. All six SARS-CoV-2 positive clinical specimens available in our laboratory with a D399N nucleocapsid mutation and CT < 31 were not detected by the Sofia 2 but detected by the Abbott BinaxNOW COVID-19 Ag Card, while clinical specimens with the T205I mutation were detected by both assays. Testing of recombinant SARS-CoV-2 nucleocapsid with these variants demonstrated an approximate 1000-fold loss in sensitivity for the Quidel Sofia SARS Antigen FIA test associated with the D399N mutation, while the BinaxNOW and Quidel Quickvue SARS Antigen tests were unaffected by the mutation. The D399N nucleocapsid mutation has been relatively uncommon to date, appearing in only 0.02% of genomes worldwide at time of writing. Our results demonstrate how routine pathogen genomics can be integrated into the clinical microbiology laboratory to investigate diagnostic edge cases, as well as the importance of profiling antigenic diversity outside of the spike protein for SARS-CoV-2 diagnostics.

Deep vein thrombosis and pulmonary embolism among hospitalized coronavirus disease 2019-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system.

OBJECTIVE: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course. METHODS: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary end point was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary end point was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH. RESULTS: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH. CONCLUSIONS: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.

Telemedicine in vascular surgery during the coronavirus disease-2019 pandemic: A multisite healthcare system experience.

OBJECTIVE: To assess the introduction of telemedicine as an alternative to the traditional face-to-face encounters with vascular surgery patients in the era of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective review of prospectively collected data on face-to-face and telemedicine interactions was conducted at a multisite health care system from January to August 2020 in vascular surgery patients during the COVID-19 pandemic. The end point is direct patient satisfaction comparison between face-to-face and telemedicine encounters/interactions prior and during the pandemic. RESULTS: There were 6262 patient encounters from January 1, 2020, to August 6, 2020. Of the total encounters, 790 (12.6%) were via telemedicine, which were initiated on March 11, 2020, after the World Health Organization's declaration of the COVID-19 pandemic. These telemedicine encounters were readily adopted and embraced by both the providers and patients and remain popular as an option to patients for all types of visits. Of these patients, 78.7% rated their overall health care experience during face-to-face encounters as very good and 80.6% of patients rated their health care experience during telemedicine encounters as very good (P = .78). CONCLUSIONS: Although the COVID-19 pandemic has produced unprecedented consequences to the practice of medicine and specifically of vascular surgery, our multisite health care system has been able to swiftly adapt and adopt telemedicine technologies for the care of our complex patients. Most important, the high quality of patient-reported satisfaction and health care experience has remained unchanged.

ALiEM Connect: Large-Scale, Interactive, Virtual Residency Programming in Response to COVID-19.

PROBLEM: The COVID-19 pandemic restricted in-person gatherings, including residency conferences. The pressure to quickly reorganize educational conferences and convert content to a remote format overwhelmed many programs. This article describes the pilot event of a large-scale, interactive, virtual educational conference modeled, designed, and implemented by Academic Life in Emergency Medicine (ALiEM), called ALiEM Connect. APPROACH: The pilot ALiEM Connect event was conceptualized and implemented within a 2-week period in March 2020. The pilot was livestreamed via a combination of Zoom and YouTube and was archived by YouTube. Slack was used as a backchannel to allow interaction with other participants and engagement with the speakers (via moderators who posed questions from the backchannel to the speakers live during the videoconference). OUTCOMES: The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was used for program evaluation, showing that 64 U.S. Accreditation Council for Graduate Medical Education-accredited emergency medicine residency programs participated in the pilot event, with 1,178 unique users during the event (reach). For effectiveness, 93% (139/149) of trainees reported the pilot as enjoyable and 85% (126/149) reported it was equivalent to or better than their usual academic proceedings. Adoption for ALiEM Connect was fairly good with 64/237 (27%) of invited residency programs registering and participating in the pilot event. Implementation was demonstrated by nearly half of the livestream viewers (47%, 553/1,178) interacting in the backchannel discussion, sending a total of 4,128 messages in the first 4 hours. NEXT STEPS: The final component of the RE-AIM framework, maintenance, will take more time to evaluate. Further study is required to measure the educational impact of events like the ALiEM Connect pilot. The ALiEM Connect model could potentially be used to replace educational conferences that have been canceled or to implement and/or augment a large-scale, shared curriculum among residency programs in the future.

Emergency Department Utilization for Emergency Conditions During COVID-19.

STUDY OBJECTIVE: We use a national emergency medicine clinical quality registry to describe recent trends in emergency department (ED) visitation overall and for select emergency conditions. METHODS: Data were drawn from the Clinical Emergency Department Registry, including 164 ED sites across 35 states participating in the registry with complete data from January 2019 through November 15, 2020. Overall ED visit counts, as well as specific emergency medical conditions identified by International Classification of Diseases, Tenth Revision, Clinical Modification code (myocardial infarction, cerebrovascular accident, cardiac arrest/ventricular fibrillation, and venous thromboembolisms), were tabulated. We plotted biweekly visit counts overall and across specific geographic regions. RESULTS: The largest declines in visit counts occurred early in the pandemic, with a nadir in April 46% lower than the 2019 monthly average. By November, overall ED visit counts had increased, but were 23% lower than prepandemic levels. The proportion of all ED visits that were for the select emergency conditions increased early in the pandemic; however, total visit counts for acute myocardial infarction and cerebrovascular disease have remained lower in 2020 compared with 2019. Despite considerable geographic and temporal variation in the trajectory of the coronavirus disease 2019 outbreak, the overall pattern of ED visits observed was similar across regions and time. CONCLUSION: The persistent decline in ED visits for these time-sensitive emergency conditions raises the concern that coronavirus disease 2019 may continue to impede patients from seeking essential care. Efforts thus far to encourage individuals with concerning signs and symptoms to seek emergency care may not have been sufficient.

Yield of Head Imaging in Ambulatory and Hospitalized Patients With SARS-CoV-2: A Multi-Center Study of 8675 Patients.

BACKGROUND AND PURPOSE: To describe the neurological and cerebrovascular findings in patients who tested positive for SARS-CoV-2 and underwent head imaging in ambulatory and inpatient settings. METHODS: Consecutive patients aged ≥18 years with SARS-CoV-2 infection diagnosed or treated at Mayo Clinic sites from 3/11/2020 to 7/23/2020 with head CT or brain MRI within 30 days of SARS-CoV-2 diagnosis were included. Demographics, medical history, indication for SARS-CoV-2 testing, neurologic symptoms, indication for brain imaging, neuroimaging findings, etiology of cerebrovascular events, and hospital course were abstracted from medical records. RESULTS: Of 8,675 patients with SARS-CoV-2, 180 (2.07%) had head imaging. Mean age of the entire cohort was 42 ± 18 years, whereas mean age of those with head imaging was 62 ± 19 years. Common indications for imaging were headache (34.4%), encephalopathy (33.4%), focal neurologic symptom (16.7%), and trauma (13.9%). While 86.1% of patients who underwent head imaging had normal exams, cerebrovascular events occurred in 18 patients (0.21% of the total cohort). Of patients with cerebrovascular events, 8 (44.5%) had acute infarct; 6 (33.3%), acute intracranial hemorrhage; 5 (2.8%), subacute infarct; and 1 (0.6%) posterior reversible encephalopathy syndrome. In the thirteen patients with ischemic stroke, 6 (46.2%) had cryptogenic stroke; 3 (23.1%), other defined causes; 2 (15.4%), small vessel stroke; 1 (7.7%), large vessel stroke; and 1 (7.7%) cardioembolic stroke. CONCLUSION: In ambulatory and hospitalized patients with SARS-CoV-2 infection, the rate of head imaging is low, with common indications of encephalopathy and headache. Cerebrovascular events occurred rarely, and cryptogenic stroke was the most common stroke mechanism.

Inhibition of Coronavirus Entry In Vitro and Ex Vivo by a Lipid-Conjugated Peptide Derived from the SARS-CoV-2 Spike Glycoprotein HRC Domain.

The emergence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of the 2019 coronavirus disease (COVID-19), has erupted into a global pandemic that has led to tens of millions of infections and hundreds of thousands of deaths worldwide. The development of therapeutics to treat infection or as prophylactics to halt viral transmission and spread is urgently needed. SARS-CoV-2 relies on structural rearrangements within a spike (S) glycoprotein to mediate fusion of the viral and host cell membranes. Here, we describe the development of a lipopeptide that is derived from the C-terminal heptad repeat (HRC) domain of SARS-CoV-2 S that potently inhibits infection by SARS-CoV-2. The lipopeptide inhibits cell-cell fusion mediated by SARS-CoV-2 S and blocks infection by live SARS-CoV-2 in Vero E6 cell monolayers more effectively than previously described lipopeptides. The SARS-CoV-2 lipopeptide exhibits broad-spectrum activity by inhibiting cell-cell fusion mediated by SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV) and blocking infection by live MERS-CoV in cell monolayers. We also show that the SARS-CoV-2 HRC-derived lipopeptide potently blocks the spread of SARS-CoV-2 in human airway epithelial (HAE) cultures, an ex vivo model designed to mimic respiratory viral propagation in humans. While viral spread of SARS-CoV-2 infection was widespread in untreated airways, those treated with SARS-CoV-2 HRC lipopeptide showed no detectable evidence of viral spread. These data provide a framework for the development of peptide therapeutics for the treatment of or prophylaxis against SARS-CoV-2 as well as other coronaviruses.IMPORTANCE SARS-CoV-2, the causative agent of COVID-19, continues to spread globally, placing strain on health care systems and resulting in rapidly increasing numbers of cases and mortalities. Despite the growing need for medical intervention, no FDA-approved vaccines are yet available, and treatment has been limited to supportive therapy for the alleviation of symptoms. Entry inhibitors could fill the important role of preventing initial infection and preventing spread. Here, we describe the design, synthesis, and evaluation of a lipopeptide that is derived from the HRC domain of the SARS-CoV-2 S glycoprotein that potently inhibits fusion mediated by SARS-CoV-2 S glycoprotein and blocks infection by live SARS-CoV-2 in both cell monolayers (in vitro) and human airway tissues (ex vivo). Our results highlight the SARS-CoV-2 HRC-derived lipopeptide as a promising therapeutic candidate for SARS-CoV-2 infections.