Symptomatic Ventricular Bigeminy and Trigeminy Associated With COVID-19.

Cardiac manifestations of COVID-19 are well-described in the current literature, although electrocardiogram analyses of COVID-19 patients are limited. The most common arrhythmias experienced by patients with COVID-19 include sinus tachycardia and atrial fibrillation. Ventricular bigeminy associated with COVID-19 is exceedingly rare and requires further studies to determine its incidence and clinical significance. Here, we present the case of a 57-year-old male with no prior cardiac history who was found to have COVID-19 and new-onset, symptomatic premature ventricular contraction bigeminy. This case highlights a rare potential association between COVID-19 and ventricular bigeminy/trigeminy.

The Neurosurgery Match: COVID Comparison and Bibliometric Analysis.

INTRODUCTION: Because of the effect of COVID on academic opportunities, as well as limitations on travel, away rotations and in-person interviews, COVID-related changes could impact the neurosurgical resident demographics. Our aim was to retrospectively review the demographics of the previous four years of neurosurgery residents, provide bibliometric analysis of successful applicants, and analyze for the effects of COVID on the match cycle. METHODS: All AANS residency program websites were examined for a list of demographic characteristics for current post-graduate year (PGY) 1 to 4. Gathered information included gender, undergraduate and medical institution and state, medical degree status, and prior graduate programs. RESULTS: A total of 114 institutions and 946 residents were included in the final review. 676 (71.5%) of the residents included in the analysis were male. Of the 783 who studied within the United States, 221 (28.2%) residents stayed within the same state of his or her medical school. 104 of 555 (18.7%) residents stayed within the same state of his or her undergraduate school. Demographic information as well as geographic switching relative to medical school, undergraduate school, and hometown showed no significant changes between pre-COVID and COVID-matched cohorts overall. The median number of publications per resident significantly increased for the COVID-matched cohort (median, 1; interquartile range (IQR), 0-4.75) when compared to the non-COVID-matched cohort (median, 1; IQR, 0-3, p = 0.004) as did first author publications (median, 1; IQR, 0-1 vs median, 1; IQR, 0-1; p = 0.015), respectively. The number of residents matching into the same region in the Northeast relative to undergraduate degree was significantly greater after COVID (56 (58%) vs 36 (42%), p = 0.026). The West demonstrated a significant increase in the mean number of total publications (4.0 ± 8.5 vs 2.3 ± 4.2, p = 0.02) and first author publications (1.24 ± 2.33 vs 0.68 ± 1.47, p = 0.02) after COVID, with the increase in first author publications being significant in a test of medians. CONCLUSION: Herein we characterized the most recently matched neurosurgery applicants, paying particular attention to changes over time in relation to the onset of the pandemic. Apart from publication volume, characteristics of residents and geographical preferences did not change with the influence of COVID-induced changes in the application process.

Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19.

Introduction: There remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19. Methods: Blood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured. Results: Differences in biomarkers between those who did and did not develop severe disease or death 7 days after presentation were analyzed. After adjustment for multiple comparisons, RAGE, SARS-CoV-2 nucleocapsid viral antigen, interleukin (IL)-6, IL-10 and tumor necrosis factor receptor (TNFR)-1 were significantly elevated in the group who developed severe disease (all p<0.05). In a multivariable regression model, RAGE and SARS-CoV-2 nucleocapsid viral antigen remained significant risk factors for development of severe disease (both p<0.05), and each had sensitivity and specificity >80% on cut-point analysis. Discussion: Elevated RAGE and SARS-CoV-2 nucleocapsid viral antigen on emergency department presentation are strongly associated with development of severe disease at 7 days. These findings are of clinical relevance for patient prognostication and triage as hospital systems continue to be overwhelmed. Further studies are warranted to determine the feasibility and utility of point-of care measurements of these biomarkers in the emergency department setting to improve patient prognostication and triage.

Adapting a Medical School Cancer Research Education Program to the Virtual Environment: a Mixed-Methods Study.

With cancer incidence increasing worldwide, physicians with cancer research training are needed. The Scholars in Oncology-Associated Research (SOAR) cancer research education program was developed to train medical students in cancer research while exposing them to the breadth of clinical oncology. Due to the COVID-19 pandemic, SOAR transitioned from in-person in 2019 to virtual in 2020 and hybrid in 2021. This study investigates positive and negative aspects of the varying educational formats. A mixed-methods approach was used to evaluate the educational formats. Pre- and post-surveys were collected from participants to assess their understanding of cancer as a clinical and research discipline. Structured interviews were conducted across all three cohorts, and thematic analysis was used to generate themes. A total of 37 students participated in SOAR and completed surveys (2019 n = 11, 2020 n = 14, and 2021 n = 12), and 18 interviews were conducted. Understanding of oncology as a clinical (p < 0.01 for all) and research discipline (p < 0.01 for all) improved within all three cohorts. There was no difference between each cohort's improvement in research understanding (p = 0.6). There was no difference between each cohort's understanding of oncology-related disciplines as both clinical and research disciplines (p > 0.1 for all). Thematic analysis demonstrated that hybrid and in-person formats were favored over a completely virtual one. Our findings demonstrate that a medical student cancer research education program is effective using in-person or hybrid formats for research education, although virtual experiences may be suboptimal to learning about clinical oncology.

Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants

The accelerated development of the first generation COVID-19 vaccines has saved millions of lives, and potentially more from the long-term sequelae of SARS-CoV-2 infection. The most successful vaccine candidates have used the full-length SARS-CoV-2 spike protein as an immunogen. As expected of RNA viruses, new variants have evolved and quickly replaced the original wild-type SARS-CoV-2, leading to escape from natural infection or vaccine induced immunity provided by the original SARS-CoV-2 spike sequence. Next generation vaccines that confer specific and targeted immunity to broadly neutralising epitopes on the SARS-CoV-2 spike protein against different variants of concern (VOC) offer an advance on current booster shots of previously used vaccines. Here, we present a targeted approach to elicit antibodies that neutralise both the ancestral SARS-CoV-2, and the VOCs, by introducing a specific glycosylation site on a non-neutralising epitope of the RBD. The addition of a specific glycosylation site in the RBD based vaccine candidate focused the immune response towards other broadly neutralising epitopes on the RBD. We further observed enhanced cross-neutralisation and cross-binding using a DNA-MVA CR19 prime-boost regime, thus demonstrating the superiority of the glycan engineered RBD vaccine candidate across two platforms and a promising candidate as a broad variant booster vaccine.

External validation of the ADA score for predicting thrombosis among acutely ill hospitalized medical patients from the APEX Trial.

The ADA (Age-D-dimer-Albumin) score was developed to identify hospitalized patients at an increased risk for thrombosis in the coronavirus infectious disease-19 (COVID-19) setting. The study aimed to validate the ADA score for predicting thrombosis in a non-COVID-19 medically ill population from the APEX trial. The APEX trial was a multinational, randomized trial that evaluated the efficacy and safety of betrixaban vs. enoxaparin among acutely ill hospitalized patients at risk for venous thromboembolism. The study endpoints included the composite of arterial or venous thrombosis and its components. Metrics of model calibration and discrimination were computed for assessing the performance of the ADA score as compared to the IMPROVE score, a well-validated VTE risk assessment model. Among 7,119 medical inpatients, 209 (2.9%) had a thrombosis event up to 77 days of follow-up. The ADA score demonstrated good calibration for both arterial and venous thrombosis, whereas the IMPROVE score had adequate calibration for venous thrombosis (p > 0.05 from the Hosmer-Lemeshow test). For discriminating arterial and venous thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.620 [95% CI: 0.582 to 0.657] vs. 0.590 [95% CI: 0.556 to 0.624]; ∆ c statistic = 0.030 [95% CI: -0.022 to 0.081]; p = 0.255). Similarly, for discriminating arterial thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.582 [95% CI: 0.534 to 0.629] vs. 0.609 [95% CI: 0.564 to 0.653]; ∆ c statistic = -0.027 [95% CI: -0.091 to 0.036]; p = 0.397). For discriminating venous thrombosis, the ADA score was modestly superior to the IMPROVE score (c statistic = 0.664 [95% CI: 0.607 to 0.722] vs. 0.573 [95% CI: 0.521 to 0.624]; ∆ c statistic = 0.091 [95% CI: 0.011 to 0.172]; p = 0.026). The ADA score had a higher sensitivity (0.579 [95% CI: 0.512 to 0.646]; vs. 0.440 [95% CI: 0.373 to 0.507]) but lower specificity (0.625 [95% CI: 0.614 to 0.637] vs. 0.747 [95% CI: 0.737 to 0.758]) than the IMPROVE score for predicting thrombosis. Among acutely ill hospitalized medical patients enrolled in the APEX trial, the ADA score demonstrated good calibration but suboptimal discrimination for predicting thrombosis. The findings support the use of either the ADA or IMPROVE score for thrombosis risk assessment. The applicability of the ADA score to non-COVID-19 populations warrants further research.Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

Posterior Glottic Injury Following Prolonged Intubation in COVID-19 Patients.

OBJECTIVE: The objective of this study was to characterize the risk factors for posterior glottic injury (PGI) in patients with coronavirus disease 2019 (COVID-19) who underwent prolonged intubation. STUDY DESIGN: This was a case-control study designed to assess the risk factors associated with development of PGI in COVID-19 patients who underwent prolonged intubation. SETTING: This single-center study was conducted at a tertiary care academic hospital in a metropolitan area. METHODS: We retrospectively reviewed patients who underwent prolonged intubation (≥7 days) for COVID-19 and compared those with PGI to those without. Patient demographics, comorbidities, and intubation characteristics were compared. Factors associated with PGI development among COVID-19 patients were assessed using multivariate regression. RESULTS: We identified 56 patients who presented with PGI following prolonged intubation for COVID-19 and 60 control patients who underwent prolonged intubation for COVID-19 but did not develop PGI. On univariate analyses, the number of reintubations due to failed extubation efforts was significantly associated with development of PGI (odds ratio [OR], 2.9; 95% CI, 1.4-6.2). On multivariate analyses, patients with cardiovascular disease (OR, 3.3; 95% CI, 1.2-9.0); non-COVID-19 respiratory illnesses, which included obstructive sleep apnea and asthma (OR, 5.9; 95% CI, 2.0-17.8); and diabetes mellitus (OR, 11.6; 95% CI, 3.7-36.6) were more likely to develop PGI. CONCLUSION: Our results represent the largest case-control study investigating risk factors for PGI in the setting of prolonged intubation specific to COVID-19. Our study suggests a significant role of comorbidities associated with poor wound healing with development of PGI.

Estimated reimbursement impact of COVID-19 on emergency physicians.

BACKGROUND: The delivery and financing of health care services were altered in unprecedented ways by COVID-19 and subsequent policy responses. We estimated reimbursement losses to emergency physicians in 2020 compared to 2019 related to shifting acute care utilization during COVID-19. METHODS: This was an observational analysis of the Clinical Emergency Department Registry (CEDR) and the Nationwide Emergency Department Sample (NEDS). Study sample included all ED visits from a sample of 214 emergency department (ED) sites in the CEDR in 2019 and 2020 as well as all ED visits in the NEDS in 2019. We identified level of service billing code for evaluation and management (E&M) services, insurance payer, and geographic location of ED visits across sites in the CEDR and linked these to fee schedules to estimate total professional reimbursement across sites. Our primary analysis was to estimate reimbursement in 2020 compared to 2019 across the CEDR sites. In our secondary analysis, we linked sites in the CEDR to those in NEDS to estimate nationwide reimbursement. RESULTS: Total E&M reimbursement for emergency physicians in the CEDR was $1.6 billion in 2019 and $1.3 billion in 2020, reflecting a 19.7% decline year over year ($308 million loss). In our secondary analysis, we estimate nationwide losses of $6.6 billion, a -19.4% decline year over year. If emergency physicians had received maximum allowable federal relief funds via CARES Act Phases 1 to 3 (2% of 2019 revenue) this would sum to $680 million (2% of the $34 billion) or 10.3% of the estimated $6.6 billion pandemic-related losses. CONCLUSIONS: Our analyses provide an estimate of the scale of economic impacts of the COVID-19 pandemic. These findings warrant consideration for policymaker relief and future redesign of emergency care financing. Ultimately, the COVID-19 pandemic likely expanded known cracks in the financing of health care into steep fault lines.

Effects of the circulating environment of COVID-19 on platelet and neutrophil behavior.

Introduction: Thromboinflammatory complications are well described sequalae of Coronavirus Disease 2019 (COVID-19), and there is evidence of both hyperreactive platelet and inflammatory neutrophil biology that contributes to the thromoinflammatory milieu. It has been demonstrated in other thromboinflammatory diseases that the circulating environment may affect cellular behavior, but what role this environment exerts on platelets and neutrophils in COVID-19 remains unknown. We tested the hypotheses that 1) plasma from COVID-19 patients can induce a prothrombotic platelet functional phenotype, and 2) contents released from platelets (platelet releasate) from COVID-19 patients can induce a proinflammatory neutrophil phenotype. Methods: We treated platelets with COVID-19 patient and disease control plasma, and measured their aggregation response to collagen and adhesion in a microfluidic parallel plate flow chamber coated with collagen and thromboplastin. We exposed healthy neutrophils to platelet releasate from COVID-19 patients and disease controls and measured neutrophil extracellular trap formation and performed RNA sequencing. Results: We found that COVID-19 patient plasma promoted auto-aggregation, thereby reducing response to further stimulation ex-vivo. Neither disease condition increased the number of platelets adhered to a collagen and thromboplastin coated parallel plate flow chamber, but both markedly reduced platelet size. COVID-19 patient platelet releasate increased myeloperoxidasedeoxyribonucleic acid complexes and induced changes to neutrophil gene expression. Discussion: Together these results suggest aspects of the soluble environment circulating platelets, and that the contents released from those neutrophil behavior independent of direct cellular contact.

Glycan masking of a non-neutralising epitope enhances neutralising antibodies targeting the RBD of SARS-CoV-2 and its variants.

The accelerated development of the first generation COVID-19 vaccines has saved millions of lives, and potentially more from the long-term sequelae of SARS-CoV-2 infection. The most successful vaccine candidates have used the full-length SARS-CoV-2 spike protein as an immunogen. As expected of RNA viruses, new variants have evolved and quickly replaced the original wild-type SARS-CoV-2, leading to escape from natural infection or vaccine induced immunity provided by the original SARS-CoV-2 spike sequence. Next generation vaccines that confer specific and targeted immunity to broadly neutralising epitopes on the SARS-CoV-2 spike protein against different variants of concern (VOC) offer an advance on current booster shots of previously used vaccines. Here, we present a targeted approach to elicit antibodies that neutralise both the ancestral SARS-CoV-2, and the VOCs, by introducing a specific glycosylation site on a non-neutralising epitope of the RBD. The addition of a specific glycosylation site in the RBD based vaccine candidate focused the immune response towards other broadly neutralising epitopes on the RBD. We further observed enhanced cross-neutralisation and cross-binding using a DNA-MVA CR19 prime-boost regime, thus demonstrating the superiority of the glycan engineered RBD vaccine candidate across two platforms and a promising candidate as a broad variant booster vaccine.

In silico study of novel niclosamide derivatives, SARS-CoV-2 nonstructural proteins catalytic residue-targeting small molecules drug candidates.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated coronavirus disease 2019 (COVID-19) infection remains a global pandemic and health emergency with overwhelming social and economic impacts throughout the world. Therapeutics for COVID-19 are limited to only remdesivir; therefore, there is a need for combined, multidisciplinary efforts to develop new therapeutic molecules and explore the effectiveness of existing drugs against SARS-CoV-2. In the present study, we reported eight (SCOV-L-02, SCOV-L-09, SCOV-L-10, SCOV-L-11, SCOV-L-15, SCOV-L-18, SCOV-L-22, and SCOV-L-23) novel structurally related small-molecule derivatives of niclosamide (SCOV-L series) for their targeting potential against angiotensin-converting enzyme-2 (ACE2), type II transmembrane serine protease (TMPRSS2), and SARS-COV-2 nonstructural proteins (NSPs) including NSP5 (3CLpro), NSP3 (PLpro), and RdRp. Our correlation analysis suggested that ACE2 and TMPRSS2 modulate host immune response via regulation of immune-infiltrating cells at the site of tissue/organs entries. In addition, we identified some TMPRSS2 and ACE2 microRNAs target regulatory networks in SARS-CoV-2 infection and thus open up a new window for microRNAs-based therapy for the treatment of SARS-CoV-2 infection. Our in vitro study revealed that with the exception of SCOV-L-11 and SCOV-L-23 which were non-active, the SCOV-L series exhibited strict antiproliferative activities and non-cytotoxic effects against ACE2- and TMPRSS2-expressing cells. Our molecular docking for the analysis of receptor-ligand interactions revealed that SCOV-L series demonstrated high ligand binding efficacies (at higher levels than clinical drugs) against the ACE2, TMPRSS2, and SARS-COV-2 NSPs. SCOV-L-18, SCOV-L-15, and SCOV-L-09 were particularly found to exhibit strong binding affinities with three key SARS-CoV-2's proteins: 3CLpro, PLpro, and RdRp. These compounds bind to the several catalytic residues of the proteins, and satisfied the criteria of drug-like candidates, having good adsorption, distribution, metabolism, excretion, and toxicity (ADMET) pharmacokinetic profile. Altogether, the present study suggests the therapeutic potential of SCOV-L series for preventing and managing SARs-COV-2 infection and are currently under detailed investigation in our lab.

A consensus viewpoint on the role of direct factor Xa inhibitors in the management of cancer-associated venous thromboembolism in the UK.

OBJECTIVE: Cancer patients are at high risk of venous thromboembolism (VTE), a significant cause of cancer-related death. Historically, low molecular weight heparins (LMWH) were the gold standard therapy for cancer-associated VTE, but recent evidence supports the use of direct factor Xa inhibitors in cancer-associated VTE and this is now reflected in many guidelines. However, uptake of direct factor Xa inhibitors varies and guidance on the use of direct factor Xa inhibitors in specific cancer sub-populations and clinical situations is lacking. This review presents consensus expert opinion alongside evaluation of evidence to support healthcare professionals in the use of direct factor Xa inhibitors in cancer-associated VTE. METHODS: Recent guidelines, meta-analyses, reviews and clinical studies on anticoagulation therapy for cancer-associated VTE were used to direct clinically relevant topics and evidence to be systematically discussed using nominal group technique. The consensus manuscript and recommendations were developed based on these discussions. RESULTS: Considerations when prescribing anticoagulant therapy for cancer-associated VTE include cancer site and stage, systemic anti-cancer therapy (including vascular access), drug-drug interactions, length of anticoagulation, quality of life and needs during palliative care. Treatment of patients with kidney or liver impairment, gastrointestinal disorders, extremes of bodyweight, elevated bleeding or recurrence risk, VTE recurrence and COVID-19 is discussed. CONCLUSION: Anticoagulant therapy for cancer-associated VTE patients should be carefully selected with consideration given to the relative benefits of specific drugs when individualizing care. Direct factor Xa inhibitors are typically the treatment of choice for preventing VTE recurrence in non-cancer patients and should also be considered as such for cancer-associated VTE in most situations.

Rapid selection of sotrovimab escape variants in SARS-CoV-2 Omicron infected immunocompromised patients.

BACKGROUND: Monoclonal antibodies (mAb) targeting SARS-CoV-2 are predominantly less effective against Omicron variants. Immunocompromised patients often experience prolonged viral shedding and are therefore at increased risk for viral escape mutations, when mAbs are used as monotherapy. METHODS: In an observational, prospective cohort, 57 patients infected with Omicron variants receiving sotrovimab alone or in combination with remdesivir were followed. The study endpoints were a decrease in SARS-CoV-2-RNA <106 copies/ml in nasopharyngeal swabs at day 21 and the emergence of resistance mutations at days 7, 14, and 21 after sotrovimab administration. All SARS-CoV-2 samples were analyzed by whole-genome sequencing, individual variants within the quasispecies were subsequently quantified and further characterized by a pseudovirus neutralization assay. RESULTS: 47/57 patients (82.5%) were infected with Omicron/BA.1 and 10/57 (17.5%) with Omicron/BA.2. The vast majority of patients (43/57, 75.4%) were immunodeficient, predominantly due to immunosuppression after organ transplantation or hematologic malignancies. 21 days after sotrovimab administration, 12/43 (27.9%) of immunodeficient patients had prolonged viral shedding compared to 1/14 (7.1%) immunocompetent patients (p = 0.011). Longitudinal sequencing revealed that 14/43 (32.6%) immunodeficient patients had in part Omicron-specific viral spike protein mutations (e.g., P337S and/or E340D/V) that substantially reduced susceptibility to sotrovimab in a pseudovirus neutralization assay. Combination therapy with remdesivir significantly reduced the selection of escape variants. CONCLUSIONS: Immunocompromised patients face a considerable risk of prolonged viral shedding and emergence of escape mutations after early therapy with sotrovimab. These findings underscore the importance of careful monitoring and the need to conduct dedicated clinical trials for this patient population.

Shared Decision-Making in General Surgery: Prospective Comparison of Telemedicine vs In-Person Visits.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has accelerated a shift toward virtual telemedicine appointments with surgeons. While this form of healthcare delivery has potential benefits for both patients and surgeons, the quality of these interactions remains largely unstudied. We hypothesize that telemedicine visits are associated with lower quality of shared decision-making. STUDY DESIGN: We performed a mixed-methods, prospective, observational cohort trial. All patients presenting for a first-time visit at general surgery clinics between May 2021 and June 2022 were included. Patients were categorized by type of visit: in-person vs telemedicine. The primary outcome was the level of shared decision-making as captured by top box scores of the CollaboRATE measure. Secondary outcomes included quality of shared decision-making as captured by the 9-item Shared Decision-Making Questionnaire and satisfaction with consultation survey. An adjusted analysis was performed accounting for potential confounders. A qualitative analysis of open-ended questions for both patients and practitioners was performed. RESULTS: During a 13-month study period, 387 patients were enrolled, of which 301 (77.8%) underwent in-person visits and 86 (22.2%) underwent telemedicine visits. The groups were similar in age, sex, employment, education, and generic quality-of-life scores. In an adjusted analysis, a visit type of telemedicine was not associated with either the CollaboRATE top box score (odds ratio 1.27; 95% CI 0.74 to 2.20) or 9-item Shared Decision-Making Questionnaire (ß -0.60; p = 0.76). Similarly, there was no difference in other outcomes. Themes from qualitative patient and surgeon responses included physical presence, time investment, appropriateness for visit purpose, technical difficulties, and communication quality. CONCLUSIONS: In this large, prospective study, there does not appear to be a difference in quality of shared decision making in patients undergoing in-person vs telemedicine appointments.

Pediatric mental health visits with prolonged length of stay in community emergency departments during COVID-19.

Objectives: To characterize trends in pediatric mental health visit counts, including visits for prolonged length of stay (LOS), in a sample of emergency departments (EDs) from 29 states during COVID-19. Methods: We performed a secondary analysis of the Clinical Emergency Data Registry from January 2020 through December 2021. We reported trends in pediatric mental health visit counts overall and for those with prolonged ED LOS. We reported incident rate ratios (IRRs) for monthly counts compared to January 2020. Among visits with LOS >24 hours, we reported on the most common diagnostic categories. Results: There were 107 EDs from 29 states with available complete data in 2020 and 2021. Pediatric mental health visit counts resulting in a LOS greater than 6, 12, and 24 hours were higher for much of 2021. At their peak, there were 604 visits with LOS >12 hours (IRR, 2.14; 95% confidence interval [CI], 1.86-2.47) and 262 visits (IRR, 2.46; 95% CI, 1.97-3.09) with LOS >24 hours in April 2021. Pediatric mental health visits with LOS >12 hours and >24 hours made up 20.9% and 7.3% of pediatric mental health visits overall, respectively. For visits with ED LOS >24 hours, the most common diagnostic categories were suicide or self-injury, depressive disorders, and mental health syndrome. Conclusions: In this sample of 107 EDs in 29 states, visit counts with prolonged LOS >24 hours more than doubled in some months since the arrival of COVID-19. These findings are indicative of an increasingly strained emergency and mental health system.

Disparities in virtual cardiology visits among Veterans Health Administration patients during the COVID-19 pandemic.

Objective: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Veterans Health Administration (VA) rapidly expanded virtual care (defined as care delivered by video and phone), raising concerns about technology access disparities (ie, the digital divide). Virtual care was somewhat established in primary care and mental health care prepandemic, but video telehealth implementation was new for most subspecialties, including cardiology. We sought to identify patient characteristics of virtual and video-based care users in VA cardiology clinics nationally during the first year of the COVID-19 pandemic. Materials and Methods: Cohort study of Veteran patients across all VA facilities with a cardiology visit January 1, 2019-March 10, 2020, with follow-up January 1, 2019-March 10, 2021. Main measures included cardiology visits by visit type and likelihood of receiving cardiology-related virtual care, calculated with a repeated event survival model. Results: 416 587 Veterans with 1 689 595 total cardiology visits were analyzed; average patient age was 69.6 years and 4.3% were female. Virtual cardiology care expanded dramatically early in the COVID-19 pandemic from 5% to 70% of encounters. Older, lower-income, and rural-dwelling Veterans and those experiencing homelessness were less likely to use video care (adjusted hazard ratio for ages 75 and older 0.80, 95% confidence interval (CI) 0.75-0.86; for highly rural residents 0.77, 95% CI 0.68-0.87; for low-income status 0.94, 95% CI 0.89-0.98; for homeless Veterans 0.85, 95% CI 0.80-0.92). Conclusion: The pandemic worsened the digital divide for cardiology care for many vulnerable patients to the extent that video visits represent added value over phone visits. Targeted interventions may be necessary for equity in COVID-19-era access to virtual cardiology care.

Bronchopulmonary Fistula Development in an Elderly Male With COVID-19 Infection.

COVID-19 pneumonia can cause a wide range of complications including pneumothorax and empyema. However, in severe cases, it can lead to bronchopulmonary fistula (BPF) formation and a persistent air leak due to a connection between the pleural space and the bronchial tree. We report the case of a 77-year-old man with a history of hypertension, who presented to the emergency department for evaluation of dyspnea. Admission labs were significant for a positive rapid antigen SARS-Cov-2 test and elevated troponin I. A chest x-ray demonstrated patchy interstitial opacification and ground glass appearance bilaterally. Within the first 24 hours of presentation, the patient developed a right-sided spontaneous pneumothorax and had a 14 French pigtail catheter placed. The patient subsequently developed a persistent air leak after chest tube placement and required video-assisted thoracoscopic surgery (VATS) with talc pleurodesis and a 32 French chest tube placement. In this unique case, we describe an elderly patient's experience of bronchopulmonary fistula formation as a complication of COVID-19 pneumonia and the successful management of this complication with VATS.

HOGVAX: Exploiting Peptide Overlaps to Maximize Population Coverage in Vaccine Design with Application to SARS-CoV-2 (preprint)

Peptide vaccines present a safe and cost-efficient alternative to traditional vaccines. Their efficacy depends on the peptides included in the vaccine and the ability of major histocompatibility complex (MHC) molecules to bind and present these peptides. Due to the high diversity of MHC alleles, their diverging peptide binding specificities, and physical constraints on the maximum length of peptide vaccine constructs, choosing a set of peptides that effectively achieve immunization across a large proportion of the population is challenging. Here, we present HOGVAX, a combinatorial optimization approach to select peptides that maximize population coverage. The key idea behind HOGVAX is to exploit overlaps between peptide sequences to include a large number of peptides in limited space and thereby also cover rare MHC alleles. We formalize the vaccine design task as a theoretical problem, which we call the Maximum Scoring k-Superstring Problem (MSKS). We show that MSKS is NP-hard, reformulate it into a graph problem using the hierarchical overlap graph (HOG), and present a haplotype-aware variant of MSKS to take linkage disequilibrium between MHC loci into account. We give an integer linear programming formulation for the graph problem and provide an open source implementation. We demonstrate on a SARS-CoV-2 case study that HOGVAX-designed vaccine formulations contain significantly more peptides than vaccine sequences built from concatenated peptides. We predict over 98% population coverage and high numbers of per-individual presented peptides, leading to robust immunity against new pathogens or viral variants.

Benefits of Early Thoracic Surgery in the Elderly During the COVID-19 Pandemic: Lessons Learned From Performing a Video-Assisted Thoracotomy.

Elderly patients are often considered poor surgical candidates for intra-thoracic operations due to the number of comorbidities, increased risks associated with general anesthesia, decreased cardiopulmonary reserve, and overall increased frailty. In addition, coronavirus disease 2019 (COVID-19) is a critical psychosocial factor that, through secondary effects, can prevent patients from receiving optimal care. Patients are reduced to having limited contact with family, often a vital support system, which can contribute to feelings of hopelessness, loneliness, and depression. We report the case of a 95-year-old female who presented to the emergency department with increasing supplemental oxygen requirements two weeks after a ground-level fall. She was found to have multiple rib fractures and a left-sided hemothorax. Initial management included aggressive respiratory therapy, multiple pigtail chest tubes, and thrombolytics; however, these measures failed to drain the intrathoracic hematoma. Her care was complicated by the psychosocial and isolation factors of COVID-19 which led to the patient exhibiting symptoms of hopelessness, grief, lack of appetite, and loneliness. As conservative management did not improve her clinical care the patient required a video-assisted thoracoscopic surgery (VATS) to manage the retained hemothorax and facilitate re-expansion of her atelectatic lung. Once the patient was removed from COVID-19 precautions, she was taken to surgery and postoperatively the patient reported minimal pain, participated more in physical therapy, and increased her oral intake. In this unique case, a 95-year-old patient with a hemothorax that was successfully treated with a VATS had her clinical care complicated by the psychosocial implications of COVID-19.