Faculty Bibliography

Introduction: We sought to describe the demographic characteristics, clinical features, and outcomes of a cohort of patients who presented to our emergency departments with mpox (formerly known as monkeypox) infection between May 1"“August 1, 2022. Case Series: We identified 145 patients tested for mpox, of whom 79 were positive. All positive cases were among cisgender men, and the majority (92%) were among men who have sex with men. A large number of patients (39%) were human immunodeficiency virus (HIV) positive. There was wide variation in emergency department (ED) length of stay (range 2"“16 hours, median 4 hours) and test turnaround time (range 1"“11 days, median 4 days). Most patients (95%) were discharged, although a substantial proportion (22%) had a return visit within 30 days, and 28% ultimately received tecrovirimat. Conclusion: Patients who presented to our ED with mpox had similar demographic characteristics and clinical features as those described in other clinical settings during the 2022 outbreak. While there were operational challenges to the evaluation and management of these patients, demonstrated by variable lengths of stay and frequent return visits, most were able to be discharged.

UNLABELLED:Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES/OBJECTIVE:To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS/METHODS:Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES/METHODS:Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS:single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

Similar to the early phases of the COVID-19 pandemic, New York City was the national epicenter of the ongoing 2022 mpox (formerly monkeypox) outbreak. Cases quickly began to rise in July 2022, primarily in gay, bisexual, or other men who have sex with men. Tools in the form of a reliable diagnostic test, an effective vaccine, and a viable treatment option have been available from the onset, although logistically complex to roll out. The special pathogens program at NYC Health + Hospitals/Bellevue, the flagship facility for the largest public hospital system in the United States, collaborated with multiple departments within Bellevue, the hospital system, and the NYC Department of Health and Mental Hygiene, to swiftly establish ambulatory testing, immunizations, patient-centered inpatient care, and outpatient therapeutics. With the ongoing mpox outbreak, hospitals and local health departments must prepare a systemwide response to identify and isolate patients and provide high-quality care. Findings from our experience can help guide institutions in developing a multipronged, comprehensive response to the ongoing mpox outbreak.

IMPORTANCE: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN, SETTING, AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log²increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10^-5). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

Background. Though reinfection with SARS-CoV-2 is well documented, there remains uncertainty about the potential for more severe symptoms with reinfections compared to index infections. Methods. Patients who received SARS-CoV-2 PCR testing between March 1, 2020 and March 1, 2021 at New York City Health and Hospitals (NYC H+H) facilities and had two positive tests>=90 days apart were included in the analysis. Clinical and demographic data were extracted from the electronic medical record. Manual chart review was done to confirm symptomatology, assess COVID-19 related hospital admissions, and determine WHO disease severity. Patients were then classified as unlikely reinfection, possible reinfection, or probable reinfection based on symptomatology, PCR and antibody testing, and lack of alternative diagnoses. Patients were classified as 'unable to be assessed' if symptomatology could not be assessed for both episodes of PCR positivity. Results. During our study timeframe, 1,255,584 unique patients received at least one SARS-CoV-2 PCR test, 265 of whom had two positive tests>=90 days apart. We categorized 20 patients as unable to be assessed, 28 as unlikely reinfection (1 persistent PCR positivity, 27 unlikely true infection at index or second PCR-positive episode), and 217 as possible or probable reinfection. Of the 217, at their index episode 79 had an asymptomatic infection (36.4%) and 17 were severe or critical (7.8%). At their second episode, 162 patients had an asymptomatic infection (74.7%), and 5 were severe or critical (2.3%). Only 24 patients with possible/probable reinfection had a more severe COVID reinfection than index infection, and 20 of the 24 had asymptomatic index infections. Three patients were hospitalized at both episodes, and two deaths possibly attributable to COVID-19 reinfection were noted in this cohort. Figure 3: Change in WHO disease severity classification from index to second infection among probable/possible reinfection cases (n=217) Red indicates increase in disease severity from index to reinfection (n=24), blue indicates decrease in disease severity from index to reinfection (n=100), white indicates no change (n=74) and gray indicates unable to assess disease severity at index or second infection (n=19). Conclusion. COVID-19 reinfection was rare in a high incidence setting among patients tested at NYC H+H facilities. Disease severity was generally milder in reinfection, although severe and critical disease occurred in a small number of patients.These findings from earlier in the pandemic (presumably wild-type and alpha variant) provide data for comparison in understanding how reinfection is evolving with newer variants

Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity.

OBJECTIVES/OBJECTIVE:To evaluate how key aspects of New York State Ventilator Allocation Guidelines (NYSVAG)-Sequential Organ Failure Assessment score criteria and ventilator time trials -might perform with respect to the frequency of ventilator reallocation and survival to hospital discharge in a simulated cohort of COVID-19 patients. METHODS:Single center retrospective observational and simulation cohort study of 884 critically-ill COVID-19 patients undergoing ventilator allocation per NYSVAG. RESULTS:742 patients (83.9%) would have had their ventilator reallocated during the 11-day observation period, 280 (37.7%) of whom would have otherwise survived to hospital discharge if provided a ventilator. Only 65 (18.1%) of the observed surviving patients would have survived by NYSVAG. Extending ventilator time trials from 2 to 5 days resulted in a 49.2% increase in simulated survival to discharge. CONCLUSIONS:In the setting of a protracted respiratory pandemic, implementation of NYSVAG or similar protocols could lead to a high degree of ventilator reallocation, including withdrawal from patients who might otherwise survive. Longer ventilator time trials might lead to improved survival for COVID-19 patients given their protracted respiratory failure. Further studies are needed to understand the survival of patients receiving reallocated ventilators to determine whether implementation of NYSVAG would improve overall survival.

The National Emerging Special Pathogens Training and Education Center (NETEC) was established in 2015 to improve the capabilities of healthcare facilities to provide safe and effective care to patients with Ebola and other special pathogens in the United States. Through NETEC, a collaborative network of 10 Regional Emerging Special Pathogen Treatment Centers (RESPTCs) undertook readiness activities that included potential respiratory pathogens. These preparations, which took place before the COVID-19 pandemic, established a foundation of readiness that enabled RESPTCs to play a pivotal role in the US COVID-19 pandemic response. As initial COVID-19 cases were detected in the United States, RESPTCs provided essential isolation capacity, supplies, and subject matter expertise that allowed for additional time for healthcare systems to prepare. Through the Special Pathogen Research Network, RESPTCs rapidly enrolled patients into early clinical trials. During periods of high community transmission, RESPTCs provided educational, clinical, and logistical support to a wide range of healthcare and nonhealthcare settings. In this article, we describe how NETEC and the RESPTC network leveraged this foundation of special pathogen readiness to strengthen the national healthcare system's response to the COVID-19 pandemic. NETEC and the RESPTC network have proven to be an effective model that can support the national response to future emerging special pathogens.