Changes in Acute ED Visits by Race/Ethnicity During the Early COVID-19 Pandemic.

Emergency department (ED) visits for conditions unrelated to the Coronavirus Disease 2019 (COVID-19) pandemic decreased during the early pandemic, raising concerns about critically ill patients forgoing care and increasing their risk of adverse outcomes. It is unclear if Hispanic and Black adults, who have a high prevalence of chronic conditions, sought medical assistance for acute emergencies during this time. This study used 2018-2020 ED visit data from the largest safety net hospital in Los Angeles County to estimate ED visit differences for cardiac emergencies, diabetic complications, and strokes, during the first societal lockdown among Black and Hispanic patients using time series analyses. Emergency department visits were lower than the expected levels during the first societal lockdown. However, after the lockdown ended, Black patients experienced a rebound in ED visits while visits for Hispanics remained depressed. Future research could identify barriers Hispanics experienced that contributed to prolonged ED avoidance.

Responding to the coronavirus disease-2019 pandemic with innovative data use: The role of data challenges

Innovative, responsible data use is a critical need in the global response to the coronavirus disease-2019 (COVID-19) pandemic. Yet potentially impactful data are often unavailable to those who could utilize it, particularly in data-poor settings, posing a serious barrier to effective pandemic mitigation. Data challenges, a public call-to-action for innovative data use projects, can identify and address these specific barriers. To understand gaps and progress relevant to effective data use in this context, this study thematically analyses three sets of qualitative data focused on/based in low/middle-income countries: (a) a survey of innovators responding to a data challenge, (b) a survey of organizers of data challenges, and (c) a focus group discussion with professionals using COVID-19 data for evidence-based decision-making. Data quality and accessibility and human resources/institutional capacity were frequently reported limitations to effective data use among innovators. New fit-for-purpose tools and the expansion of partnerships were the most frequently noted areas of progress. Discussion participants identified building capacity for external/national actors to understand the needs of local communities can address a lack of partnerships while de-siloing information. A synthesis of themes demonstrated that gaps, progress, and needs commonly identified by these groups are relevant beyond COVID-19, highlighting the importance of a healthy data ecosystem to address emerging threats. This is supported by data holders prioritizing the availability and accessibility of their data without causing harm;funders and policymakers committed to integrating innovations with existing physical, data, and policy infrastructure;and innovators designing sustainable, multi-use solutions based on principles of good data governance.

Psychiatric Emergencies in Los Angeles County During, and After, Initial COVID-19 Societal Restrictions: An Interrupted Time-Series Analysis.

Emergency department (ED) visits for psychiatric care in the US reportedly declined during the COVID-19 pandemic. This work, however, does not control for strong temporal patterning in visits before the pandemic and does not examine a potential "rebound" in demand for psychiatric care following the relaxation of initial societal restrictions. Here, we examine COVID-19-related perturbations in psychiatric care during and after the 1st stage of societal restrictions in the largest safety-net hospital in Los Angeles. We retrieved psychiatric ED visit data (98,888 total over 156 weeks, Jan 2018 to Dec 2020) from Los Angeles County + USC Medical Center. We applied interrupted time series methods to identify and control for autocorrelation in psychiatric ED visits before examining their relation with the 1st stage of societal restrictions (i.e., March 13 to May 8, 2020), as well as the subsequent "rebound" period of relaxed restrictions (i.e., after May 8, 2020). Psychiatric ED visits fell by 78.13 per week (i.e., 12%) during the 1st stage of societal restrictions (SD = 23.99, p < 0.01). Reductions in ED visits for alcohol use, substance use, and (to a lesser extent) anxiety disorders accounted for the overall decline. After the 1st stage of societal restrictions, however, we observe no "rebound" above expected values in psychiatric ED visits overall (coef = - 16.89, SD = 20.58, p = 0.41) or by diagnostic subtype. This pattern of results does not support speculation that, at the population level, foregoing ED care during initial societal restrictions subsequently induced a psychiatric "pandemic" of urgent visits.

Cardiac Surgery Outcomes During the COVID-19 Pandemic Worsened Across All Socioeconomic Statuses.

BACKGROUND: Increasing socioeconomic distress has been associated with worse cardiac surgery outcomes. The extent to which the pandemic affected cardiac surgical access and outcomes remains unknown. We sought to examine the relationship between the COVID-19 pandemic and outcomes after cardiac surgery by socioeconomic status. METHODS: All patients undergoing a Society of Thoracic Surgeons (STS) index operation in a regional collaborative, the Virginia Cardiac Services Quality Initiative (2011-2022), were analyzed. Patients were stratified by timing of surgery before vs during the COVID-19 pandemic (March 13, 2020). Hierarchic logistic regression assessed the relationship between the pandemic and operative mortality, major morbidity, and cost, adjusting for the Distressed Communities Index (DCI), STS predicted risk of mortality, intraoperative characteristics, and hospital random effect. RESULTS: A total of 37,769 patients across 17 centers were included. Of these, 7269 patients (19.7%) underwent surgery during the pandemic. On average, patients during the pandemic were less socioeconomically distressed (DCI 37.4 vs DCI 41.9; P < .001) and had a lower STS predicted risk of mortality (2.16% vs 2.53%, P < .001). After risk adjustment, the pandemic was significantly associated with increased mortality (odds ratio 1.398; 95% CI, 1.179-1.657; P < .001), cost (+$4823, P < .001), and STS failure to rescue (odds ratio 1.37; 95% CI, 1.10-1.70; P = .005). The negative impact of the pandemic on mortality and cost was similar regardless of DCI. CONCLUSIONS: Across all socioeconomic statuses, the pandemic is associated with higher cost and greater risk-adjusted mortality, perhaps related to a resource-constrained health care system. More patients during the pandemic were from less distressed communities, raising concern for access to care in distressed communities.

COVID-19 case counts and COVID-19 related Emergency Department visits: differences by immigration status, March-December 2020.

BACKGROUND: Undocumented immigrants face barriers to health care access, which may have been exacerbated during the early days of the COVID-19 pandemic. We test whether undocumented immigrants in Los Angeles County accessed COVID-19 related medical care by examining their Emergency Department (ED) patterns through high and low periods of COVID-19 infection. If undocumented immigrants were underutilizing or foregoing health care, we expect null or weaker associations between COVID-19 cases and COVID-19 related ED visits relative to Medi-Cal patients. METHODS: We analyzed all ED visits to the Los Angeles County + University of Southern California (LAC + USC) Medical Center between March - December 2020 (n = 85,387). We conducted logistic regressions with Los Angeles County weekly COVID-19 case counts as our main independent variable and an interaction between case counts and immigration status, stratified by age (over and under 65 years). RESULTS: We found that undocumented immigrants under 65 years old had a higher odds for a COVID-19 related ED visit compared to Medi-Cal patients and that both undocumented and Medi-Cal patients had higher odds of a COVID-19 related ED visit as COVID-19 cases in Los Angeles County increased. For patients over 65 years, Medi-Cal patients actually had a weaker association between ED visits and county COVID-19 counts; as COVID-19 case counts rose, the odds of a COVID-19 related ED visit increased for the undocumented patients. CONCLUSION: While the overall likelihood of undocumented patients having a COVID-19 related ED visit varies compared to Medi-Cal patients - for younger patients, the odds is higher; for older patients, the odds is lower - it does not appear that undocumented patients underutilized the ED during the early COVID-19 pandemic relative to Medi-Cal patients. The ED may be a viable source of contact for this high-risk population for future outreach.

A platform technology for generating subunit vaccines against diverse viral pathogens.

The COVID-19 pandemic response has shown how vaccine platform technologies can be used to rapidly and effectively counteract a novel emerging infectious disease. The speed of development for mRNA and vector-based vaccines outpaced those of subunit vaccines, however, subunit vaccines can offer advantages in terms of safety and stability. Here we describe a subunit vaccine platform technology, the molecular clamp, in application to four viruses from divergent taxonomic families: Middle Eastern respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), Lassa virus (LASV) and Nipah virus (NiV). The clamp streamlines subunit antigen production by both stabilising the immunologically important prefusion epitopes of trimeric viral fusion proteins while enabling purification without target-specific reagents by acting as an affinity tag. Conformations for each viral antigen were confirmed by monoclonal antibody binding, size exclusion chromatography and electron microscopy. Notably, all four antigens tested remained stable over four weeks of incubation at 40°C. Of the four vaccines tested, a neutralising immune response was stimulated by clamp stabilised MERS-CoV spike, EBOV glycoprotein and NiV fusion protein. Only the clamp stabilised LASV glycoprotein precursor failed to elicit virus neutralising antibodies. MERS-CoV and EBOV vaccine candidates were both tested in animal models and found to provide protection against viral challenge.

Emergency Department Utilization Among Undocumented Latino Patients During the COVID-19 Pandemic.

OBJECTIVE: To determine whether Latino undocumented immigrants had a steeper decline in Emergency Department (ED) utilization compared to Latino Medi-Cal patients in a Los Angeles safety-net hospital, March 13, 2020, to May 8, 2020. STUDY DESIGN: The data were extracted from patient medical records for ED visits at LAC + USC Medical Center from January 2018 to September 2020. We analyzed weekly ED encounters among undocumented Latino patients in the nine-week period after COVID was declared a national emergency. We applied time-series routines to identify and remove autocorrelation in ED encounters before examining its relation with the COVID-19 pandemic. We included Latino patients 18 years of age and older who were either on restricted or full-scope Medi-Cal (n = 230,195). RESULTS: All low-income Latino patients, regardless of immigration status, experienced a significant decline in ED utilization during the first nine weeks of the pandemic. Undocumented patients, however, experienced an even steeper decline. ED visits for this group fall below expected levels between March 13, 2020, and May 8, 2020 (coef. = - 38.67; 95% CI = - 71.71, - 5.63). When applied to the weekly mean of ED visits, this translates to a 10% reduction below expected levels in ED visits during this time period. CONCLUSION: Undocumented immigrants' health care utilization was influenced by external events that occurred early in the pandemic, such as strict stay-at-home orders and the public charge rule change. Health care institutions and local policy efforts could work to ensure that hospitals are safer spaces for undocumented immigrants to receive care without immigration concerns.

Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates.

Nipah virus (NiV) and respiratory syncytial virus (RSV) possess two surface glycoproteins involved in cellular attachment and membrane fusion, both of which are potential targets for vaccines. The majority of vaccine development is focused on the attachment (G) protein of NiV, which is the immunodominant target. In contrast, the fusion (F) protein of RSV is the main target in vaccine development. Despite this, neutralising epitopes have been described in NiV F and RSV G, making them alternate targets for vaccine design. Through rational design, we have developed a vaccine strategy applicable to phylogenetically divergent NiV and RSV that comprises both the F and G proteins (FxG). In a mouse immunization model, we found that NiV FxG elicited an improved immune response capable of neutralising pseudotyped NiV and a NiV mutant that is able to escape neutralisation by two known F-specific antibodies. RSV FxG elicited an immune response against both F and G and was able to neutralise RSV; however, this was inferior to the immune response of F alone. Despite this, RSV FxG elicited a response against a known protective epitope within G that is conserved across RSV A and B subgroups, which may provide additional protection in vivo. We conclude that inclusion of F and G antigens within a single design provides a streamlined subunit vaccine strategy against both emerging and established pathogens, with the potential for broader protection against NiV.

Lifestyle, Exercise and Activity Package for People living with Progressive Multiple Sclerosis (LEAP-MS): adaptions during the COVID-19 pandemic and remote delivery for improved efficiency.

The LEAP-MS (Lifestyle, Exercise and Activity Package for People living with Progressive Multiple Sclerosis) study has developed an individualised supported self-management approach for physical activity for people with progressive multiple sclerosis (MS) and severe disability. The intervention has been evaluated in a single-arm feasibility study with embedded process evaluation. The feasibility study was due to open to recruitment during the COVID-19 2020-2021 pandemic, 1 month into the first UK-wide lockdown. We worked rapidly to implement adaptions to the trial procedures and intervention delivery that we believe are applicable to randomised controlled trials. Recruitment became predominantly via self-referral. Electronic consent was employed, with consent discussions occurring over the telephone. Registration, consent, eligibility assessment and data collection as well as the intervention (online physical activity tool) were via a secure, encrypted multi-user web-based platform for participants, physiotherapists and researchers accessible via various hardware. Physiotherapy consultations, as well as the process evaluation, were conducted remotely using video conferencing software or the telephone. A remote training package for physiotherapists and site initiations was also developed and electronic site files employed. Our adaptions are extremely topical given the COVID-19 situation, and whilst not what we had originally planned, have enabled successful delivery of the feasibility study and are relevant to conducting randomised controlled trials and meeting the needs of people with MS who are far more isolated than ever before. TRIAL REGISTRATION: ClinicalTrials.gov NCT03951181 . Registered on 15 May 2019.

Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.

OBJECTIVES: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia). METHODS: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat. RESULTS: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. CONCLUSION: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.

ACE2 and Furin Expressions in Oral Epithelial Cells Possibly Facilitate COVID-19 Infection via Respiratory and Fecal-Oral Routes.

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear. Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level. Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results. Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal-oral routes.

Maternal-Neonatal Dyad Outcomes of Maternal COVID-19 Requiring Extracorporeal Membrane Support: A Case Series.

OBJECTIVE: This study aimed to describe two cases of acute respiratory distress syndrome (ARDS) secondary to novel coronavirus disease 2019 (COVID-19) in pregnant women requiring extracorporeal membrane oxygenation (ECMO), and resulting in premature delivery. STUDY DESIGN: The clinical course of two women hospitalized with ARDS due to COVID-19 care in our intensive care (ICU) is summarized; both participants provided consent to be included in this case series. RESULTS: Both women recovered with no clinical sequelae. Neonatal outcomes were within the realm of expected for prematurity with the exception of coagulopathy. There was no vertical transmission to the neonates. CONCLUSION: This case series highlights that ECMO is a feasible treatment in the pregnant woman with severe COVID-19 and that delivery can be performed safely on ECMO with no additional risk to the fetus. While ECMO carries its natural risks, it should be considered a viable option during pregnancy and the postpartum period. KEY POINTS: · COVID-19 may present with a more severe course in pregnancy.. · ECMO may be used in pregnant woman with severe COVID-19.. · Delivery can be performed on ECMO without added fetal risk..