Sociodemographic Comparison of Children With High-risk Medical Conditions Referred vs Identified Through Screening Plus Outreach for COVID-19 Therapeutics.

Importance: Minoritized groups are less likely to receive COVID-19 therapeutics, but few studies have identified potential methods to reduce disparities. Objective: To determine whether screening plus outreach, when compared with referral alone, increases identification of vulnerable pediatric patients at high risk for severe disease eligible for COVID-19 therapeutics from low-resourced communities. Design, Setting, and Participants: A retrospective cohort study of COVID-19 medication allocation between January 1, 2022, and February 15, 2022, at Lurie Children's Hospital, a quaternary care children's hospital, in Chicago, Illinois. The cohorts were pediatric patients referred for COVID-19 therapeutics or with a positive SARS-CoV-2 polymerase chain reaction within the hospital system followed by outreach. Screening involved daily review of positive cases of SARS-CoV-2, followed by medical record review for high-risk conditions, and communication with clinicians and/or patients and families to offer therapy. Exposures: Diagnosis of COVID-19. Main Outcomes and Measures: The primary measure was difference in child opportunity index (COI) scores between the 2 cohorts. Secondary measures included presence and duration of symptoms at diagnosis, medication uptake, race and ethnicity, insurance type, qualifying medical condition, sex, primary language, and age. Results: Of 145 total patients, the median (IQR) age was 15 (13-17) years, and most were male (87 participants [60.0%]), enrolled in public insurance (83 participants [57.2%]), and members of minoritized racial and ethnic groups (103 participants [71.0%]). The most common qualifying conditions were asthma and/or obesity (71 participants [49.0%]). From 9869 SARS-CoV-2 tests performed, 94 eligible patients were identified via screening for COVID-19 therapeutics. Fifty-one patients were identified via referral. Thirty-two patients received medication, of whom 8 (25%) were identified by screening plus outreach alone. Compared with referred patients, patients in the screening plus outreach group were more likely to have moderate, low, or very low COI composite scores (70 patients [74.5%] vs 27 patients [52.9%]); public insurance (65 patients [69.1%] vs 18 patients [35.3%]); and asthma or obesity (60 patients [63.8%] vs 11 patients [21.6%]). Patients in the referral group were more likely to be non-Hispanic White (23 patients [45.1%] vs 19 patients [20.2%]) and receive medication (24 patients [47.1%] vs 8 patients [8.5%]). Conclusions and Relevance: Compared with referral patients, screening plus outreach patients for COVID-19 medications were more socially vulnerable, with lower COI scores, and more likely to have asthma or obesity. Future studies should investigate communication strategies to improve uptake of these medications after outreach.

Measurements and Simulations of Aerosol Released while Singing and Playing Wind Instruments.

Outbreaks from choir performances, such as the Skagit Valley Choir, showed that singing brings potential risk of COVID-19 infection. There is less known about the risks of airborne infection from other musical performances, such as playing wind instruments or performing theater. In addition, it is important to understand methods that can be used to reduce infection risk. In this study, we used a variety of methods, including flow visualization, aerosol and CO2 measurements, and computational fluid dynamics (CFD) modeling to understand the different components that can lead to transmission risk from musical performance and risk mitigation. This study was possible because of a partnership across academic departments and institutions and collaboration with the National Federation of State High School Associations and the College Band Directors National Association. The interdisciplinary team enabled us to understand the various aspects of aerosol transmission risk from musical performance and to quickly implement strategies in music classrooms during the COVID-19 pandemic. We found that plumes from musical performance were highly directional, unsteady and varied considerably in time and space. Aerosol number concentration measured at the bell of the clarinet was comparable to that of singing. Face and bell masks attenuated plume velocities and lengths and decreased aerosol concentrations measured in front of the masks. CFD modeling showed differences between indoor and outdoor environments and that the lowest risk of airborne COVID-19 infection occurred at less than 30 min of exposure indoors and less than 60 min outdoors.

Utilizing Google trends to monitor coronavirus vaccine interest and hesitancies.

INTRODUCTION: Vaccine hesitancy remains a serious challenge for ending the coronavirus disease 2019 (COVID-19) pandemic. Digital media has played an immense role in the spread of information during the pandemic. One method to gauge public interest in COVID-19 related information is to examine patterns of online search queries. METHODS: Google Trends (GT) was used to analyze results for search terms relating to COVID-19 vaccine misinformation, information, and accessibility from October 1st, 2020 to May 27th, 2021. GT allows you to compare multiple queries at one time. The resultant relative search volumes (RSVs)range from 0 to 100. The search term andpoint in time on the graph that has the greatest search volume is given a score of 100 and all other terms and times are given values relative to that maximum. Search interest peaks were analyzed by subgroups (misinformation, information seeking, and access seeking) and across key time points throughout the pandemic. RESULTS: GT analysis revealed that search interest related to vaccine misinformation, general information, and access seeking changed in relation to events taking place throughout the pandemic. The most commonly searched terms in each subgroup were: "Covid vaccine infertility", "Covid vaccine side effects", and "Covid vaccine appointment". Searches related to misinformation peaked in December 2020. Search terms in the general information category peaked in April 2021. RSVs for access seeking terms peaked in March 2021 and have decreased since April 2021. CONCLUSION: Misinformation RSVs were highest after FDA authorization and have multiple repeated spikes after subsequent vaccine announcements. General information seeking terms peaked concurrently with increased vaccination uptake in the United States. Search interest has decreased with wider vaccine availability, despite many individuals in the United States remaining unvaccinated. GT can be used to monitor trends in public attitudes and misinformation regarding COVID-19 vaccines and further target education.

Nosocomial transmission of hepatitis E virus and development of chronic infection: The wider impact of COVID-19.

BACKGROUND: Transmission of hepatitis E virus (HEV) within the healthcare setting is extremely rare. Additionally, the development of chronic HEV infection in association with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection and/or its immunomodulatory therapy has not been reported previously. AIMS: To describe the investigation and management of a nosocomial HEV transmission incident during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Epidemiological and molecular investigation of two individuals hospitalised with COVID-19 who were both diagnosed with HEV infection. RESULTS: Findings from our investigation were consistent with transmission of HEV from one patient with a community-acquired HEV infection to another individual (identical HEV sequences were identified in the two patients), most likely due to a breach in infection control practices whilst both patients shared a bed space on the intensive care unit (ICU). Chronic HEV infection requiring treatment with ribavirin developed in one patient with prolonged lymphopaenia attributable to COVID-19 and/or the immunomodulators received for its treatment. Further investigation did not identify transmission of HEV to any other patients or to healthcare workers. CONCLUSIONS: The extraordinary demands that the COVID-19 pandemic has placed on all aspects of healthcare, particularly within ICU settings, has greatly challenged the ability to consistently maintain optimal infection prevention and control practices. Under the significant pressures of the COVID-19 pandemic a highly unusual nosocomial HEV transmission incident occurred complicated further by progression to a chronic HEV infection in one patient.

Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England.

BACKGROUND: Contradicting assumptions have been made about the effectiveness of SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) receiving immunomodulatory disease-modifying therapies (DMTs) based on the quantification of humoral and cellular immune responses. This study aimed to understand changes in the risk of SARS-CoV-2 infection among the total population of patients receiving MS DMTs in England following mass vaccination. METHODS: This is a retrospective analysis of national data collected prospectively and longitudinally. National Health Service (NHS) England and NHS Improvement (NHSE/I) hold prescribing data on all commissioned MS DMTs in England. United Kingdom Health Security Agency (UKHSA) has been collecting data on all registered SARS-CoV-2 test results, including polymerase chain reaction and rapid antigen tests. All patients receiving MS DMTs were identified using NHSE/I datasets. All patients receiving MS DMTs with SARS-CoV-2 infection (i.e., positive test) from March 2020 to August 2021 were identified by merging NHSE/I and UKHSA datasets. Similar data for the general population were captured using publicly available datasets of the United Kingdom government. The incidence rate ratios (IRR) of SARS-CoV-2 infection among patients receiving MS DMTs compared to the general population during the pre-vaccination (November 2020 to January 2021) and post-vaccination (June to August 2021) periods were calculated. RESULTS: A mean (standard deviation) of 41,208 (4,301) patients received an MS DMT in England during each month from March 2020 to August 2021. The IRR (95% confidence interval) of infection in patients taking ocrelizumab versus the general population increased from 1.13 (0.97-1.31) during the pre-vaccination period to 1.79 (1.57-2.03) during the post-vaccination period. For patients on fingolimod, it increased from 0.87 (0.73-1.02) to 1.40 (1.20-1.63) during the same periods. There were no significant changes for patients on other MS DMTs. CONCLUSION: SARS-CoV-2 vaccines offer less protection against infection to patients taking ocrelizumab or fingolimod, who have an impaired immune response to vaccines, than the general population. These findings will have implications for vaccination policies.

The Use of Telemonitoring in Managing the COVID-19 Pandemic: Pilot Implementation Study.

BACKGROUND: Most people with COVID-19 self-manage at home. However, the condition can deteriorate quickly, and some people may develop serious hypoxia with relatively few symptoms. Early identification of deterioration allows effective management with oxygen and steroids. Telemonitoring of symptoms and physiological signs may facilitate this. OBJECTIVE: The aim of this study was to design, implement, and evaluate a telemonitoring system for people with COVID-19 who are self-managing at home and are considered at significant risk of deterioration. METHODS: A multidisciplinary team developed a telemonitoring protocol using a commercial platform to record symptoms, pulse oximetry, and temperature. If symptoms or physiological measures breached targets, patients were alerted and asked to phone for an ambulance (red alert) or for advice (amber alert). Patients attending COVID-19 assessment centers, who were considered fit for discharge but at risk of deterioration, were shown how to use a pulse oximeter and the monitoring system, which they were to use twice daily for 2 weeks. Patients could interact with the system via app, SMS, or touch-tone phone. Written guidance on alerts was also provided. Following consent, patient data on telemonitoring usage and alerts were linked to data on the use of service resources. Subsequently, patients who had either used or not used the telemonitoring service, including those who had not followed advice to seek help, agreed to brief telephone interviews to explore their views on, and how they had interacted with, the telemonitoring system. Interviews were recorded and analyzed thematically. Professionals involved in the implementation were sent an online questionnaire asking them about their perceptions of the service. RESULTS: We investigated the first 116 patients who used the service. Of these patients, 71 (61.2%) submitted data and the remainder (n=45, 38.8%) chose to self-monitor without electronic support. Of the 71 patients who submitted data, 35 (49%) received 152 alerts during their 2-week observation. A total of 67 red alerts were for oxygen saturation (SpO2) levels of ≤93%, and 15 red alerts were because patients recorded severe breathlessness. Out of 71 patients, 14 (20%) were admitted to hospital for an average stay of 3.6 (SD 4.5) days. Of the 45 who used written guidance alone, 7 (16%) were admitted to hospital for an average stay of 4.0 (SD 4.2) days and 1 (2%) died. Some patients who were advised to seek help did not do so, some because parameters improved on retesting and others because they felt no worse than before. All patients found self-monitoring to be reassuring. Of the 11 professionals who used the system, most found it to be useful and easy to use. Of these 11 professionals, 5 (45%) considered the system "very safe," 3 (27%) thought it "could be safer," and 3 (27%) wished to have more experience with it before deciding. In total, 2 (18%) felt that SpO2 trigger thresholds were too high. CONCLUSIONS: Supported self-monitoring of patients with COVID-19 at home is reassuring to patients, is acceptable to clinicians, and can detect important signs of deterioration. Worryingly, some patients, because they felt well, occasionally ignored important signs of deterioration. It is important, therefore, to emphasize the importance of the early investigation and treatment of asymptomatic hypoxia at the time when patients are initiated and in the warning messages that are sent to patients.

SARS-CoV-2 Monoclonal Antibodies in Children: Ethical Considerations.

The use of monoclonal antibodies in children with certain conditions and at high risk for severe COVID-19 has been approved by the US Food and Drug Administration under the Emergency Use Authorization mechanism of the Federal Food, Drug, and Cosmetic Act. No data on the tolerability or efficacy of these therapies in persons <18 years of age are available; there is risk. Whether they will work is unknown, but they could. A disproportionate number of these children who meet the criteria for treatment with mAbs are from communities of black, Native American, and other race. How should health systems, hospitals, and clinicians balance the tensions between being seen as experimenting with an untested drug as opposed to withholding a potentially life-saving treatment? This article identifies, analyzes, and makes recommendations on the methods by which health systems, hospitals, and individual clinicians can ethically balance these tensions.

Severe Acute Respiratory Syndrome Coronavirus-2 Infections in Critical Care Staff: Beware the Risks Beyond the Bedside.

OBJECTIVES: Critical care workers were considered to be at high risk of severe acute respiratory syndrome coronavirus-2 infection from patients during the first wave of the pandemic. Staff symptoms, previous swab testing, and antibody prevalence were correlated with patient admissions to investigate this assumption. DESIGN: Cross-sectional study. SETTING: A large critical care department in a tertiary-care teaching hospital in London, United Kingdom. SUBJECTS: Staff working in critical care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants completed a questionnaire and provided a serum sample for severe acute respiratory syndrome coronavirus-2 antibody testing over a 3-day period in April 2020. We compared the timing of symptoms in staff to the coronavirus disease 2019 patient admissions to critical care. We also identified factors associated with antibody detection. Of 625 staff 384 (61.4%) reported previous symptoms and 124 (19.8%) had sent a swab for testing. Severe acute respiratory syndrome coronavirus-2 infection had been confirmed in 37 of those swabbed (29.8%). Overall, 21% (131/625) had detectable severe acute respiratory syndrome coronavirus-2 antibody, of whom 9.9% (13/131) had been asymptomatic. The peak onset of symptoms among staff occurred 2 weeks before the peak in coronavirus disease 2019 patient admissions. Staff who worked in multiple departments across the hospital were more likely to be seropositive. Staff with a symptomatic household contact were also more likely to be seropositive at 31.3%, compared with 16.2% in those without (p < 0.0001). CONCLUSIONS: Staff who developed coronavirus disease 2019 were less likely to have caught it from their patients in critical care. Other staff, other areas of the hospital, and the wider community are more likely sources of infection. These findings indicate that personal protective equipment was effective at preventing transmission from patients. However, staff also need to maintain protective measures away from the bedside.

Pharmacological Inhibition of Acid Sphingomyelinase Prevents Uptake of SARS-CoV-2 by Epithelial Cells.

The acid sphingomyelinase/ceramide system plays an important role in bacterial and viral infections. Here, we report that either pharmacological inhibition of acid sphingomyelinase with amitriptyline, imipramine, fluoxetine, sertraline, escitalopram, or maprotiline or genetic downregulation of the enzyme prevents infection of cultured cells or freshy isolated human nasal epithelial cells with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vesicular stomatitis virus (VSV) pseudoviral particles (pp-VSV) presenting SARS-CoV-2 spike protein (pp-VSV-SARS-CoV-2 spike), a bona fide system mimicking SARS-CoV-2 infection. Infection activates acid sphingomyelinase and triggers a release of ceramide on the cell surface. Neutralization or consumption of surface ceramide reduces infection with pp-VSV-SARS-CoV-2 spike. Treating volunteers with a low dose of amitriptyline prevents infection of freshly isolated nasal epithelial cells with pp-VSV-SARS-CoV-2 spike. The data justify clinical studies investigating whether amitriptyline, a safe drug used clinically for almost 60 years, or other antidepressants that functionally block acid sphingomyelinase prevent SARS-CoV-2 infection.

Sphingosine prevents binding of SARS-CoV-2 spike to its cellular receptor ACE2.

Sphingosine has been shown to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown whether sphingosine can be also employed to prevent viral infections. To test this hypothesis, we analyzed whether sphingosine regulates the infection of cultured and freshly isolated ex vivo human epithelial cells with pseudoviral particles expressing SARS-CoV-2 spike (pp-VSV-SARS-CoV-2 spike) that served as a bona fide system mimicking SARS-CoV-2 infection. We demonstrate that exogenously applied sphingosine suspended in 0.9% NaCl prevents cellular infection with pp-SARS-CoV-2 spike. Pretreatment of cultured Vero epithelial cells or freshly isolated human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with pp-VSV-SARS-CoV-2 spike. Mechanistically, we demonstrate that sphingosine binds to ACE2, the cellular receptor of SARS-CoV-2, and prevents the interaction of the receptor-binding domain of the viral spike protein with ACE2. These data indicate that sphingosine prevents at least some viral infections by interfering with the interaction of the virus with its receptor. Our data also suggest that further preclinical and finally clinical examination of sphingosine is warranted for potential use as a prophylactic or early treatment for coronavirus disease-19.