Impact of HIV self-testing for oral pre-exposure prophylaxis scale-up on drug resistance and HIV outcomes in western Kenya: a modelling study.

BACKGROUND: Community-based oral pre-exposure prophylaxis (PrEP) provision has the potential to expand PrEP coverage. HIV self-testing can facilitate PrEP community-based delivery but might have lower sensitivity than facility-based HIV testing, potentially leading to inappropriate PrEP use among people with HIV and subsequent development of drug resistance. We aimed to evaluate the impact of HIV self-testing use for PrEP scale-up. METHODS: We parameterised an agent-based network model, EMOD-HIV, to simulate generic tenofovir disoproxil fumarate and emtricitabine PrEP scale-up in western Kenya using four testing scenarios: provider-administered nucleic acid testing, provider-administered rapid diagnostic tests detecting antibodies, blood-based HIV self-testing, or oral fluid HIV self-testing. Scenarios were compared with a no PrEP counterfactual. Individuals aged 18-49 years with one or more heterosexual partners who screened HIV-negative were eligible for PrEP. We assessed the cost and health impact of rapid PrEP scale-up with high coverage over 20 years, and the budget impact over 5 years, using various HIV testing modalities. FINDINGS: PrEP coverage of 29% was projected to avert approximately 54% of HIV infections and 17% of HIV-related deaths among adults aged 18-49 years over 20 years; health impacts were similar across HIV testing modalities used to deliver PrEP. The percentage of HIV infections with PrEP-associated nucleoside reverse transcriptase inhibitor (NRTI) drug resistance was 0·6% (95% uncertainty intervals 0·4-0·9) in the blood HIV self-testing scenario and 0·8% (0·6-1·0) in the oral HIV self-testing scenario, compared with 0·3% (0·2-0·3) in the antibody rapid diagnostic testing scenario and 0·2% (0·1-0·2) in the nucleic acid testing scenario. Accounting for background NRTI resistance, we found similarly low proportions of drug resistance across scenarios. The budget impact of implementing PrEP using HIV self-testing and provider-administered rapid diagnostic tests were similar, while nucleic acid testing was approximately 50% more costly. INTERPRETATION: Scaling up PrEP using HIV self-testing has similar health impacts, costs, and low risk of drug resistance as provider-administered rapid diagnostic tests. Policy makers should consider leveraging HIV self-testing to expand PrEP access among those at HIV risk. FUNDING: The Bill and Melinda Gates Foundation.

The critical role of the specialized social worker as part of ED/hospital-based elder mistreatment response teams.

The emergency department and hospital provide a unique and important opportunity to identify elder mistreatment and offer intervention. To help manage these complex cases, multi-disciplinary response teams have been launched. In developing these teams, it quickly became clear that social workers play a critical role in responding to elder mistreatment. Their unique skillset allows them to establish close connections with community resources, collaborate with various hospital stakeholders, support patients/families/caregivers through challenging situations, navigate the legal and protective systems, and balance patient safety and quality of life in disposition decision-making. The role of the social worker on these multi-faceted teams includes conducting a comprehensive biopsychosocial assessment, helping to develop a safe discharge plan, and making appropriate referrals, among other responsibilities. Any institution considering developing a multi-disciplinary program should recognize the critical importance of social work.

Evaluating the implementation of a pharmacy hackathon pilot.

BACKGROUND AND PURPOSE: The need for disruptive innovation within the pharmacy profession is well documented in the literature. However, there is a lack of proper training on innovation and creative thinking for student pharmacists and limited time or incentive for health care practitioners to be innovative. Hosting an innovation event, such as a hackathon, can teach innovative strategies and incentivize innovation by student pharmacists. Thus, the aim of this study was to to assess the feasibility and student perception of an inaugural school of pharmacy hackathon pilot. EDUCATIONAL ACTIVITY AND SETTING: A hackathon pilot was planned on a distant site campus. Over the course of four months, a planning team, consisting of a faculty member and a student leader in the American Pharmacy Association-Academy of Student Pharmacists, met every other week to plan the event. Outcomes included: change in student excitement and interest related to the hackathon, number of participants, and change in student confidence in the ability to perform steps in the innovation process. FINDINGS: The average level of excitement prior to the event increased, and student confidence related to the ability to perform each step in the innovation process improved. Additionally, students agreed that they would be interested in attending a similar event in the future and would recommend the event to a friend. SUMMARY: Hosting a healthcare hackathon at a school of pharmacy is an enjoyable way for pharmacy students to practice and gain confidence with innovation skills while addressing Accreditation Council for Pharmacy Education Standard 4.3.

CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington, to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1 January 2020-31 May 2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00-5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12-5.91; staff: 3.86, 95% CI 2.43-5.79). Most infections were asymptomatic at the time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity than routine surveillance (2.7% versus 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings.

Previous Health Care Experiences' Influence on Health Care Perceptions Among Residents of Six Homeless Shelters in Seattle, Washington, July-October 2021.

Purpose: The study purpose was to learn and describe 1) where homeless shelter residents receive health care, 2) what contributes to positive or negative health care experiences among shelter residents, and 3) shelter resident perceptions toward health care. Methods: Semi-structured interviews (SSIs) utilizing purposive sampling and focus group discussions (FGDs) utilizing convenience sampling were conducted at 6 homeless shelters in Seattle-King County, Washington, during July-October 2021. All residents (age ≥18) were eligible to participate. SSIs were conducted with 25 residents, and 8 FGDs were held. Thematic analysis was conducted using Dedoose. Results: Participants received health care in settings ranging from no regular care to primary care providers. Four elements emerged as contributing positively and negatively to health care experiences: 1) ability to access health care financially, physically, and technologically; 2) clarity of communication from providers and staff about appointment logistics, diagnoses, and treatment options; 3) ease of securing timely follow-up services; and 4) respect versus stigma and discrimination from providers and staff. Participants who felt positively toward health care found low- or no-cost care to be widely available and encouraged others to seek care. However, some participants described health care in the United States as greedy, classist, discriminatory, and untrustworthy. Participants reported delaying care and self-medicating in anticipation of discrimination. Conclusions: Findings demonstrate that while people experiencing homelessness can have positive experiences with health care, many have faced negative interactions with health systems. Improving the patient experience for those experiencing homelessness can increase engagement and improve health outcomes.

Seeking Excellence in End of Life Care UK (SEECare UK): a UK multi-centred service evaluation.

OBJECTIVE: To evaluate the care of patients dying in hospital without support from specialists in palliative care (SPC), better understand their needs and factors influencing their care. METHODS: Prospective UK-wide service evaluation including all dying adult inpatients unknown to SPC, excluding those in emergency departments/intensive care units. Holistic needs were assessed through a standardised proforma. RESULTS: 88 hospitals, 284 patients. 93% had unmet holistic needs, including physical symptoms (75%) and psycho-socio-spiritual needs (86%). People were more likely to have unmet needs and require SPC intervention at a district general hospital (DGH) than a teaching hospital/cancer centre (unmet need 98.1% vs 91.2% p0.02; intervention 70.9% vs 50.8% p0.001) and when end-of-life care plans (EOLCP) were not used (unmet need 98.3% vs 90.3% p0.006; intervention 67.2% vs 53.3% p0.02). Multivariable analyses demonstrated the independent influence of teaching/cancer hospitals (adjusted OR (aOR)0.44 CI 0.26 to 0.73) and increased SPC medical staffing (aOR1.69 CI 1.04 to 2.79) on need for intervention, however, integrating the use of EOLCP reduced the impact of SPC medical staffing. CONCLUSION: People dying in hospitals have significant and poorly identified unmet needs. Further evaluation is required to understand the relationships between patient, staff and service factors influencing this. The development, effective implementation and evaluation of structured individualised EOLCP should be a research funding priority.

Burden of long COVID among adults experiencing sheltered homelessness: a longitudinal cohort study in King County, WA between September 2020-April 2022.

BACKGROUND: People experiencing homelessness (PEH) are at increased risk for acquiring SARS-CoV-2, but the burden of long COVID in this population is unknown. METHODS: We conducted a matched prospective cohort study to assess the prevalence, characteristics, and impact of long COVID among sheltered PEH in Seattle, WA between September 2020-April 2022. Adults ≥ 18 years, residing across nine homeless shelters with active respiratory virus surveillance, were eligible to complete in-person baseline surveys and interval follow-up phone surveys. We included a subset of 22 COVID-19-positive cases who tested positive or inconclusive for SARS-CoV-2 and 44 COVID-19-negative controls who tested negative for SARS-CoV-2, frequency matched on age and sex. Among controls, 22 were positive and 22 were negative for one of 27 other respiratory virus pathogens. To assess the impact of COVID-19 on the risk of symptom presence at follow-up (day 30-225 post-enrollment test), we performed log-linear regression with robust standard errors, adjusting for confounding by shelter site and demographic variables determined a priori. RESULTS: Of 53 eligible COVID-19 cases, 22 (42%) completed ≥ 1 follow-up survey. While five (23%) cases reported ≥ 1 symptom at baseline, this increased to 77% (10/13) between day 30-59 and 33% (4/12) day 90 + . The most commonly reported symptoms day 30 + were fatigue (27%) and rhinorrhea (27%), with 8 (36%) reporting symptoms that interfered with or prevented daily activities. Four (33%) symptomatic cases reported receiving medical care outside of a medical provider at an isolation facility. Of 44 controls, 12 (27%) reported any symptoms day 90 + . Risk of any symptoms at follow-up was 5.4 times higher among COVID-19 cases compared to controls (95% CI: 2.7-10.5). CONCLUSIONS: Shelter residents reported a high prevalence of symptoms 30 + days after their SARS-CoV-2 detection, though few accessed medical care for persistent illness. The impact of COVID-19 extends beyond acute illness and may exacerbate existing challenges that marginalized populations face in maintaining their health and wellbeing.

Differences in influenza vaccination by gender identity and state-level gender equity policies: Behavioral Risk Factor Surveillance System, 2015-2019.

BACKGROUND: It is estimated that there are one million transgender and over 340,000 gender non-conforming people in the United States, many of whom face significant health disparities including access to healthcare. Although previous studies have reported greater vaccine uptake in women compared to men, national-level estimates of influenza vaccine uptake among transgender and non-binary people are unknown. This study aims to characterize differences in influenza vaccine uptake by gender identity and examine associations between vaccination status and state-level gender equity policies. METHODS: We used cross-sectional data from adults participating in the 2015-2019 United States Behavioral Risk Factors Surveillance System surveys. Weighted prevalence differences (PDs) and associated confidence intervals (CIs) of being unvaccinated against influenza by self-reported gender identity were estimated using generalized linear regression models. RESULTS: Compared to cisgender women (unvaccinated prevalence = 57.3%), the prevalence of being unvaccinated was significantly higher among cisgender men (64.4%; PD = 7.0 per 100, 95% CI: 6.7-7.4), transgender women (65.4%; PD = 8.1 per 100, 95% CI 4.0-12.2), transgender men (64.6%; PD = 7.3 per 100, 95% CI: 2.7-11.8), and gender non-conforming individuals (64.6%; PD = 7.2 per 100, 95% CI: 1.3-13.2). This pattern was similar among individuals living in states with protective versus restrictive gender equity policies. CONCLUSIONS: Our results identified a disparity in influenza vaccine uptake among individuals across the gender spectrum. To improve vaccine equity, future research should explore barriers to and facilitators of vaccine uptake by gender identity, which could inform policies and health promotion interventions to improve uptake co-designed and implemented with the transgender and non-binary communities.

Defining the value of faculty primary care clinical pharmacists.

BACKGROUND: Demonstrating the value of comprehensive medication management (CMM) within clinical faculty sites is a challenge when balancing patient volume with academic responsibilities. Utilizing an evidence-based implementation system for CMM, faculty primary care clinical pharmacists (PCCPs) standardized CMM within their practice sites. OBJECTIVE: The primary objective of this project was to define the value of faculty PCCPs. METHODS: An Ambulatory Care Summit was hosted to identify opportunities for consistency of CMM. Following the summit, the CMM implementation team (faculty PCCPs and project manager) utilized CMM implementation tools from the Comprehensive Medication Management in Primary Care Research Team. Additionally, a strategic plan was developed to enhance practice management, improve fidelity, and determine key performance indicators (KPIs). Five faculty-mentored student projects assessed value of faculty-delivered CMM in primary care clinics. Data included medication adherence metrics, clinic quality metrics, diabetes metrics, acute healthcare utilization rates, and a physician satisfaction survey. RESULTS: Among those receiving CMM, adherence improved 14% (P = 0.022), 119 clinic quality metrics were achieved, HbA1c ≤ 9% improved 45% (p < 0.001), average HbA1c decreased by 1.73% (p < 0.001), and medication preventable acute care utilization within the referral reason decreased. Over 90% of physicians surveyed agreed the faculty PCCP is a valuable team member, improved patients' health, and improved effectiveness/efficiency. Four student posters were presented at national conferences and 18 student pharmacists were engaged in various aspects of the project. CONCLUSION: Incorporating CMM at faculty primary care clinics provides value. To demonstrate this value, faculty must align KPIs with institution-specific payer contracts.

Unleashing the Power of the Right Brain.

We envision a paradigm shift where our profession no longer follows but leads the charge to develop a whole mind approach in our pharmacists. Left brain skills remain critical but are no longer sufficient to combat the current threats of abundance, automation, and outsourcing within the pharmacy landscape. It is vital that pharmacists be skilled problem solvers and empathizers. We must capitalize on characteristics that make pharmacists essential while innovating new opportunities and jobs. We call on the Academy to reimagine curricular design and offer deliberate messaging and modeling that fosters a higher priority on right brain skill development.

COVID-19 and the malaria elimination agenda in Africa: Re-shifting the focus.

The global Coronavirus disease 2019 (COVID-19) pandemic has resulted in public health, political, scientific and private sector response at an unprecedented scale. However, this shift in focus has caused widespread disruption to global health services and has the potential to reverse gains made in efforts to control malaria. If health systems are not able to maintain malaria control interventions while managing the response to the COVID-19 pandemic, malaria cases will increase, thereby placing even more strain on already overtaxed systems. Using a Narrative Review Approach, this commentary explores the impact of COVID-19 on progress made with malaria control and prevention strategies in Africa; and discusses possible mitigation steps to aid community resilience building, through proactive planning and implementation of integrated, inclusive and sustainable strategies to re-shift the focus to attain the malaria elimination goals. We propose strengthening community partnerships, where academia and communities should collaborate and these knowledge-sharing strategies be implemented in order for awareness and interventions to become more networked, inclusive, resilient and effective. Communities should be viewed as 'thought partners', who challenge conventional strategies and aid in developing innovative approaches to community resilience building.

Trends and factors associated with change in COVID-19 vaccination intent among residents and staff in six Seattle homeless shelters, March 2020 to August 2021.

Introduction: Achieving high COVID-19 vaccination coverage in homeless shelters is critical in preventing morbidity, mortality, and outbreaks, however, vaccination coverage remains lower among people experiencing homelessness (PEH) than the general population. Methods: We conducted a cross-sectional study to retrospectively describe attitudes and identify factors associated with change in COVID-19 vaccination intent among shelter residents and staff during March 2020 - August 2021. To identify factors associated with change in COVID-19 vaccine intent becoming more positive overall compared to other attitudes, we utilized a Poisson model to calculate Risk Ratios with robust standard errors, adjusting for confounding by shelter site and demographic variables determined a priori. Results: From July 12 - August 2, 2021, 97 residents and 20 staff participated in surveys across six shelters in Seattle King County, Washington. Intent to be vaccinated against COVID-19 increased from 45.3 % (n = 53) when recalling attitudes in March 2020 to 74.4 % (n = 87) as of August 2021, and was similar among residents and staff. Many participants (43.6 %, n = 51) indicated feeling increasingly accepting about receiving a COVID-19 vaccine since March 2020, while 13.7 % (n = 16) changed back and forth, 10.3 % (n = 12) became more hesitant, and 32.5 % (n = 38) had no change in intent. In the model examining the relationship between becoming more positive about receiving a COVID-19 vaccine compared to all other attitudes (n = 116), we found a 57.2 % increase in vaccine acceptability (RR 1.57; 95 % CI: 1.01, 2.45) among those who reported worsening mental health since the start of the pandemic. Conclusions: Findings highlight opportunities to improve communication with residents and staff about COVID-19 vaccination and support a need for continued dialogue and a person-centered approach to understanding the sociocultural complexities and dynamism of vaccine attitudes at shelters.Clinical Trial Registry Number: NCT04141917.

Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA.

To determine the epidemiology of human parainfluenza virus in homeless shelters during the COVID-19 pandemic, we analyzed data and sequences from respiratory specimens collected in 23 shelters in Washington, USA, during 2019-2021. Two clusters in children were genetically similar by shelter of origin. Shelter-specific interventions are needed to reduce these infections.

The clinical and genomic epidemiology of seasonal human coronaviruses in congregate homeless shelter settings: A repeated cross-sectional study.

Background: The circulation of respiratory viruses poses a significant health risk among those residing in congregate settings. Data are limited on seasonal human coronavirus (HCoV) infections in homeless shelter settings. Methods: We analysed data from a clinical trial and SARS-CoV-2 surveillance study at 23 homeless shelter sites in King County, Washington between October 2019-May 2021. Eligible participants were shelter residents aged ≥3 months with acute respiratory illness. We collected enrolment data and nasal samples for respiratory virus testing using multiplex RT-PCR platform including HCoV. Beginning April 1, 2020, eligibility expanded to shelter residents and staff regardless of symptoms. HCoV species was determined by RT-PCR with species-specific primers, OpenArray assay or genomic sequencing for samples with an OpenArray relative cycle threshold <22. Findings: Of the 14,464 samples from 3281 participants between October 2019-May 2021, 107 were positive for HCoV from 90 participants (median age 40 years, range: 0·9-81 years, 38% female). HCoV-HKU1 was the most common species identified before and after community-wide mitigation. No HCoV-positive samples were identified between May 2020-December 2020. Adults aged ≥50 years had the highest detection of HCoV (11%) among virus-positive samples among all age-groups. Species and sequence data showed diversity between and within HCoV species over the study period. Interpretation: HCoV infections occurred in all congregate homeless shelter site age-groups with the greatest proportion among those aged ≥50 years. Species and sequencing data highlight the complexity of HCoV epidemiology within and between shelters sites. Funding: Gates Ventures, Centers for Disease Control and Prevention, National Institute of Health.

The Clinical and Genomic Epidemiology of Rhinovirus in Homeless Shelters-King County, Washington.

BACKGROUND: Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. METHODS: We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019-May 2021. Shelter residents or guardians aged ≥3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After 1 April 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. RESULTS: There were 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (COVID-19) pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for ≤4 months. CONCLUSIONS: RV infections persisted through community mitigation measures and were most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes, each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic. CLINICAL TRIALS REGISTRATION: NCT04141917.

Maintaining face mask use before and after achieving different COVID-19 vaccination coverage levels: a modelling study.

BACKGROUND: Face mask wearing has been an important part of the response to the COVID-19 pandemic. As vaccination coverage progresses in countries, relaxation of such practices is increasing. Subsequent COVID-19 surges have raised the questions of whether face masks should be encouraged or required and for how long. Here, we aim to assess the value of maintaining face masks use indoors according to different COVID-19 vaccination coverage levels in the USA. METHODS: In this computational simulation-model study, we developed and used a Monte Carlo simulation model representing the US population and SARS-CoV-2 spread. Simulation experiments compared what would happen if face masks were used versus not used until given final vaccination coverages were achieved. Different scenarios varied the target vaccination coverage (70-90%), the date these coverages were achieved (Jan 1, 2022, to July 1, 2022), and the date the population discontinued wearing face masks. FINDINGS: Simulation experiments revealed that maintaining face mask use (at the coverage seen in the USA from March, 2020, to July, 2020) until target vaccination coverages were achieved was cost-effective and in many cases cost saving from both the societal and third-party payer perspectives across nearly all scenarios explored. Face mask use was estimated to be cost-effective and usually cost saving when the cost of face masks per person per day was ≤US$1·25. In all scenarios, it was estimated to be cost-effective to maintain face mask use for about 2-10 weeks beyond the date that target vaccination coverage (70-90%) was achieved, with this added duration being longer when the target coverage was achieved during winter versus summer. Factors that might increase the transmissibility of the virus (eg, emergence of the delta [B.1.617.2] and omicron [B.1.1.529] variants), or decrease vaccine effectiveness (eg, waning immunity or escape variants), or increase social interactions among certain segments of the population, only increased the cost savings or cost-effectiveness provided by maintaining face mask use. INTERPRETATION: Our study provides strong support for maintaining face mask use until and a short time after achieving various final vaccination coverage levels, given that maintaining face mask use can be not just cost-effective, but even cost saving. The emergence of the omicron variant and the prospect of future variants that might be more transmissible and reduce vaccine effectiveness only increases the value of face masks. FUNDING: The Agency for Healthcare Research and Quality, the National Institute of General Medical Sciences, the National Science Foundation, the National Center for Advancing Translational Sciences, and the City University of New York.

The actin nucleator Spir-1 is a virus restriction factor that promotes innate immune signalling.

Cellular proteins often have multiple and diverse functions. This is illustrated with protein Spir-1 that is an actin nucleator, but, as shown here, also functions to enhance innate immune signalling downstream of RNA sensing by RIG-I/MDA-5. In human and mouse cells lacking Spir-1, IRF3 and NF-κB-dependent gene activation is impaired, whereas Spir-1 overexpression enhanced IRF3 activation. Furthermore, the infectious virus titres and sizes of plaques formed by two viruses that are sensed by RIG-I, vaccinia virus (VACV) and Zika virus, are increased in Spir-1 KO cells. These observations demonstrate the biological importance of Spir-1 in the response to virus infection. Like cellular proteins, viral proteins also have multiple and diverse functions. Here, we also show that VACV virulence factor K7 binds directly to Spir-1 and that a diphenylalanine motif of Spir-1 is needed for this interaction and for Spir-1-mediated enhancement of IRF3 activation. Thus, Spir-1 is a new virus restriction factor and is targeted directly by an immunomodulatory viral protein that enhances virus virulence and diminishes the host antiviral responses.

Trends in COVID-19 vaccination intent and factors associated with deliberation and reluctance among adult homeless shelter residents and staff, 1 November 2020 to 28 February 2021 - King County, Washington.

INTRODUCTION: Little is known about COVID-19 vaccination intent among people experiencing homelessness. This study assesses surveyed COVID-19 vaccination intent among adult homeless shelter residents and staff and identifies factors associated with vaccine deliberation (responded "undecided") and reluctance (responded "no"), including time trends. METHODS: From 11/1/2020-2/28/21, we conducted repeated cross-sectional surveys at nine shelters in King County, WA as part of ongoing community-based SARS-CoV-2 surveillance. We used a multinomial model to identify characteristics associated with vaccine deliberation and reluctance. RESULTS: A total of 969 unique staff (n = 297) and residents (n = 672) participated and provided 3966 survey responses. Among residents, 53.7% (n = 361) were vaccine accepting, 28.1% reluctant, 17.6% deliberative, and 0.6% already vaccinated, whereas among staff 56.2% were vaccine accepting, 14.1% were reluctant, 16.5% were deliberative, and 13.1% already vaccinated at their last survey. We observed higher odds of vaccine deliberation or reluctance among Black/African American individuals, those who did not receive a seasonal influenza vaccine, and those with lower educational attainment. There was no significant trend towards vaccine acceptance. CONCLUSIONS: Strong disparities in vaccine intent based on race, education, and prior vaccine history were observed. Increased vaccine intent over the study period was not detected. An intersectional, person-centered approach to addressing health inequities by public health authorities planning vaccination campaigns in shelters is recommended. Clinical Trial Registry Number: NCT04141917.

Should countries switch to using five- or ten-dose rotavirus vaccines now that they are available?

INTRODUCTION: Single-dose rotavirus vaccines, which are used by a majority of countries, are some of the largest-sized vaccines in immunization programs, and have been shown to constrain supply chains and cause bottlenecks. Efforts have been made to reduce the size of the single-dose vaccines; however, with two-dose, five-dose and ten-dose options available, the question then is whether using multi-dose instead of single-dose rotavirus vaccines will improve vaccine availability. METHODS: We used HERMES-generated simulation models of the vaccine supply chains of the Republic of Benin, Mozambique, and Bihar, a state in India, to evaluate the operational and economic impact of implementing each of the nine different rotavirus vaccine presentations. RESULTS: Among single-dose rotavirus vaccines, using Rotarix RV1 MMP (multi-monodose presentation) led to the highest rotavirus vaccine availability (49-80%) and total vaccine availability (56-79%), and decreased total costs per dose administered ($0.02-$0.10) compared to using any other single-dose rotavirus vaccine. Using two-dose ROTASIIL decreased rotavirus vaccine availability by 3-6% across each supply chain compared to Rotarix RV1 MMP, the smallest single-dose vaccine. Using a five-dose rotavirus vaccine improved rotavirus vaccine availability (52-92%) and total vaccine availability (60-85%) compared to single-dose and two-dose vaccines. Further, using the ten-dose vaccine led to the highest rotavirus vaccine availability compared to all other rotavirus vaccines in both Benin and Bihar. CONCLUSION: Our results show that countries that implement five-dose or ten-dose rotavirus vaccines consistently reduce cold chain constraints and achieve higher rotavirus and total vaccine availability compared to using either single-dose or two-dose rotavirus vaccines.