HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.

CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies.

A Bifunctional Spray Coating Reduces Contamination on Surfaces by Repelling and Killing Pathogens.

Surface-mediated transmission of pathogens is a major concern with regard to the spread of infectious diseases. Current pathogen prevention methods on surfaces rely on the use of biocides, which aggravate the emergence of antimicrobial resistance and pose harmful health effects. In response, a bifunctional and substrate-independent spray coating is presented herein. The bifunctional coating relies on wrinkled polydimethylsiloxane microparticles, decorated with biocidal gold nanoparticles to induce a "repel and kill" effect against pathogens. Pathogen repellency is provided by the structural hierarchy of the microparticles and their surface chemistry, whereas the kill mechanism is achieved using functionalized gold nanoparticles embedded on the microparticles. Bacterial tests with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa reveal a 99.9% reduction in bacterial load on spray-coated surfaces, while antiviral tests with Phi6─a bacterial virus often used as a surrogate to SARS-CoV-2─demonstrate a 98% reduction in virus load on coated surfaces. The newly developed spray coating is versatile, easily applicable to various surfaces, and effective against various pathogens, making it suitable for reducing surface contamination in frequently touched, heavy traffic, and high-risk surfaces.

Determinants of social distancing adherence.

Introduction: Governments and public health authorities across many jurisdictions implemented social (physical) distancing measures to contain the spread of the 2019 novel coronavirus disease (COVID-19). Adherence to these measures is variable and likely influenced by various factors. This study aimed to 1) identify the individual sociodemographic, COVID-19 and social distancing related, and psychological determinants of social distancing adherence, and 2) explore regional differences in social distancing adherence in the United States (U.S.) and English-speaking Canada based on each region's discrepant response to social distancing restrictions. Methods: A web-based repeated cross-sectional survey was conducted in 4,942 English-speaking participants from the four most populous U.S. states, specifically New York, California, Texas, and Florida, and Canada (www.covid19-database.com). The study was conducted at two timepoints, from May 1 to 5, 2020 (n = 1,019, Canadian participants only) and from July 6 to 10, 2020 (n = 3,923). Separate univariate models were computed for individual sociodemographic, COVID-19 and social distancing related, and psychological determinants of social distancing adherence. To determine the total variance explained, a univariate analysis including all of the determinants was performed. Regional differences in social distancing were compared between the four U.S. states and Canada, and between the U.S. as a whole and Canada. Results: Adherence to social distancing was higher in May (mean = 4.4/5.0±0.7) compared to July (mean = 4.3/5.0±0.7) [t (4940) = 6.96, p < 0.001], likely a reflection of relaxing restrictions. There were no regional differences in adherence. Sociodemographic, COVID-19 and social distancing related, and psychological determinants explained 10, 36, and 23% of the variance of social distancing adherence, respectively. Higher perceived seriousness of COVID-19 [ß (SE) = 0.39 (0.01), p < 0.001, partial η2 = 0.22], lower risk propensity [ß (SE) = -0.15 (0.01), p < 0.001, partial η2 = 0.06], germ aversion [ß (SE) = 0.12 (0.01), p < 0.001, partial η2 = 0.03], age [ß (SE) = 0.01 (0.00), p < 0.001, partial η2 = 0.02], and greater social support [ß (SE) = 0.03 (0.00), p < 0.001, partial η2 = 0.02] had the largest effects on social distancing adherence. Conclusion: Public service initiatives to emphasize the serious consequences of infection and targeted interventions toward certain sociodemographic groups, such as younger adults and vulnerable individuals in greater need of social support, may help enhance the public's adherence to social distancing measures during subsequent waves of COVID-19 and future pandemics.

Determinants of social distancing adherence

Introduction Governments and public health authorities across many jurisdictions implemented social (physical) distancing measures to contain the spread of the 2019 novel coronavirus disease (COVID-19). Adherence to these measures is variable and likely influenced by various factors. This study aimed to 1) identify the individual sociodemographic, COVID-19 and social distancing related, and psychological determinants of social distancing adherence, and 2) explore regional differences in social distancing adherence in the United States (U.S.) and English-speaking Canada based on each region's discrepant response to social distancing restrictions. Methods A web-based repeated cross-sectional survey was conducted in 4,942 English-speaking participants from the four most populous U.S. states, specifically New York, California, Texas, and Florida, and Canada (www.covid19-database.com). The study was conducted at two timepoints, from May 1 to 5, 2020 (n = 1,019, Canadian participants only) and from July 6 to 10, 2020 (n = 3,923). Separate univariate models were computed for individual sociodemographic, COVID-19 and social distancing related, and psychological determinants of social distancing adherence. To determine the total variance explained, a univariate analysis including all of the determinants was performed. Regional differences in social distancing were compared between the four U.S. states and Canada, and between the U.S. as a whole and Canada. Results Adherence to social distancing was higher in May (mean = 4.4/5.0±0.7) compared to July (mean = 4.3/5.0±0.7) [t(4940) = 6.96, p < 0.001], likely a reflection of relaxing restrictions. There were no regional differences in adherence. Sociodemographic, COVID-19 and social distancing related, and psychological determinants explained 10, 36, and 23% of the variance of social distancing adherence, respectively. Higher perceived seriousness of COVID-19 [β (SE) = 0.39 (0.01), p < 0.001, partial η2 = 0.22], lower risk propensity [β (SE) = −0.15 (0.01), p < 0.001, partial η2 = 0.06], germ aversion [β (SE) = 0.12 (0.01), p < 0.001, partial η2 = 0.03], age [β (SE) = 0.01 (0.00), p < 0.001, partial η2 = 0.02], and greater social support [β (SE) = 0.03 (0.00), p < 0.001, partial η2 = 0.02] had the largest effects on social distancing adherence. Conclusion Public service initiatives to emphasize the serious consequences of infection and targeted interventions toward certain sociodemographic groups, such as younger adults and vulnerable individuals in greater need of social support, may help enhance the public's adherence to social distancing measures during subsequent waves of COVID-19 and future pandemics.

COVID-19 behavior determinants dataset.

The COVID-19 Behavior Determinants Database (http://covid19-database.com) is a research project that examined the sociodemographic and psychological determinants of COVID-19 related attitudes and behaviors. It is a comprehensive web-based survey that was administered to adults ages 18 or older (total n=8070) from the United States of America (n = 5326), including the four most populous states, specifically New York, California, Florida, and Texas, and Canada (n = 2744), including all provinces, except Quebec. The survey was collected at three timepoints, May 2020 (n=1019), July 2020 (n=4027), and March 2021 (n=3024). Participants provided detailed sociodemographic information and completed a battery of psychological assessments. Participants also provided information about prior testing for COVID-19 and perceived seriousness of COVID-19 and the need for current physical (social) distancing restrictions. The database is helpful to researchers and public health policy decision-makers who are interested in investigating and identifying the determinants of COVID-19 related attitudes and behaviors in North America.

Protocol for a systematic review of interventions targeting mental health, cognition or psychological well-being among individuals with long COVID.

INTRODUCTION: For some people, COVID-19 infection leads to negative health impacts that can last into the medium or long term. The long-term sequelae of COVID-19 infection, or 'long COVID', negatively affects not only physical health, but also mental health, cognition or psychological well-being. Complex, integrated interventions are recommended for long COVID, including psychological components; however, the effectiveness of such interventions has yet to be critically evaluated. This protocol describes a systematic review to be conducted of scientific literature reporting on clinical trials of interventions to promote mental health, cognition or psychological well-being among individuals with long COVID. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A health sciences librarian will identify the relevant literature through comprehensive systematic searches of Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, medRxiv, PsyArXiv, China National Knowledge Internet and WANFANG Data databases, as well as The Cochrane Central Register of Controlled Trials, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Studies will be selected through a title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data extracted will include intervention descriptions and efficacy metrics. Data will be narratively synthesised; if the data allow, a meta-analysis will be conducted. Risk of bias assessment will be conducted using the Cochrane Risk of Bias 2.0 tool. ETHICS AND DISSEMINATION: Ethical approval for systematic reviews is not required. As researchers and clinicians respond to the new clinical entity that long COVID represents, this review will synthesise a rapidly emerging evidence base describing and testing interventions to promote mental health, cognition or psychological well-being. Results will therefore be disseminated through an open-access peer-reviewed publication and conference presentations to inform research and clinical practice. PROSPERO REGISTRATION NUMBER: CRD42022318678.

Epidemiology of Antibiotic Use and Drivers of Cross-Border Procurement in a Mexican American Border Community.

Background: The U.S.-Mexico Border is an area of opportunity for improved health care access; however, gaps remain as to how and where U.S. border residents, particularly those who are underinsured, obtain care. Antibiotics are one of the most common reported drivers of cross-border healthcare access and a medication of particular concern since indiscriminate or inappropriate use is associated with antimicrobial resistance. In addition, many studies assessing preferences for Mexican pharmaceuticals and healthcare in U.S. border residents were done prior to 2010 when many prescription medications, including antibiotics, were available over the counter in Mexico. Methods: Data used in this study were collected during the baseline examination of an ongoing longitudinal cohort study in Starr Country, Texas, one of 14 counties on the Texas-Mexico border. Participants self-reported the name, date of use, and the source country of each antibiotic used in the past 12 months. Logistic regression was used to determine social, cultural, and clinical features associated with cross-border procurement of antibiotics. Results: Over 10% of the study cohort reported using antibiotics in the past 30 days with over 60% of all rounds used in the past 12 months sourced from Mexico. A lack of health insurance and generation score, a measure of acculturation, were the strongest predictors of cross-border procurement of antibiotics. Conclusions: Factors previously associated with cross-border acquisition of antibiotics are still present despite changes in 2010 to prescription drug regulations in Mexico. These results may be used to inform future public health initiatives to provide culturally sensitive education about responsible antibiotic stewardship and to address barriers to U.S. healthcare and pharmaceutical access in medically underserved, impoverished U.S.-Mexico border communities.

Commentary: Mindfulness Interventions for the Black Community

In 2020, the American Psychological Association reported that the triple pandemic of COVID-19, the economic crises, and the racism pandemic have been especially damaging for the Black community (American Psychological Association, 2020;Shullman, 2020). Malone and Hargons' (2021) case study reflects an awareness of intersectional identities that align with some of the key leaders in the Black Lives Matter Movement (Black Lives Matter, 2021). Author Note Correspondence concerning this article should be addressed to Eric M. Brown, Counseling and Special Education Dept., DePaul University, 2247 N. Halstead, Chicago, IL, 60614 Email: eric.brown@depaul.edu Author Eric M. Brown (PhD in Counselor Education and Supervision, Old Dominion University) is a licensed professional counselor in Illinois and an Assistant Professor in the Counseling program at DePaul University.

Vaccine Hesitancy Is a Barrier to Achieving Equitable Herd Immunity Among Racial Minorities

Introduction: Racial minority groups have been disproportionately affected by the 2019 novel coronavirus disease (COVID-19). Vaccine hesitancy may be a major barrier to achieving equitable herd immunity and must be addressed to reduce the excess morbidity and mortality of COVID-19 in disproportionately affected communities. This study aimed to determine if COVID-19 vaccine hesitancy, and its factors vaccine complacency and confidence, are more prominent among disproportionately affected racial minority groups. Methods:We collected data from participants aged 18 years or older from the four most populous U.S. states, including New York, California, Florida, and Texas, and Canada. Data were collected using a web-based survey platform. Data are available at http://www.covid19-database.com. Results:Data from 4,434 participants were included [mean (SD) age = 48.7 (17.2) and 50.4% women]. Vaccine hesitancy was higher in Black, Indigenous (Native American and Indigenous People of Canada, including First Nations, Inuit and Métis), and Latinx compared to White participants, while no difference was found between East Asian and White participants. The group differences in vaccine hesitancy for Indigenous and Black compared to White participants remained after controlling for sociodemographic factors. Determinants of vaccine complacency were equivalent between disproportionately affected racial groups and white participants. Vaccine confidence (i.e., trust in vaccine benefit) was generally lower in all racial groups compared to White participants. Differences in vaccine mistrust comparing Black and East Asian to White participants remained after controlling for sociodemographic factors. Discussion:Disproportionately affected racial minorities may have higher vaccine hesitancy and lower confidence in COVID-19 vaccines. Public health and other relevant government services should address vaccine hesitancy among racial minorities using a culturally sensitive, community-centered approach to attain equitable herd immunity.

Individual determinants of COVID-19 vaccine hesitancy.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) vaccine hesitancy is a barrier to achieving herd immunity, and thus, a prominent public health concern. This study aimed to identify the determinants of COVID-19 vaccine hesitancy based on the World Health Organization's '3Cs' model (i.e., confidence, complacency, and convenience) in the United States (U.S.) and Canada. METHODS: Data from 7678 adults ages 18 or older were collected from the four most populous U.S. States, specifically New York, California, Florida, and Texas, and from English-speaking Canada at three timepoints, in May and July 2020, and March 2021 using a web-based survey (www.covid19-database.com). Sociodemographic information was collected, and comprehensive psychological assessments were administered. Univariate analyses were performed to identify the individual determinants of vaccine hesitancy, which were categorized as: 1) vaccine confidence, 2) vaccine complacency, 3) sociodemographic, and 4) other psychological factors. A series of models were computed using these categorizations. RESULTS: Mistrust of vaccine benefit (ß(SE) = 0.67(0.01), p<0.001, partial η2 = 0.26) and lower perceived seriousness of COVID-19 (ß(SE) = 0.68(0.02), p<0.001, partial η2 = 0.12) were the principal determinants of vaccine hesitancy. Right-wing political affiliation (ß(SE) = 0.32(0.02), p<0.001, partial η2 = 0.03), higher risk propensity (ß(SE) = 0.24(0.02), p<0.001, partial η2 = 0.03), and less negative mental health effects of the COVID-19 pandemic (ß(SE) = 0.20(0.01), p<0.001, partial η2 = 0.03) were the main sociodemographic and psychological determinants. Other sociodemographic determinants included younger age, women, race, and employment status. Lack of vaccine confidence and complacency explained 38% and 21% of the variance in vaccine hesitancy, respectively; whereas, sociodemographic and psychological determinants explained 13% and 11% of the variance in vaccine hesitancy, respectively. DISCUSSION: Targeted and tailored public health interventions that enhance the public's confidence in vaccines and emphasize the risk and seriousness of COVID-19 may address COVID-19 vaccine hesitancy. Efforts directed toward specific marginalized and underserved groups may be required to promote vaccine confidence.

Development and Implementation of Businesses That Care in Zacatecas, Mexico.

As part of the Global Smart Drinking Goals campaign launched in 2018 in 6 "City Pilots" around the world, the Businesses That Care (BTC; Empresas Que se Cuidan in Spanish) prevention system was developed and implemented in Zacatecas, Mexico. BTC is a private business sector adaptation of the Communities That Care prevention system. BTC is designed to address underage alcohol use through a combination of a company-led prevention system, an adapted family-based prevention program with parents employed at participating companies, and environmental prevention strategies for company employees. BTC was designed to be congruent with other health and safety efforts in the region (e.g., media campaign, road safety, and school prevention efforts). This study presents the feasibility and adoption of the BTC system in Zacatecas. Process implementation measures indicated successful participant recruitment, retention, and adherence to intervention protocols. The first 4 stages of BTC implementation were completed within 14 months, with Stage 5 being interrupted by the COVID-19 pandemic. BTC Prevention Committee members, made up of employees from BTC participating companies, received 9 out of 10 BTC trainings/workshops during this time. Results provide evidence of the acceptability and feasibility for private companies to implement a prevention system approach for reducing youth alcohol use.

An assessment of outpatient clinic room ventilation systems and possible relationship to disease transmission.

BACKGROUND: With healthcare shifting to the outpatient setting, this study examined whether outpatient clinics operating in business occupancy settings were conducting procedures in rooms with ventilation rates above, at, or below thresholds defined in the American National Standards Institute/American Society of Heating, Refrigerating and Air-Conditioning Engineers/American Society for Health Care Engineering Standard 170 for Ventilation in Health Care Facilities and whether lower ventilation rates and building characteristics increase the risk of disease transmission. METHODS: Ventilation rates were measured in 105 outpatient clinic rooms categorized by services rendered. Building characteristics were evaluated as determinants of ventilation rates, and risk of disease transmission was estimated using the Gammaitoni-Nucci model. RESULTS: When compared to Standard 170, 10% of clinic rooms assessed did not meet the minimum requirement for general exam rooms, 39% did not meet the requirement for treatment rooms, 83% did not meet the requirement for aerosol-generating procedures, and 88% did not meet the requirement for procedure rooms or minor surgical procedures. CONCLUSIONS: Lower than standard air changes per hour were observed and could lead to an increased risk of spread of diseases when conducting advanced procedures and evaluating persons of interest for emerging infectious diseases. These findings are pertinent during the SARS-CoV-2 pandemic, as working guidelines are established for the healthcare community.

Analysis of the Impact of the COVID-19 Pandemic on the Multidisciplinary Management of Breast Cancer: Review from the American Society of Breast Surgeons COVID-19 and Mastery Registries.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in rapid and regionally different approaches to breast cancer care. METHODS: In order to evaluate these changes, a COVID-19-specific registry was developed within the American Society of Breast Surgeons (ASBrS) Mastery that tracked whether decisions were usual or modified for COVID-19. Data on patient care entered into the COVID-19-specific registry and the ASBrS Mastery registry from 1 March 2020 to 15 March 2021 were reviewed. RESULTS: Overall, 177 surgeons entered demographic and treatment data on 2791 patients. Mean patient age was 62.7 years and 9.0% (252) were of African American race. Initial consultation occurred via telehealth in 6.2% (173) of patients and 1.4% (40) developed COVID-19. Mean invasive tumor size was 2.1 cm and 17.8% (411) were node-positive. In estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) disease, neoadjuvant endocrine therapy (NET) was used as the usual approach in 6.9% (119) of patients and due to COVID-19 in an additional 31% (542) of patients. Patients were more likely to receive NET due to COVID-19 with increasing age and if they lived in the Northeast or Southeast (odds ratio [OR] 1.1, 2.3, and 1.7, respectively; p < 0.05). Genomic testing was performed on 51.5% (781) of estrogen-positive patients, of whom 20.7% (162) had testing on the core due to COVID-19. Patients were less likely to have core biopsy genomic testing due to COVID-19 if they were older (OR 0.89; p = 0.01) and more likely if they were node-positive (OR 4.0; p < 0.05). A change in surgical approach due to COVID-19 was reported for 5.4% (151) of patients. CONCLUSION: The ASBrS COVID-19 registry provided a platform for monitoring treatment changes due to the pandemic, highlighting the increased use of NET.

Universal masking to control healthcare-associated transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

OBJECTIVES: To assess extent of a healthcare-associated outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and to evaluate the effectiveness of infection control measures, including universal masking. DESIGN: Outbreak investigation including 4 large-scale point-prevalence surveys. SETTING: Integrated VA healthcare system with 2 facilities and 330 beds. PARTICIPANTS: Index patient and 250 exposed patients and staff. METHODS: We identified exposed patients and staff and classified them as probable and confirmed cases based on symptoms and testing. We performed a field investigation and an assessment of patient and staff interactions to develop probable transmission routes. Infection prevention interventions included droplet and contact precautions, employee quarantine, and universal masking with medical and cloth face masks. We conducted 4 point-prevalence surveys of patient and staff subsets using real-time reverse-transcriptase polymerase chain reaction for SARS-CoV-2. RESULTS: Among 250 potentially exposed patients and staff, 14 confirmed cases of coronavirus disease 2019 (COVID-19) were identified. Patient roommates and staff with prolonged patient contact were most likely to be infected. The last potential date of transmission from staff to patient was day 22, the day universal masking was implemented. Subsequent point-prevalence surveys in 126 patients and 234 staff identified 0 patient cases and 5 staff cases of COVID-19, without evidence of healthcare-associated transmission. CONCLUSIONS: Universal masking with medical face masks was effective in preventing further spread of SARS-CoV-2 in our facility in conjunction with other traditional infection prevention measures.

B cell genomics behind cross-neutralization of SARS-CoV-2 variants and SARS-CoV.

Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.

N95 respirator reuse, decontamination methods, and microbial burden: A randomized controlled trial.

PURPOSE: To evaluate the effectiveness and ease of N95 respirator decontamination methods in a clinic setting and to identify the extent of microbial colonization on respirators associated with reuse. METHODS: In a prospective fashion, N95 respirators (n = 15) were randomized to a decontamination process (time, dry heat, or ultraviolet C light [UVC]) in outpatient clinics. Each respirator was re-used up to 5 separate clinic sessions. Swabs on each respirator for SARS-CoV-2, bacteria, and fungi were obtained before clinic, after clinic and post-treatment. Mask integrity was checked after each treatment (n = 68). Statistical analyses were performed to determine factors for positive samples. RESULTS: All three decontamination processes reduced bacteria counts similarly. On multivariate mixed model analysis, there were an additional 8.1 colonies of bacteria (95% CI 5.7 to 10.5; p < 0.01) on the inside compared to the outside surface of the respirators. Treatment resulted in a decrease of bacterial load by 8.6 colonies (95% CI -11.6 to -5.5; p < 0.01). Although no decontamination treatment affected the respirator filtration efficiency, heat treatments were associated with the breakdown of thermoplastic elastomer straps. Contamination with fungal and SARS-CoV-2 viral particles were minimal to non-existent. CONCLUSIONS: Time, heat and UVC all reduced bacterial load on reused N95 respirators. Fungal contamination was minimal. Heat could permanently damage some elastic straps making the respirators nonfunctional. Given its effectiveness against microbes, lack of damage to re-treated respirators and logistical ease, UVC represents an optimal decontamination method for individual N95 respirators when reuse is necessary.