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Play encourages physical and social activity creativity, and risk-taking. However, unstructured and risky play is on the decline. Our qualitative study explored the perspectives of Play Ambassadors, who facilitated a community-based loose parts play intervention ('play hubs') in Calgary parks during the COVID-19 pandemic. Using semi-structured interviews with 12 Play Ambassadors, four main topics emerged. "Experiences Supporting Unstructured Play" reflected how they supported play and their perceptions and observations of the play hubs. "Learning to Take Risks in Play" reflected how Play Ambassadors' views on risk and facilitating risky play evolved. "Value of the Play Hubs" reflected Play Ambassador perspectives on the community and personal impacts of the play hubs. "Supporting Play during a Pandemic" highlighted the challenges encountered in delivering the play hubs. Our findings suggest that community-based play programs in local parks may be a viable strategy for encouraging play, especially when traditional opportunities are restricted. more...

At a time of transition into adulthood, tertiary study places additional stresses on the mental wellbeing of students. The continual assessment, long teaching hours, and expectation of professionalism that is expected from students within clinical programmes places even more burden on these students. Then in 2020, with the COVID-19 lockdown, there were significant changes to how these programs were delivered. We surveyed the mental wellbeing of our undergraduate students in the Bachelor of Optometry and Bachelor of Pharmacy programmes at the University of Auckland in 2019 and 2020. Using validated screening questionnaires, we found a high level of anxiety and depression in both years, however, in 2020 following the lockdown, anxiety levels in our students decreased. We found that the leading stressor was academic stress, and levels of anxiety were inversely correlated with perceived academic success. Therefore, we believe the lockdown, which provided both a break from clinical stresses and a change in teaching modality to online delivery, provided a period of relief, despite the potential stressful environment regarding COVID-19. To help alleviate the high level of distress in our students, lessons could be learned to decrease the stress levels in our students by continuing with alternative teaching and assessment styles. more...

The need to virtually collaborate across distributed locations has drastically increased. Developments such as the COVID-19 pandemic and new IT platforms like the metaverse have spurred a host of new immersive social applications that are accessed through head-mounted displays. This is expected to stimulate a surge in research on extended reality-supported collaborative learning (XRCL) which refers to distributed collaboration situations where immersive technology such as head-mounted displays are used as a medium for collaborative learning. The primary aim of this article is to critically examine the potential pedagogical benefits and limitations of using XRCL with the objective of developing a theoretical framework that describes the fundamental factors that make immersive collaborative learning unique: the theory of immersive collaborative learning (TICOL). In TICOL, we propose that technological features, social affordances, and pedagogical techniques can foster four psychological factors that we define as fundamentally different in XRCL compared to collaboration that occurs through traditional systems (e.g., laptops): social presence, physical presence, body ownership, and agency. These are central factors that we hypothesize can transform the processes and contexts of collaboration through their influence on the quality of cognitive and socio-emotional social interaction, the social space, and ultimately learning outcomes. Since XRCL research is in its infancy, we hope that TICOL can provide a theoretical basis for developing the field by motivating researchers to empirically challenge and build on our hypotheses and ultimately develop a deeper understanding of if and how immersive media influences collaborative learning. more...

Leaders in higher education regularly find themselves at the intersection of change, torn between their institution's history and culture, the intrinsic value of education, market needs, and the desires of alumni, current, and prospective students. Higher education is often labeled reluctant to change, and many believe any change initiative not aligned with the institution's culture is almost certain to fail. This study provides evidence that leaders in higher education can implement change that is incongruent with organizational culture while maintaining harmony among the institution's ideals and constituents. University X, a medium-sized, highly regarded public institution located in a rural area, implemented its first fully online degree program, which was widely perceived as being incongruent with the organization's culture. A detailed analysis of eight environmental factors and an adaptation of Kotter's (1996) eight-step change model contributed to the overall success of this change. The keys to implementation were developing an in-depth understanding of the culture while ensuring there was both a need for change and adequate support among stakeholders. Developing a group to champion and sustain the initiative was also critical. The common thread throughout the entire change process was the frequent and effective communication maintained by the organizational leaders. The culture shift initiated by the change also allowed the institution to move quickly to transition to alternative teaching methods during the COVID-19 pandemic of 2020. more...

Background: Phase angle (PhA) obtained by bioelectrical impedance analysis (BIA) works as a predictor of clinical outcomes. Specific cutoff values for longitudinal changes and their relationship with clinical outcomes are still undetermined for patients with critical illness. Thus, the aim of this study was to analyze the association between longitudinal changes in PhA during intensive care unit (ICU) stay and all-cause 90-day mortality in patients critically ill with COVID-19., Methods: This was a retrospective cohort study of adults critically ill with COVID-19 undergoing invasive mechanical ventilation with a length of stay >14 days. BIA was performed at ICU admission and at days 7 and 14 of ICU stay; PhA and hydration parameters were collected. Differences between survivors and nonsurvivors were assessed. Longitudinal changes were evaluated using repeated-measures analysis of variance. A receiver operating characteristics curve for PhA declined (%) during the first 14 days, and all-cause 90-day mortality was performed. Survival probability was reported using hazard ratios (HR)., Results: One-hundred nine patients were included. The change in the value of PhA was close to 17.1%. Nonsurvivors had a higher prevalence of individuals with a decrease in PhA >22.2% (area under the curve = 0.65) in the first 14 days in comparison with survivors (70% vs 34.8%, P < 0.01). PhA decrease >22.2% at 14 days was a significant predictor of all-cause 90-day mortality (HR = 2.2, 95% CI 1.71-3.6, P = 0.04)., Conclusion: Changes in PhA are associated with all-cause 90-day mortality. Future studies should be directed to interventions to prevent changes in this nutrition marker., (© 2024 American Society for Parenteral and Enteral Nutrition.) more...

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1-4. Despite the clinical evidence1,5-7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8-10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID. more...

Polymerase chain reaction (PCR) requires thermal cycling and enzymatic reactions for sequence amplification, hampering their applications in point-of-care (POC) settings. Magnetic bioassays based on magnetic particle spectroscopy (MPS) and magnetic nanoparticles (MNPs) are isothermal, wash-free, and can be quantitative. Realizing them amplification- and enzyme-free on a benchtop device, they will become irreplaceable for POC applications. Here we demonstrate a first-in-class magnetic signal amplification circuit (MAC) that enables detection of whole genome of SARS-CoV-2 by combining the specificity of toehold-mediated DNA strand displacement with the magnetic response of MNPs to declustering processes. Using MAC, we detect the N gene of SARS-CoV-2 samples at a concentration of 10 4 RNA copies/μl as determined by droplet digital PCR. Further, we demonstrate that MAC can reliably distinguish between SARS-CoV-2 and other human coronaviruses. Being a wash-, amplification- and enzyme-free biosensing concept and working at isothermal conditions (25 °C) on a low-cost benchtop MPS device, our MAC biosensing concept offers several indispensable features for translating nucleic acid detection to POC applications., (© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.) more...

The COVID-19 pandemic underscored the promise of monoclonal antibody-based prophylactic and therapeutic drugs1-3 and revealed how quickly viral escape can curtail effective options4,5. When the SARS-CoV-2 Omicron variant emerged in 2021, many antibody drug products lost potency, including Evusheld and its constituent, cilgavimab4-6. Cilgavimab, like its progenitor COV2-2130, is a class 3 antibody that is compatible with other antibodies in combination4 and is challenging to replace with existing approaches. Rapidly modifying such high-value antibodies to restore efficacy against emerging variants is a compelling mitigation strategy. We sought to redesign and renew the efficacy of COV2-2130 against Omicron BA.1 and BA.1.1 strains while maintaining efficacy against the dominant Delta variant. Here we show that our computationally redesigned antibody, 2130-1-0114-112, achieves this objective, simultaneously increases neutralization potency against Delta and subsequent variants of concern, and provides protection in vivo against the strains tested: WA1/2020, BA.1.1 and BA.5. Deep mutational scanning of tens of thousands of pseudovirus variants reveals that 2130-1-0114-112 improves broad potency without increasing escape liabilities. Our results suggest that computational approaches can optimize an antibody to target multiple escape variants, while simultaneously enriching potency. Our computational approach does not require experimental iterations or pre-existing binding data, thus enabling rapid response strategies to address escape variants or lessen escape vulnerabilities. more...

San Francisco implemented one of the most intensive, comprehensive, multipronged COVID-19 pandemic responses in the United States using 4 core strategies: (1) aggressive mitigation measures to protect populations at risk for severe disease, (2) prioritization of resources in neighborhoods highly affected by COVID-19, (3) timely and adaptive data-driven policy making, and (4) leveraging of partnerships and public trust. We collected data to describe programmatic and population-level outcomes. The excess all-cause mortality rate in 2020 in San Francisco was half that seen in 2019 in California as a whole (8% vs 16%). In almost all age and race and ethnicity groups, excess mortality from COVID-19 was lower in San Francisco than in California overall, with markedly diminished excess mortality among people aged >65 years. The COVID-19 response in San Francisco highlights crucial lessons, particularly the importance of community responsiveness, joint planning, and collective action, to inform future pandemic response and advance health equity. more...

ObjectivesTo identify incident SARS-CoV-2 infections and inform effective mitigation strategies in university settings, we piloted an integrated symptom and exposure monitoring and testing system among a cohort of university students and employees.DesignProspective cohort study.SettingA public university in California from June to August 2020.Participants2180 university students and 738 university employees.Primary outcome measuresAt baseline and endline, we tested participants for active SARS-CoV-2 infection via quantitative PCR (qPCR) test and collected blood samples for antibody testing. Participants received notifications to complete additional qPCR tests throughout the study if they reported symptoms or exposures in daily surveys or were selected for surveillance testing. Viral whole genome sequencing was performed on positive qPCR samples, and phylogenetic trees were constructed with these genomes and external genomes.ResultsOver the study period, 57 students (2.6%) and 3 employees (0.4%) were diagnosed with SARS-CoV-2 infection via qPCR test. Phylogenetic analyses revealed that a super-spreader event among undergraduates in congregate housing accounted for at least 48% of cases among study participants but did not spread beyond campus. Test positivity was higher among participants who self-reported symptoms (incidence rate ratio (IRR) 12.7; 95% CI 7.4 to 21.8) or had household exposures (IRR 10.3; 95% CI 4.8 to 22.0) that triggered notifications to test. Most (91%) participants with newly identified antibodies at endline had been diagnosed with incident infection via qPCR test during the study.ConclusionsOur findings suggest that integrated monitoring systems can successfully identify and link at-risk students to SARS-CoV-2 testing. As the study took place before the evolution of highly transmissible variants and widespread availability of vaccines and rapid antigen tests, further research is necessary to adapt and evaluate similar systems in the present context. more...

COVID-19 oral treatments require initiation within 5 days of symptom onset. Although antigen tests are less sensitive than RT-PCR, rapid results could facilitate entry to treatment. We collected anterior nasal swabs for BinaxNOW and RT-PCR testing and clinical data at a walk-up, community site in San Francisco, California between January and June 2022. SARS-CoV-2 genomic sequences were generated from positive samples and classified according to subtype and variant. Monte Carlo simulations were conducted to estimate the expected proportion of SARS-CoV-2 infected persons who would have been diagnosed within 5 days of symptom onset using RT-PCR versus BinaxNOW testing. Among 25,309 persons tested with BinaxNOW, 2,799 had concomitant RT-PCR. 1137/2799 (40.6%) were SARS-CoV-2 RT-PCR positive. We identified waves of predominant omicron BA.1, BA.2, BA.2.12, BA.4, and BA.5 among 720 sequenced samples. Among 1,137 RT-PCR positive samples, 788/1137 (69%) were detected by BinaxNOW; 94% (669/711) of those with Ct value more...

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P more...

While SARS-CoV-2 vaccines prevent severe disease effectively, postvaccination "breakthrough" COVID-19 infections and transmission among vaccinated individuals remain ongoing concerns. We present an in-depth characterization of transmission and immunity among vaccinated individuals in a household, revealing complex dynamics and unappreciated comorbidities, including autoimmunity to type 1 interferon in the presumptive index case. more...

The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies. more...

BackgroundSARS-CoV-2 rapid antigen tests are an important public health tool.ObjectiveTo evaluate field performance of the BinaxNOW rapid antigen test (Abbott) compared with reverse transcriptase polymerase chain reaction (RT-PCR) for detecting infection with the Omicron variant of SARS-CoV-2.DesignCross-sectional surveillance study.SettingFree, walk-up, outdoor, urban community testing and vaccine site led by Unidos en Salud, serving a predominantly Latinx community highly impacted by COVID-19.ParticipantsPersons seeking COVID-19 testing in January 2022.MeasurementsSimultaneous BinaxNOW and RT-PCR from nasal, cheek, and throat swabs, including cycle threshold (Ct) measures; a lower Ct value is a surrogate for higher amounts of virus.ResultsAmong 731 persons tested with nasal swabs, there were 296 (40.5%) positive results on RT-PCR; 98.9% were the Omicron variant. BinaxNOW detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a Ct value below 30, 82.1% (CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (CI, 60% to 71%) of all who were positive on RT-PCR. Among 75 persons with simultaneous nasal and cheek swabs, BinaxNOW using a cheek swab failed to detect 91% (20 of 22) of specimens that were positive on BinaxNOW with a nasal swab. Among persons with simultaneous nasal and throat swabs who were positive on RT-PCR with a Ct value below 30, 42 of 49 (85.7%) were detected by nasal BinaxNOW, 23 of 49 (46.9%) by throat BinaxNOW, and 44 of 49 (89.8%) by either.LimitationParticipants were a cross-sectional sample from a community-based sentinel surveillance site, precluding study of viral or symptom dynamics.ConclusionBinaxNOW detected persons with high SARS-CoV-2 levels during the Omicron surge, enabling rapid responses to positive test results. Cheek or throat swabs should not replace nasal swabs. As currently recommended, high-risk persons with an initial negative BinaxNOW result should have repeated testing.Primary funding sourceUniversity of California, San Francisco. more...

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine-needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we evaluated the T cell receptor sequences and phenotype of lymph node TFH. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLA-DPB1∗04-restricted response to S167-180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine. more...

BackgroundSequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during 22 November to 1 December, 2020, and 10-29 January 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.ResultsA total of 12 124 tests were performed yielding 1099 positives. From these, 928 high-quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%).ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants. Summary: We observed a growing prevalence and modestly elevated attack rate for "West Coast" severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility. more...

BackgroundThe COVID-19 pandemic created challenges in clinical research operations that required immediate and lasting changes.OjbectivesThe purpose of this study was to explore adaptations to clinical trial research due to COVID-19 and develop a theoretical framework of emergent strategies related to pandemic mitigation in a national network of Alzheimer's disease clinical trial sites.DesignThis qualitative study used a grounded theory approach including semi-structured interviews, constant comparative methods, and multi-level, iterative coding.ParticipantsTwenty-six member sites of the Alzheimer's Clinical Trial Consortium participated with a total of 49 participants.ResultsFindings demonstrate processes of adaptation following COVID-19 onset including establishing safety as priority, focus on scientific preservation, accommodations (creating policies, leadership mindset, maintaining operations, and determining research procedures), and evaluation of changes throughout the course of the pandemic. Communication and maintaining integrity were vital throughout these processes.ConclusionProcesses of accommodation among clinical research sites during the pandemic provide critical insights and direction for future clinical trials development and emergent methods in Alzheimer's disease and other therapeutic areas. more...

ObjectiveTo evaluate implementation of a community-engaged approach to scale up COVID-19 mass testing in low-income, majority-Latino communities.MethodsIn January 2021, we formed a community-academic "Latino COVID-19 Collaborative" with residents, leaders, and community-based organizations (CBOs) from majority-Latinx, low-income communities in three California counties (Marin/Merced/San Francisco). The collaborative met monthly to discuss barriers/facilitators for COVID-19 testing, and plan mass testing events informed by San Francisco's Unidos en Salud "test and respond" model, offering community-based COVID-19 testing and post-test support in two US-census tracts: Canal (Marin) and Planada (Merced). We evaluated implementation using the RE-AIM framework. To further assess testing barriers, we surveyed a random sample of residents who did not attend the events.ResultsFifty-five residents and CBO staff participated in the Latino collaborative. Leading facilitators identified to increase testing were extended hours of community-based testing and financial support during isolation. In March-April 2021, 1,217 people attended mass-testing events over 13 days: COVID-19 positivity was 3% and 1% in Canal and Planada, respectively. The RE-AIM evaluation found: census tract testing coverage of 4.2% and 6.3%, respectively; 90% of event attendees were Latino, 89% had household income more...

IntroductionUntil vaccines became available in late 2020, our ability to prevent the spread of COVID-19 within countries depended largely on voluntary adherence to mitigation measures. However, individual decision-making regarding acceptable COVID-19 risk is complex. To better understand decision-making regarding COVID-19 risk, we conducted a qualitative substudy within a larger Berkeley COVID-19 Safe Campus Initiative (BCSCI) during the summer of 2020, and completed a mixed-methods analysis of factors influencing decision-making.Materials and methodsWe interviewed 20 participants who tested positive for SARS-CoV-2 and 10 who remained negative, and analyzed quantitative survey data from 3,324 BCSCI participants. The BCSCI study enrolled university-affiliated people living in the local area during summer of 2020, collected data on behaviors and attitudes toward COVID-19, and conducted SARS-CoV-2 testing at baseline and endline.ResultsAt baseline, 1362 students (57.5%) and 285 non-students (35.1%) said it had been somewhat or very difficult to comply with COVID-19-related mandates. Most-cited reasons were the need to go out for food/essentials, difficulty of being away from family/friends, and loneliness. Eight interviewees explicitly noted they made decisions partially because of others who may be at high risk. We did not find significant differences between the behaviors of students and non-students.DiscussionDespite prevailing attitudes about irresponsibility of college students during the COVID-19 pandemic, students in our study demonstrated a commitment to making rational choices about risk behavior, not unlike non-students around them. Decision-making was driven by perceived susceptibility to severe disease, need for social interaction, and concern about risk to others. A harm reduction public health approach may be beneficial. more...

The 3C protease (3C Pro) plays a significant role in the life cycle of picornaviruses from replication to translation, making it an attractive target for structure-based design of drugs against picornaviruses. The structurally related 3C-like protease (3CL Pro) is an important protein involved in the replication of coronaviruses. With the emergence of COVID-19 and consequent intensive research into 3CL Pro, development of 3CL Pro inhibitors has emerged as a popular topic. This article compares the similarities of the target pockets of various 3C and 3CL Pros from numerous pathogenic viruses. This article also reports several types of 3C Pro inhibitors that are currently undergoing extensive studies and introduces various structural modifications of 3C Pro inhibitors to provide a reference for the development of new and more effective inhibitors of 3C Pro and 3CL Pro., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.) more...

BackgroundMany persons with active SARS-CoV-2 infection experience mild or no symptoms, presenting barriers to COVID-19 prevention. Regular temperature screening is nonetheless used in some settings, including university campuses, to reduce transmission potential. We evaluated the potential impact of this strategy using a prospective university-affiliated cohort.MethodsBetween June and August 2020, 2912 participants were enrolled and tested for SARS-CoV-2 by PCR at least once (median: 3, range: 1-9). Participants reported temperature and symptoms daily via electronic survey using a previously owned or study-provided thermometer. We assessed feasibility and acceptability of daily temperature monitoring, calculated sensitivity and specificity of various fever-based strategies for restricting campus access to reduce transmission, and estimated the association between measured temperature and SARS-CoV-2 test positivity using a longitudinal binomial mixed model.ResultsMost participants (70.2%) did not initially have a thermometer for taking their temperature daily. Across 5481 total person months, the average daily completion rate of temperature values was 61.6% (median: 67.6%, IQR: 41.8-86.2%). Sensitivity for SARS-CoV-2 ranged from 0% (95% CI 0-9.7%) to 40.5% (95% CI 25.6-56.7%) across all strategies for self-report of possible COVID-19 symptoms on day of specimen collection, with corresponding specificity of 99.9% (95% CI 99.8-100%) to 95.3% (95% CI 94.7-95.9%). An increase of 0.1 °F in individual mean body temperature on the same day as specimen collection was associated with 1.11 increased odds of SARS-CoV-2 positivity (95% CI 1.06-1.17).ConclusionsOur study is the first, to our knowledge, that examines the feasibility, acceptability, and effectiveness of daily temperature screening in a prospective cohort during an infectious disease outbreak, and the only study to assess these strategies in a university population. Daily temperature monitoring was feasible and acceptable; however, the majority of potentially infectious individuals were not detected by temperature monitoring, suggesting that temperature screening is insufficient as a primary means of detection to reduce transmission of SARS-CoV-2. more...

Among 3302 persons tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by BinaxNOWTM and reverse transcription polymerase chain reaction (RT-PCR) in a community setting, rapid assay sensitivity was 100%/98.5%/89% using RT-PCR cycle thresholds of 30, 35, and no threshold. The specificity was 99.9%. Performance was high across ages and those with and without symptoms. Rapid resulting permitted immediate public health action. more...

Of 4133 persons surveyed at a low-barrier coronavirus disease 2019 (COVID-19) test site with high positivity in an urban Latinx community in January 2021, 86% indicated that they would accept a COVID-19 vaccination. The top reasons for vaccine hesitancy included concerns around side effects and safety and distrust of health care systems. more...

Of 4133 persons surveyed at a low-barrier coronavirus disease 2019 (COVID-19) test site with high positivity in an urban Latinx community in January 2021, 86% indicated that they would accept a COVID-19 vaccination. The top reasons for vaccine hesitancy included concerns around side effects and safety and distrust of health care systems. more...

BackgroundGlobally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients are often overlooked in health systems. Essential Emergency and Critical Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low cost and low complexity for the identification and treatment of critically ill patients across all medical specialties. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19.MethodsIn a Delphi process, consensus (>90% agreement) was sought from a diverse panel of global clinical experts. The panel iteratively rated proposed treatments and actions based on previous guidelines and the WHO/ICRC's Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent and feasible package of clinical processes plus a list of hospital readiness requirements.ResultsThe 269 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 requirements, plus additions specific for COVID-19.ConclusionThe study has specified the content of care that should be provided to all critically ill patients. Implementing EECC could be an effective strategy for policy makers to reduce preventable deaths worldwide. more...

ObjectiveGiven the variability in crisis standards of care (CSC) guidelines during the COVID-19 pandemic, we investigated the racial and ethnic differences in prioritization between 3 different CSC triage policies (New York, Massachusetts, USA), as well as a first come, first served (FCFS) approach, using a single patient population.MethodsWe performed a retrospective cohort study of patients with intensive care unit (ICU) needs at a tertiary hospital on its peak COVID-19 ICU census day. We used medical record data to calculate a CSC score under 3 criteria: New York, Massachusetts with full comorbidity list (Massachusetts1), and MA with a modified comorbidity list (Massachusetts2). The CSC scores, as well as FCFS, determined which patients were eligible to receive critical care under 2 scarcity scenarios: 50 versus 100 ICU bed capacity. We assessed the association between race/ethnicity and eligibility for critical care with logistic regression.ResultsOf 211 patients, 139 (66%) were male, 95 (45%) were Hispanic, 23 (11%) were non-Hispanic Black, and 69 (33%) were non-Hispanic White. Hispanic patients had the fewest comorbidities. Assuming a 50 ICU bed capacity, Hispanic patients had significantly higher odds of receiving critical care services across all CSC guidelines, except FCFS. However, assuming a 100 ICU bed capacity, Hispanic patients had greater odds of receiving critical care services under only the Massachusetts2 guidelines (odds ratio, 2.05; 95% CI, 1.09 to 3.85).ConclusionVarying CSC guidelines differentially affect racial and ethnic minority groups with regard to risk stratification. The equity implications of CSC guidelines require thorough investigation before CSC guidelines are implemented. more...

BackgroundThere is an urgent need to understand the dynamics and risk factors driving ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during shelter-in-place mandates.MethodsWe offered SARS-CoV-2 reverse-transcription polymerase chain reaction (PCR) and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (aged ≥4 years) and workers in a San Francisco census tract (population: 5174) at outdoor, community-mobilized events over 4 days. We estimated SARS-CoV-2 point prevalence (PCR positive) and cumulative incidence (antibody or PCR positive) in the census tract and evaluated risk factors for recent (PCR positive/antibody negative) vs prior infection (antibody positive/PCR negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions.ResultsWe tested 3953 persons (40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black). Overall, 2.1% (83/3871) tested PCR positive: 95% were Latinx and 52% were asymptomatic when tested; 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR positive. Among 2598 tract residents, estimated point prevalence of PCR positives was 2.3% (95% confidence interval [CI], 1.2%-3.8%): 3.9% (95% CI, 2.0%-6.4%) among Latinx persons vs 0.2% (95% CI, .0-.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95% CI, 4.0%-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter in place and maintain income, frontline service work, unemployment, and household income more...

We evaluated the performance of the Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured severe acute respiratory syndrome coronavirus 2 yielded a human observable threshold between 1.6 × 104-4.3 × 104 viral RNA copies (cycle threshold [Ct], 30.3-28.8). Among 878 subjects tested, 3% (26 of 878) were positive by reverse-transcription polymerase chain reaction, of whom 15 of 26 had a Ct more...

BackgroundRapid coronavirus disease 2019 (COVID-19) diagnosis and isolation of infectious persons are critical to stopping forward transmission, and the care cascade framework can identify gaps in the COVID-19 response.MethodsWe described a COVID-19 symptom to isolation cascade and barriers among symptomatic persons who tested polymerase chain reaction positive for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) at a low-barrier testing site serving a low-income Latinx community in San Francisco. Steps in the cascade are defined as days from symptom onset to test, test to result, and result to counseling on self-isolation. We examined SARS-CoV-2 cycle threshold (Ct) values to assess the likelihood of infectiousness on the day of testing and during missed isolation days.ResultsAmong 145 persons, 97% were Latinx and 81% had an income of more...

BackgroundColleges and universities across the country are struggling to develop strategies for effective control of COVID-19 transmission as students return to campus.Methods and findingsWe conducted a prospective cohort study with students living on or near the UC Berkeley campus from June 1st through August 18th, 2020 with the goal of providing guidance for campus reopening in the safest possible manner. In this cohort, we piloted an alternative testing model to provide access to low-barrier, high-touch testing and augment student-driven testing with data-driven adaptive surveillance that targets higher-risk students and triggers testing notifications based on reported symptoms, exposures, or other relevant information. A total of 2,180 students enrolled in the study, 51% of them undergraduates. Overall, 6,247 PCR tests were administered to 2,178 students over the two-month period. Overall test positivity rate was 0.9%; 2.6% of students tested positive. Uptake and acceptability of regular symptom and exposure surveys was high; 98% of students completed at least one survey, and average completion rate was 67% (Median: 74%, IQR: 39%) for daily reporting of symptoms and 68% (Median: 75%, IQR: 40%) for weekly reporting of exposures. Of symptom-triggered tests, 5% were PCR-positive; of exposure-triggered tests, 10% were PCR-positive. The integrated study database augmented traditional contact tracing during an outbreak; 17 potentially exposed students were contacted the following day and sent testing notifications. At study end, 81% of students selected their desire "to contribute to UC Berkeley's response to COVID-19" as a reason for their participation in the Safe Campus study.ConclusionsOur results illustrate the synergy created by bringing together a student-friendly, harm reduction approach to COVID-19 testing with an integrated data system and analytics. We recommend the use of a confidential, consequence-free, incentive-based daily symptom and exposure reporting system, coupled with low-barrier, easy access, no stigma testing. Testing should be implemented alongside a system that integrates multiple data sources to effectively trigger testing notifications to those at higher risk of infection and encourages students to come in for low-barrier testing when needed. more...

Purpose: To understand vaccine attitudes of Latinx parents highly impacted by COVID-19. Methods: In April 2021, we surveyed parents about their attitudes for COVID-19 vaccination of their children at a community-based outdoor testing/vaccination site serving predominantly low-income Latinx persons in San Francisco. Results: Among 1033 parents (75% Latinx), 92% would "definitely" or "probably" vaccinate their children. Vaccine concerns were higher for younger children and included side effects and impacts on fertility. Doctors and community organizations were noted as trusted sources of information, including among vaccine-concerned parents. Conclusion: Latinx parents accessing neighborhood-based COVID-19 testing/vaccination services are highly motivated to vaccinate their children for COVID-19. more...

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants' experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility. more...

BackgroundCOVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and "activation" components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage.MethodsOur community-academic-public health partnership, "Unidos en Salud," utilized a theory-informed approach to design our "Motivate, Vaccinate, and Activate" COVID-19 vaccination strategy. Our strategy's design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, "neighborhood" vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients ≥16 years old were used in the evaluation.ResultsThere were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32-56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew ≥3). Among clients who received both vaccine doses (n = 729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to ≥3) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence.ConclusionsA multi-component, "Motivate, Vaccinate, and Activate" community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated. more...

We have a new and unprecedented opportunity to mitigate the suffering, death and inequities of COVID-19 in the United States with vaccine boosters-if we deploy them effectively, rapidly, and widely with simplified messaging to all eligible adults. more...

Background: Different pathogens can cause community-acquired pneumonia (CAP); however, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has re-emphasized the vital role of respiratory viruses as a cause of CAP. The aim was to explore differences in metabolic profile, body composition, physical capacity, and inflammation between patients hospitalized with CAP caused by different etiology., Methods: A prospective study of Danish patients hospitalized with CAP caused by SARS-CoV-2, influenza, or bacteria. Fat (FM) and fat-free mass (FFM) were assessed with bioelectrical impedance analysis. Physical activity and capacity were assessed using questionnaires and handgrip strength. Plasma (p)-glucose, p-lipids, hemoglobin A1c (HbA1c), p-adiponectin, and cytokines were measured., Results: Among 164 patients with CAP, etiology did not affect admission levels of glucose, HbA1c, adiponectin, or lipids. Overall, 15.2% had known diabetes, 6.1% had undiagnosed diabetes, 51.3% had pre-diabetes, 81% had hyperglycemia, and 60% had low HDL-cholesterol, with no difference between groups. Body mass index, FM, and FFM were similar between groups, with 73% of the patients being characterized with abdominal obesity, although waist circumference was lower in patients with COVID-19. Physical capacity was similar between groups. More than 80% had low handgrip strength and low physical activity levels. Compared to patients with influenza, patients with COVID-19 had increased levels of interferon (IFN)-γ (mean difference (MD) 4.14; 95% CI 1.36-12.58; p = 0.008), interleukin (IL)-4 (MD 1.82; 95% CI 1.12-2.97; p = 0.012), IL-5 (MD 2.22; 95% CI 1.09-4.52; p = 0.024), and IL-6 (MD 2.41; 95% CI 1.02-5.68; p = 0.044) and increased IFN-γ (MD 6.10; 95% CI 2.53-14.71; p < 0.001) and IL-10 (MD 2.68; 95% CI 1.53-4.69; p < 0.001) compared to patients with bacterial CAP, but no difference in IL-1β, tumor necrosis factor-α, IL-8, IL-18, IL-12p70, C-reactive protein, and adiponectin., Conclusion: Despite higher inflammatory response in patients with COVID-19, metabolic profile, body composition, and physical capacity were similar to patients with influenza and bacterial CAP., (© 2022. The Author(s).) more...

BackgroundAfter a COVID-19 diagnosis, vulnerable populations face considerable logistical and financial challenges to isolate and quarantine. We developed and evaluated a novel, community-based approach ('Test-to-Care' Model) designed to address these barriers for socioeconomically vulnerable Latinx individuals with newly diagnosed COVID-19 and their households.MethodsThis three-week demonstration project was nested within an epidemiologic surveillance study in a primarily Latinx neighborhood in the Mission district of San Francisco, California. The Test-to-Care model was developed with input from community members and public health leaders. Key components included: (1) provision of COVID-19-related education and information about available community resources, (2) home deliveries of material goods to facilitate safe isolation and quarantine (groceries, personal protective equipment and cleaning supplies), and (3) longitudinal clinical and social support. Newly SARS-CoV-2 PCR-positive participants were eligible to participate. Components of the model were delivered by the Test-to-Care team, which was comprised of healthcare providers and community health workers (CHWs) who provided longitudinal clinic- and community-based support for the duration of the isolation period to augment existing services from the Department of Public Health (DPH). We evaluated the Test-to-Care Model using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Framework and drew upon multiple data sources including: programmatic data, informal interviews with participants and providers/CHWs and structured surveys among providers/CHWs.ResultsOverall, 83 participants in the surveillance study were diagnosed with COVID-19, of whom 95% (79/83) were Latinx and 88% (65/74) had an annual household income more...

Objectives: We hypothesized that the amount of antigen produced in the body during a COVID-19 infection might differ between patients, and that maximum concentrations would predict the degree of both inflammation and outcome for patients., Methods: Eighty-four hospitalized and SARS-CoV-2 PCR swab-positive patients, were followed with blood sampling every day until discharge or death. A total of 444 serial EDTA plasma samples were analyzed for a range of biomarkers: SARS-CoV-2 nuclear antigen and RNA concentration, complement activation as well as several inflammatory markers, and KL-6 as a lung marker. The patients were divided into outcome groups depending on need of respiratory support and death/survival., Results: Circulating SARS-CoV-2 nuclear antigen levels were above the detection limit in blood in 65 out of 84 COVID-19 PCR swab-positive patients on day one of hospitalization, as was viral RNA in plasma in 30 out of 84. In all patients, complete antigen clearance was observed within 24 days. There were definite statistically significant differences between the groups depending on their biomarkers, showing that the concentrations of virus RNA and antigen were correlated to the inflammatory biomarker levels, respiratory treatment and death., Conclusions: Viral antigen is cleared in parallel with the virus RNA levels. The levels of antigens and SARS-CoV-2 RNA in the blood correlates with the level of IL-6, inflammation, respiratory failure and death. We propose that the antigens levels together with RNA in blood can be used to predict the severity of disease, outcome, and the clearance of the virus from the body., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.) more...