Survey of white-footed mice in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses (preprint)

Diverse mammalian species display susceptibility to and infection with SARS-CoV-2. Potential SARS-CoV-2 spillback into rodents is understudied despite their host role for numerous zoonoses and human proximity. We assessed exposure and infection among white-footed mice (Peromyscus leucopus) in Connecticut, USA. We observed 1% (6/540) wild-type neutralizing antibody seroprevalence among 2020-2022 residential mice with no cross-neutralization of variants. We detected no SARS-CoV-2 infections via RT-qPCR, but identified non-SARS-CoV-2 betacoronavirus infections via pan-coronavirus PCR among 1% (5/468) of residential mice. Sequencing revealed two divergent betacoronaviruses, preliminarily named Peromyscus coronavirus-1 and -2. Both belong to the Betacoronavirus 1 species and are ~90% identical to the closest known relative, Porcine hemagglutinating encephalomyelitis virus. Low SARS-CoV-2 seroprevalence suggests white-footed mice may not be sufficiently susceptible or exposed to SARS-CoV-2 to present a long-term human health risk. However, the discovery of divergent, non-SARS-CoV-2 betacoronaviruses expands the diversity of known rodent coronaviruses and further investigation is required to understand their transmission extent.

Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication (preprint)

G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules.

A phase 1, randomized, placebo-controlled, dose-ranging study to evaluate the safety and immunogenicity of an mRNA-based chikungunya virus vaccine in healthy adults.

BACKGROUND: Chikungunya, a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), causes a significant global health burden, and there is currently no approved vaccine to prevent chikungunya disease. In this study, the safety and immunogenicity of a CHIKV mRNA vaccine candidate (mRNA-1388) were evaluated in healthy participants in a CHIKV-nonendemic region. METHODS: This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study enrolled healthy adults (ages 18-49 years) between July 2017 and March 2019 in the United States. Participants were randomly assigned (3:1) to receive 2 intramuscular injections 28 days apart with mRNA-1388 in 3 dose-level groups (25 µg, 50 µg, and 100 µg) or placebo and were followed for up to 1 year. Safety (unsolicited adverse events [AEs]), tolerability (local and systemic reactogenicity; solicited AEs), and immunogenicity (geometric mean titers [GMTs] of CHIKV neutralizing and binding antibodies) of mRNA-1388 versus placebo were evaluated. RESULTS: Sixty participants were randomized and received ≥ 1 vaccination; 54 (90 %) completed the study. mRNA-1388 demonstrated favorable safety and reactogenicity profiles at all dose levels. Immunization with mRNA-1388 induced substantial and persistent humoral responses. Dose-dependent increases in neutralizing antibody titers were observed; GMTs (95 % confidence intervals [CIs]) at 28 days after dose 2 were 6.2 (5.1-7.6) for mRNA-1388 25 µg, 53.8 (26.8-108.1) for mRNA-1388 50 µg, 92.8 (43.6-197.6) for mRNA-1388 100 µg, and 5.0 (not estimable) for placebo. Persistent humoral responses were observed up to 1 year after vaccination and remained higher than placebo in the 2 higher mRNA-1388 dose groups. The development of CHIKV-binding antibodies followed a similar trend as that observed with neutralizing antibodies. CONCLUSIONS: mRNA-1388, the first mRNA vaccine against CHIKV, was well tolerated and elicited substantial and long-lasting neutralizing antibody responses in healthy adult participants in a nonendemic region. CLINICALTRIALS: gov: NCT03325075.

The Use of Qualitative Methods to Guide the Development of the Border Resilience Scale in a Participatory Research Study.

U.S.-Mexico border residents experience pervasive social and ecological stressors that contribute to a high burden of chronic disease. However, the border region is primarily composed of high-density Mexican-origin neighborhoods, a characteristic that is most commonly health-promoting. Understanding factors that contribute to border stress and resilience is essential to informing the effective design of community-level health promotion strategies. La Vida en La Frontera is a mixed-methods, participatory study designed to understand factors that may contribute to border resilience in San Luis, Arizona. The study's initial qualitative phase included interviews with 30 Mexican-origin adults exploring community perceptions of the border environment, cross-border ties, and health-related concepts. Border residents described the border as a Mexican enclave characterized by individuals with a common language and shared cultural values and perspectives. Positive characteristics related to living in proximity to Mexico included close extended family relationships, access to Mexican food and products, and access to more affordable health care and other services. Based on these findings, we co-designed the 9-item Border Resilience Scale that measures agreement with the psychosocial benefits of these border attributes. Pilot data with 60 residents suggest there are positive sociocultural attributes associated with living in border communities. Further research should test if they mitigate environmental stressors and contribute to a health-promoting environment for residents.

Home food procurement associated with improved food security during the COVID-19 pandemic (preprint)

Home food procurement (HFP), including gardening, is associated with food security and improved health behaviors and outcomes. In the beginning of the COVID-19 pandemic, HFP increased in many high-income countries; yet little evidence has demonstrated what impact HFP had on food security. Furthermore, existing HFP studies are largely qualitative from unrepresentative samples, limiting population-level understanding of HFP engagement and impact. Using data from a representative sample of residents (n=988) in northern New England in the United States conducted in Spring/Summer 2021, we explore the relationship between HFP engagement in the first year of the pandemic and changes in food security status. We employ matching techniques to compare food security outcomes in households with observably similar demographic and social characteristics, and examine food security outcomes in three periods among households who do and do not participate in HFP. Our results show that nearly 60% of respondents engaged in at least one kind of HFP in the first year of the COVID-19 pandemic, with food insecure households being more likely to do HFP. Food insecure households (both newly and chronically food insecure) were also more likely to do HFP activities for the first time or more intensely than they had previously. Newly food insecure households were the most likely to engage in HFP overall, especially gardening. Furthermore, HFP engagement early in the COVID-19 pandemic is associated with improved food security for food insecure households in the 9-12 months after the start of the pandemic, though these improvements were primarily associated with newly, not chronically, food insecure households. Future research about HFP should continue to explore multiple HFP strategies and their potentially myriad relationships to food security, diet, and health outcomes.

Clinically stable covid-19 patients presenting to acute unscheduled episodic care venues have increased risk of hospitalization: secondary analysis of a randomized control trial.

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial. METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive patients).We report the primary composite outcome of cardiopulmonary hospitalizations, symptomatic venous thromboembolism, myocardial infarction, stroke, transient ischemic attack, systemic arterial thromboembolism, or death among stable outpatients stratified by enrollment setting, AUEC versus MC. A propensity score for AUEC enrollment was created, and Cox proportional hazards regression with inverse probability weighting (IPW) was used to compare the primary outcome by enrollment location. RESULTS: Among the 657 ACTIV-4B patients randomized, 533 (81.1%) with known enrollment setting data were included in this analysis, 227 from AUEC settings and 306 from MC settings. In a multivariate logistic regression model, time from COVID test, age, Black race, Hispanic ethnicity, and body mass index were associated with AUEC enrollment. Irrespective of trial treatment allocation, patients enrolled at an AUEC setting were 10-times more likely to suffer from the adjudicated primary outcome, 7.9% vs. 0.7%; p < 0.001, compared with patients enrolled at a MC setting. Upon Cox regression analysis adjustment patients enrolled at an AUEC setting remained at significant risk of the primary composite outcome, HR 3.40 (95% CI 1.46, 7.94). CONCLUSIONS: Patients with clinically stable COVID-19 presenting to an AUEC enrollment setting represent a population at increased risk of arterial and venous thrombosis complications, hospitalization for cardiopulmonary events, or death, when adjusted for other risk factors, compared with patients enrolled at a MC setting. Future outpatient therapeutic trials and clinical therapeutic delivery programs of clinically stable COVID-19 patients may focus on inclusion of higher-risk patient populations from AUEC engagement locations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498273.

Evaluation of Measurement Properties and Differential Item Functioning in the English and French Versions of the University of California, Los Angeles, Loneliness Scale-6: A Scleroderma Patient-Centered Intervention Network (SPIN) Study.

OBJECTIVE: Loneliness has been associated with poorer health-related quality of life but has not been studied in patients with systemic sclerosis (SSc). The current study was undertaken to examine and compare the psychometric properties of the English and French versions of the University of California, Los Angeles, Loneliness Scale-6 (ULS-6) in patients with SSc during the COVID-19 pandemic. METHODS: This study used baseline cross-sectional data from 775 adults enrolled in the Scleroderma Patient-Centered Intervention Network (SPIN) COVID-19 Cohort. Reliability and validity of ULS-6 scores overall and between languages were evaluated using confirmatory factor analysis (CFA), differential item functioning (DIF) through the multiple-indicator multiple-cause (MIMIC) model, omega/alpha calculation, and correlations of hypothesized convergent relationships. RESULTS: CFA for the total sample supported the single-factor structure (comparative fit index [CFI] 0.96, standardized root mean residual [SRMR] 0.03), and all standardized factor loadings for items were large (0.60-0.86). The overall MIMIC model with language as a covariate fit well (CFI 0.94, SRMR 0.04, root mean square error of approximation 0.11). Statistically significant DIF was found for 3 items across language (ßitem2  = 0.14, P < 0.001; ßitem4  = -0.07, P = 0.01; ßitem6  = 0.13, P < 0.001), but these small differences were without practical measurement implications. Analyses demonstrated high internal consistency with no language-based convergent validity differences. CONCLUSION: Analyses demonstrated evidence of acceptable reliability and validity of ULS-6 scores in English- and French-speaking adults with SSc. DIF analysis supported use of the ULS-6 to examine comparative experiences of loneliness without adjusting for language.

Supporting US healthcare providers for successful vaccine communication.

BACKGROUND: While many healthcare providers (HCPs) have navigated patients' vaccine concerns and questions prior to the rollout of the COVID-19 vaccines, sentiments surrounding the COVID-19 vaccines have presented new and distinct challenges. OBJECTIVE: To understand the provider experience of counseling patients about COVID-19 vaccinations, aspects of the pandemic environment that impacted vaccine trust, and communication strategies providers found supportive of patient vaccine education. METHODS: 7 focus groups of healthcare providers were conducted and recorded during December 2021 and January 2022, at the height of the Omicron wave in the United States. Recordings were transcribed, and iterative coding and analysis was applied. RESULTS: 44 focus group participants representing 24 US states with the majority (80%) fully vaccinated at the time of data collection. Most participants were doctors (34%) or physician's assistants and nurse practitioners (34%). The negative impact of COVID-19 misinformation on patient-provider communication at both intrapersonal and interpersonal levels as well as barriers and facilitators to patient vaccine uptake are reported. People or sources that play a role in health communication ("messengers") and persuasive messages that impact behavior or attitudes towards vaccination ("messages") are described. Providers expressed frustration in the need to continuously address vaccine misinformation in clinical appointments among patients who remained unvaccinated. Many providers found value in resources that provided up-to-date and evidence-based information as COVID-19 guidelines continued to change. Additionally, providers indicated that patient-facing materials designed to support vaccination education were not frequently available, but they were the most valuable to providers in a changing information environment. CONCLUSIONS: While vaccine decision-making is complex and hinges on diverse factors such as health care access (i.e., convenience, expense) and individual knowledge, providers can play a major role in navigating these factors with their patients. But to strengthen provider vaccine communication and promote vaccine uptake, a comprehensive communication infrastructure must be sustained to support the patient-provider dyad. The findings provide recommendations to maintain an environment that facilitates effective provider-patient communication at the community, organizational and policy levels. There is a need for a unified multisectoral response to reinforce the recommendations in patient settings.

QTQTN motif upstream of the furin-cleavage site plays a key role in SARS-CoV-2 infection and pathogenesis.

The furin cleavage site (FCS), an unusual feature in the SARS-CoV-2 spike protein, has been spotlighted as a factor key to facilitating infection and pathogenesis by increasing spike processing. Similarly, the QTQTN motif directly upstream of the FCS is also an unusual feature for group 2B coronaviruses (CoVs). The QTQTN deletion has consistently been observed in in vitro cultured virus stocks and some clinical isolates. To determine whether the QTQTN motif is critical to SARS-CoV-2 replication and pathogenesis, we generated a mutant deleting the QTQTN motif (ΔQTQTN). Here, we report that the QTQTN deletion attenuates viral replication in respiratory cells in vitro and attenuates disease in vivo. The deletion results in a shortened, more rigid peptide loop that contains the FCS and is less accessible to host proteases, such as TMPRSS2. Thus, the deletion reduced the efficiency of spike processing and attenuates SARS-CoV-2 infection. Importantly, the QTQTN motif also contains residues that are glycosylated, and disruption of its glycosylation also attenuates virus replication in a TMPRSS2-dependent manner. Together, our results reveal that three aspects of the S1/S2 cleavage site-the FCS, loop length, and glycosylation-are required for efficient SARS-CoV-2 replication and pathogenesis.

A Scoping Review of Vitamin D for Nonskeletal Health: A Framework for Evidence-based Clinical Practice.

BACKGROUND: Low serum 25-hydroxy-vitamin D [25(OH)D] levels are prevalent worldwide. Although the benefits of vitamin D supplementation have focused on skeletal disorders (eg, rickets, osteomalacia, osteoporosis), emerging evidence for nonskeletal health merits further discussion. PURPOSE: The purpose of this review was to critically examine the vitamin D supplementation literature pertaining to nonskeletal health to help guide clinicians. METHODS: A scoping review that included observational studies and randomized clinical trials (RCTs) was performed. Evidence from meta-analyses and individual RCTs are discussed, and controversies and future directions are considered. FINDINGS: 25(OH)D deficiency is a ubiquitous condition associated with multiple nonskeletal diseases, including cardiometabolic (heart disease, diabetes, and kidney disease), immune (HIV/AIDS and cancer), lung (from traditional chronic disorders to coronavirus disease 2019), and gut diseases. Vitamin D deficiency also affects health across the life span (children, pregnant, and elderly), mental illness, and reproduction in both men and women. In contrast, vitamin D supplementation does not necessarily improve major medical outcomes, even when low 25(OH)D levels are treated. Screening for 25(OH)D status remains an important practice, primarily for high-risk patients (eg, elderly, women with osteoporosis, people with low exposure to sunlight). It is reasonable to supplement with vitamin D to treat 25(OH)D deficiency, such that if beneficial nonskeletal health occurs, this may be considered as a coadjutant instead of the central tenet of the disease. Furthermore, optimizing dosing regimens is an important clinical consideration. IMPLICATIONS: Although 25(OH)D deficiency is prevalent in nonskeletal diseases, there is no uniform evidence that vitamin D supplementation improves major medical outcomes, even when low 25(OH)D levels are corrected. Findings from RCTs warrant caution due to possible selection bias. Overall, vitamin D supplementation must be guided by circulating levels as a reasonable medical practice to correct 25(OH)D deficiency.

The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis.

STUDY QUESTION: What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines? SUMMARY ANSWER: There is no evidence that COVID-19 vaccines are associated with an increased risk of miscarriage. WHAT IS KNOWN ALREADY: In response to the COVID-19 pandemic, the mass roll-out of vaccines helped to boost herd immunity and reduced hospital admissions, morbidity, and mortality. Still, many were concerned about the safety of vaccines for pregnancy, which may have limited their uptake among pregnant women and those planning a pregnancy. STUDY DESIGN, SIZE, DURATION: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception until June 2022 using a combination of keywords and MeSH terms. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included observational and interventional studies that enrolled pregnant women and evaluated any of the available COVID-19 vaccines compared to placebo or no vaccination. We primarily reported on miscarriage in addition to ongoing pregnancy and/or live birth. MAIN RESULTS AND THE ROLE OF CHANCE: We included data from 21 studies (5 randomized trials and 16 observational studies) reporting on 149 685 women. The pooled rate of miscarriage among women who received a COVID-19 vaccine was 9% (n = 14 749/123 185, 95% CI 0.05-0.14). Compared to those who received a placebo or no vaccination, women who received a COVID-19 vaccine did not have a higher risk of miscarriage (risk ratio (RR) 1.07, 95% CI 0.89-1.28, I2 35.8%) and had comparable rates for ongoing pregnancy or live birth (RR 1.00, 95% CI 0.97-1.03, I2 10.72%). LIMITATIONS, REASONS FOR CAUTION: Our analysis was limited to observational evidence with varied reporting, high heterogeneity and risk of bias across included studies, which may limit the generalizability and confidence in our findings. WIDER IMPLICATIONS OF THE FINDINGS: COVID-19 vaccines are not associated with an increase in the risk of miscarriage or reduced rates of ongoing pregnancy or live birth among women of reproductive age. The current evidence remains limited and larger population studies are needed to further evaluate the effectiveness and safety of COVID-19 vaccination in pregnancy. STUDY FUNDING/COMPETING INTEREST(S): No direct funding was provided to support this work. M.P.R. was funded by the Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. B.H.A.W. hold a personal development award from the National Institute of Health Research in the UK. All authors declare no conflict of interest. REGISTRATION NUMBER: CRD42021289098.

Analysis of Failure Rates for COVID-19 Entrance Screening at a US Academic Medical Center.

This quality improvement study analyzes the rate of failures in entrance screening for COVID-19 among individuals entering a large academic medical center.

Two cases of challenging cutaneous lymphoid infiltrates presenting in the context of COVID-19 vaccination: a reactive lymphomatoid papulosis-like eruption and a bona fide lymphoma.

COVID-19 infection and vaccination may be associated with a wide variety of cutaneous and immune manifestations. Here, we describe two patients who presented with monoclonal cutaneous T-cell infiltrates that showed cytologic and immunophenotypic features concerning for lymphoma shortly following COVID-19 vaccination. In one case, the eruption completely resolved. The second patient showed initial resolution, but her disease recurred and progressed following a breakthrough SARS-CoV-2 infection. These cases suggest that immune stimulation following exposure to SARS-Cov-2 protein(s) in vaccine or infection may facilitate the development of a lymphoma or lymphoproliferative disorder in susceptible individuals. Moreover, they demonstrate that separating these cases from pseudolymphomatous reactive conditions is often challenging and requires close clinical correlation.

Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection

The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution result in the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants. Graphical To understand the intrahost evolution of SARS-CoV-2 from a single patient chronically infected for at least 471 days, Chaguza et al. use whole genome sequencing to estimate the evolutionary rate, the genetic divergence of viral lineages, relative mutation rates, and frequency of mutational variants during the course of the infection.

"Wearing a High Heel and a House Shoe at the Same Time": Parents' Information Needs While Navigating Change in their Child's Behavioral Care

Change is an inevitable part of a parent's role, whether due to their child's development, family life, or external events. To understand the information needs of parents navigating change, we studied the effects of the COVID-19 pandemic as a widely experienced disruption in the lives of parents and children. We interviewed 16 parents about their caregiving experience as the COVID-19 pandemic collapsed boundaries between home, school, and work. In particular, we asked about adjustments to behavioral care, or the social learning, supports, and interventions through which children develop social and emotional skills. We focused on parents of children already receiving accommodations and behavioral support from their school, to understand how disruptions in these services affected the role of the parent in meeting their child's individual needs. Applying role theory and the Kübler-Ross change curve, we describe the coping mechanisms that parents used to navigate the stages of change, as well as the information needs that remained unmet, despite their efforts. We discuss how practitioner-initiated and parent-centered supports can be designed around the lived experience of change, by accommodating a parent's capacity to accept and use help at different stages. © 2022 ACM.

SARS-CoV-2 Uses Nonstructural Protein 16 To Evade Restriction by IFIT1 and IFIT3.

Understanding the molecular basis of innate immune evasion by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important consideration for designing the next wave of therapeutics. Here, we investigate the role of the nonstructural protein 16 (NSP16) of SARS-CoV-2 in infection and pathogenesis. NSP16, a ribonucleoside 2'-O-methyltransferase (MTase), catalyzes the transfer of a methyl group to mRNA as part of the capping process. Based on observations with other CoVs, we hypothesized that NSP16 2'-O-MTase function protects SARS-CoV-2 from cap-sensing host restriction. Therefore, we engineered SARS-CoV-2 with a mutation that disrupts a conserved residue in the active site of NSP16. We subsequently show that this mutant is attenuated both in vitro and in vivo, using a hamster model of SARS-CoV-2 infection. Mechanistically, we confirm that the NSP16 mutant is more sensitive than wild-type SARS-CoV-2 to type I interferon (IFN-I) in vitro. Furthermore, silencing IFIT1 or IFIT3, IFN-stimulated genes that sense a lack of 2'-O-methylation, partially restores fitness to the NSP16 mutant. Finally, we demonstrate that sinefungin, an MTase inhibitor that binds the catalytic site of NSP16, sensitizes wild-type SARS-CoV-2 to IFN-I treatment and attenuates viral replication. Overall, our findings highlight the importance of SARS-CoV-2 NSP16 in evading host innate immunity and suggest a target for future antiviral therapies. IMPORTANCE Similar to other coronaviruses, disruption of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NSP16 function attenuates viral replication in a type I interferon-dependent manner. In vivo, our results show reduced disease and viral replication at late times in the hamster lung, but an earlier titer deficit for the NSP16 mutant (dNSP16) in the upper airway. In addition, our results confirm a role for IFIT1 but also demonstrate the necessity of IFIT3 in mediating dNSP16 attenuation. Finally, we show that targeting NSP16 activity with a 2'-O-methyltransferase inhibitor in combination with type I interferon offers a novel avenue for antiviral development.

Comparison of Student Outcomes in a Course-Based Undergraduate Research Experience: Face-to-Face, Hybrid, and Online Delivery of a Biology Laboratory

Course-based undergraduate research experiences (CUREs) incorporate authentic research instead of confirmatory exercises into laboratory courses. Following the COVID-19 pandemic, there has been a general shift in instructional modalities from face-to-face (F2F) towards hybrid and online teaching. Student impacts caused by the abrupt shift to online teaching have been characterized, but comparisons between modalities for CUREs are missing. Therefore, we evaluated student learning and attitudinal outcomes in F2F, hybrid, and online delivery of an introductory college biology CURE. Additionally, we compared student outcomes between White/Asian students and persons excluded due to ethnicity or race (PEER) in these modalities. There were significant learning differences between modalities, but there were no significant learning differences by PEER status. Of six attitudinal variables, one varied significantly by modality and three varied significantly for PEER students. These results suggest that CUREs can be adapted to the online or hybrid modality with minimal impacts on student outcomes.

Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection.

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.

A survey of COVID-19 vaccine acceptance across 23 countries in 2022.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continued to mutate and spread in 2022 despite the introduction of safe, effective vaccines and medications. Vaccine hesitancy remains substantial, fueled in part by misinformation. Our third study of Coronavirus Disease 2019 (COVID-19) vaccine hesitancy among 23,000 respondents in 23 countries (Brazil, Canada, China, Ecuador, France, Germany, Ghana, India, Italy, Kenya, Mexico, Nigeria, Peru, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Turkey, the United Kingdom and the United States), surveyed from 29 June to 10 July 2022, found willingness to accept vaccination at 79.1%, up 5.2% from June 2021. Hesitancy increased in eight countries, however, ranging from 1.0% (United Kingdom) to 21.1% (South Africa). Almost one in eight (12.1%) vaccinated respondents are hesitant about booster doses. Overall support for vaccinating children under 18 years of age increased slightly but declined among parents who were personally hesitant. Almost two in five (38.6%) respondents reported paying less attention to new COVID-19 information than previously, and support for vaccination mandates decreased. Almost a quarter (24%) of those who became ill reported taking medications to combat COVID-19 symptoms. Vaccination remains a cornerstone of the COVID-19 pandemic response, but broad public support remains elusive. These data can be used by health system decisionmakers, practitioners, advocates and researchers to address COVID-19 vaccine hesitancy more effectively.