Katherine D. Ellingson

Background: Age is a crucial factor in COVID-19 risk and severity, however its role in humoral immunity is unclear. This study compares associations between age and immune response following COVID-19 vaccination and SARS-CoV-2 infection. Methods: Data from the Arizona Healthcare, Emergency Response, and Other Essential Workers study (AZ-HEROES), a prospective cohort, were used to create two analytic groups: 1) a post-vaccination cohort including individuals who received two doses of the monovalent ancestral mRNA COVID-19 vaccine without prior SARS-CoV-2 infection; and 2) a post-infection cohort including unvaccinated individuals after primary infection. The analysis included data from September 2020 to April 2023. Children (<18 years) and adults (18 + years) were compared using linear regression, with immune response measured using log-transformed area under the curve (AUC) for receptor-binding domain (RBD) and spike protein subunit (S2). Finer age groups (<12, 12−17, 18−50, 50+) were also described. Adjusted models controlled for chronic conditions, medications, days since vaccination or infection, recent exposure to SARS-CoV-2 (post-vaccination only), strain type (post-infection only), and sociodemographic variables. Results: The post-vaccination analysis included 749 participants, while the post-infection analysis included 203 participants. Participants were predominantly non-Hispanic White adults, with median ages of 43 and 40 years in the post-vaccination and post-infection cohorts, respectively. Most reported no chronic conditions. In adjusted post-vaccination analysis, adults had 7% higher RBD AUC (95% CI: 1.01–1.13) and 20% higher S2 AUC (95% CI: 1.13, 1.28) than children, although these results were attenuated when restricted to individuals taking the BNT162b2 vaccine only. Post-infection, adults had 22% higher S2 AUC (95% CI: 1.05, 1.40), while RBD differences were not significant. By finer age breakdown, adolescents (12−17 years) had stronger responses than children younger than 12 post-vaccination, with 26% higher RBD AUC (95% CI: 1.13–1.40) and 29% higher S2 AUC (95% CI: 1.14–1.46). Conclusions: COVID-19 immune responses differ between children and adults, with adolescents exhibiting stronger immune response to vaccination than children younger than 12, however vaccine dosage may play a role in this observed difference. Age-related differences after infection were limited to S2 antibody responses.

Introduction: Antibiotic use drives antimicrobial resistance, and optimizing prescribing in skilled nursing facilities (SNFs) – which care for medically complex residents in congregate settings characterized by frequent care transitions and diagnostic uncertainty – presents unique challenges. Antimicrobial stewardship (AMS) in SNFs has therefore become a focus of quality improvement efforts by federal and state health agencies. We aimed to identify factors that facilitate and hinder AMS implementation in SNFs. Methods: A qualitative study of AMS implementation was conducted in Southern Arizona SNFs randomly sampled to represent urban/suburban, border, and rural regions. Semi-structured interviews were conducted with administrators, clinicians, and nonclinical staff within participating facilities. Interview transcripts were analyzed using constant comparative analysis, with both directed and emergent coding, facilitated by NVivo 12 software. Findings: From 04/13/2019 through 12/13/2019, 57 interviews were conducted with 9 administrators, 38 clinical providers, and 10 nonclinical staff across 6 urban/suburban, 2 border, and 2 rural facilities. Analysis identified two thematic categories: "influencer themes," which describe specific barriers and facilitators to AMS implementation, and "system themes," which characterize SNFs as complex adaptive systems shaped by interacting staff roles, care transition challenges, and differing perceptions of AMS practices within the same facility. Key facilitators included effective internal communication, ongoing AMS education, and clinician AMS champions. Primary barriers included poor interfacility communication during care transitions, limited access to diagnostic resources, enculturated prescribing norms, and tension between immediate infection control priorities and long-term AMS goals. Conclusions: Findings suggest that AMS implementation in Arizona SNFs is best understood as a systems-level process emerging from interactions among staff roles, organizational workflows, and care transitions, rather than solely from individual prescribing decisions. Recognizing SNFs as complex adaptive systems highlights the importance of communication structures, local champions, and feedback mechanisms. It underscores the need for coordination strategies within and across SNFs to sustain AMS interventions.

Background/Objectives: The COVID-19 pandemic affected antimicrobial stewardship in healthcare, including Skilled Nursing Facilities (SNFs). This study aimed to (1) assess the appropriateness of antibiotic prescriptions for urinary tract infections (UTIs) and respiratory tract infections (RTIs) and identify predictors of inappropriate use; (2) analyze changes in prescribing practices relative to the pandemic’s onset. Methods: A retrospective review of electronic medical records from a 300-bed SNF (March 2019–March 2021) identified suspected UTIs and RTIs based on laboratory tests and antibiotic requests. Antibiotic prescription appropriateness was defined by clinical and microbiological alignment with the McGeer criteria, which are standardized infection definitions for long-term care residents, for UTI and RTI. Logistic regression models identified predictors of inappropriate prescribing, and an interrupted time-series analysis (ITS) examined trends relative to the pandemic onset (11 March 2020) in Arizona. Results: Among 370 antibiotic prescriptions, 77% of UTI and 61% of RTI prescriptions were inappropriate per the McGeer criteria. Acute dysuria and increased urgency were associated with lower odds of inappropriate UTI prescribing. For RTIs, a positive COVID-19 test increased the odds of inappropriate prescribing, while fever and acute functional decline lowered them. UTI prescriptions and inappropriateness overall increased during the pandemic, but no significant ITS trends emerged. For RTIs, no significant changes in prescribing or inappropriateness relative to the pandemic were observed. Findings emphasize the need for robust antimicrobial stewardship during and after public health emergencies.

Background: Black and Hispanic communities are under-represented in cognitive ageing research. MindCrowd is an online platform that offers interactive cognitive games and facilitates research. We sought to assess participation in MindCrowd and willingness to be contacted for future studies by race, ethnicity and other demographic variables. Methods: Adults were recruited into MindCrowd through national media campaigns and enhanced local engagement (ELE) in and around four cities with robust black (Atlanta and Baltimore) and Hispanic (Miami and Tucson) populations. Recruiting in ELE regions involved direct contact with potential participants via community forums or established research cohorts. Participation was defined as completing two 5-minute cognitive games and a demographic questionnaire, and participation incidence was calculated per 100 000 adults using census data and was compared by region using incidence rate ratios (IRRs). Willingness to be contacted for future research was defined as participants submitting an email address for researcher follow-up and was modelled as a binary outcome using logistic regression to generate adjusted ORs (aORs) for age, sex, region, race and ethnicity. Results: From 17 June 2022 to 28 December 2023, 49 934 adults participated in MindCrowd. Nationwide, the majority were female (87.2%) and >50 years old (75.2%). In ELE regions, 8.4% of participants were black versus 2.3% in non-ELE regions; 21.8% were Hispanic in ELE regions versus 16.4% in non-ELE regions. MindCrowd participation incidence was higher in ELE than non-ELE regions (32.4 vs 17.9 per 100 000 adults; IRR=1.78, 95% CI, 1.73 to 1.83). Overall, 42.1% of participants nationwide were willing to be contacted for future research, with elevated odds for all ELE regions (vs collective non-ELE regions). Compared with white participants, black participants had 23% higher odds of willingness to be contacted (aOR=1.23; 95% CI, 1.10 to 1.36); compared with non-Hispanic participants, Hispanic participants had 20% higher odds (aOR=1.20; 95% CI, 1.13 to 1.27). Conclusions: Following nationwide and regional efforts to recruit a diverse participant pool into the online platform MindCrowd, regions with ELE had higher rates of participation than the rest of the nation across race and ethnicity categories. Controlling for region, black and Hispanic individuals showed marginal but statistically elevated willingness to be contacted for future research.

Background/Objectives: The COVID-19 pandemic affected antimicrobial stewardship in healthcare, including Skilled Nursing Facilities (SNFs). This study aimed to (1) assess the appropriateness of antibiotic prescriptions for urinary tract infections (UTIs) and respiratory tract infections (RTIs), and identify predictors of inappropriate use, and (2) analyze changes in prescribing practices relative to the pandemic’s onset. Methods: A retrospective review of electronic medical records from a 300-bed SNF (March 2019 - March 2021) identified suspected UTIs and RTIs based on laboratory tests and antibiotic requests. Antibiotic prescription appropriateness was defined by clinical and microbiological alignment with the McGeer criteria, which are standardized infection definitions for long-term care residents, for UTI and RTI. Logistic regression models identified predictors of inappropriate prescribing, and an interrupted time-series analysis (ITS) examined trends relative to the pandemic onset (March 11, 2020) in Arizona. Results: Among 370 antibiotic prescriptions, 77% of UTI and 61% of RTI prescriptions were inappropriate per the McGeer criteria. Acute dysuria and increased urgency were associated with lower odds of inappropriate UTI prescribing. For RTIs, a positive COVID-19 test increased odds of inappropriate prescribing, while fever and acute functional decline lowered them. UTI prescriptions and inappropriateness overall increased during the pandemic, but no significant ITS trends emerged. For RTIs, no significant changes in prescribing or inappropriateness relative to the pandemic were observed. Conclusions: Over two-thirds of antibiotics prescribed for UTI and RTI were inappropriate, with these trends persisting during the pandemic. Findings emphasize the need for robust antimicrobial stewardship during and after public health emergencies.

Background: Generation time, representing the interval between infection events in primary and secondary cases, is important for understanding disease transmission dynamics including predicting the effective reproduction number (Rt), which informs public health decisions. While previous estimates of SARS-CoV-2 generation times have been reported for early Omicron variants, there is a lack of data for subsequent sub-variants, such as XBB. Methods: We estimated SARS-CoV-2 generation times using data from the Respiratory Virus Transmission Network – Sentinel (RVTN-S) household transmission study conducted across seven U.S. sites from December 2021 to May 2023. The study spanned three Omicron sub-periods dominated by the sub-variants BA.1/2, BA.4/5, and XBB. We employed a Susceptible-Exposed-Infectious-Recovered (SEIR) model with a Bayesian data augmentation method that imputes unobserved infection times of cases to estimate the generation time. Findings: The estimated mean generation time for the overall Omicron period was 3.5 days (95% credible interval, CrI: 3.3-3.7). During the sub-periods, the estimated mean generation times were 3.8 days (95% CrI: 3.4-4.2) for BA.1/2, 3.5 days (95% CrI: 3.3-3.8) for BA.4/5, and 3.5 days (95% CrI: 3.1-3.9) for XBB. Interpretation: Our study provides estimates of generation times for the Omicron variant, including the sub-variants BA.1/2, BA.4/5, and XBB. These up-to-date estimates specifically address the gap in knowledge regarding these sub-variants and are consistent with earlier studies. They enhance our understanding of SARS-CoV-2 transmission dynamics by aiding in the prediction of Rt, offering insights for improving COVID-19 modeling and public health strategies. Funding: Centers for Disease Control and Prevention, and National Center for Advancing Translational Sciences.

The generation time, representing the interval between infections in primary and secondary cases, is essential for understanding and predicting the transmission dynamics of seasonal influenza, including the real-time effective reproduction number (Rt). However, comprehensive generation time estimates for seasonal influenza, especially post the 2009 influenza pandemic, are lacking. We estimated the generation time utilizing data from a 7-site case-ascertained household study in the United States over two influenza seasons, 2021/2022 and 2022/2023. More than 200 individuals who tested positive for influenza and their household contacts were enrolled within 7 days of the first illness in the household. All participants were prospectively followed for 10 days completing daily symptom diaries and collecting nasal swabs, which were tested for influenza via RT-PCR. We analyzed these data by modifying a previously published Bayesian data augmentation approach that imputes infection times of cases to obtain both intrinsic (assuming no susceptible depletion) and realized (observed within household) generation times. We assessed the robustness of the generation time estimate by varying the incubation period, and generated estimates of the proportion of transmission before symptomatic onset, infectious period, and latent period. We estimated a mean intrinsic generation time of 3.2 (95% credible interval, CrI: 2.9-3.6) days, with a realized household generation time of 2.8 (95% CrI: 2.7-3.0) days. The generation time exhibited limited sensitivity to incubation period variation. Estimates of the proportion of transmission that occurred before symptom onset, the infectious period, and the latent period were sensitive to variation in incubation periods. Our study contributes to the ongoing efforts to refine estimates of the generation time for influenza. Our estimates, derived from recent data following the COVID-19 pandemic, are consistent with previous pre-pandemic estimates, and will be incorporated into real-time Rt estimation efforts.

Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. Methods: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021–August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14–59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. Results: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). Conclusions: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.

: Aedes aegypti is the primary vector of dengue virus and threatens 3.9 billion people living in many tropical and subtropical countries. Prevention and reduction of dengue and other Aedes-borne viruses, including Zika and chikungunya, requires control of mosquito populations. Community mobilization and input are essential components of vector control efforts. Many vector control campaigns do not engage communities prior to implementation, leading to program failure. Those that do often conduct basic knowledge, attitude, and practice surveys that are not designed to explicitly elicit preferences. Here, we applied a novel stated preference elicitation tool, best-worst choice, to understand preferences, willingness to participate, and willingness to pay for mosquito control in dengue-endemic communities of Peñuelas, Puerto Rico. Findings revealed that the community preferred mosquito control programs that are 1) applied at the neighborhood level, 2) implemented by the local government, and 3) focused specifically on reducing disease transmission (e.g., dengue) instead of mosquito nuisance. Programs targeting the reduction of disease transmission and higher educational level of participants increased willingness to participate. Participants were willing to pay an average of $72 annually to have a program targeting the reduction of diseases such as dengue. This study serves as a model to engage communities in the design of mosquito control programs and improve stakeholders’ decision-making.

Antibiotic resistance has worsened since the start of the COVID-19 pandemic because of overstrained healthcare and laboratory systems, disrupted antimicrobial stewardship programs, and overuse of antibiotics. Community-based antibiotic use during the pandemic in the United States (US) and Mexico, including the socially vulnerable border region, is poorly characterized and does not account for non-prescription antibiotic use. The goal of this study was to assess the association between antibiotic use and infection with, or worry about, COVID-19 in the US and Mexico. a=High school diploma or equivalent including GED, b=4-year, and c=Household income in previous year before taxes, d=Other includes multiple races, e= adjusted for only significant covariates: COVID-19 infection status, age, race, education, and country of residence. Acronyms: AIN=American Indian or Alaskan Native, MXN= Mexican peso, NHPI=Native Hawaiian or Pacific Islander, OR= odds ratio, SD=standard deviation, USD= US Dollars. Significant findings in bold. An online cross-sectional survey with monetary incentive was deployed through Amazon Mechanical Turk to adults in the US and Mexico with enhanced recruitment through flyers at clinics and COVID-19 testing sites in the border regions of the US and Mexico (defined as within 100km of the border). Responses (n=981) were collected from 8/8/2020 to 8/4/2021. Logistic regression models were specified to model any (prescription and non-prescription) antibiotic use for “flu- or COVID-like” symptoms since March 2020. Predictors of interest were history of laboratory-confirmed SARS-CoV-2 infection and general worry about COVID-19. Models were adjusted for sex, age, ethnicity, race, education, income, insurance status, and country of residence. A total of 688 participants were used in the analysis, excluding 293 who did not answer the antibiotic use question. 29% reported already being infected and 78% reported being worried about COVID-19. After adjusting for significant covariates, those who reported a history of infection and worries about COVID-19 at the time of the survey had increased odds of using antibiotics for flu- or COVID-like symptoms: OR=26.7 (95% CI: 12.5-49.2) and OR=7.6 (95% CI: 3.6-16.4), respectively. Conversely, residing in Mexico decreased the odds of antibiotic use for those who had concerns about COVID-19: OR=0.3 (95% CI: 0.1-0.6) in adjusted models. Findings suggest that worry about COVID-19 drove higher odds of antibiotic use, which could potentially be attributed to uncertainty, misinformation, and political turmoil during this time period. The relationships did not appear to be affected by sex, ethnicity, income, and insurance which suggests more research is needed. All Authors: No reported disclosures