IMPORTANCE: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking. OBJECTIVE: To characterize the composition, diversity, and correlates of the oral microbiome in US adults. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012). EXPOSURES: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics. MAIN OUTCOMES AND MEASURES: Oral microbiome measures, characterized through 16S ribosomal RNA gene sequencing, included α diversity (observed amplicon sequence variants [ASVs], Faith phylogenetic diversity, Shannon-Weiner Index, and Simpson Index); β diversity (unweighted UniFrac, weighted UniFrac, and Bray-Curtis dissimilarity); and prevalence and relative abundance at phylum level through genus level. Analyses accounted for the NHANES complex sample design. RESULTS: This study included 8237 US adults aged 18 to 69 years, representing 202 314 000 individuals (102 813 000 men [50.8%]; mean [SD] age, 42.3 [14.4] years; 9.3% self-reported as Mexican American, 12.1% as non-Hispanic Black, 64.7% as non-Hispanic White, 5.9% as other Hispanic, and 8.1% as other non-Hispanic individuals). The oral microbiome encompassed 37 bacterial phyla, 99 classes, 212 orders, 446 families, and 1219 genera. Five phyla (Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria) and 6 genera (Veillonella, Streptococcus, Prevotella 7, Rothia, Actinomyces, and Gemella) were present in nearly all US adults (weighted prevalence, >99%). These genera were the most abundant, accounting for 65.7% of total abundance. Observed ASVs showed a quadratic pattern with age (peak at 30 years), were similar by sex, significantly lower among non-Hispanic White individuals, and increased with greater body mass index (BMI), alcohol use, and periodontal disease severity. All covariates together accounted for a modest proportion of oral microbiome variability as measured by β diversity: R2 = 8.7% (95% CI, 8.4%-9.1%) for unweighted UniFrac, R2 = 7.2% (95% CI, 6.6%-7.7%) for weighted UniFrac, and R2 = 6.3% (95% CI, 3.1%-6.7%) for Bray-Curtis matrices. By contrast, relative abundance of a few genera explained a high percentage of variability in β diversity for weighted UniFrac: Aggregatibacter (R2 = 22.4%; 95% CI, 22.1%-22.8%), Lactococcus (R2 = 21.6%; 95% CI, 20.9%-22.3%), and Haemophilus (R2 = 18.4%; 95% CI, 18.1%-18.8%). Prevalence and relative abundance of numerous genera were associated with age, race and ethnicity, smoking, BMI categories, alcohol use, and periodontal disease severity. CONCLUSIONS AND RELEVANCE: This cross-sectional study of the oral microbiome in US adults showed that a few genera were universally present and a different set of genera explained a high percentage of oral microbiome diversity across the population. This comprehensive characterization provides a contemporary reference standard for future studies.

BACKGROUND: Long-acting injectable antiretrovirals (LAI-ARVs) for HIV prevention and treatment have been demonstrated in clinical trials to be non-inferior to daily oral medications, providing an additional option to help users overcome the challenges of daily adherence. Approval and implementation of these regimens in low- and middle-income settings have been limited. METHOD: This study describes the anticipated barriers and facilitators to implementing LAI-ARVs in Vietnam to inform future roll-out. From July to August 2022, we conducted 27 in-depth interviews with healthcare workers and public health stakeholders involved in HIV programs at national, provincial, and clinic levels across four provinces in Vietnam. The interviews followed a semi-structured questionnaire and were audio recorded. Data were analyzed using a rapid thematic analysis approach to identify facilitators and barriers to the adoption of LAI-ARVs. RESULTS: In total, 27 participants from 4 provinces were interviewed including 14 (52%) men and 13 (48%) women. Participants median age was 48 years and they had 11.5 years of experience with HIV services and programs. Perceived user-level facilitators included the greater convenience of injectables in comparison to oral regimens, while barriers included the increased frequency of visits, fear of pain and side effects, and cost. Clinic-level facilitators included existing technical capacity to administer injections and physical storage availability in district health centers, while barriers included lack of space and equipment for administering injections for HIV-related services, concerns about cold chain maintenance for LAI-ART, and workload for healthcare workers. Health system-level facilitators included existing mechanisms for medication distribution, while barriers included regulatory approval processes and concerns about supply chain continuity. CONCLUSION: Overall, participants were optimistic about the potential impact of LAI-ARVs but highlighted important considerations at multiple levels needed to ensure successful implementation in Vietnam. CLINICAL TRIAL NUMBER: Not applicable.

IMPORTANCE: Although influenza vaccination has been found to be safe in pregnancy, few studies have assessed repeated influenza vaccination over successive pregnancies, including 2 vaccinations in a year, in terms of adverse perinatal outcomes. OBJECTIVE: To examine the association of seasonal influenza vaccination across successive pregnancies with adverse perinatal outcomes and whether the association varies by interpregnancy interval (IPI) and vaccine type (quadrivalent or trivalent). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included individuals with at least 2 successive singleton live-birth pregnancies between January 1, 2004, and December 31, 2018. Data were collected from the Vaccine Safety Datalink, a collaboration between the Centers for Disease Control and Prevention and integrated health care organizations. Data analysis was performed between January 8, 2021, and July 17, 2024. EXPOSURES: Influenza vaccination was identified using vaccine administration codes. The vaccinated cohort consisted of people who received influenza vaccines during the influenza season (August 1 through April 30) in 2 successive pregnancies. The comparator cohort consisted of people identified as unvaccinated during both pregnancies. MAIN OUTCOMES AND MEASURES: Main outcomes were risk of preeclampsia or eclampsia, placental abruption, fever, preterm birth, preterm premature rupture of membranes, chorioamnionitis, and small for gestational age among individuals with and without vaccination in both pregnancies. Adjusted relative risks (RRs) from Poisson regression were used to assess the magnitude of associations. The associations with adverse outcomes by IPI and vaccine type were evaluated. RESULTS: Of 82 055 people with 2 singleton pregnancies between 2004 and 2018, 44 879 (54.7%) had influenza vaccination in successive pregnancies. Mean (SD) age at the start of the second pregnancy was 32.2 (4.6) years for vaccinated individuals and 31.2 (5.0) years for unvaccinated individuals. Compared with individuals not vaccinated in both pregnancies, vaccination in successive pregnancies was not associated with increased risk of preeclampsia or eclampsia (adjusted RR, 1.10; 95% CI, 0.99-1.21), placental abruption (adjusted RR, 1.01; 95% CI, 0.84-1.21), fever (adjusted RR, 0.87; 95% CI, 0.47-1.59), preterm birth (adjusted RR, 0.83; 95% CI, 0.78-0.89), preterm premature rupture of membranes (RR, 1.00; 95% CI, 0.94-1.06), chorioamnionitis (adjusted RR, 1.03; 95% CI, 0.90-1.18), or small for gestational age birth (adjusted RR, 0.99; 95% CI, 0.93-1.05). IPI and vaccine type did not modify the observed associations. CONCLUSIONS AND RELEVANCE: In this large cohort study of successive pregnancies, influenza vaccination was not associated with increased risk of adverse perinatal outcomes, irrespective of IPI and vaccine type. Findings support recommendations to vaccinate pregnant people or those who might be pregnant during the influenza season.

Households are a primary setting for transmission of SARS-CoV-2. We examined the role of prior SARS-CoV-2 immunity on the risk of infection in household close contacts. Households in the United States with an individual who tested positive for SARS-CoV-2 during September 2021-May 2023 were enrolled if the index case's illness began ≤6 days prior. Household members had daily self-collected nasal swabs tested by RT-PCR for SARS-CoV-2. The effects of prior SARS-CoV-2 immunity (vaccination, prior infection, or hybrid immunity) on SARS-CoV-2 infection risk among household contacts were assessed by robust, clustered multivariable Poisson regression. Of 1,532 contacts (905 households), 8% had immunity from prior infection alone, 51% from vaccination alone, 29% hybrid immunity, and 11% had no prior immunity. Sixty percent of contacts tested SARS-CoV-2-positive during follow-up. The adjusted risk of SARS-CoV-2 infection was lowest among contacts with vaccination and prior infection (aRR: 0.81, 95% CI: 0.70, 0.93, compared with contacts with no prior immunity) and was lowest when the last immunizing event occurred ≤6 months before COVID-19 affected the household (aRR: 0.69, 95% CI: 0.57, 0.83). In high-transmission settings like households, immunity from COVID-19 vaccination and prior infection was synergistic in protecting household contacts from SARS-CoV-2 infection.

BACKGROUND: Nirmatrelvir/ritonavir (N/R) reduces severe outcomes from coronavirus disease 2019 (COVID-19); however, rebound after treatment has been reported. We compared symptom and viral dynamics in individuals with COVID-19 who completed N/R treatment and similar untreated individuals. METHODS: We identified symptomatic participants who tested severe acute respiratory syndrome coronavirus 2-positive and were N/R eligible from a COVID-19 household transmission study. Index cases from ambulatory settings and their households contacts were enrolled. We collected daily symptoms, medication use, and respiratory specimens for quantitative polymerase chain reaction for 10 days during March 2022-May 2023. Participants who completed N/R treatment (treated) were propensity score matched to untreated participants. We compared symptom rebound, viral load (VL) rebound, average daily symptoms, and average daily VL by treatment status measured after N/R treatment completion or 7 days after symptom onset if untreated. RESULTS: Treated (n = 130) and untreated participants (n = 241) had similar baseline characteristics. After treatment completion, treated participants had greater occurrence of symptom rebound (32% vs 20%; P = .009) and VL rebound (27% vs 7%; P < .001). Average daily symptoms were lower among treated participants without symptom rebound (1.0 vs 1.6; P < .01) but not statistically lower with symptom rebound (3.0 vs 3.4; P = .5). Treated participants had lower average daily VLs without VL rebound (0.9 vs 2.6; P < .01) but not statistically lower with VL rebound (4.8 vs 5.1; P = .7). CONCLUSIONS: Individuals who completed N/R treatment experienced fewer symptoms and lower VL but rebound occured more often compared with untreated individuals. Providers should prescribe N/R, when indicated, and communicate rebound risk to patients.

BACKGROUND: Detection and containment of hospital outbreaks currently depend on variable and personnel-intensive surveillance methods. Whether automated statistical surveillance for outbreaks of health care-associated pathogens allows earlier containment efforts that would reduce the size of outbreaks is unknown. METHODS: We conducted a cluster-randomized trial in 82 community hospitals within a larger health care system. All hospitals followed an outbreak response protocol when outbreaks were detected by their infection prevention programs. Half of the hospitals additionally used statistical surveillance of microbiology data, which alerted infection prevention programs to outbreaks. Statistical surveillance was also applied to microbiology data from control hospitals without alerting their infection prevention programs. The primary outcome was the number of additional cases occurring after outbreak detection. Analyses assessed differences between the intervention period (July 2019 to January 2022) versus baseline period (February 2017 to January 2019) between randomized groups. A post hoc analysis separately assessed pre-coronavirus disease 2019 (Covid-19) and Covid-19 pandemic intervention periods. RESULTS: Real-time alerts did not significantly reduce the number of additional outbreak cases (intervention period versus baseline: statistical surveillance relative rate [RR]=1.41, control RR=1.81; difference-in-differences, 0.78; 95% confidence interval [CI], 0.40 to 1.52; P=0.46). Comparing only the prepandemic intervention with baseline periods, the statistical outbreak surveillance group was associated with a 64.1% reduction in additional cases (statistical surveillance RR=0.78, control RR=2.19; difference-in-differences, 0.36; 95% CI, 0.13 to 0.99). There was no similarly observed association between the pandemic versus baseline periods (statistical surveillance RR=1.56, control RR=1.66; difference-in-differences, 0.94; 95% CI, 0.46 to 1.92). CONCLUSIONS: Automated detection of hospital outbreaks using statistical surveillance did not reduce overall outbreak size in the context of an ongoing pandemic. (Funded by the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT04053075. Support for HCA Healthcare's participation in the study was provided in kind by HCA.).

IMPORTANCE: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed. OBJECTIVE: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020. INTERVENTION: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education. MAIN OUTCOMES AND MEASURES: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies. RESULTS: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups. CONCLUSIONS AND RELEVANCE: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03697070.

IMPORTANCE: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed. OBJECTIVE: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI. DESIGN, SETTING, AND PARTICIPANTS: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020). INTERVENTIONS: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education. MAIN OUTCOMES AND MEASURES: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods. RESULTS: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively. CONCLUSIONS AND RELEVANCE: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03697096.

Clinical severity scores facilitate comparisons to understand risk factors for severe illness. For the 2022 multinational monkeypox clade IIb virus outbreak, we developed a 7-item Mpox Severity Scoring System (MPOX-SSS) with initial variables refined by data availability and parameter correlation. Application of MPOX-SSS to the first 200 patients diagnosed with mpox revealed higher scores in those treated with tecovirimat, presenting >3 days after symptom onset, and with CD4 counts <200 cells/mm3. For individuals evaluated repeatedly, serial scores were concordant with clinical observations. The pilot MPOX-SSS demonstrated good discrimination, distinguished change over time, and identified higher scores in expected groups.

OBJECTIVE: To assess the validity of electronic health record (EHR)-based influenza vaccination data among adults in a multistate network. METHODS: Following the 2018-2019 and 2019-2020 influenza seasons, surveys were conducted among a random sample of adults who did or did not appear influenza-vaccinated (per EHR data) during the influenza season. Participants were asked to report their influenza vaccination status; self-report was treated as the criterion standard. Results were combined across survey years. RESULTS: Survey response rate was 44.7% (777 of 1740) for the 2018-2019 influenza season and 40.5% (505 of 1246) for the 2019-2020 influenza season. The sensitivity of EHR-based influenza vaccination data was 75.0% (95% confidence interval [CI] 68.1, 81.1), specificity 98.4% (95% CI 92.9, 99.9), and negative predictive value 73.9% (95% CI 68.0, 79.3). CONCLUSIONS: In a multistate research network across two recent influenza seasons, there was moderate concordance between EHR-based vaccination data and self-report.

This report is a compendium of all current recommendations for the prevention of measles, rubella, congenital rubella syndrome (CRS), and mumps. The report presents the recent revisions adopted by the Advisory Committee on Immunization Practices (ACIP) on October 24, 2012, and also summarizes all existing ACIP recommendations that have been published previously during 1998-2011 (CDC. Measles, mumps, and rubella--vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1998;47[No. RR-8]; CDC. Revised ACIP recommendation for avoiding pregnancy after receiving a rubellacontaining vaccine. MMWR 2001;50:1117; CDC. Updated recommendations of the Advisory Committee on Immunization Practices [ACIP] for the control and elimination of mumps. MMWR 2006;55:629-30; and, CDC. Immunization of healthcare personnel: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2011;60[No. RR-7]). Currently, ACIP recommends 2 doses of MMR vaccine routinely for children with the first dose administered at age 12 through 15 months and the second dose administered at age 4 through 6 years before school entry. Two doses are recommended for adults at high risk for exposure and transmission (e.g., students attending colleges or other post-high school educational institutions, healthcare personnel, and international travelers) and 1 dose for other adults aged ≥18 years. For prevention of rubella, 1 dose of MMR vaccine is recommended for persons aged ≥12 months. At the October 24, 2012 meeting, ACIP adopted the following revisions, which are published here for the first time. These included: • For acceptable evidence of immunity, removing documentation of physician diagnosed disease as an acceptable criterion for evidence of immunity for measles and mumps, and including laboratory confirmation of disease as a criterion for acceptable evidence of immunity for measles, rubella, and mumps. • For persons with human immunodeficiency virus (HIV) infection, expanding recommendations for vaccination to all persons aged ≥12 months with HIV infection who do not have evidence of current severe immunosuppression; recommending revaccination of persons with perinatal HIV infection who were vaccinated before establishment of effective antiretroviral therapy (ART) with 2 appropriately spaced doses of MMR vaccine once effective ART has been established; and changing the recommended timing of the 2 doses of MMR vaccine for HIV-infected persons to age 12 through 15 months and 4 through 6 years. • For measles postexposure prophylaxis, expanding recommendations for use of immune globulin administered intramuscularly (IGIM) to include infants aged birth to 6 months exposed to measles; increasing the recommended dose of IGIM for immunocompetent persons; and recommending use of immune globulin administered intravenously (IGIV) for severely immunocompromised persons and pregnant women without evidence of measles immunity who are exposed to measles. As a compendium of all current recommendations for the prevention of measles, rubella, congenital rubella syndrome (CRS), and mumps, the information in this report is intended for use by clinicians as baseline guidance for scheduling of vaccinations for these conditions and considerations regarding vaccination of special populations. ACIP recommendations are reviewed periodically and are revised as indicated when new information becomes available.

We assessed serum neutralization of Omicron BA.5 in children following SARS-CoV-2 infection during the Delta or Omicron BA.1/BA.2 variant period. Convalescent BA.5 titers were higher following infections during the Omicron BA.1/BA.2 vs Delta variant period, and in vaccinated vs unvaccinated children. Titers against BA.5 did not differ by age group.

Human papillomavirus (HPV) vaccination can dramatically reduce the incidence of HPV-associated cancers. However, HPV vaccination coverage in rural areas is lower than in urban areas, and overall HPV vaccination coverage in the United States remains lower than other adolescent vaccines. We conducted 20 qualitative interviews with adolescent healthcare providers and clinic staff in urban and rural Minnesota and assessed their perspectives on HPV vaccination. Guiding interview topics included: strategies to persuade families to vaccinate their children, the impact of the patient-provider relationship and the clinical environment on vaccination uptake, and provider perceptions of parents' vaccine attitudes. In thematic analysis, all participants reported using common vaccination strategies, such as framing the HPV vaccine in terms of cancer prevention. The analysis also revealed three themes described as occurring uniquely or more intensely in rural communities than urban communities: the rural value of choice or independence, the spread of misinformation, and close-knit, multifaceted patient-provider relationships in clinical practice. Interventions aimed at increasing HPV vaccination should consider the distinctive circumstances of rural healthcare providers and patients.

Both SARS-CoV-2 and influenza virus can be transmitted by asymptomatic, presymptomatic, or symptomatic infected persons. We assessed effects on work attendance while ill before and during the COVID-19 pandemic in the United States by analyzing data collected prospectively from persons with acute respiratory illnesses enrolled in a multistate study during 2018-2022. Persons with previous hybrid work experience were significantly less likely to work onsite on the day before through the first 3 days of illness than those without that experience, an effect more pronounced during the COVID-19 pandemic than during prepandemic influenza seasons. Persons with influenza or COVID-19 were significantly less likely to work onsite than persons with other acute respiratory illnesses. Among persons with positive COVID-19 test results available by the second or third day of illness, few worked onsite. Hybrid and remote work policies might reduce workplace exposures and help reduce spread of respiratory viruses.

OBJECTIVE: Racial and ethnic disparities in influenza vaccination coverage among pregnant women in the United States have been documented. This study assessed the contribution of vaccine-related attitudes to coverage disparities. METHODS: Surveys were conducted following the 2019-2020 and 2020-2021 influenza seasons in a US research network. Using electronic health record data to identify pregnant women, random samples were selected for surveying; non-Hispanic Black women and influenza-unvaccinated women were oversampled. Regression-based decomposition analyses were used to assess the contribution of vaccine-related attitudes to racial and ethnic differences in influenza vaccination. Data were combined across survey years, and analyses were weighted and accounted for survey design. RESULTS: Survey response rate was 41.2% (721 of 1748) for 2019-2020 and 39.3% (706 of 1798) for 2020-2021. Self-reported influenza vaccination was higher among non-Hispanic White respondents (79.4% coverage, 95% CI 73.1%-85.7%) than Hispanic (66.2% coverage, 95% CI 52.5%-79.9%) and non-Hispanic Black (55.8% coverage, 95% CI 50.2%-61.4%) respondents. For all racial and ethnic groups, a high proportion (generally >80%) reported being seen for care, recommended for influenza vaccination, and offered vaccination. In decomposition analyses, vaccine-related attitudes (e.g., worry about vaccination causing influenza; concern about vaccine safety and effectiveness) explained a statistically significant portion of the observed racial and ethnic disparities in vaccination. Maternal age, education, and health status were not significant contributors after controlling for vaccine-related attitudes. CONCLUSIONS: In a setting with relatively high influenza vaccination coverage among pregnant women, racial and ethnic disparities in coverage were identified. Vaccine-related attitudes were associated with the disparities observed.

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. INTERVENTION: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). MAIN OUTCOMES AND MEASURES: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. RESULTS: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). CONCLUSIONS AND RELEVANCE: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03140423.

PURPOSE: This study assessed efficacy of one-time COVID-19 booster reminder/recall for booster eligible adolescents in a health-care system in Wisconsin. METHODS: COVID-19 booster eligible patients aged 12-17 years were randomized 1:1 to receive one reminder/recall message from the health-care system using the parent's preferred communication method (intervention) or no reminder/recall (usual care) in May 2022. RESULTS: Reminder/recall was sent to 2,146/4,296 (50%) adolescent patients. During the 90-day evaluation period following randomization, booster dose receipt was 2.0 percentage points (CI: 0.3%-3.7%) higher in the intervention (10.0%) versus usual care groups (8.0%). Among patients with ≥1 preventive visit during the evaluation period, uptake was 7.5 percentage points higher in the intervention (16.4%) versus usual care groups (8.9%). DISCUSSION: A single COVID-19 booster dose reminder/recall resulted in a small but statistically significant increase in booster dose receipt, though uptake overall was low. Additional strategies are needed to increase uptake.

Evaluations of vaccine effectiveness (VE) are important to monitor as COVID-19 vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or SARS-CoV-2 testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, VE of mRNA vaccines against COVID-19 was 91% (95% CI: 83-95) for full vaccination and 75% (95% CI: 55-87) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.Competing Interest StatementMPN reports grants from Merck &amp; Co. outside the submitted work. RKZ reports grants from Sanofi Pasteur outside the submitted work. GKB reports grants from Merck &amp; Co outside the submitted work and consulting fees from New World Medical, LLC. ETM reports grants from Merck &amp; Co. outside the submitted work and consulting fees from Pfizer. ASM reports consulting fees from Sanofi Pasteur and Seqirus. LEL reports grants from Xcenda, Inc., eMAXHealth, AstraZeneca, Pfizer, Evidera outside the submitted work. MLJ reports grants from Sanofi Pasteur. All other authors report nothing to disclose.Funding StatementThis work was supported by the US Centers for Disease Control and Prevention through cooperative agreements U01IP001034-U01IP001039. At Pittsburgh, the project was also supported by the National Institutes of Health through grant ULTR001857.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Centers for Disease Control and Prevention IRB project determination numbers for included projects: 0900f3eb81c2e791, 0900f3eb81c52dc5; 0900f3eb81c52420, 0900f3eb81bc746b, 6238All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesDe-identified dataset can be made available upon request

Background: The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. Method(s): Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Finding(s): 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. Interpretation(s): The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. Funding(s): Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged >=50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19, but protection offered by COVID-19 vaccines in the context of known exposure is unknown. Symptomatic outpatients reporting acute onset of COVID-19-like illness and tested for SARSCoV-2 infection were enrolled. Among 2,229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2 positive. Using the test-negative design, adjusted vaccine effectiveness was 71% (95% confidence interval, 49%-83%) among fully vaccinated participants reporting contact versus 80% (95% CI, 72%-86%) among those without. This study supports COVID-19 vaccination and highlights the importance of efforts to increase vaccination coverage. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

During a period of Omicron variant circulation, we estimated relative VE of COVID-19 mRNA booster vaccination versus primary two-dose series in an ongoing community cohort. Relative VE was 66% (95% CI: 46%, 79%) favoring the booster dose compared to primary series vaccination. Our results support current booster recommendations. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Background. In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness for the first time since the beginning of the COVID-19 pandemic. We estimated influenza vaccine effectiveness against lab-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. Methods. Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged >=6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and SARS-CoV-2 vaccination, participants who tested positive for SARS-CoV-2 were excluded from vaccine effectiveness estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity and general health status. Results. Among 6,260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1,948 SARS-CoV-2 positive patients, 4,312 patients were included in analyses of influenza VE; 2,463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95%CI, 20-49%) overall; 40% (95%CI, 24-53%) for those aged 6 months-49 years; and 10% (95%CI, -60-49%) for those aged >=50 years. Conclusion. Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons, with no measurable protection among older adults. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Reduced COVID-19 vaccine effectiveness (VE) has been observed with increasing predominance of the Delta variant. In a prospective rural community cohort of 1265 participants, VE against symptomatic and asymptomatic SARS-CoV-2 infection was 56% for mRNA COVID-19 vaccines. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background. Studies have reported that prior-season influenza vaccination is associated with higher risk of clinical influenza infection among vaccinees in a given season. Understanding the underlying causes requires consideration of within-season waning and recent infection. Methods. Using the US Flu Vaccine Effectiveness (VE) Network data over 8 influenza seasons (2011-2012 to 2018-2019), we estimated the effect of prior-season vaccination on the odds of clinical infection in a given season, after accounting for waning vaccine protection using regression methods. We adjusted for potential confounding by recent clinical infection using inverse-probability weighting. We investigated theoretically whether unmeasured subclinical infection in the prior season, which is more likely in the non-repeat vaccinees, could explain the repeat vaccination effect. Results. Repeat vaccinees vaccinated earlier in a season by one week. After accounting for waning VE, repeat vaccinees were still more likely to test positive for influenza A(H3N2) (OR=1.11, 95% CI:1.02-1.21) but not for influenza B (OR=1.03, 95% CI:0.89-1.18) or A(H1N1) (OR=1.03, 95% CI:0.90-1.19) compared to those vaccinated in the given season only. Recent clinical infection with the homologous (sub)type protected against clinical infection with A(H3N2) or B. Individuals with clinical infection in one season had 1.11 (95% CI:1.03-1.19) times the odds of switching vaccination status in the following season. Adjusting for recent clinical infections did not strongly influence the estimated effect of prior-season vaccination. Adjusting for subclinical infection could theoretically attenuate this effect. Conclusion. Waning protection and recent clinical infection were insufficient to explain observed reduced VE in repeat vaccinees with a test-negative design. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

OBJECTIVES: Examine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. METHODS: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged ≥65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age.

During late March–late May, COVID-19 incidence was highest among adults aged ≥80 years, with a peak in incidence in the week beginning April 12. In June, incidence increased in all age groups, with the most rapid rate of increase and highest overall incidence among young adults aged 18–24 years; the rate in this group continues to be the highest among all age groups. Incidence steadily increased among children and adolescents (aged 0–17 years). The incidence in high school–aged persons (aged 14–17 years) was markedly higher than that in younger children by early July, then decreased before increasing in September. During late September–early October, weekly incidence decreased among young adults aged 18–24 years only, then continued to steadily increase among all age groups through November 14.

Early in the pandemic, from mid-March to mid-May, COVID-19 incidence was highest among residents of large central and large fringe metropolitan areas. Beginning in mid-April, incidence in large metropolitan (central and fringe) areas declined and then increased similarly among all urban-rural areas. In September 2020, COVID-19 incidence sharply increased, and it remains highest among residents of medium/small metropolitan areas and micropolitan/noncore areas, indicating increased spread into rural communities. In October, weekly incidence was increasing steadily among all urban-rural areas.

BACKGROUND AND OBJECTIVES: Infants and children are at increased risk of severe influenza virus infection and its complications. Influenza vaccine effectiveness (VE) varies by age, influenza season, and influenza virus type/subtype. This study's objective was to examine the effectiveness of inactivated influenza vaccine against outpatient influenza illness in the pediatric population over 9 influenza seasons after the 2009 A(H1N1) pandemic. METHODS: During the 2011-2012 through the 2019-2020 influenza seasons at outpatient clinics at 5 sites of the US Influenza Vaccine Effectiveness Network, children aged 6 months to 17 years with an acute respiratory illness were tested for influenza using real-time, reverse-transcriptase polymerase chain reaction. Vaccine effectiveness was estimated using a test-negative design. RESULTS: Among 24 148 enrolled children, 28% overall tested positive for influenza, 3017 tested positive for influenza A(H3N2), 1459 for influenza A(H1N1)pdm09, and 2178 for influenza B. Among all enrollees, 39% overall were vaccinated, with 29% of influenza cases and 43% of influenza-negative controls vaccinated. Across all influenza seasons, the pooled VE for any influenza was 46% (95% confidence interval, 43-50). Overall and by type/subtype, VE against influenza illness was highest among children in the 6- to 59-month age group compared with older pediatric age groups. VE was lowest for influenza A(H3N2) virus infection. CONCLUSIONS: Analysis of multiple seasons suggested substantial benefit against outpatient illness. Investigation of host-specific or virus-related mechanisms that may result in differences by age and virus type/subtype may help further efforts to promote increased vaccination coverage and other influenza-related preventative measures.