The ongoing ‘Observational Research on the Impact and Outcomes of Norovirus’ (ORION) study is a prospective, community-based cohort study of acute gastroenteritis (AGE), and specifically norovirus (NoV) gastroenteritis (NGE), burden among adults with underlying medical conditions who may be at higher risk for severe NGE. From January–March 2025, we recruited adults (≥18 years) with pre-specified “high-risk” medical conditions [e.g., cardiovascular disease, gastrointestinal (GI) or immunocompromising (IC) conditions] and otherwise healthy controls from 4 Kaiser Permanente (KP) sites. Study participants report new onset of AGE weekly, defined as ≥1 vomiting episode and/or ≥3 diarrhea episodes in a 24-hour period. Participants with AGE: (1) complete surveys about illness severity, quality of life impacts, and exacerbation of underlying conditions and (2) self-collect stool specimens for multiplex GI pathogen testing. Here we report AGE episodes per 100 person-weeks (PW) and laboratory testing results through April 2025. Participant observation continues through December 2025. We enrolled 3,527 participants across the 4 sites, described in Table 1. Participants reported 525 AGE episodes over 15,329 PWs (incidence of 3.4/100 PW). AGE incidence peaked around 5-7/100 PWs in January/February and declined in March/April. Among participants with AGE (Table 2), most were female (66%) and either 35-49 years (36%) or 50-64 years (24%); 41% had IC conditions, 34% had GI conditions; 34% had obesity, and only 6% were otherwise healthy. Six AGE episodes involved hospitalization. In 325 stool specimens tested to date, 30% (n=98) had ≥1 pathogen detected and 5% (n=15) were NoV-positive (Table 3), with genotype GII comprising 87% of NoV-positive specimens. Burden of NGE in individuals with underlying medical conditions is not well understood and is often extrapolated from studies of medically attended AGE, which underestimate community disease burden. ORION will provide valuable AGE and NGE burden estimates from the community setting and allow for improved assessment of disease severity for adults with high-risk underlying medical conditions. Mark A. Schmidt, PhD, MPH, AstraZeneca: Grant/Research Support|HilleVax: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support Holly C. Groom, MPH, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support Jennifer L. Kuntz, MS, PhD, Astra Zeneca: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Pfizer: Grant/Research Support Claudia Steiner, PhD, Moderna, Inc: Grant/Research Support Michael J. Miller, DrPH, American Journal of Health-System Pharmacy: Honoraria|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|The American Society of Health-System Pharmacists, Inc: Grant/Research Support Lisa Jackson, MD, MPH, Moderna: Grant/Research Support Jennifer K. Meece, PhD, CSL Seqirus: Grant/Research Support|GSK: Grant/Research Support|ModernaTX: Grant/Research Support John F. Dickerson, PhD, AstraZeneca: Grant/Research Support|HilleVax: Grant/Research Support|Moderna: Grant/Research Support Michelle Blake, PhD, MSc, HBSc, Moderna: Employment|Moderna: Stocks/Bonds (Public Company) Christine Kim, PhD, MSPH, Director, Moderna, Inc.: Employee|Director, Moderna, Inc.: Stocks/Bonds (Public Company) Wen-Hsing Wu, MS, Moderna: Stocks/Bonds (Public Company) Carly A. Crocker, BS, Moderna: Employment|Moderna: Stocks/Bonds (Public Company) Brandon J. Patterson, PharmD, PhD, Moderna: Employment|Moderna: Stocks/Bonds (Private Company) Meklit Workneh, MD, MPH, Moderna: Stocks/Bonds (Public Company) Lee Quist, DO, MBA, Moderna: Stocks/Bonds (Public Company) Katherine B. Carlson, PhD, MPH, Moderna: Employee|Moderna: Stocks/Bonds (Private Company)

Human metapneumovirus (HMPV) and human parainfluenza viruses (HPIV 1-4) are common causes of seasonal respiratory illness, but their household transmission dynamics remain poorly defined. We analyzed weekly symptom data and nasal swabs from a prospective household surveillance study in Washington and Oregon from June 2022 to March 2024. Swabs were tested for HMPV and HPIV, and a subset underwent whole-genome sequencing. Distinct index cases occurred in 236 (23%) and 341 (36%) of 1,040 households for HMPV and HPIV, respectively. Household secondary attack rates (SAR) and median generation times were similar for HMPV (8.7%, 7 days) and HPIV (7.3%, 7 days). Sequenced samples reflected contemporaneous circulating strains during the same period, with household sequences clustering closely together. High-quality viral whole genome sequences were recovered for two or more individuals within a household in a total of 26 households for HMPV and 45 households for HPIV. Intra-household pairwise nucleotide (nt) distance ranged from 0 to 14 nt (median 0) for HMPV and 0-8 nt (median 1) for HPIV when cases occurred 0-15 days apart. Transmission occurred primarily from children to adults, emphasizing the importance of childcare- and school-associated spread and supporting child-focused prevention strategies to reduce household transmission.

BACKGROUND:Portal vein thrombosis (PVT) is a common sequela of cirrhosis. Despite regression of fibrosis/cirrhosis observed among some patients after disease-specific treatment, few studies have considered the role of treatment and response on risk of PVT among patients with cirrhosis across different liver disease states. We considered aetiological treatment and response as well as whether non-selective beta-blockers (NSBBs), statins, and anticoagulants were associated with risk of PVT. METHODS:We used data for patients with cirrhosis (compensated or decompensated) from two large, US-based multisite cohort studies. Patients with hepatitis C (HCV) were drawn from the Chronic Hepatitis Cohort Study. Patients with primary biliary cholangitis (PBC) were drawn from the Fibrotic Liver Disease Consortium. Risk for PVT was assessed using a discrete survival model that includes both fixed covariates and time-dependent variables. RESULTS:Among 6659 HCV patients, 274 developed PVT across ~13 years of follow-up. Significant risk factors included time-varying decompensated cirrhosis (adjusted hazard ratio [aHR] 27.41, 95% confidence interval [CI] 15.89-47.30), male sex (aHR 1.48, 95% CI 1.12-1.94), and use of NSBBs (aHR 2.07, 95% CI 1.61-2.67). Among 786 PBC patients, 67 developed PVT across ~8 years of follow-up. Use of NSBBs was the only significant PVT risk factor in these patients (aHR 2.56, 95% CI 1.52-4.31). Neither sustained virological response [SVR] after antiviral treatment (HCV patients) nor response to ursodeoxycholic acid [UDCA] treatment (PBC patients) was associated with risk of PVT. CONCLUSIONS:In two large well-characterized samples of cirrhotic patients with HCV or PBC, disease-specific treatments were not associated with PVT risk. NSBB treatment was independently associated with > 2 times the risk of PVT in both samples, regardless of compensated or decompensated status.

BACKGROUND:Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States. METHODS:We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model. RESULTS:RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection ≥1 week and contact age ≤12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with ≥2 RSV infections were similar when occurring within ≤14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2). CONCLUSIONS:Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.

During 2022-2024, a total of 35 of 1,040 households had a distinct symptomatic index case of enterovirus D68; estimated symptomatic secondary infection rate was 13.6%. Sequences from patients within households clustered closely; we observed 0-2 pairwise nucleotide differences between household cases 6-14 days apart.

OBJECTIVES:To analyze the extent and risk factors of household influenza transmission using molecular testing and viral genomes. METHODS:In a community-based cohort in the United States during 2022-2024, participants self-collected weekly nasal swabs. Swabs were tested for influenza by RT-PCR; genomic sequencing was performed. Index cases had the first influenza detection within households. Factors associated with household transmission were evaluated using Poisson regression. RESULTS:Influenza transmission was detected in 56/303 influenza-positive households with a distinct index case. Most (82%) index cases were symptomatic; 16% of children vs 28% of adults were asymptomatic. 89/941 household contacts were infected 1-7 days after the index (secondary household infection risk: 9.5%, 95% CI: 7.3, 12.2). Index and secondary case median ages were 11 and 24 years, respectively. A greater proportion of contacts were infected when the index case was symptomatic (11%) vs asymptomatic (5%). Higher viral load was associated with 3.1 (1.7, 5.8) times higher risk of secondary infection. Most (13/16) index-secondary case pairs with available sequences differed by ≤3 nucleotides. CONCLUSIONS:Most household index cases were symptomatic children. Higher viral load and presence of symptoms among index cases were associated with household transmission. Home-based surveillance can assess household transmission using case chronology and genomics.

BACKGROUND:Households remain high-risk settings for SARS-CoV-2 transmission. Identifying contemporaneous risk factors for infection among household contacts of an index case can guide public health strategies. METHODS:We conducted a prospective observational household study in Oregon and Washington, USA, during 2022-2024. Participants completed enrollment, weekly, and follow-up symptom surveys and submitted sera and weekly nasal swabs. Swabs were tested for SARS-CoV-2 by polymerase chain reaction (PCR) ; a subset of positive specimens underwent whole genome sequencing. Sera was tested for SARS-CoV-2 antibodies. We evaluated individual and household-level factors associated with risk of SARS-CoV-2 infection after 1-14 days (likely secondary infection) among household contacts within households with a distinct (ie, single) index case. RESULTS:Overall, we identified 617 households with a distinct index case, of which 46% were children. The estimated secondary infection rate was 16% (95% CI 13.6%, 18.8%), reflecting 203 secondary infections among 1267 household contacts. Among household contacts, factors associated with secondary infection included low anti-nucleocapsid antibody titers (RR: 1.88, 95% CI 1.34, 2.64), or residing with an index case who was symptomatic (RR: 1.85; 95% CI 1.04, 3.23), or had viral detection >1 week (RR: 2.15, 95% CI 1.55, 2.97). Among 136 sequenced index-secondary case pairs, 128 (94%) shared SARS-CoV-2 lineages. CONCLUSION:During 2022-2024, 1 in 7 household contacts of index cases were infected within two weeks, with higher rates in contacts with lower antibody levels and when index cases had symptoms or longer viral detection. These findings can inform ongoing strategies to mitigate SARS-CoV-2 community transmission.

OBJECTIVES:Little is known about the impact of Clostridioides difficile infection (CDI) on health-related quality of life (HRQoL) among adults in the community. We examined the impact of CDI on HRQoL among adults with CDI in the outpatient setting and compared it to HRQoL among patients without CDI. METHODS:We conducted a prospective study among adult Kaiser Permanente members ≥50 years with CDI in the outpatient setting (cases) and members ≥45 years who had an outpatient encounter without diarrhea or C. difficile (controls). Cases and controls were not hospitalized within 7 days. Cases and controls completed the EQ-5D-5L at baseline and after 60 days. RESULTS:Our analyses included 213 adults with CDI and 426 adults without CDI. Adults with and without CDI reported similar perceived health status [median visual analogue scale (VAS) of 80.0 and 81.0, (p = 0.08)] and utility index scores [median of 0.9 for both; (p = 0.16)] before illness. On their worst day, adults with CDI reported lower perceived health status and utility index scores, compared to pre-infection (p < 0.0001). Decrements in median VAS and utility indices among adults with CDI from pre-infection to worst day were significantly greater than decrements among adults without CDI (p < 0.0001 for both). At 60 days, adults with and without CDI had VAS and utility index scores similar to pre-illness levels. CONCLUSIONS:Adults with CDI experienced significant reductions in HRQoL on the worst day of illness that were greater than that experienced by those without CDI. HRQoL among adults with CDI at 60 days was similar to pre-infection levels.

OBJECTIVE:Sustained virological response (SVR) in patients with hepatitis C virus (HCV) is associated with slower progression of cirrhosis. Likewise, statin treatment is associated with delayed cirrhosis progression, but most studies of statin use in chronic liver disease include patients with multiple disease aetiologies. We use a unique time-dependent analysis to evaluate the interplay between antiviral treatment and statin use and the risk of decompensated cirrhosis (DC) among patients with HCV over time. METHODS:Using data from the US-based retrospective Chronic Hepatitis Cohort Study, we evaluated the impact of time-varying antiviral treatment status and statin use on risk of DC after propensity score weighting for HCV treatment selection bias. We used a pseudo-observation approach to compress data into discrete time intervals using 1 year as the landmark interval (INT), where each 'INT' has a value of 0 (at index) through 15 (15 years postindex) or the date of last follow-up. Time from the index date to the event of incident DC was the main outcome of interest. Death was considered a competing risk. RESULTS:A total of 16 275 patients with HCV (with 93 343 intervals) were observed (2006-2018), with 1718 incidents of DC and 2398 deaths. By year 15, the proportion of patients without antiviral treatment decreased from 36% to 11%; statin use increased from 12% to 28%. Compared with no antiviral treatment, SVR was associated with reduced risk of DC (SVR: adjusted HR (aHR) 0.17, 95% CI 0.14 to 0.21). Statin use was also associated with lower risk of decompensation (aHR 0.68, 95% CI 0.58 to 0.80) independent of cirrhosis status; such reduced risks varied but were sustained across treatment status groups. Additional risk factors included body mass index >25, male sex and multiple comorbidities. CONCLUSIONS:Both SVR and statin treatment were associated with reduced risk of decompensation in patients with HCV. These findings may inform clinical management to reduce the risk of DC among patients with HCV.

Household transmission of EV-D68 was identified in 35 of 1040 households (3.4%) in the Pacific Northwest between 2022-2024, with an estimated secondary attack rate of 15%. Sequences from within households clustered closely with 0 to 2 pairwise nucleotide differences (median 1) between cases 6-14 days apart (median 7). ### Competing Interest Statement H. Y. C. reports consulting with Ellume, Pfizer, and the Bill and Melinda Gates Foundation. She has served on advisory boards for Vir, Merck and Abbvie; conducted CME teaching with Medscape, Vindico, and Clinical Care Options; and received research funding from Gates Ventures, and support and reagents from Ellume and Cepheid outside of the submitted work. P.R. reports consulting with Aicuris outside of the submitted work. J. A. E. reports consulting with Abbvie, Ark Biopharmaceuticals, Sanofi Pasteur, Moderna, Meissa Vaccines, AstraZeneca, and Pfizer, Inc. outside of the submitted work, and has received research funding from AstraZeneca, Merck, GlaxoSmithKline, and Pfizer. J. L. K. reported research funding not related to the submitted work from Pfizer, Novartis, and Vir Biotechnology. A.L.G. reports contract testing to UW from Abbott, Cepheid, Novavax, Pfizer, Janssen and Hologic, research support from Gilead, outside of the described work. All other authors report no potential conflicts. ### Funding Statement The CASCADIA study was funded by the Centers for Disease Control and Prevention (research contract number 75D30121C12297 to Kaiser Foundation Hospitals). The funders were not involved in the design of the study and do not have any ownership over the management and conduct of the study, the data, or the rights to publish. Computational analyses were supported by Fred Hutch Scientific Computing (National Institutes of Health Office of Research Infrastructure Programs grant no. S10OD028685) and University of Washington Laboratory Medicine Informatics. This analysis was funded by the Washington State Department of Health Northwest Pathogen Genomics Center of Excellence (WA DOH contract number HED29377-1, Federal grant number NU50CK000630). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Kaiser Permanente gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I 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). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript.

Abstract Background Household transmission is a major driver of SARS-CoV-2 spread. Viral genomic sequencing is a powerful tool for evaluation of putative within-household transmission. Characteristics of participants from multi-participant households with one or more positive tests for SARS-CoV-2 Methods CASCADIA, a prospective household cohort study that enrolled individuals in Oregon and Washington state, conducted active surveillance for respiratory viral infection through weekly symptom surveys and self-collected nasal swabs. Additional swabs and surveys were collected when new symptoms were reported or after an initial positive or inconclusive SARS-CoV-2 PCR test. Here we examine all positive SARS-CoV-2 test results from households with > 2 members enrolled in the study. Tests resulting as inconclusive were not considered. We also analyze genomic data generated from these positive swabs, limiting consideration to the first SARS-CoV-2 genome from each person and to households with sequenced samples from > 2 participants collected ≤ 14 days apart. Relationships among samples from the same household were assessed by determining the genetic (hamming) distance between genomes and the Pango lineage of each genome using Nextclade. Characteristics of pairs of positive samples from different study participants within the same household. Consideration was limited to the first sequenced sample from each participant and to pairs of samples collected 14 days apart or less. Results Between July 2022 to May 2023, 597 participants from 341 households with > 2 participants tested positive for SARS-CoV-2 (Table 1). Positive tests from > 2 participants collected ≤ 14 days apart were observed in 143 of these households. 93 households had sequence data for samples from > 2 persons collected ≤ 14 days apart. 5 (5%) of these households had 2 viral lineages detected with a median of 11 (range 4 – 14) days between detection of the first and second lineages (Figure 1). Two lineages were detected in 3 out of 6 sample pairs collected in the same household exactly 14 days apart. Among the 88 households with one lineage detected, samples from all participants were genetically identical (genetic distance of 0) in 60% (51/88). Conclusion SARS-CoV-2 genomes were identical in most households with sequence data from multiple cases detected ≤ 14 days apart. Multiple viral lineages were detected in a subset of the remaining households, suggesting > 1 viral introduction event rather than intra-household transmission. This data will aid in interpretation of household-based studies of SARS-CoV-2 that lack sequence data. Disclosures Mark A. Schmidt, PhD, MPH, HilleVax: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Vir Biotechnology: Grant/Research Support Jennifer L. Kuntz, MS, PhD, Hillevax, Inc: Grant/Research Support Stephen P. Fortmann, MD, Pfizer: Grant/Research Support Holly C. Groom, MPH, Hillevax: Grant/Research Support|Moderna: Grant/Research Support Richard A. Mularski, MD, MSHS, MCR, Pfizer, Inc: Grant/Research Support Neil D. Yetz, M.P.H., N/A: Expert Testimony Janet A. Englund, MD, Abbvie: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Speaker at meeting|SanofiPasteur: Advisor/Consultant|Shinogi: Advisor/Consultant Helen Y. Chu, MD, MPH, Abbvie: Advisor/Consultant|Merck: Advisor/Consultant|Vir: Advisor/Consultant

Supplementary Table 2 describes characteristics of HCV patients at baseline for lung cancer

Invasive Escherichia coli disease (IED) incidence has increased over recent years among aging populations and has rising antimicrobial resistance. Here, we report on a comparative, cross-sectional, retrospective analysis of US patients with IED to quantify IED-related healthcare resource utilization (HCRU), costs, and impact on health-related quality of life (HRQoL). This study included Kaiser Permanente Northwest (KPNW) members aged ≥ 60 years enrolled between July 2019 and January 2020. Patients were divided into three groups: Group 1 had experienced a recent IED episode (≤ 3 weeks before enrollment); Group 2 had experienced a former IED episode (13–18 months before enrollment); Group 3 was at risk with no prior history of IED. Data were collected from electronic hospital records, a patient survey, and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Mean costs were adjusted according to individual follow-up. Patient characteristics were generally consistent across Groups 1 (n = 289), 2 (n = 319), and 3 (n = 340). Inpatient hospitalization was observed in 84

OBJECTIVE:American Association for the Study of Liver Disease guidelines recommend regular testing of alkaline phosphatase (ALP) among patients with primary biliary cholangitis (PBC) to monitor disease progression and response to treatment with ursodeoxycholic acid (UDCA), but previous studies have shown that adherence to recommended testing intervals is low. We used data from the Fibrotic Liver Disease (FOLD) Consortium to evaluate rates of adherence among US routine care patients. METHODS:PBC cases were confirmed with chart abstraction. Patients from three FOLD sites (Henry Ford Health (Detroit, MI), Kaiser Permanente-Southern California (Los Angeles, California) and Kaiser Permanente-Northwest (Portland, Oregon)) were observed from 1 January 2018 through 31 December 2021. We divided our evaluation of adherence to monitoring guidelines into two segments: (1) the first 12 months post-UDCA initiation; and (2) >12 months post-UDCA initiation. RESULTS:A total of 1756 patients were identified for the 2018-2021 period; 67 patients did not receive UDCA and were excluded from the sample. A total of 1689 patients were included in one or both segments (segment 1: 740, segment 2: 1689). Only 52% of patients received appropriate ALP testing to ascertain response to UDCA after roughly 1 year of treatment; rates were significantly higher among patients with specialist care compared with those without (54% vs 45%, p=0.001). For the period following the first year of UDCA treatment, the observed monitoring rate was 67%, where hepatology or gastroenterology specialist care was associated with significantly higher rates of monitoring (65%-78%) compared with those without care from a specialist (30%-57%, p<0.0001) with the same level of comorbidity. CONCLUSION:In a large US PBC cohort, there were concerning levels of non-adherence to recommended biochemical monitoring. Receipt of care from a specialist was associated with higher rates of monitoring. Strategies to increase rates of biochemical testing are needed.

Background Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge.Methods We analyzed data from 3 cohort studies spanning 1 September 2022 to 31 July 2023 to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs irrespective of symptoms, participated in annual blood draws, and completed periodic surveys, which included vaccination status and infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated by Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination.Results Among 3344 adults, the adjusted VE of a bivalent vaccine against infection was 37.2% (95% CI, 12.3%-55.7%) within 7 to 59 days of vaccination and 21.1% (95% CI, -0.5% to 37.1%) within 60 to 179 days of vaccination when compared with participants who were unvaccinated or had received an original monovalent vaccine dose >= 180 days prior. Overall, the adjusted VE of a bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI, 46.0%-74.5%) within 7 to 179 days of vaccination and 39.4% (95% CI, 12.5%-61.6%) at >= 180 days when compared with naive participants who were unvaccinated or had received a monovalent vaccine dose >= 180 days prior.Conclusions Adults with prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection. According to data from 3 prospective cohort studies where participants collected weekly nasal swabs, protection from COVID-19 vaccination against SARS-CoV-2 infection and symptomatic illness was highest among adults with prior infection and recent vaccination. Recent vaccination alone provided moderate protection.

Supplementary Table 5 shows characteristics of HCV patients at baseline for prostate cancer

BACKGROUND:While acute gastroenteritis (AGE) occurs year-round, norovirus has a winter seasonality in the United States. OBJECTIVE:We analyzed norovirus seasonality within a US integrated healthcare delivery system from 2016-2019. METHODS:Electronic medical records were collected for acute gastroenteritis (AGE) encounters with specific ICD-9/10 codes or clinical stool testing. Norovirus percent positivity was calculated as the 8-week centered rolling average. Temperature and absolute humidity data were measured via weather station. The relationship between these factors and weekly norovirus episodes were modeled via negative binomial models. RESULTS:From 2016-2019, there were 198,181 AGE episodes reported; among the 18,998 episodes tested, 892 (5%) were norovirus positive. Norovirus percent positivity peaked in epidemiologic week 7 at 9%. Two negative binomial models showed significant inverse relationships between weekly number of norovirus episodes and both temperature and absolute humidity. CONCLUSION:Norovirus AGE exhibited winter seasonality from 2016-2019, associated with lower temperatures and humidity. Understanding this seasonality may help predict peak transmission periods and their impact on healthcare resources.

Abstract Background Clinical trials for norovirus (NoV) vaccines are underway. Prior research has found generally positive attitudes toward a potential NoV vaccine, but there is limited understanding of how the COVID-19 pandemic may have impacted attitudes toward novel vaccines. Methods We identified medically-attended acute gastroenteritis (MAAGE) encounters among Kaiser Permanente Northwest members of all ages based on ICD-10 diagnostic codes, occurring from 11/17/2023-4/18/2024. Participants were asked to complete surveys which included questions about their level of agreement with the need for and willingness to get a potential NoV, as well as whether the COVID-19 pandemic impacted attitudes about vaccines.Figure 2.How has the COVID-19 pandemic changed attitudes about vaccines? Distribution of responses, by age group, November 2023-April 2024. Results Of 8,363 adults and 666 parents/guardians of children with MAAGE who were invited to participate, 553 (6.6%) adults and 38 (5.8%) guardians consented and completed surveys. Among adults, median age was 46 (range 18-90) years; most were female (76%) and of white race (84%). Among children of parents/guardians, median age was 4 (range 0-17) years; 58% were female and 89% were white. Overall, 37% of adult MAAGE patients agreed that a NoV vaccine was needed to prevent illness for themselves and 47% agreed that a vaccine was needed to protect the community; 56% agreed that they would get a NoV vaccine if available. When stratified by age group (18-49 yrs., 50-64 yrs., 65+ yrs.), the oldest respondents had the most favorable responses, with 63% of adults 65+ years indicating that they would get a potential vaccine (Fig 1). Among guardians, 61% agreed a vaccine was needed to prevent their child from getting ill and 74% agreed the community was in need of a NoV vaccine. Overall, 68% agreed they would vaccinate their child. When asked how the COVID-19 pandemic had impacted attitudes about vaccines, most respondents indicated there was either no change (37-42%) or they had increasingly positive attitudes (26-41%); a minority (6-16%) reported more negative attitudes (Fig 2). Conclusion In this sample of patients with recent MAAGE events, over 60% of adults 65+ and child guardians expressed willingness to get a NoV vaccine for themselves or their child. More respondents reported a positive shift in comparison to a negative shift in attitude towards vaccines following the COVID-19 pandemic. Disclosures Holly C. Groom, MPH, Hillevax: Grant/Research Support|Moderna: Grant/Research Support Matthew T. Slaughter, MS, Moderna: Grant/Research Support Judy L. Donald, MA, HilleVax: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Vir Biotechnology: Grant/Research Support Emma Viscidi, PhD, MHS, Moderna: Stocks/Bonds (Public Company) John F. Dickerson, PhD, Janssesn: Grant/Research Support|Moderna: Grant/Research Support|Novartis: Grant/Research Support|Pfizer: Grant/Research Support Maureen O'Keeffe-Rosetti, MS, Hillevax: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Mark A. Schmidt, PhD, MPH, HilleVax: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Vir Biotechnology: Grant/Research Support Laura H. Hendrix, MS, Moderna Therapeutics Ltd.: Stocks/Bonds (Private Company) Katherine B. Carlson, PhD, MPH, Moderna: Stocks/Bonds (Private Company)