Natoli, Traci L.

Objective Respiratory syncytial virus (RSV) is an important viral pathogen in children, older adults and adults with certain high-risk conditions. In our prospective community-based cohort study of adults 50 years and older before the COVID-19 pandemic, the incidence of RSV acute respiratory infection (ARI) was 48.6 cases/1000 person-years (PY), which decreased to near zero during the COVID-19 pandemic. Our objective was to determine the incidence of RSV-ARI during the 2 years following the initial phase of the pandemic (2021–2022 and 2022–2023). Design This is a community-based prospective cohort study. Setting Adults living in southeast Minnesota from October 2021 to September 2022 (year 3) and October 2022 to September 2023 (year 4). Participants Adults≥50 years (n=2500). Primary and secondary outcomes We calculated incidence and attack rates for RSV-ARI as primary outcome and reported hospitalisations, pneumonia and death following ARI as secondary outcome. Results There were 2500 participants in the study with a mean age of 68.2 years (SD 9.3) at the start of year 3. Participants were predominantly female (60%), non-Hispanic white (96%) and residing in urban areas (76%). The incidence rate of RSV-ARI was 6.12/1000 PY (95% CI 3.42 to 10.09) in 2021–2022 and 16.40/1000 PY (95% CI 11.66 to 22.42) in 2022–2023. We noted higher attack rates of RSV-ARI during the winter months. There were no hospitalisations, pneumonia or deaths within 30 days of RSV-ARI. Conclusions Compared with the period before the COVID-19 pandemic, RSV-ARI incidence was lower in both 2021–2022 and 2022–2023 periods. In 2022–2023, the incidence increased 2.7-fold compared with the 2021–2022 period. The observed incidence rates, particularly the significant increase in the most recent season, underscore the continued public health relevance of RSV-ARI and support the rationale for ongoing RSV vaccination efforts to mitigate its overall burden in the population.

Abstract Background Data on respiratory syncytial virus (RSV) acute respiratory infection (ARI) among community-dwelling U.S. adults aged 18 to 64 years, particularly those with high-risk conditions (HRC), remain limited. This study estimated incidence and attack rates of RSV-ARI and RSV lower respiratory tract disease (LRTD) in adults with and without HRCs. Methods A multistate, community-based prospective cohort of adults aged 18 to 64 years with and without HRCs was followed from October 2022 to September 2024. Incidence rates and annual attack rates of RSV-ARI and RSV-LRTD were calculated by HRC presence and age group. Results Of 3375 adults with at least 1 HRC, the RSV-ARI incidence rate was 17.9 per 1000 person-years (attack rates: year 1, 1.87%; year 2, 1.56%), compared with 14.8 per 1000 person-years (year 1, 1.33%; year 2, 1.50%) among adults without HRCs. RSV-LRTD incidence was 10.0 per 1000 person-years in adults with HRCs versus 5.7 per 1000 person-years in those without. Asthma, congenital immunodeficiency, and immunosuppressive medication use were associated with increased incidence of RSV-ARI and RSV-LRTD; whereas adults with solid organ transplant and chronic kidney disease had a significantly higher incidence rate of RSV-LRTD compared to those without these conditions. Adults aged 18 to 49 years with HRCs had significantly higher RSV-LRTD incidence (9.6 vs 4.3 per 1000 person-years). After adjustment for age and sex, having ≥1 HRC was associated with a 62% increased RSV-LRTD risk, rising to 117% among adults aged 18 to 49 years. Conclusions Adults with HRCs—particularly asthma, congenital immunodeficiency, chronic kidney disease, immunosuppressive medication use, and solid organ transplant—experienced higher RSV-ARI and RSV-LRTD incidence. The elevated RSV-LRTD burden was most pronounced in adults aged 18 to 49 years with HRCs.

Abstract Background/Objective: Decentralized research has many advantages; however, little is known about the representativeness of a source population in decentralized studies. We recruited participants aged 18-64 years from four states from June to December 2022 for a prospective cohort study to assess viral epidemiology. Our aim was to determine the association between age, gender, race/ethnicity, rurality, and socioeconomic status (SES) on study participation in a decentralized prospective cohort study. Methods: We consented 9,286 participants from 231,099 (4.0%) adults with the mean age of 45.6 years (±12.0). We used an electronic decentralized approach for recruitment. Consented participants were more likely to be non-Hispanic White, female, older, urban residents, have more health conditions, and possessed higher socioeconomic status (SES) compared to those non-consented. Results: We observed an interaction between SES and race-ethnicity on the odds of consent (P = 0.006). Specifically, SES did not affect non-Hispanic white participation rates(OR 1.24 95% CI 1.16 – 1.32] for the highest SES quartile compared to those with the lowest SES quartile) as much as it did participants combined across the other races (OR 1.73; 95% CI 1.45 – 2.98]) Conclusion: The relationship between SES and consent rates might be disproportionately greater in historically disadvantaged groups, compared to non-Hispanic White. It suggests that instead of focusing on enrollment of specific minority groups in research, there is value in future research exploring and addressing the diversity of barriers to trials within minority groups. Our study highlights that decentralized studies need to address social determinants of health, especially in under-resourced populations.

Abstract Background The incidence of respiratory syncytial virus (RSV)–acute respiratory infection (ARI) in community-dwelling adults after the Omicron variant of the COVID-19 pandemic is unknown. Our aim was to assess the incidence of RSV-ARI in adults aged 18 to 64 years over 2 consecutive RSV seasons (October–April 2022–2024) in 4 US states. Methods This community-based prospective cohort study comprised 7501 participants in Minnesota, Wisconsin, Florida, and Arizona. We calculated RSV-ARI and RSV–lower respiratory tract disease (LRTD) incidence and attack rates. We reported unadjusted incidence by age group, gender, race and ethnicity, Charlson Comorbidity Index, socioeconomic status, residential state, and rural/urban setting. Results Seasons 1 and 2 had 2250 and 2377 ARI episodes, respectively, with an RSV-ARI positivity rate of 5.5% for season 1 and 5.8% for season 2 among those tested. In season 1, the overall incidence of RSV-ARI was 27.71 (95% CI, 22.82–33.34) per 1000 person-years (1.49% attack rate). Almost half (49.0%) had RSV-LRTD, with an incidence of 13.53 (95% CI, 10.19–17.61) per 1000 person-years (0.73% attack rate). In season 2, the RSV-ARI and RSV-LRTD incidence rates were 26.39 (95% CI, 21.73–31.75) per 1000 person-years (1.51% attack rate) and 12.43 (95% CI, 9.31–16.26) per 1000 person-years (0.72% attack rate). RSV-ARI incidence peaked in November 2022 and December 2023. Conclusions Our observations suggest that RSV-ARI incidence and seasonal pattern are shifting to prepandemic RSV epidemiology.

Introduction: Using a digital process that leverages electronic health records (EHRs) can ease many of the challenges presented by the traditional enrollment process for clinical trials. We tested if automated batch enrollment using a technology-enabled subject recruitment system (TESRS) enhances recruitment while preserving representation of research subjects for the study population in our study setting. Methods: An ongoing community-based prospective adult cohort study was used to randomize 600 subjects who were eligible by age and residential address to TESRS (n = 300) and standard mailing method (n = 300), respectively, for 3 months. Then, TESRS was initiated and included automatic identification of patients’ preference for being contacted (online patient portal vs postal mail) from EHRs and automatic sending out of invitation letters followed by completion of a short online survey for checking eligibility and the digital consent process if eligible. We compared (1) median time to consent from invitation sent out per subject and total subjects recruited after a 3-month recruitment period, (2) the estimated study staff’s time, and (3) representation of sociodemographic characteristics (e.g., age, sex, race, SES measured by HOUSES index, and rural residence) between subjects recruited via TESRS and those via traditional mailing methods. Results: Median age of randomized subjects (n = 600) was 63 years with 52.0% female and 89.2% non-Hispanic White. Over a 3-month period, results showed consent rate via TESRS was 13% (39/297) similar to 11% (31/295) via standard mailing. However, recruitment was significantly faster with the TESRS approach (median 7 vs 26 days) given the study staff’s effort. Study staff’s time saved by using TESRS compared to standard mailing approach was estimated at 40 min per subject (equivalent to 200 h for 300 subjects). No significant differences in characteristics of research subjects from the study population were found. Conclusion: Our study demonstrated the utility of TESRS as a subject recruitment digital technology which significantly enhanced the recruitment effort while reducing the study staff burden of recruitment while maintaining the consistency of characteristics of recruited subjects. The strategy and support for implementing and testing TESRS in other study settings should be considered.

Importance Little is known about the burden and outcomes of respiratory syncytial virus (RSV)–positive acute respiratory infection (ARI) in community-dwelling older adults. Objective To assess the incidence of RSV-positive ARI before and during the COVID-19 pandemic, and to assess outcomes for RSV-positive ARI in older adults. Design, Setting, and Participants This was a community-based cohort study of adults residing in southeast Minnesota that followed up with 2325 adults aged 50 years or older for 2 RSV seasons (2019-2021) to assess the incidence of RSV-positive ARI. The study assessed outcomes at 2 to 4 weeks, 6 to 7 months, and 12 to 13 months after RSV-positive ARI. Exposure RSV-positive and -negative ARI. Main Outcomes and Measures RSV status was the main study outcome. Incidence and attack rates of RSV-positive ARI were calculated during each RSV season, including before (October 2019 to April 2020) and during (October 2020 to April 2021) COVID-19 pandemic, and further calculated during non-RSV season (May to September 2021) for assessing impact of COVID-19. The self-reported quality of life (QOL) by Short-Form Health Survey-36 (SF-36) and physical functional measures (eg, 6-minute walk and spirometry) at each time point was assessed. Results In this study of 2325 participants, the median (range) age of study participants was 67 (50-98) years, 1380 (59%) were female, and 2240 (96%) were non-Hispanic White individuals. The prepandemic incidence rate of RSV-positive ARI was 48.6 (95% CI, 36.9-62.9) per 1000 person-years with a 2.50% (95% CI, 1.90%-3.21%) attack rate. No RSV-positive ARI case was identified during the COVID-19 pandemic RSV season. Incidence of 10.2 (95% CI, 4.1-21.1) per 1000 person-years and attack rate of 0.42%; (95% CI, 0.17%-0.86%) were observed during the summer of 2021. Based on prepandemic RSV season results, participants with RSV-positive ARI (vs matched RSV-negative ARI) reported significantly lower QOL adjusted mean difference (limitations due to physical health, −16.7 [95% CI, −31.8 to −1.8]; fatigue, −8.4 [95% CI, −14.3 to −2.4]; and difficulty in social functioning, −11.9 [95% CI, −19.8 to −4.0] within 2 to 4 weeks after RSV-positive ARI [ie, short-term outcome]). Compared with participants with RSV-negative ARI, those with RSV-positive ARI also had lower QOL (fatigue: −4.0 [95% CI, −8.5 to −1.3]; difficulty in social functioning, −5.8 [95% CI, −10.3 to −1.3]; and limitation due to emotional problem, −7.0 [95% CI, −12.7 to −1.3] at 6 to 7 months after RSV-positive ARI [intermediate-term outcome]; fatigue, −4.4 [95% CI, −7.3 to −1.5]; difficulty in social functioning, −5.2 [95% CI, −8.7 to −1.7] and limitation due to emotional problem, −5.7 [95% CI, −10.7 to −0.6] at 12-13 months after RSV-positive ARI [ie, long-term outcomes]) independent of age, sex, race and/or ethnicity, socioeconomic status, and high-risk comorbidities. Conclusions and Relevance In this cohort study, the burden of RSV-positive ARI in older adults during the pre-COVID-19 period was substantial. After a reduction of RSV-positive ARI incidence from October 2020 to April 2021, RSV-positive ARI re-emerged during the summer of 2021. RSV-positive ARI was associated with significant long-term lower QOL beyond the short-term lower QOL in older adults.