Background: In August 2023, the Centers for Disease Control and Prevention recommended nirsevimab, a long-acting monoclonal antibody, for all U.S. infants aged <8 months entering or born during their first respiratory syncytial virus (RSV) season. Our aim was to estimate nirsevimab effectiveness against RSV-associated emergency department (ED) encounters and hospitalisation among U.S. infants during the 2023–2024 RSV season. Methods: We conducted a test-negative analysis using electronic health record (EHR) data from 6 healthcare systems, including ED encounters and hospitalizations with a diagnosis of RSV-like illness (RLI) during October 8, 2023–March 31, 2024, among infants aged <8 months as of October 1, 2023, or born during the study period. Nirsevimab effectiveness was estimated by comparing children who received nirsevimab with those who did not among RSV-positive and RSV-negative encounters, adjusting for age, race and ethnicity, sex, calendar day, and geographic region and excluding infants whose mother received RSV vaccination during pregnancy. Findings: Among 5039 ED encounters with RLI among infants in their first RSV season, 2045 (41%) were RSV-positive and 446 (9%) received nirsevimab, with a median time since dose of 52 days (interquartile range [IQR]: 27–84 days). Among 1025 hospitalizations with RLI among infants in their first RSV season, 605 (59%) were RSV-positive and 95 (9%) received nirsevimab, with a median time since dose of 48 days (IQR: 24–82 days). Nirsevimab effectiveness was 77% (95% CI: 69%–83%) against RSV-associated ED encounters and 98% (95% CI: 95%–99%) against RSV-associated hospitalisation. Interpretation: Nirsevimab was effective in preventing RSV-associated ED encounters and hospitalisation among infants in their first RSV season, with greatest protection against hospitalisation. However, these estimates reflect a short interval from nirsevimab administration to RLI onset. Since nirsevimab is a passive immunization and concentration is expected to wane over time, it is important to continue monitoring effectiveness to assess effectiveness with increased time since dose. Funding: This work was supported by the Centers for Disease Control and Prevention (contracts 75D30121D12779 to Westat and 75D30123C18039 to Kaiser Foundation Hospitals). © 2025 Elsevier B.V., All rights reserved.

Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.

BACKGROUND: To inform prevention strategies, we assessed the extent of SARS-CoV-2 transmission and settings in which transmission occurred in a Georgia public school district. METHODS: During December 1, 2020-January 22, 2021, SARS-CoV-2-infected index cases and their close contacts in schools were identified by school and public health officials. For in-school contacts, we assessed symptoms and offered SARS-CoV-2 RT-PCR testing; performed epidemiologic investigations and whole-genome sequencing to identify in-school transmission; and calculated secondary attack rate (SAR) by school setting (e.g., sports, elementary school classroom), index case role (i.e., staff, student), and index case symptomatic status. RESULTS: We identified 86 index cases and 1,119 contacts, 688 (63.1%) of whom received testing. Fifty-nine (8.7%) of 679 contacts tested positive; 15 (17.4%) of 86 index cases resulted in ≥2 positive contacts. Among 55 persons testing positive with available symptom data, 31 (56.4%) were asymptomatic. Highest SAR were in indoor, high-contact sports settings (23.8%, 95% confidence interval [CI] 12.7, 33.3), staff meetings/lunches (18.2%, CI 4.5-31.8), and elementary school classrooms (9.5%, CI 6.5-12.5). SAR was higher for staff (13.1%, CI 9.0-17.2) versus student index cases (5.8%, CI 3.6-8.0) and for symptomatic (10.9%, CI 8.1-13.9) versus asymptomatic index cases (3.0%, CI 1.0-5.5). CONCLUSIONS: Indoor sports may pose a risk to the safe operation of in-person learning. Preventing infection in staff members, through measures that include COVID-19 vaccination, is critical to reducing in-school transmission. Because many positive contacts were asymptomatic, contact tracing should be paired with testing, regardless of symptoms.

On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic (1). As of March 28, 2020, a total of 571,678 confirmed COVID-19 cases and 26,494 deaths have been reported worldwide (2). Reports from China and Italy suggest that risk factors for severe disease include older age and the presence of at least one of several underlying health conditions (3,4). U.S. older adults, including those aged ≥65 years and particularly those aged ≥85 years, also appear to be at higher risk for severe COVID-19-associated outcomes; however, data describing underlying health conditions among U.S. COVID-19 patients have not yet been reported (5). As of March 28, 2020, U.S. states and territories have reported 122,653 U.S. COVID-19 cases to CDC, including 7,162 (5.8%) for whom data on underlying health conditions and other known risk factors for severe outcomes from respiratory infections were reported. Among these 7,162 cases, 2,692 (37.6%) patients had one or more underlying health condition or risk factor, and 4,470 (62.4%) had none of these conditions reported. The percentage of COVID-19 patients with at least one underlying health condition or risk factor was higher among those requiring intensive care unit (ICU) admission (358 of 457, 78%) and those requiring hospitalization without ICU admission (732 of 1,037, 71%) than that among those who were not hospitalized (1,388 of 5,143, 27%). The most commonly reported conditions were diabetes mellitus, chronic lung disease, and cardiovascular disease. These preliminary findings suggest that in the United States, persons with underlying health conditions or other recognized risk factors for severe outcomes from respiratory infections appear to be at a higher risk for severe disease from COVID-19 than are persons without these conditions.

BACKGROUND: Group A Streptococcus (GAS) is a leading cause of acute respiratory infections frequently resulting in antibiotic prescribing. Vaccines against GAS are currently in development. METHODS: We estimated the incidence of healthcare visits and antibiotic prescribing for pharyngitis, sinusitis, and acute otitis media (AOM) in the United States using nationally-representative surveys of outpatient care provision, supplemented by insurance claims data. We estimated the proportion of these episodes attributable to GAS, and to GAS emm types included in a proposed 30-valent vaccine. We used these outputs to estimate the incidence of outpatient visits and antibiotic prescribing preventable by GAS vaccines with various efficacy profiles under infant and school-age dosing schedules. RESULTS: GAS pharyngitis causes 19.1 (95%CI: 17.3-21.1) outpatient visits and 10.2 (9.0-11.5) antibiotic prescriptions per 1,000 US persons aged 0-64 years, annually. GAS pharyngitis causes 93.2 (82.3-105.3) visits and 53.2 (45.2-62.5) antibiotic prescriptions per 1,000 children ages 3-9 years, annually, representing 5.9% (5.1-7.0%) of all outpatient antibiotic prescribing in this age group. Collectively, GAS-attributable pharyngitis, sinusitis, and AOM cause 26.9 (23.9-30.8) and 16.1 (14.0-18.7) outpatient visits and antibiotic prescriptions per 1,000 population, annually. A 30-valent GAS vaccine meeting the WHO 80% efficacy target could prevent 5.4% (4.6-6.4%) of outpatient antibiotic prescriptions among children aged 3-9 years. If vaccine prevention of GAS pharyngitis made routine antibiotic treatment of pharyngitis unnecessary, up to 17.1% (15.0-19.6%) of outpatient antibiotic prescriptions among children aged 3-9 years could be prevented. CONCLUSIONS: An efficacious GAS vaccine could prevent substantial incidence of pharyngitis infections and associated antibiotic prescribing in the United States.