{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:11:46Z","timestamp":1788487906764,"version":"build-2803163510"},"posted":{"date-parts":[[2026,6,24]]},"group-title":"Epidemiology","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01AI179874"],"award-info":[{"award-number":["R01AI179874"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01AI137093"],"award-info":[{"award-number":["R01AI137093"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Nirsevimab has been widely administered in the United States since 2023 to protect infants and young children from severe disease caused by respiratory syncytial virus (RSV). Although early post-licensure studies have shown high effectiveness against medically attended RSV infection, uncertainty remains about the durability of protection, effectiveness beyond the first RSV season, and the extent to which changing RSV seasonality influences real-world effectiveness.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To estimate the effectiveness of nirsevimab against medically attended RSV infection across three consecutive RSV seasons and to examine how effectiveness varies by season and time since immunization.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a test-negative case-control study utilizing electronic health records of infants and young children tested for RSV by polymerase chain reaction in outpatient and inpatient settings within the Yale New Haven Health System between October 1, 2023, and March 1, 2026. Effectiveness of nirsevimab was estimated using multivariable logistic regression, adjusting for age, weekly RSV activity, pre-existing risk factors, and other potential confounders. Variation in effectiveness was examined by season, encounter setting, and time since immunization up to 24 months.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, 17,755 infants and young children were tested for RSV infection, of whom 2,388 (13.4%) were cases and 15,367 (86.6%) were controls. The overall effectiveness of nirsevimab was 67.3% (95% confidence interval [CI]: 59.8, 73.3%) against all medically-attended RSV infections, 60.2% (95% CI: 49.6, 68.5%) against RSV-associated outpatient visits, and 88.9% (95% CI: 82.3, 93.0%) against RSV-associated hospitalization. Effectiveness against medically attended RSV infection declined across seasons, from 76.7% (95% CI: 60.5, 86.3%) in 2023\/24 to 54.4% (95% CI: 33.0, 68.9%) in 2025\/26. Lower season-specific effectiveness in later seasons corresponded with progressively delayed RSV activity over. Protection against RSV-associated hospitalization declined with increasing time since immunization, from 92.5% (95% credible interval [CrI]: 85.9, 96.4%) at 1 month, to 77.2% (95% CrI: 60.4, 87.6%) at 6 months, and 39.9% (95% CrI: 2.4, 63.3%) at 12 months post-immunization, after which effectiveness plateaued.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Nirsevimab remained effective against RSV-associated hospitalization through 6 to 12 months after immunization. Delayed RSV activity was associated with lower effectiveness, highlighting the importance of aligning administration with local RSV circulation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.22.26356264","type":"posted-content","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:20:26Z","timestamp":1782364826000},"source":"Crossref","is-referenced-by-count":1,"title":["Durability and Seasonal Variation in the Effectiveness of Nirsevimab over Three Seasons in Connecticut"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2805-0171","authenticated-orcid":false,"given":"Hanmeng","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Aparicio-Llorente","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Infectious Diseases and Global Health, Yale School of Medicine, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua L.","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7604-3638","authenticated-orcid":false,"given":"Lee","family":"Kennedy-Shaffer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia E.","family":"Pitzer","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Weinberger","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1897-6581","authenticated-orcid":false,"given":"Carlos R.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Infectious Diseases and Global Health, Yale School of Medicine, New Haven, CT, USA"},{"name":"Department of Biostatistics, Section of Health Informatics, Yale School of Public Health, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the PROVE-ID Group Authors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026062703350734000_2026.06.22.26356264v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)00478-0"},{"key":"2026062703350734000_2026.06.22.26356264v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-026-12574-6"},{"key":"2026062703350734000_2026.06.22.26356264v1.3","unstructured":"RSV Immunization Guidance for Infants and Young Children. Available: https:\/\/www.cdc.gov\/rsv\/hcp\/vaccine-clinical-guidance\/infants-young-children.html"},{"key":"2026062703350734000_2026.06.22.26356264v1.4","unstructured":"CDC. RSV Vaccine Guidance for Pregnant Women. In: Respiratory Syncytial Virus Infection (RSV) [Internet]. 13 Feb 2025 [cited 17 Apr 2025]. Available: https:\/\/www.cdc.gov\/rsv\/hcp\/vaccine-clinical-guidance\/pregnant-people.html"},{"key":"2026062703350734000_2026.06.22.26356264v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1913556"},{"key":"2026062703350734000_2026.06.22.26356264v1.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110275"},{"key":"2026062703350734000_2026.06.22.26356264v1.7","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S2352-4642(22)00321-2","article-title":"Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: a pooled analysis of randomised controlled trials","volume":"7","year":"2023","journal-title":"Lancet Child Adolesc Health"},{"key":"2026062703350734000_2026.06.22.26356264v1.8","doi-asserted-by":"crossref","unstructured":"Ares-G\u00f3mez S , Mallah N , Santiago-P\u00e9rez M-I , Pardo-Seco J , P\u00e9rez-Mart\u00ednez O , Otero-Barr\u00f3s M-T , et al. Effectiveness and impact of universal prophylaxis with nirsevimab in infants against hospitalisation for respiratory syncytial virus in Galicia, Spain: initial results of a population-based longitudinal study. Lancet Infect Dis. 2024.","DOI":"10.1016\/S1473-3099(24)00215-9"},{"key":"2026062703350734000_2026.06.22.26356264v1.9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1001\/jamapediatrics.2024.5572","article-title":"Respiratory syncytial virus disease burden and nirsevimab effectiveness in young children from 2023-2024","volume":"179","year":"2025","journal-title":"JAMA Pediatr"},{"key":"2026062703350734000_2026.06.22.26356264v1.10","doi-asserted-by":"crossref","first-page":"e250380","DOI":"10.1001\/jamanetworkopen.2025.0380","article-title":"Estimated effectiveness of nirsevimab against respiratory syncytial virus","volume":"8","year":"2025","journal-title":"JAMA Netw Open"},{"key":"2026062703350734000_2026.06.22.26356264v1.11","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1001\/jamapediatrics.2025.5778","article-title":"Effectiveness and impact of maternal RSV immunization and nirsevimab on medically attended RSV in US children","volume":"180","year":"2026","journal-title":"JAMA Pediatr"},{"key":"2026062703350734000_2026.06.22.26356264v1.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110362"},{"key":"2026062703350734000_2026.06.22.26356264v1.13","doi-asserted-by":"crossref","first-page":"e232598","DOI":"10.1001\/jamanetworkopen.2023.2598","article-title":"Estimation of COVID-19 mRNA vaccine effectiveness and COVID-19 illness and severity by vaccination status during Omicron BA.4 and BA.5 sublineage periods","volume":"6","year":"2023","journal-title":"JAMA Netw Open"},{"key":"2026062703350734000_2026.06.22.26356264v1.14","doi-asserted-by":"publisher","DOI":"10.1214\/09-STS313"},{"key":"2026062703350734000_2026.06.22.26356264v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3697"},{"key":"2026062703350734000_2026.06.22.26356264v1.16","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.17345935"},{"key":"2026062703350734000_2026.06.22.26356264v1.17","unstructured":"R Core Team (2024). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. Available: https:\/\/www.R-project.org\/"},{"key":"2026062703350734000_2026.06.22.26356264v1.18","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S2352-4642(25)00093-8","article-title":"Real-world effectiveness of nirsevimab against respiratory syncytial virus disease in infants: a systematic review and meta-analysis","volume":"9","year":"2025","journal-title":"Lancet Child Adolesc Health"},{"key":"2026062703350734000_2026.06.22.26356264v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00742-X"},{"key":"2026062703350734000_2026.06.22.26356264v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00570-X"},{"key":"2026062703350734000_2026.06.22.26356264v1.21","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwy163"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.22.26356264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T10:35:19Z","timestamp":1782556519000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.06.22.26356264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":21,"URL":"https:\/\/doi.org\/10.64898\/2026.06.22.26356264","relation":{},"subject":[],"published":{"date-parts":[[2026,6,24]]},"subtype":"preprint"}}