{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:28:37Z","timestamp":1785864517106,"version":"3.56.0"},"reference-count":17,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000276","name":"Department of Health and Social Care","doi-asserted-by":"publisher","award":["COVID-19surveillancestudies"],"award-info":[{"award-number":["COVID-19surveillancestudies"]}],"id":[{"id":"10.13039\/501100000276","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["222907"],"award-info":[{"award-number":["222907"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023699","name":"Health Data Research UK","doi-asserted-by":"crossref","award":["LOND1"],"award-info":[{"award-number":["LOND1"]}],"id":[{"id":"10.13039\/501100023699","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"crossref","award":["302435"],"award-info":[{"award-number":["302435"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns7:p>Background We have previously demonstrated that older residents of long-term care facilities (LTCF) in the UK show levels of anti-spike antibodies that are comparable to the general population following primary series and booster vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data on the humoral response to other SARS-CoV-2 proteins associated with natural infection are scarce in this vulnerable population. Methods We measured quantitative levels of anti-nucleocapsid antibodies in blood samples taken from LTCF residents and staff after initial and repeat SARS-CoV-2 infections, between December 2020 and March 2023. Data on SARS-CoV-2 infection and vaccination were obtained through linkage to national datasets. Linear mixed effects models were used to investigate anti-nucleocapsid antibody levels, using log10 scale, in relation to time from most recent infection. This included evaluation of associations between repeat infection, staff\/resident status, age, sex, Omicron infection and vaccination history and peak antibody level and slope of decline with time. Results We analysed 405 antibody observations from 220 residents and 396 observations from 215 staff. Repeat infection was associated with 8.5-fold (95%CI 4.9-14.8-fold) higher initial (peak) median anti-nucleocapsid antibody level, with steeper subsequent slope of decline. There were no significant differences in antibody level associated with resident (vs. staff) status or age, but Omicron infection was associated with 3.6-fold (95%CI 2.4\u20135.4-fold) higher levels. There was stronger evidence of waning of antibody levels over time in a sensitivity analysis in which observations were censored in cases with suspected undetected repeat infection. Conclusions We found similar levels of anti-nucleocapsid antibody in residents and staff of LTCFs. Repeat infection and infection with an Omicron strain were associated with higher peak values. There was evidence of waning of anti-nucleocapsid antibody levels over time.<\/ns7:p>","DOI":"10.12688\/wellcomeopenres.20750.1","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T04:45:06Z","timestamp":1708317906000},"page":"45","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti-nucleocapsid antibody levels following initial and repeat SARS-CoV-2 infections in a cohort of long-term care facility residents in England (VIVALDI)"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8705-3281","authenticated-orcid":false,"given":"Oliver","family":"Stirrup","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokhan","family":"Tut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-642X","authenticated-orcid":false,"given":"Maria","family":"Krutikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Lancaster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borscha","family":"Azmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Monakhov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-1967","authenticated-orcid":false,"given":"Paul","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-6232","authenticated-orcid":false,"given":"Andrew","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Copas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-2555","authenticated-orcid":false,"given":"Laura","family":"Shallcross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2024,2,19]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1804-13","DOI":"10.1093\/ije\/dyab176","article-title":"Penetration and impact of COVID-19 in long term care facilities in England: population surveillance study.","volume":"50","author":"D Chudasama","year":"2022","journal-title":"Int J Epidemiol."},{"key":"ref-2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac694","article-title":"Clinical Effectiveness of SARS-CoV-2 Booster Vaccine Against Omicron Infection in Residents and Staff of Long-term Care Facilities: A Prospective Cohort Study (VIVALDI).","volume":"10","author":"O Stirrup","year":"2022","journal-title":"Open Forum Infect Dis."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"e13-e21","DOI":"10.1016\/S2666-7568(21)00282-8","article-title":"Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England.","volume":"3","author":"M Krutikov","year":"2022","journal-title":"Lancet Healthy Longev."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"1877-1881","DOI":"10.1093\/infdis\/jiac146","article-title":"Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Antibody Levels Following Second Dose of ChAdOx1 nCov-19 or BNT162b2 Vaccine in Residents of Long-term Care Facilities in England (VIVALDI).","volume":"226","author":"O Stirrup","year":"2022","journal-title":"J Infect Dis."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"93-104","DOI":"10.1038\/s43587-022-00328-3","article-title":"Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes.","volume":"3","author":"G Tut","year":"2023","journal-title":"Nat Aging."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"553","DOI":"10.12688\/wellcomeopenres.20278.1","article-title":"VIVALDI Cohort Profile: Using linked, routinely collected data and longitudinal blood sampling to characterise COVID-19 infections, vaccinations, and related outcomes in care home staff and residents in England [version 1; peer review: awaiting peer review].","volume":"8","author":"M Krutikov","year":"2023","journal-title":"Wellcome Open Res."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"232","DOI":"10.12688\/wellcomeopenres.16193.2","article-title":"Study Protocol: Understanding SARS-Cov-2 infection, immunity and its duration in care home residents and staff in England (VIVALDI) [version 2; peer review: 2 approved].","volume":"5","author":"M Krutikov","year":"2020","journal-title":"Wellcome Open Res."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"e96-e8","DOI":"10.1016\/j.jinf.2022.07.003","article-title":"Rapid reinfections with different or same Omicron SARS-CoV-2 sub-variants.","volume":"85","author":"I Vera-Lise","year":"2022","journal-title":"J Infect."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"104-11","DOI":"10.1016\/j.ijid.2022.07.053","article-title":"Nucleocapsid and spike antibody responses following virologically confirmed SARS-CoV-2 infection: an observational analysis in the Virus Watch community cohort.","volume":"123","author":"A Navaratnam","year":"2022","journal-title":"Int J Infect Dis."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"e699-e709","DOI":"10.1093\/cid\/ciab004","article-title":"The Duration, Dynamics, and Determinants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Responses in Individual Healthcare Workers.","volume":"73","author":"S Lumley","year":"2021","journal-title":"Clin Infect Dis."},{"key":"ref-11","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00986-22","article-title":"Detecting Waning Serological Response with Commercial Immunoassays: 18-Month Longitudinal Follow-up of Anti-SARS-CoV-2 Nucleocapsid Antibodies.","volume":"10","author":"Y Nakagama","year":"2022","journal-title":"Microbiol Spectr."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"545-56","DOI":"10.1016\/j.jinf.2022.09.004","article-title":"Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study.","volume":"85","author":"A Atti","year":"2022","journal-title":"J Infect."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"1323-1329","DOI":"10.3201\/eid2907.230173","article-title":"Trajectory and Demographic Correlates of Antibodies to SARS-CoV-2 Nucleocapsid in Recently Infected Blood Donors, United States.","volume":"29","author":"J Haynes","year":"2023","journal-title":"Emerg Infect Dis."},{"key":"ref-14","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac677","article-title":"Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients.","volume":"10","author":"S Dhakal","year":"2023","journal-title":"Open Forum Infect Dis."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"573-607","DOI":"10.1016\/j.jinf.2022.08.015","article-title":"Sensitivity of anti-SARS-CoV-2 nucleocapsid protein antibody for breakthrough infections during the epidemic of the Omicron variants.","volume":"85","author":"T Mizoue","year":"2022","journal-title":"J Infect."},{"key":"ref-16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0266852","article-title":"Does a humoral correlate of protection exist for SARS-CoV-2? A systematic review.","volume":"17","author":"J Perry","year":"2022","journal-title":"PLoS One."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"267-269","DOI":"10.1016\/j.jinf.2023.06.018","article-title":"Nucleocapsid-specific antibodies as a correlate of protection against SARS-CoV-2 reinfection in children.","volume":"87","author":"A Dowell","year":"2023","journal-title":"J Infect."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-45\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-45\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-45\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T08:35:10Z","timestamp":1716971710000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-45\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,19]]},"references-count":17,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.20750.1","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.22962.r80457","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.22962.r84354","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.22962.r80457","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.22962.r84354","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,19]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-45\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.22962.r80457, Eric J Nilles, Brigham and Women\u2019s Hospital, Boston, MA, 10 May 2024, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-45\/v1#referee-response-80457","order":0,"name":"referee-response-80457","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.22962.r84354, Liam Townsend, Trinity College Dublin, Dublin, 29 May 2024, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-45\/v1#referee-response-84354","order":1,"name":"referee-response-84354","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [222907, <a href=https:\/\/doi.org\/10.35802\/222907>https:\/\/doi.org\/10.35802\/222907<\/a>; a Wellcome Trust Clinical PhD Fellowship award to MK]. It is independent research funded by the Department of Health and Social Care (COVID-19 surveillance studies). LS is funded by a National Institute for Health and Care Research Professorship (302435). AH is supported by Health Data Research UK (LOND1), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}