{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:18:04Z","timestamp":1783394284766,"version":"3.54.6"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.22942.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000}}],"reference-count":56,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00011\/1;MR\/W021315\/1"],"award-info":[{"award-number":["MC_UU_00011\/1;MR\/W021315\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019415","name":"Elizabeth Blackwell Institute for Health Research, University of Bristol","doi-asserted-by":"publisher","award":["204813\/Z\/16\/Z"],"award-info":[{"award-number":["204813\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100019415","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["SpringboardAwardSB007\\100173"],"award-info":[{"award-number":["SpringboardAwardSB007\\100173"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202802\/Z\/16\/Z"],"award-info":[{"award-number":["202802\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217065"],"award-info":[{"award-number":["217065"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/V028448\/1"],"award-info":[{"award-number":["MR\/V028448\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns5:p>Background The study of non-hospitalised COVID-19 cases provides a context for improved understanding of the immune response to existing and new infections. Population-based cohorts provide a unique opportunity to do this in relation to rich longitudinal pre- and pan-pandemic data. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990\u20131992 and has subsequently followed participants for over 30\u00a0years. Methods A study comprising three clinic visits was implemented, in response to the COVID-19 pandemic, amongst ALSPAC participants to measure SARS-CoV-2 specific humoral and cellular responses longitudinally. Here we present data from the first clinic in December 2020 before the start of the UK vaccination campaign and examine associations with a set of exemplar pre- and pan-pandemic health factors. Results We observed humoral and cellular memory immune responses to SARS-CoV-2 infection in mild cases of COVID-19 up to 9\u00a0months post-infection. Symptomatic infection elicited a memory immune response of greater magnitude, though there was variation in response in both asymptomatic and symptomatic individuals. We examined health factors associated with severe COVID-19 and found that cardio-metabolomic, respiratory and immune-related health factors associate with a memory immune response of higher magnitude. For example, in older participants (mean age 58\u00a0years), higher BMI was associated with an immune memory response of greater magnitude, particularly with anti-S and anti-N binding antibodies. Conclusions We set out to illustrate the use of cohort studies to deliver detailed immunological data and to provide example analyses of how life course health factors can be examined in relation to the immune response following a widespread and novel infection. We expanded this assessment to include longitudinally assessed traits, opening up the potential for the more common use of longitudinal population studies for the better understanding the aetiology of infection outcome.<\/ns5:p>","DOI":"10.12688\/wellcomeopenres.22942.2","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T11:39:06Z","timestamp":1781350746000},"page":"580","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SARS-CoV-2 memory response in non-hospitalised cases: immunology in the context of a population-based cohort study"],"prefix":"10.12688","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3506-160X","authenticated-orcid":false,"given":"Ruth E.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Population Health Sciences Bristol England Bristol Medical School, University of Bristol"},{"name":"MRC Integrative Epidemiology Unit Bristol England University of Bristol"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milla","family":"Kibble","sequence":"additional","affiliation":[{"name":"Population Health Sciences Bristol England Bristol Medical School, University of Bristol"},{"name":"Department of Applied Mathematics and Theoretical Physics Cambridge England University of Cambridge"},{"name":"MRC Integrative Epidemiology Unit Bristol England University of Bristol"},{"name":"Department of Twin Research and Genetic Epidemiology London England King's College London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Santopaolo","sequence":"additional","affiliation":[{"name":"School of Cellular and Molecular Medicine Bristol England University of Bristol Faculty of Medical and Veterinary Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Milodowski","sequence":"additional","affiliation":[{"name":"Faculty of Health and 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An emphasis on self-screening at a population level [version 2; peer review: 1 approved, 2 approved with reservations].","volume":"6","author":"K Northstone","year":"2021","journal-title":"Wellcome Open Res."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.12688\/wellcomeopenres.16950.2","article-title":"The Avon Longitudinal Study of Parents and Children - a resource for COVID-19 research: questionnaire data capture November 2020 \u2013 March 2021 [version 2; peer review: 2 approved].","volume":"6","author":"D Smith","year":"2021","journal-title":"Wellcome Open Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"283","DOI":"10.12688\/wellcomeopenres.17294.2","article-title":"The Avon Longitudinal Study of Parents and Children - a resource for COVID-19 research: antibody testing results, April \u2013 June 2021 [version 2; peer review: 2 approved].","volume":"6","author":"D Major-Smith","year":"2022","journal-title":"Wellcome Open Res."},{"key":"ref29","author":"R Mitchell","year":"August 6,2024"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1037-1040","DOI":"10.1038\/s41591-020-0916-2","article-title":"Real-time tracking of self-reported symptoms to predict potential COVID-19.","volume":"26","author":"C Menni","year":"2020","journal-title":"Nat Med."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/s41467-021-27797-1","article-title":"Immunoglobulin signature predicts risk of post-acute COVID-19 syndrome.","volume":"13","author":"C Cervia","year":"2022","journal-title":"Nat Commun."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"968317","DOI":"10.3389\/fimmu.2022.968317","article-title":"Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2.","volume":"13","author":"A Halliday","year":"2022","journal-title":"Front Immunol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"203-206.e3","DOI":"10.1016\/j.jaci.2020.04.009","article-title":"Association of respiratory allergy, asthma, and expression of the SARS-CoV-2 receptor ACE2.","volume":"146","author":"D Jackson","year":"2020","journal-title":"J Allergy Clin Immunol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"900-912","DOI":"10.1136\/thoraxjnl-2021-217487","article-title":"Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK).","volume":"77","author":"H Holt","year":"2022","journal-title":"Thorax."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e63033","DOI":"10.7554\/eLife.63033","article-title":"Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population.","volume":"10","author":"H Julkunen","year":"2021","journal-title":"eLife."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"526-534","DOI":"10.1016\/S2213-2600(18)30099-7","article-title":"Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies. 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infection in convalescent samples from severe, moderate and mild COVID-19 cases.","volume":"12","author":"J Castillo-Olivares","year":"2021","journal-title":"Front Immunol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"618685","DOI":"10.3389\/fimmu.2020.618685","article-title":"Distinct features and functions of systemic and mucosal humoral immunity among SARS-CoV-2 convalescent individuals.","volume":"11","author":"S Butler","year":"2021","journal-title":"Front Immunol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"74-85","DOI":"10.1038\/s41590-020-00808-x","article-title":"SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition.","volume":"22","author":"A Nelde","year":"2021","journal-title":"Nat Immunol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"70-80","DOI":"10.1093\/infdis\/jiab176","article-title":"Differential T-cell reactivity to endemic Coronaviruses and SARS-CoV-2 in community and Health Care Workers.","volume":"224","author":"A Silva","year":"2021","journal-title":"J Infect Dis."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"5749","DOI":"10.1038\/s41467-020-19478-2","article-title":"Collider bias undermines our understanding of COVID-19 disease risk and severity.","volume":"11","author":"G Griffith","year":"2020","journal-title":"Nat Commun."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"327-340","DOI":"10.1111\/imm.13475","article-title":"The effect of age on the magnitude and longevity of Th1-directed CD4 T-cell responses to SARS-CoV-2.","volume":"166","author":"R Nattrass","year":"2022","journal-title":"Immunology."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"4678","DOI":"10.1038\/s41467-021-24938-4","article-title":"SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection.","volume":"12","author":"C Cohen","year":"2021","journal-title":"Nat Commun."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"e13496","DOI":"10.1111\/obr.13496","article-title":"COVID-19, obesity, and immune response 2 years after the pandemic: a timeline of scientific advances.","volume":"23","author":"M Belchior-Bezerra","year":"2022","journal-title":"Obes Rev."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"760288","DOI":"10.3389\/fimmu.2021.760288","article-title":"Obesity correlates with pronounced aberrant innate immune responses in hospitalized aged COVID-19 patients.","volume":"12","author":"M Zulu","year":"2021","journal-title":"Front Immunol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1547-1553","DOI":"10.1002\/oby.23208","article-title":"The association between obesity and peak antibody titer response in COVID-19 infection.","volume":"29","author":"S Soffer","year":"2021","journal-title":"Obesity (Silver Spring)."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"427-432","DOI":"10.1038\/s41366-021-01016-9","article-title":"The majority of SARS-CoV-2-specific antibodies in COVID-19 patients with obesity are autoimmune and not neutralizing.","volume":"46","author":"D Frasca","year":"2022","journal-title":"Int J Obes (Lond)."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"377-381","DOI":"10.1016\/j.jbi.2008.08.010","article-title":"Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.","volume":"42","author":"P Harris","year":"2009","journal-title":"J Biomed Inform."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:09:13Z","timestamp":1783393753000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,13]]},"references-count":56,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.22942.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/wellcomeopenres.22942.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.29671.r158113","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.29671.r158113","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,13]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.29671.r158113, Sadhana Sharma, All India Institute of Medical Sciences, Patna, 07 Jul 2026, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v2#referee-response-158113","order":0,"name":"referee-response-158113","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.25262.r114788, Angela Crawley, University of Ottawa, Ottawa, Ontario, 30 Dec 2024, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v1#referee-response-114788","order":1,"name":"referee-response-114788","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Nic Timpson<\/b>; \n<i>Posted: 01 Jun 2026<\/i>; \n<b>Please find below a response to review comments (responses flagged as \u201c**\u201d):<\/b> &nbsp;  \n<b>Comments to Authors:<\/b> \n<i>This was a very interesting cohort opportunity to study pre- and pan-pandemic responses. The value of such longitudinal efforts is critically important to informing appropriate and effect public health responses to threats to human health.&nbsp; The use of multi-parameter ELISAs and the neutralization assay further strengthens the data value.<\/i>  \n<b>**We were delighted to receive this feedback and also overall approval for the manuscript as submitted. The overarching aim of this work is to use existing data and illustrative examples to demonstrate the utility of longitudinal data in the context of charting immunological response to a novel infection challenge. This clearly sets out the scope of the paper and hence the response to our second review. Thanks again for the comments. &nbsp;<\/b>  \n<b>Reviewer comments:<\/b> \n<i>&quot;Statistical analysis of immune response correlations are very simple, and not integrative, allowing only for univariate interpretations. Although, Fig 8 does go into some detail on this point. An understanding of how multiple variables work together to drive particular immune responses would be achieved through more in-depth integrative, systems analyses and perhaps other such studies could be referenced (e.g., Cuperlovic-Culf M. et al., iScience 2024).&quot;<\/i>  \n<b>**As mentioned above, the purpose \u2013 hence scope \u2013 of this manuscript was to present the potential for the analysis of life course factors and potential contributions to the immunological responses to novel challenge. The analysis brought together are for this purpose and whilst we completely agree with the appeal of using these data for more integrative analyses, that is out of scope for this specific report. We understand the potential for the types of analyses referred to and we agree that it would be interesting to evaluate in future work, where sample size allows, how multiple variables interact in relation to immune responses. Here we consider immune response to infection in a relatively small immune-na&iuml;ve, non-hospitalised cohort.  Further work using these data and considering a more comprehensive description of longitudinal immunological response has been published alongside this work (albeit with less incorporation of life course data). This can be seen here:&nbsp; Baum HE et al. Hybrid B- and T-Cell Immunity Associates With Protection Against Breakthrough Infection After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination in Avon Longitudinal Study of Parents and Children (ALSPAC) Participants. J Infect Dis. 2025 Aug 14;232(2):e327-e340. doi: 10.1093\/infdis\/jiaf246. Erratum in: J Infect Dis. 2026 Mar 18:jiag161. doi: 10.1093\/infdis\/jiag161. PMID: 40392230; PMCID: PMC12349941.<\/b>  \n<i>&quot;Color schemes used across figures are not consistent, or not clarified (e.g., Fig 4 - what is red and black?)&nbsp; &quot;<\/i>  \n<b>**Thanks for this comment. Overall, the colour schemes are not the same (or linked) across the various figures because they are not attempting to suggest that there are common threads running between each presentation. We wanted figures to be essentially stand-alone and to this extent would suggest that the colour schemes remain as they are.&nbsp; We do, however, concede that the labelling of figure 4 is not clear. To this end, we have incorporated a new legend into this figure and submitted it as part of this response.<\/b>","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-580\/v2#referee-comment-6588","order":2,"name":"referee-comment-6588","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was funded by UK Research and Innovation (UKRI) through the UKRI rapid response call for COVID (MR\/V028448\/1; PI - Paul Moss; Title  - A UK underpinning platform to study immunology and immunopathology of COVID-19: The UK Coronavirus Immunology Consortium; Date awarded - 17\/08\/2020). \r\n\r\nNJT was supported by Wellcome Trust Investigator (202802), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215-2001), the MRC Integrative Epidemiology Unit (MC_UU_00011\/1) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281\/A29019). REM is supported by the MRC Integrative Epidemiology Unit (MC_UU_00011\/1). MK is supported by the Medical Research Council (MR\/W021315\/1). MS is supported by the Academy of Medical Sciences (Springboard Award SB007\\100173).\r\n\r\nThis work was supported by the Elizabeth Blackwell Institute, University of Bristol, with funding from the Wellcome Trust ISSF3 grant 204813 and the University\u2019s alumni and friends (LW, LR, AH, AD, AF and OF).\r\n\r\nThe UK Medical Research Council and Wellcome (217065) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and REM, NJT, LW and LR will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http:\/\/www.bristol.ac.uk\/alspac\/external\/documents\/grant-acknowledgements.pdf). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe.\r\n\r\nThe funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"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"}]}}