{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:39:46Z","timestamp":1760834386177,"version":"build-2065373602"},"reference-count":26,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"unspecified","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health and Care Research","award":["NIHR302338"],"award-info":[{"award-number":["NIHR302338"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,11,1]]},"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Understanding how RNA viral load changes (viral load kinetics) during acute infection in SARS-CoV-2 can help to identify when and which patients are most infectious. We seek to summarise existing data on the longitudinal RNA viral load kinetics of SARS-CoV-2 sampled from different parts of the respiratory tract (nose, nasopharynx, oropharynx, saliva and exhaled breath) and how this may vary with age, sex, ethnicity, immune status, disease severity, vaccination, treatment and virus variant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>We will conduct a systematic review and meta-analysis, using studies identified through MEDLINE and EMBASE (via Ovid). All research studies reporting primary data on longitudinal RNA viral load kinetics of infected patients with SARS-CoV-2 will be included. Methodological quality will be assessed using a validated checklist for longitudinal studies as well as predefined quality criteria for assessment of individual-level RNA viral load. Should the data allow, we will aim to perform individual patient-level meta-analysis. Our primary outcomes are duration to, and quantity of peak RNA viral load, and total duration of viral load shedding within different respiratory compartments. Secondary outcomes include duration of lateral flow antigen and virus culture positivity and variation of RNA viral load by age, immune status, disease severity, vaccination, treatment, lateral flow tests, viral culture positivity and SARS-CoV-2 variant. Study-level effects affecting observations, but not related to properties of the patient, such as the PCR platform and gene target will also be recorded. Random-effects models will estimate the population mean and individual-level variation in viral shedding conditional on the aforementioned variables. Finally, we will summarise the key mechanistic models used in the literature to reconstruct individual-level viral kinetics and estimate how different factors shape viral dynamics over time.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>Ethical approval is not needed as data will be obtained from published articles or studies with data that have already received and ethical review for analysis. Manuscript(s) will be prepared for publication.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Systematic review protocol registration<\/jats:title>\n                  <jats:p>PROSPERO ID: CRD42023385315<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-085127","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T07:20:42Z","timestamp":1733124042000},"page":"e085127","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Defining within-host SARS-CoV-2 RNA viral load kinetics during acute COVID-19 infection within different respiratory compartments and their respective associations with host infectiousness: a protocol for a systematic review and meta-analysis"],"prefix":"10.1136","volume":"14","author":[{"given":"Daniel","family":"Pan","sequence":"first","affiliation":[{"name":"Development Centre for Population Health, University of Leicester, Leicester, UK"},{"name":"Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK"},{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"},{"name":"Oxford Big Data Institute, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2337-4799","authenticated-orcid":false,"given":"Christopher A","family":"Martin","sequence":"additional","affiliation":[{"name":"Development Centre for Population Health, University of Leicester, Leicester, UK"},{"name":"Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK"},{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0603-9091","authenticated-orcid":false,"given":"Joshua","family":"Nazareth","sequence":"additional","affiliation":[{"name":"Development Centre for Population Health, University of Leicester, Leicester, UK"},{"name":"Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK"},{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirley","family":"Sze","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, University of Leicester, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-2627","authenticated-orcid":false,"given":"Amani","family":"Al-Oraibi","sequence":"additional","affiliation":[{"name":"Development Centre for Population Health, University of Leicester, Leicester, UK"},{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Lifespan and Population Health, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9946-2509","authenticated-orcid":false,"given":"Mayuri","family":"Gogoi","sequence":"additional","affiliation":[{"name":"Development Centre for Population Health, University of Leicester, Leicester, UK"},{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Grolmusova","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK"},{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pip","family":"Divall","sequence":"additional","affiliation":[{"name":"Education Centre Library, University Hospitals of Leicester NHS Trust, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Decker","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eve","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"},{"name":"Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Hay","sequence":"additional","affiliation":[{"name":"Oxford Big Data Institute, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca F.","family":"Baggaley","sequence":"additional","affiliation":[{"name":"Development Centre for Population Health, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne L","family":"Wyllie","sequence":"additional","affiliation":[{"name":"Department of Epidemiology of Microbial Diseases, Yale University, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iain","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erol","family":"Gaillard","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"},{"name":"Department of Paediatric Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura B","family":"Nellums","sequence":"additional","affiliation":[{"name":"College of Population Health, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6026-5295","authenticated-orcid":false,"given":"Tristan William","family":"Clark","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, University of Southampton, Southampton, UK"},{"name":"Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK"},{"name":"NIHR Southampton Biomedical Research Centre, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan Nguyen","family":"Van-Tam","sequence":"additional","affiliation":[{"name":"Lifespan and Population Health, University of Nottingham, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J","family":"Cowling","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Infectious Disease Epidemiology and Control, Hong Kong School of Public Health, Hong Kong, Hong Kong"},{"name":"Laboratory of Data Discovery for Health Limited, Hong Kong Science and Technology Parks Corporation, Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. D\u00e9irdre","family":"Hollingsworth","sequence":"additional","affiliation":[{"name":"Oxford Big Data Institute, University of Oxford, Oxford, UK"},{"name":"NDM Centre for Global Health Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Gray","sequence":"additional","affiliation":[{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"},{"name":"Department of Population Health Sciences, University of Leicester, Leicester, UK"},{"name":"NIHR Applied Research Collaborative East Midlands, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Barer","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"},{"name":"Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1521-9964","authenticated-orcid":false,"given":"Manish","family":"Pareek","sequence":"additional","affiliation":[{"name":"Development Centre for Population Health, University of Leicester, Leicester, UK"},{"name":"Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK"},{"name":"Department of Respiratory Sciences, University of Leicester, Leicester, UK"},{"name":"Leicester NIHR Biomedical Research Centre, Leicester, UK"},{"name":"NIHR Applied Research Collaborative East Midlands, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"2025101814415056000_14.12.e085127.1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00648-4"},{"key":"2025101814415056000_14.12.e085127.2","doi-asserted-by":"crossref","DOI":"10.1126\/science.abg3055","article-title":"Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England","volume":"372","author":"Davies","year":"2021","journal-title":"Science"},{"key":"2025101814415056000_14.12.e085127.3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41586-021-03470-x","article-title":"Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England","volume":"593","author":"Volz","year":"2021","journal-title":"Nature New Biol"},{"key":"2025101814415056000_14.12.e085127.4","unstructured":"Kucharki A , Davies N . Eggo RFSCC-19 working group. Dynamics of B.1.617.2 in the UK from importations, traveller-linked and non-traveller-linked transmission. 2021."},{"key":"2025101814415056000_14.12.e085127.5","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/s41591-022-01780-9","article-title":"Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults","volume":"28","author":"Killingley","year":"2022","journal-title":"Nat Med"},{"key":"2025101814415056000_14.12.e085127.6","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27206"},{"key":"2025101814415056000_14.12.e085127.7","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.m3862","article-title":"Virology, transmission, and pathogenesis of SARS-CoV-2","volume":"371","author":"Cevik","year":"2020","journal-title":"BMJ"},{"key":"2025101814415056000_14.12.e085127.8","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/S2213-2600(22)00226-0","article-title":"Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study","volume":"10","author":"Hakki","year":"2022","journal-title":"Lancet Respir Med"},{"key":"2025101814415056000_14.12.e085127.9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jinf.2021.03.018","article-title":"Exhaled SARS-CoV-2 quantified by face-mask sampling in hospitalised patients with COVID-19","volume":"82","author":"Williams","year":"2021","journal-title":"J Infect"},{"key":"2025101814415056000_14.12.e085127.10","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.cmi.2022.07.005","article-title":"Exhaled SARS-CoV-2 RNA viral load kinetics measured by facemask sampling associates with household transmission","volume":"29","author":"Pan","year":"2023","journal-title":"Clin Microbiol Infect"},{"key":"2025101814415056000_14.12.e085127.11","doi-asserted-by":"publisher","DOI":"10.1101\/2020.04.16.20067835"},{"key":"2025101814415056000_14.12.e085127.12","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/S2213-2600(21)00178-8","article-title":"Saliva as a gold-standard sample for SARS-CoV-2 detection","volume":"9","author":"Tan","year":"2021","journal-title":"Lancet Respir Med"},{"key":"2025101814415056000_14.12.e085127.13","doi-asserted-by":"crossref","DOI":"10.1126\/science.abh0635","article-title":"Estimating epidemiologic dynamics from cross-sectional viral load distributions","volume":"373","author":"Hay","year":"2021","journal-title":"Science"},{"key":"2025101814415056000_14.12.e085127.14","doi-asserted-by":"crossref","DOI":"10.1186\/s12916-021-02220-0","article-title":"Modelling upper respiratory viral load dynamics of SARS-CoV-2","volume":"20","author":"Challenger","year":"2022","journal-title":"BMC Med"},{"key":"2025101814415056000_14.12.e085127.15","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/S2666-5247(20)30172-5","article-title":"SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis","volume":"2","author":"Cevik","year":"2021","journal-title":"Lancet Microbe"},{"key":"2025101814415056000_14.12.e085127.16","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/cpt.2223","article-title":"Systematic Review and Patient-Level Meta-Analysis of SARS-CoV-2 Viral Dynamics to Model Response to Antiviral Therapies","volume":"110","author":"Gastine","year":"2021","journal-title":"Clin Pharmacol Ther"},{"key":"2025101814415056000_14.12.e085127.17","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73178"},{"key":"2025101814415056000_14.12.e085127.18","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-022-07663-1","article-title":"SARS-CoV-2 viral load is associated with risk of transmission to household and community contacts","volume":"22","author":"Bhavnani","year":"2022","journal-title":"BMC Infect Dis"},{"key":"2025101814415056000_14.12.e085127.19","doi-asserted-by":"crossref","unstructured":"Killingley B , Mann AJ , Kalinova M , et al . SARS-CoV-2 human challenge in young adults. N Med 2020. doi:10.1038\/s41591-022-01780-9","DOI":"10.1038\/s41591-022-01780-9"},{"key":"2025101814415056000_14.12.e085127.20","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1056\/NEJMc2102507","article-title":"Viral Dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated persons","volume":"385","author":"Kissler","year":"2021","journal-title":"N Engl J Med"},{"key":"2025101814415056000_14.12.e085127.21","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation","volume":"350","author":"Shamseer","year":"2015","journal-title":"BMJ"},{"key":"2025101814415056000_14.12.e085127.22","unstructured":"Web plot digitizer. 2022. Available: https:\/\/apps.automeris.io\/wpd\/"},{"key":"2025101814415056000_14.12.e085127.23","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwi042"},{"key":"2025101814415056000_14.12.e085127.24","doi-asserted-by":"crossref","first-page":"e286","DOI":"10.1016\/S2666-5247(21)00089-6","article-title":"Rapid tests for quantification of infectiousness are urgently required in patients with COVID-19","volume":"2","author":"Pan","year":"2021","journal-title":"Lancet Microbe"},{"key":"2025101814415056000_14.12.e085127.25","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2288-14-135","article-title":"Estimating the sample mean and standard deviation from the sample size, median, range and\/or interquartile range","volume":"14","author":"Wan","year":"2014","journal-title":"BMC Med Res Methodol"},{"key":"2025101814415056000_14.12.e085127.26","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc2102507"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-085127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T21:42:00Z","timestamp":1760823720000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-085127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":26,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,2]]},"published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1136\/bmjopen-2024-085127"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-085127","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"type":"print","value":"2044-6055"},{"type":"electronic","value":"2044-6055"}],"subject":[],"published":{"date-parts":[[2024,12]]}}}