{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:48:47Z","timestamp":1792500527347,"version":"4.5.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003896","name":"Henry M. Jackson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003896","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The incidence of long COVID is substantial, even in people with mild to moderate acute COVID-19. The role of early viral kinetics in the subsequent development of long COVID is largely unknown, especially in individuals who were not hospitalized for acute COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional SARS-CoV-2 test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1-, 3-, 6-, 12-, and 18-months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90+ days from acute COVID-19 symptom onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Self-reported brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI \u2265 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22-0.95; muscle pain: aRR 0.28, 95% CI 0.08-0.94). Participants reporting higher severity brain fog or muscle pain at 90+ days after acute COVID-19 onset were less likely to have cleared SARS-CoV-2 RNA within 28 days. The acute viral RNA decay trajectories of participants who did and did not later go on to experience brain fog 90+ days after acute COVID-19 onset were distinct.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This work indicates that at least two long COVID symptoms - brain fog and muscle pain \u2013 at 90+ days from acute COVID-19 onset are specifically associated with prolonged time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute COVID-19. This finding provides evidence that delayed immune clearance of SARS-CoV-2 antigen or greater amount or duration of viral antigen burden in the upper respiratory tract during acute COVID-19 are directly linked to long COVID. This work suggests that host-pathogen interactions during the first few weeks after acute COVID-19 onset have an impact on long COVID risk months later.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1147549","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T08:45:37Z","timestamp":1682671537000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":47,"title":["Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Annukka A. R.","family":"Antar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe O","family":"Demko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Tornheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukari C.","family":"Manabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"6571","DOI":"10.1038\/s41467-021-26513-3","article-title":"Burdens of post-acute sequelae of covid-19 by severity of acute infection, demographics and health status","volume":"12","author":"Xie","year":"2021","journal-title":"Nat Commun"},{"key":"B2","unstructured":"Long covid household pulse survey2023"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.101019","article-title":"Characterizing long covid in an international cohort: 7 months of symptoms and their impact","volume":"38","author":"Davis","year":"2021","journal-title":"EClinicalMedicine"},{"key":"B4","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bbi.2021.12.020","article-title":"Fatigue and cognitive impairment in post-Covid-19 syndrome: a systematic review and meta-analysis","volume":"101","author":"Ceban","year":"2022","journal-title":"Brain Behav Immun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01766-7","article-title":"Studying severe long covid to understand post-infectious disorders beyond covid-19","volume":"28","author":"Brodin","year":"2022","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41590-021-01104-y","article-title":"Pathological sequelae of long-haul covid","volume":"23","author":"Mehandru","year":"2022","journal-title":"Nat Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab007","article-title":"The clinical course of covid-19 in the outpatient setting: a prospective cohort study","volume":"8","author":"Blair","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab195","article-title":"Delayed rise of oral fluid antibodies, elevated bmi, and absence of early fever correlate with longer time to sars-Cov-2 rna clearance in a longitudinally sampled cohort of covid-19 outpatients","volume":"8","author":"Antar","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab517","article-title":"Performance of the influenza patient-reported outcome plus (Flu-pro plus) instrument in patients with coronavirus disease 2019","volume":"8","author":"Richard","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a114212","article-title":"Binomial regression in glim: estimating risk ratios and risk differences","volume":"123","author":"Wacholder","year":"1986","journal-title":"Am J Epidemiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2076901","article-title":"Pathophysiology and mechanism of long covid: a comprehensive review","volume":"54","author":"Castanares-Zapatero","year":"2022","journal-title":"Ann Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05542-y","article-title":"Sars-Cov-2 infection and persistence in the human body and brain at autopsy","volume":"612","author":"Stein","year":"2022","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac722","article-title":"Persistent circulating sars-Cov-2 spike is associated with post-acute covid-19 sequelae","volume":"76","author":"Swank","year":"2022","journal-title":"Clin Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26350","article-title":"Sars-Cov-2 and mitochondrial proteins in neural-derived exosomes of covid-19","volume":"91","author":"Peluso","year":"2022","journal-title":"Ann Neurol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.746021","article-title":"Persistence of sars cov-2 S1 protein in Cd16+ monocytes in post-acute sequelae of covid-19 (Pasc) up to 15 months post-infection","volume":"12","author":"Patterson","year":"2021","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.medj.2022.04.001","article-title":"Gastrointestinal symptoms and fecal shedding of sars-Cov-2 rna suggest prolonged gastrointestinal infection","volume":"3","author":"Natarajan","year":"2022","journal-title":"Med (N Y)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1016\/j.cell.2022.01.014","article-title":"Multiple early factors anticipate post-acute covid-19 sequelae","volume":"185","author":"Su","year":"2022","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2023.0743","article-title":"Association of treatment with nirmatrelvir and the risk of post-COVID-19 condition","author":"Xie","year":"2023","journal-title":"JAMA Intern Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1147549\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T08:45:42Z","timestamp":1682671542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1147549\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":18,"alternative-id":["10.3389\/fimmu.2023.1147549"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1147549","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.01.18.23284742","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]},"article-number":"1147549"}}