{"doi":"10.3389/fimmu.2023.1147549","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","abstract":"Introduction: 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. Methods: 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. Results: 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 ≥ 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. Discussion: This work indicates that at least two long COVID symptoms - brain fog and muscle pain - 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.","journal":"Frontiers in Immunology","year":2023,"id":320391,"datarank":1.5905173009261784,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":1.0037138501119565,"self_endowment_contribution":0.586803450814222,"citer_contribution":1.0037138501119565,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":44,"citers_with_citation_signal":33,"citers_with_endowment":33,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8207,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":495798,"name":"Tong Yu","orcid":"0009-0002-9463-9085","position":1,"is_corresponding":false},{"id":724254,"name":"Zoe O Demko","orcid":"0000-0003-2122-820X","position":2,"is_corresponding":false},{"id":257981,"name":"Chen Hu","orcid":"0000-0003-4672-1981","position":3,"is_corresponding":false},{"id":333923,"name":"Jeffrey A. Tornheim","orcid":"0000-0002-1566-4622","position":4,"is_corresponding":false},{"id":391331,"name":"Paul W. Blair","orcid":"0000-0002-3817-5987","position":5,"is_corresponding":false},{"id":237962,"name":"David L. Thomas","orcid":"0000-0002-0749-925X","position":6,"is_corresponding":false},{"id":237961,"name":"Yukari C. Manabe","orcid":"0000-0001-8619-5598","position":7,"is_corresponding":false},{"id":286352,"name":"Annukka A.R. Antar","orcid":"0000-0002-6775-1103","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:07:22.377587Z","pmid":"37187756","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}