{"doi":"10.17615/m8r8-hh40","title":"Symptom and Viral Rebound in Untreated SARS-CoV-2 Infection","abstract":"BACKGROUND: Although symptom and viral rebound have been reported after nirmatrelvir-ritonavir treatment, the trajectories of symptoms and viral load during the natural course of COVID-19 have not been well described. OBJECTIVE: To characterize symptom and viral rebound in untreated outpatients with mild to moderate COVID-19. DESIGN: Retrospective analysis of participants in a randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04518410). SETTING: Multicenter trial. PATIENTS: 563 participants receiving placebo in the ACTIV-2/A5401 (Adaptive Platform Treatment Trial for Outpatients With COVID-19) platform trial. MEASUREMENTS: Participants recorded the severity of 13 symptoms daily between days 0 and 28. Nasal swabs were collected for SARS-CoV-2 RNA testing on days 0 to 14, 21, and 28. Symptom rebound was defined as a 4-point increase in total symptom score after improvement any time after study entry. Viral rebound was defined as an increase of at least 0.5 log<sub>10</sub> RNA copies/mL from the immediately preceding time point to a viral load of 3.0 log<sub>10</sub> copies/mL or higher. High-level viral rebound was defined as an increase of at least 0.5 log<sub>10</sub> RNA copies/mL to a viral load of 5.0 log<sub>10</sub> copies/mL or higher. RESULTS: Symptom rebound was identified in 26% of participants at a median of 11 days after initial symptom onset. Viral rebound was detected in 31% and high-level viral rebound in 13% of participants. Most symptom and viral rebound events were transient, because 89% of symptom rebound and 95% of viral rebound events occurred at only a single time point before improving. The combination of symptom and high-level viral rebound was observed in 3% of participants. LIMITATION: A largely unvaccinated population infected with pre-Omicron variants was evaluated. CONCLUSION: Symptom or viral relapse in the absence of antiviral treatment is common, but the combination of symptom and viral rebound is rare. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.","journal":"UNC Libraries","year":2025,"id":561543,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9424,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":396976,"name":"Judith S. Currier","orcid":"0000-0003-4279-4737","position":1,"is_corresponding":false},{"id":315361,"name":"Kara W Chew","orcid":"0000-0003-4865-4348","position":2,"is_corresponding":false},{"id":419481,"name":"Carlee Moser","orcid":"0000-0001-5601-9112","position":3,"is_corresponding":false},{"id":218333,"name":"Manish C. Choudhary","orcid":"0000-0002-3192-7840","position":4,"is_corresponding":false},{"id":65752,"name":"Michael D. Hughes","orcid":"0000-0001-8562-2316","position":5,"is_corresponding":false},{"id":108342,"name":"Alexander L. Greninger","orcid":"0000-0002-7443-0527","position":6,"is_corresponding":false},{"id":806067,"name":"Rinki Deo","orcid":null,"position":7,"is_corresponding":false},{"id":108340,"name":"Jonathan Z. Li","orcid":"0000-0001-9914-9662","position":8,"is_corresponding":false},{"id":36878,"name":"Davey M. Smith","orcid":"0000-0003-3603-1733","position":9,"is_corresponding":false},{"id":249713,"name":"Joseph J. Eron","orcid":"0000-0002-4938-0644","position":10,"is_corresponding":false},{"id":340150,"name":"David A. Wohl","orcid":"0000-0002-7764-0212","position":11,"is_corresponding":false},{"id":351140,"name":"Eric S. Daar","orcid":"0000-0003-1880-7331","position":12,"is_corresponding":false},{"id":1006550,"name":"ACTIV- A Study Team","orcid":null,"position":13,"is_corresponding":false},{"id":385130,"name":"Justin Ritz","orcid":"0000-0001-6307-4849","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:58.259104Z","pmid":null,"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":[]}