{"doi":"10.7326/m22-2381","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) 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 log10 RNA copies/mL from the immediately preceding time point to a viral load of 3.0 log10 copies/mL or higher. High-level viral rebound was defined as an increase of at least 0.5 log10 RNA copies/mL to a viral load of 5.0 log10 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. Conclusion:Symptom or viral relapse in the absence of antiviral treatment is common, but the combination of symptom and viral rebound is rare.","journal":"Annals of Internal Medicine","year":2023,"id":318581,"datarank":1.9764007217537685,"base_score":4.1588830833596715,"endowment":4.1588830833596715,"self_citation_contribution":0.6238324625039509,"citation_network_contribution":1.3525682592498176,"self_endowment_contribution":0.6238324625039509,"citer_contribution":1.3525682592498176,"corpus_percentile":null,"corpus_rank":null,"citation_count":63,"citer_count":52,"citers_with_citation_signal":21,"citers_with_endowment":21,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9082,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04518410"]},"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":218333,"name":"Manish C. 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