Symptom and viral relapse more common in COVID-19 patients without antiviral treatment

1. In this retrospective analysis, symptom and viral rebound occurred in almost one-third of coronavirus disease 2019 (COVID-19) patients that did not receive any antiviral treatment.

2. While recurrent symptom and viral rebound were common, the combination of symptom and viral rebound was rare.

Evidence Rating Level: 2 (Good)

Study Rundown: Clinical relapse has been described in patients with COVID-19 after symptom resolution in the initial episode. However, rigorous studies defining the frequency and intensity of symptom and viral rebound is lacking. This retrospective study used data from the randomized control trial, Adaptive Platform Treatment Trial, to assess the incidence of symptom and viral rebound in untreated outpatients with mild to moderate COVID-19 who received the placebo treatment. Patients completed a daily self-reported diary for 28 days, recording 13 targeted symptoms, including feverishness, cough, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain or aches, fatigue, headache, chills, nasal obstruction or congestion, nasal discharge, nausea, vomiting, and diarrhea. Daily anterior nasal swabs were also performed for the first two weeks and on day 28. Symptom and viral rebound occurred in 26% and 31% of patients, respectively. Most symptom and viral rebound were transient, with the majority lasting one day. Less than 3% of patients experienced both symptom and high-level viral rebound together. As a limitation, the study population was predominantly unvaccinated and contained pre-Omicron variants, which may reduce generalizability. The symptom assessment did not include anosmia or ageusia. Immune response to viral antigen was not assessed post-infection.

Click to read the study in AIM

In-Depth [retrospective cohort study]: In this retrospective study, the incidence of symptom and viral relapse was assessed in patients with COVID-19 who did not receive antiviral treatment. Data from adult patients within seven to ten days of mild to moderate COVID-19 symptom onset in the placebo arm of the randomized control trial, Adaptive Platform Treatment Trial ACTIV-2/A5401, was used for this analysis. For 28 days, patients provided daily self-reports of symptoms, including feverishness, cough, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain or aches, fatigue, headache, chills, nasal obstruction or congestion, nasal discharge, nausea, vomiting, and diarrhea. Daily anterior nasal swabs were collected for the first two weeks and on day 28. Of the 563 patients with daily symptom data, symptom rebound occurred in 26% at a median of 11 days after initial symptom onset. Symptom rebound due to hospitalization comprised 5% of all patients. For symptom rebound in nonhospitalized patients, 89% lasted one day. Risk factors for symptom rebound included female sex, higher total symptom score at day zero, higher risk for severe disease, shorter time since symptom onset, and higher nasal viral RNA at study enrollment. Viral rebound to 3.0 log(10) copies/mL or higher occurred in 31% of patients, and 95% of such events occurred at only one single time point before viral RNA load decreased. Participants with viral RNA rebound were less likely to have severe disease. Only 3.1% of participants experienced both symptom and viral rebound. This study provided insight into the natural trajectory of COVID-19 disease, prognostic factors of symptoms, and viral load rebound.

Image: PD

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