In a recent study published on the medRxiv* preprint server, researchers evaluated the rebound of coronavirus disease 2019 (COVID-19) in untreated COVID-19 infections.
Study: viral and symptom rebound in untreated COVID-19 infection. Image credit: Madua/Shutterstock
Background
Nirmatrelvir-ritonavir (Paxlovid) is an approved treatment for mild to moderate COVID-19 infections and risk factors for disease severity in outpatients. With widespread use of Paxlovid, several people have reported worsening of symptoms and/or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after completing the course of treatment, called post-Paxlovid rebound. Extensive research is required to understand this phenomenon.
About the study
In the current study, researchers estimated the rebound incidence of SARS-CoV-2 symptoms and virulence in untreated patients diagnosed with mild to moderate COVID-19.
The team enrolled adults 18 years and older from the ACTIV-2/A5401 platform trial conducted for outpatients with mild-to-moderate COVID-19. Viral rebound analysis was restricted to subjects who participated in the placebo arm of the phase 2 studies of ACTIV-2/A5401 and were treated with bamlanivimab 700 mg, bamlanivimab 7000 mg, and amubarvimab plus monoclonal antibodies against romlusevimab. . The team collected self-reported symptoms daily for the first 28 days.
The system rebound analysis involved an additional 301 participants who were enrolled in the placebo arm of the phase 3 trial to analyze the impact of monoclonal antibodies against romlusevimab and amubarvimab. Bamlivimab trials included subjects found to be at standard or increased risk of progression of COVID-19 disease severity. In contrast, the romlusevimab and amubarvimab trials involved only subjects who were at high risk for COVID-19 severity.
For symptom and viral rebound estimates, the team defined a simulated time point for baseline post nirmatrelvir/ritonavir that was similar to the baseline time point observed in the viral rebound analysis of the trial. nirmatrelvir-ritonavir phase 3. Additionally, the primary analysis involved participants who had five or more days of COVID-19 symptoms during study enrollment, with the baseline at the fifth day of the study. Secondary analysis included all participants who had a study visit on day 8 from symptom onset (DSSO8).
The team also collected daily anterior nasal (AN) swabs from study entry day (Day 0) through Day 14 and Day 28. In addition, bamlanivimab participants provided another sample for viral load testing on Day 21. SARS-CoV-2 ribonucleic acid (RNA) levels were estimated from the AN samples. A sample showed viral rebound if it had a 0.5 log10 or greater increase in SARS-CoV-2 RNA levels in AN samples at a baseline follow-up time point.
Total symptom scores were estimated on each study day as the total of 13 specific symptom scores that were rated based on a regular self-reported symptom diary from Day 0 to Day 28. The 13 specific symptoms included cough , fever, sore throat , shortness of breath, fatigue, body aches, chills, headache, runny nose, nasal obstruction, vomiting, diarrhea, and nausea.
Results
Study results showed that based on primary symptom and viral rebound analysis, 12% of participants had a viral rebound of 0.5 log10 or more RNA copies per mL on the fourth day after the study. The estimated minimum SARS-CoV-2 RNA rebound was 0.3 log10 or more RNA copies per mL. The team noted that 73% of participants showed a viral rebound of 0.3 log10 or more within the first five days after baseline, and 91% of participants had virulence lasting one day.
Furthermore, participants with viral RNA rebound were older than those without RNA rebound. The team also estimated frequencies associated with elevated levels of nasal RNA rebound with a minimum rebound threshold of 5.0 log10, and 5.3% of participants met this definition of virus rebound. The primary analysis also showed that 12% and 6.9% of participants had minimum threshold estimated viral rebound rates of 0.3 log10 or more and 0.5 log10 RNA copies per mL, respectively.
The main analysis also highlighted that 27% of participants showed symptom recovery after initial symptom improvement. Symptomatic rebound participants were more likely to have higher baseline levels of AN viral RNA and higher symptom scores at enrollment and baseline time points. Additionally, only 10% of participants met the criteria for symptom rebound after symptom resolution.
The team also found high levels of viral rebound with 0.5 log10 or more RNA copies per ml, accompanied by symptom rebound after initial improvement in 2.2% of participants when estimated using the criteria of primary and complementary reference, respectively. None of the participants had symptom rebound along with viral rebound with 0.5 log10 or more RNA copies per mL after initial resolution of symptoms.
Overall, the study findings showed that SARS-CoV-2 RNA rebound and COVID-19 symptoms were relatively common among participants treated for COVID-19 with any antiviral agent. The present study highlights the natural course of symptoms and viral rebound. These are essential to understand the biphasic disease course after antiviral treatments.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice or health-related behavior, or be treated as established information.
Magazine reference:
Rinki Deo, Manish C Choudhary, Carlee Moser, Justin Ritz, Eric S Daar, David A Wohl, Alexander L Greninger, Joseph J Eron, Judith S Currier, Michael D Hughes, Davey M Smith, Kara W Chew, Jonathan Z Li. (2022). Viral and symptom rebound in untreated COVID-19 infection. medRxiv. do: https://doi.org/10.1101/2022.08.01.22278278 https://www.medrxiv.org/content/10.1101/2022.08.01.22278278v1
Source: www.news-medical.net