Evaluation of differences in viral rebound and symptoms between treated and untreated Paxlovid COVID-19 patients

In a recent study published in medRxiv*Server preprint Researchers evaluated differences in viral rebound and symptoms between baxlovid-treated and untreated coronavirus 2019 (COVID-19) patients.

Study: The Paxlovid Rebound Study: A prospective cohort study to evaluate virological differences and symptom recovery between Paxlovid participants and untreated COVID-19 participants.  Image credit: ahmad.faizal / Shutterstock
Stady: The Paxlovid Rebound Study: A prospective cohort study to assess virological differences and symptom recovery between Paxlovid participants and untreated COVID-19 participants.. Image credit: ahmad.faizal / Shutterstock


Studies have documented the return or resurgence of symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with higher viral loads after Paxlovid treatment. Interestingly, studies also reported viral rebound and symptoms among individuals who were not treated with therapeutic agents that could resolve symptoms.

Research has indicated that relapses may be associated with the pharmacodynamic properties of baxlovid or the interactions of antivirals with immune responses to SARS-CoV-2. However, the peer-reviewed scientific Paxlovid reflux data was largely based on retrospective study designs.

about studying

In the prospective cohort study, the investigators prospectively compared the rebound epidemiology of Paxlovid between treated and untreated patients with acute SARS-CoV-2 infection.

The decentralized, digital study included individuals who tested positive for SARS-CoV-2 using eMed treatment-tested telehealth diagnostic kits and could be prescribed baxlovid treatment to assess SARS-CoV-2 clearance and recovery. Symptoms of COVID-19 disease. Based on the acceptability of the drugs, the participants were allocated to either the Paxlovid (treatment) group or the control group.

Only adults with SARS-CoV-2-positive Rapid Reports antigen Tests and Paxlovid prescriptions from eMed telehealth monitoring were included in the analysis.

Participants in the Paxlovid cohort were provided with email links to access study materials and remotely monitored rapid antigen test kits for at-home testing. Participants in the Paxlovid group completed their initial home testing for SARS-CoV-2 and surveys regarding COVID-19 symptoms that appeared on days 2 and 5 of Paxlovid treatment, and thereafter, each alternate day for up to 16 days, after which, individuals completed surveys About prolonged COVID/persistent symptoms at 1.0, 3.0, and 6.0 month intervals.

The team evaluated SARS-CoV-2 rebound based on test reports and COVID-19 symptom rebound based on symptoms documented by the patient and excluded individuals who could not speak English and did not reside in the United States. The main study endpoints were SARS-CoV-2 infection rates (test) and recovery of COVID-19 symptoms in the two groups after acute SARS-CoV-2 infection. Secondary study endpoints included duration of COVID-19 symptom resolution, duration of a negative SARS-CoV-2 rapid antigen test, duration between report of a negative SARS-CoV-2 test to a positive SARS-CoV-2 test rebound, and frequency of COVID-19 symptoms In the two groups during acute COVID-19, the interval was 1.0 months.


Between August 4, 2022, and November 1, 2022, 247 individuals showed willingness to participate, of which 188 individuals completed the 16.0-day procedure. The team excluded individuals who completed <2.0 surveys or had <2.0 test reports or those who filled out surveys after the indicated schedule, resulting in a sample size of 170 individuals, of whom 127 and 43 made up the treatment group and the control group, respectively. The incidence of viral rebound was 14% and 9% among baxlovid-treated and untreated individuals, respectively.

The incidence of relapse of COVID-19 symptoms among the corresponding group of individuals was 19% and 7%, respectively. No significant differences were observed in viral reversion by sex, age, comorbidities, or major symptom groups in the acute COVID-19 period or in the 1-month period. More baxlovid-treated individuals were white. In addition, the duration of SARS-CoV-2 clearance was comparable between the treatment and control groups (seven days in both groups).

Similarly, the duration between the onset of COVID-19 symptoms and the resolution of the first symptoms (median of ten days vs 11 days) and the duration between the onset of symptoms and the first negative SARS-CoV-2 rapid antigen test report (median of six days in both groups) are comparable in corresponding groups. Approximately 20% of study participants in the two groups remained positive for SARS-CoV-2 by rapid antigen test until 10.0 days after the initial positive report.

Individuals with rebounds reported less body pain than individuals who did not bounce. The frequency of Native Americans and Asians was lower among individuals with a rebound. Among controls, for two subjects, recovery of symptoms lasted <5.0 days, and for one, rebound lasted 5.0 days. The corresponding number of treated individuals was 10 and 10, respectively. In addition, for four treated individuals, >1.0% of symptoms of SARS-CoV-2 infection recovered during follow-up.


Overall, the results of the initial report of the prospective cohort study showed that relapse after removal of test positivity or symptom resolution was greater than previously reported. However, recovery rates were comparable between the two groups. Further research is required with a larger and more diverse sample and longer follow-up periods to improve understanding of relapses.

Gaining valuable insights into the clinical and demographic characteristics related to reflux development is critical for tailoring treatment duration and timing of treatment or for identifying and counseling specific populations at increased risk for developing reflux. Rebounds can lead to unintended viral transmission after individuals test SARS-CoV-2-negative, and the return of symptoms may discourage individuals from seeking treatment to prevent the development of COVID-19.

*Important note

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, directing clinical practice/health-related behaviour, or treated as hard information.

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