Less than one percent of high risk patients with Covid-19 developed rebound symptoms following treatment with nirmatrelvir/ritonavir, according to a study reported in Clinical Infectious Diseases.¹

In this study, 483 high-risk patients, median age 63 years, with recurrence Covid-19 symptoms were enrolled; 56% of the participants were women and 93% of them were fully vaccinated. They had responded successfully to the complete 5-day course of nirmatrelvir/ritonavir treatment and no other cause to explain their symptoms could be found. Patients who did not take the complete course of the medication, did not show significant symptomatic improvement or had long Covid were not included in the study. Out of the 483 patients, four (0.8%) developed rebound symptoms such as sore throat, fatigue, malaise, cough/wheezing, dyspnea, rhinorrhea and sinus congestion at a median of 9 days. These symptoms were mild in nature, while two patients (0.4%) had symptoms within a month that were unrelated to rebounding and needed intensive care. All four patients with rebound symptoms had received their mRNA vaccine booster dose in the preceding six months.

All the rebound symptoms resolved with symptomatic management; no additional Covid-19-directed treatment was necessary. No deaths occurred within 30 days of the diagnosis of Covid-19.

The authors concluded that rebound was not encountered often in high risk patients with Covid-19 following treatment with nirmatrelvir/ritonavir. They recommend more studies to further explore this phenomenon and identify risk factors that could predispose patients to rebound phenomenon.

Last month, the Centers for Disease Control and Prevention (CDC) had issued a health alert about the possibility of recurrence of Covid-19 or “Covid-19 rebound”, which manifests as either recurrence of symptoms or a positive test after a negative test. According to the CDC, this “return of symptoms may be part of the natural history of SARS-CoV-2” and it continued to recommend nirmatrelvir/ritonavir for treatment of mild to moderate Covid-19 in patients at high risk of developing severe disease. Persons with rebound symptoms should isolate themselves and observe other precautions such as wearing a mask, advises the CDC.

Reference

1. Ranganath N, et al. Rebound phenomenon after nirmatrelvir/ritonavir treatment of Coronavirus Disease-2019 in high-risk persons. Clin Infect Dis. 2022 Jun 14;ciac481. doi: 10.1093/cid/ciac481.
2. COVID-19 rebound after Paxlovid treatment. https://emergency.cdc.gov/han/2022/pdf/CDC_HAN_467.pdf, May 24, 2022.