- Paxlovid is a highly effective treatment for mild-to-moderate COVID-19 in people at high risk
- Reports have emerged in recent months of symptom rebound after Paxlovid treatment
- A small U.S. study observed mild rebounds in less than 1% of Paxlovid users
Paxlovid is the brand name of two medicines—an antiviral drug called nirmatrelvir and a booster called ritonavir, which raises the level of nirmatrelvir in the blood. Both drugs are supplied in tablet formulations and are taken twice daily for five consecutive days. Paxlovid is meant for people who test positive for SARS-CoV-2 infection and who are at high risk for developing serious symptoms of COVID-19.
Paxlovid is highly effective. Clinical trials have found that it reduces the risk of hospitalization and death by nearly 90% among unvaccinated people who have mild-to-moderate symptoms of COVID-19.
Paxlovid is available in Canada and other high-income countries though its distribution is limited.
The U.S. Food and Drug Administration (FDA)
In the past several months there have been reports from the U.S. of an apparent rebound in symptoms of COVID-19 in people who completed a course of Paxlovid. After reviewing its files, the FDA stated that in the pivotal phase III trial that led to the approval of Paxlovid, between 1% and 2% of people who received Paxlovid or placebo had “one or more positive polymerase chain reaction [PCR] tests for SARS-CoV-2 after completing their [course of Paxlovid or placebo].”
Thus, it is not clear to the agency if rebounds occasionally reported by doctors and patients who use the drug are due to an effect of Paxlovid or are a natural part of the disease course of COVID-19. Furthermore, the FDA noted that in the clinical trial there was no increased risk of hospitalization, death or viral resistance to Paxlovid among participants who had a degree of COVID-19 rebound.
According to the FDA, “These reports [of COVID-19 rebound in patients who use Paxlovid] do not change the conclusions from the Paxlovid clinical trial which demonstrated a marked reduction in hospitalization and death.”
The agency added, “There is no evidence of benefit at this time for a longer course of treatment (e.g., 10 days rather than the 5 days recommended) or repeating a treatment course of Paxlovid in patients with recurrent COVID-19 symptoms following completion of a treatment course.”
At the Mayo Clinic
A team of researchers at the Mayo Clinic in Rochester, Minnesota, has reviewed information collected from patients treated for COVID-19 with Paxlovid. The researchers analysed data from 438 people (44% men, 56% women) whose average age was 63 years. All had previously received three doses of vaccinations to reduce the risk of developing COVID-19.
The researchers found that four people (0.8%) experienced symptoms of COVID-19 rebound, on average about nine days after cessation of Paxlovid. None of them required hospitalization because of their symptoms. What’s more, the researchers stated that “all [patients] improved without requiring further COVID-19 [antiviral re-treatment].”
This news from the Mayo Clinic and the statements from the FDA should reassure healthcare providers and patients who have been treated with Paxlovid.
Cases
Below are summaries of the four people who had a documented COVID-19 rebound.
Patient 1 – A 75-year-old male with coronary artery disease, type 2 diabetes and chronic obstructive pulmonary disease. His initial symptoms were cough, runny nose, headache and fever. He initiated Paxlovid three days after testing positive with a PCR test. His symptoms resolved at the end of Paxlovid treatment.
Nineteen days later he developed worsening cough, wheezing and shortness of breath. A CT scan suggested COVID-19-related pneumonia. He recovered without the use of further antiviral drugs.
Patient 2 – A 40-year-old woman with obesity, chronic kidney disease and high blood pressure developed fever, cough, diarrhea, and racing heart beats while at rest. She tested positive on a COVID-19 home antigen test. She initiated Paxlovid three days later and her symptoms resolved by the end of therapy.
Six days later she developed sore throat and fatigue. She did not receive further antiviral therapy and recovered.
Patient 3 – A 69-year-old man with obesity and high blood pressure developed fever, cough, runny nose, muscle pain and shortness of breath. He tested positive for SARS-CoV-2 with a PCR test and started taking Paxlovid one day later. His symptoms improved after completion of therapy.
Ten days later he developed a severe cough and runny nose. He recovered without requiring re-treatment with antiviral drugs.
Patient 4 – A 70-year-old man with a history of prostate cancer, high blood pressure, abnormal cholesterol levels and obesity developed cough, fever, runny nose, headache and sore throat. He tested positive on a home antigen test and initiated Paxlovid one day later. His symptoms resolved upon completion of treatment.
Eight days later he developed symptoms of runny nose and sinus congestion, which were managed without requiring re-treatment with antiviral drugs.
Bear in mind
A shortcoming of the Mayo Clinic study is that researchers were not able to assess SARS-CoV-2 levels in the secretions of participants with COVID-19 rebound. The precise cause of COVID-19 rebound symptoms in people who develop them is not clear. The researchers recommend studies that undertake detailed immunological and virological analyses to explore this condition. Such studies should also assess potential risk factors for COVID-19 rebound.
It is reassuring that data from both the FDA and the Mayo Clinic suggest that hospitalization is unnecessary for cases of COVID-19 rebound in people who have been treated with Paxlovid. Furthermore, the analysis from the FDA suggested that rates of rebound are relatively low (less than 2%). In the current review from the Mayo Clinic, even though the study was small, rates of rebound were less than 1%.
REFERENCES:
- Ranganath N, O’Horo JC, Challener DW, et al. Rebound phenomenon after nirmatrelvir/ritonavir treatment of coronavirus disease-2019 in high-risk persons. Clinical Infectious Diseases. 2022; in press.
- Food and Drug Administration. FDA Updates on Paxlovid for Health Care Providers. 4 May 2022. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-updates-paxlovid-health-care-providers
- Rubin R. From positive to negative to positive again – The mystery of why COVID-19 rebounds in some patients who take Paxlovid. JAMA. 2022; in press.