Rare Combined Symptom and Viral Rebound in Untreated COVID-19 Patients

Brigham and Women's Hospital

After completing a course of nirmatrelvir-ritonavir, a treatment for at-risk patients who have contracted COVID-19, some patients have reported worsening symptoms and viral rebound. But does viral rebound and the reemergence of symptoms also occur in patients who are not given this treatment? To further understand this phenomenon, researchers from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, analyzed the rates of symptom and viral rebound in COVID-19 patients who did not receive nirmatrelvir-ritonavir, in comparison with those who did. The project involved 563 patients who participated in anterior nasal swabs for two weeks and 29 days of symptom tracking in a diary. Symptom tracking focused on the severity of 13 specific symptoms: feeling feverishness, coughing, 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. Participants self-assessed their symptoms on a scale of zero (absence of symptom) to three (severe symptom) and viral rebound was classified as a symptom scoring at least four points higher than the lowest score after initial improvement. The results showed that symptom rebound was found in 26 percent of participants, viral rebound in 31 percent of participants and high-level viral rebound in 13 percent of participants. However, these results were considered short-term as 89 percent of symptom rebounds and 95 percent of viral rebounds only occurred once before improving long-term. Only three percent of participants experienced both symptom and high-level viral rebound. It is important to note that most participants were unvaccinated and were infected with pre-Omicron COVID-19 variants.

"What these results show is that baseline rates of symptom and viral relapse in those not receiving treatment for COVID-19 need to be accounted for when studying the risk of rebound after antiviral therapy," said Jonathan Li, MD, of the Brigham's Division of Infectious Diseases. "In other words, you need a control group of untreated individuals when studying rates of Paxlovid rebound."

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