Patients with COVID-19 who were treated with nirmatrelvir plus ritonavir (NPR) had a viral testing rebound incidence of 14% and a symptom rebound incidence of 19%, according to study findings published in Clinical Infectious Diseases.
Research has indicated that NPR reduces the risk for severe COVID-19 symptoms in high-risk patients by 89%, said study authors; however, the medication has been under-prescribed in the wake of reports that patients completing NPR treatment have experienced a return of COVID-19 symptoms or detectable viral load — a phenomemon referred to as “rebound.” Investigators therefore sought to examine the epidemiology of COVID-19 rebound in patients with acute COVID-19 infection taking NPR.
The prospective, observational study, compared patients with acute COVID-19 infection taking NPR with a control group of similar medication-eligible individuals who independently chose not to receive NPR. Participants in were at least 18 years of age, lived in the US, had a positive rapid antigen test for SARS-CoV-2, and were prescribed NPR through a telehealth visit regardless of whether they intended to take the medicine.
Participants in both the NPR and control group were shipped a kit with 12 telehealth-proctored rapid antigen home tests. NPR-arm participants were advised to complete their first antigen test and first symptom surveys on days 2 and 5 of the 5-day NPR course, and then every other day through day 16; they then were asked to complete surveys about persistent/long COVID symptoms at 1, 3, and 6 months after treatment. The primary endpoint was the incidence of viral and symptom rebound in the NPR and control groups after acute COVID-19 infection.
The analysis included 170 participants — 127 in the NPR arm (56.7% female; 88% White) and 43 in the control arm (62.8% female; 62% White). A majority were under the age of 65 years (86% of the NPR group; 91% of the control group) and about 70% of participants in each group had at least 1 pre-existing condition. In the NPR group, 104 (82%) participants were fully vaccinated, 17 (13%) were partially vaccinated, and 6 (5%) were unvaccinated. In the control group, 30 (70%) participants were fully vaccinated, 11 (25%) were partially vaccinated, and 2 (5%) were unvaccinated.
The virus testing rebound incidence was 14.2% in the NPR treatment group, compared with 9.3% in the control group (P =.41). The symptom rebound incidence was likewise higher in the NPR treatment group (18.9%) vs the control group (7.0%) (P =.06). Notably, the between-group differences for viral rebound and symptom rebound were not statistically significant.
No notable differences were observed in viral rebound by age, sex, pre-existing conditions, or symptom groups in the 16-day follow-up. No notable differences occurred in the NPR treatment and control group symptoms at 1 month.
In the 18 participants with viral rebound in the NPR treatment group and 4 in the control group, the rebound duration was slightly increased in the NPR group compared with the control group (4.4 days vs 2.0 days, respectively).
The main limitations are the unbalanced sample size in the control cohort and a mostly White population. Also, missing data likely biased the results to show a lower incidence of rebound, and a longer follow-up may be necessary to better understand rebound.
“This preliminary report of our prospective study of both virus test-positive and symptomatic rebound suggests that rebound after clearance of test positivity or symptom resolution is higher than previously reported,” stated the investigators. “Interestingly, however, we observed that the high rate of virus rebound is both in the NPR treatment and control groups, though there was a notably higher frequency of symptom rebound among those treated with NPR.”
Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Pandit JA, Radin JM, Chiang D, et al. The COVID-19 rebound study: a prospective cohort study to evaluate viral and symptom rebound differences in participants treated with nirmatrelvir plus ritonavir versus untreated controls. Clin Infect Dis. Published online February 22, 2023. doi:10.1093/cid/ciad102