Research Health Science Specialist Department of Veterans Affairs, United States
Background: The CDC issued a health advisory on the risk of rebound COVID-19 associated with the EUA drug Paxlovid (PAX). The phenomenon has also been reported with the EUA drug, Molnupiravir (MOV). To further investigate this issue and address safe use of these medications, the VA Center for Medication Safety characterized potential rebound COVID-19 in Veterans treated with PAX or MOV via a Medication use evaluation.
Objectives: 1) Assess potential prevalence of rebound COVID-19 by vaccination status; 2) evaluate reported ADEs; 3) identify other reasons for rebound symptoms; and 4) explore medical reasons for reduced drug efficacy.
Methods: VA Administrative databases were used to identify patients who received PAX or MOV in 2022, including patients with and without coded encounters in VA 30 days post-treatment. Using standardized criteria, chart abstractors reviewed patients’ electronic medical records (EMR) to assess potential rebound COVID-19. Rebound was based on documentation of initial improvement or resolution of the index COVID-19 infection followed by worsening or recurrence of COVID-19 symptoms, regardless of a follow-up COVID-19 test. Descriptive analyses were conducted.
Results: Of 400 patients identified for review, 291 cases (142 PAX and 149 MOV) were assessed for rebound after excluding patients who were employees, completed < 5-days treatment, and had no follow-up in the EMR.
ADE was reported in 25 patients. Diarrhea (40%) and dysgeusia (36%) were the most frequently reported ADEs. Discontinuation of therapy due to an ADE was reported in 40% of PAX and 67% of MOV patients.
Evidence of rebound was found in 20 (6.9%) patients (7/142 PAX (4.9%), 13/149 MOV (8.7%)). Median age of rebound was 73 y (IQR: 64, 76), and 90% of patients received at least one dose of the Covid-19 vaccine. Median days from treatment completion date to onset of rebound symptoms was 7 days (IQR: 4, 15). Nine (45%) cases were self-reported, 3 (15%) by new positive COVID-19 test, 5 (25%) by COVID-19 medical visits, and 3 (15%) by provider during a non-COVID-19 visit.
Half of the patients with rebound COVID-19 had coexisting reasons for symptoms such as allergies, common or seasonal cold. Three (15%) cases had potential reasons for reduced drug efficacy, such as delayed initiation and drug-drug interactions with PAX.
Conclusions: Rebound COVID-19 occurs with both PAX and MOV. Patient-level chart review is useful for assessing and further delineating factors that characterize rebound. However, reliance on post-treatment patient contact with the healthcare system limits the ability to obtain a true incidence rate of rebound COVID-19. A prospective method directly contacting patients is needed to optimally assess for rebound and capture a true incidence rate.
