PROJECT SUMMARY With the increasing use of oral antiviral treatments for acute SARS-CoV-2 infection, there have been multiple reports of symptom and viral load rebound after the prescribed treatment course. The most prescribed oral antiviral is Paxlovid, and while it has become a component of test-to-treat programs, there are no incidence or prevalence numbers on Paxlovid (symptomatologic and/or virologic) rebound after the five-day treatment course. Further, the connection between symptoms, viral load rebound, and immune correlates is unknown as well. This is of utmost urgence from a public health standpoint, given the possibility of the individual remaining infectious despite Paxlovid treatment and concerns about the potential development of drug resistance. Therefore, with additional funding we propose to study the incidence, prevalence, symptomatology, virus evolution, and immune correlates of COVID-19 cases who rebound after completion of Paxlovid treatment.

PROJECT NARRATIVE As the COVID-19 pandemic ensues, the promise of ambulatory oral therapeutics has led to widespread use of Paxlovid. However, there have been significant reports of symptomatologic and virologic rebound after the current approved five-day course. To understand the epidemiology and pathophysiology of Paxlovid rebound, we will perform additional testing including virus sequencing, systems serology, and symptomatology assessments in a large cohort of COVID-19 patients who qualify for Paxlovid.