Oral COVID-19 PEP May Benefit High-Risk Groups More Than General Public: Peter J. Hotez, MD

The first and only oral anti–SARS-CoV-2 drug for postexposure prophylaxis (PEP) of COVID-19, ensitrelvir (Xocova; Shinogi), was recently approved by the FDA.¹

Although the treatment is approved for adults and adolescents aged 12 and older, PEP treatments for COVID-19 may be more beneficial for patients who are immunocompromised, in high-risk categories, or don’t respond well to vaccines, Peter Jay Hotez, MD, professor in the departments of pediatrics and molecular virology and microbiology at Baylor College of Medicine, said in an interview with The American Journal of Managed Care^®. Those who have underlying conditions, such as diabetes, or are in a nursing home may also benefit from PEP therapy for COVID-19, he said.

“I would guess it probably would not be widely used among the general population unless there's a new, entirely different variant that emerges for which currently available vaccines offer no cross-protection,” he said.

There is a new variant circulating in the US—identified in 25 states’ wastewater—nicknamed the cicada variant. The BA 3.2 variant of the Omicron strain has more than 70 mutations, raising concern that it could be more infectious and less responsive to current vaccine formulations.²

Though it hasn’t happened yet, Hotez said this new PEP treatment is still a “good” option to have should a substantially different SARS-CoV-2 variant emerge that reduces protection from currently available vaccines.

“I think that the one scenario where you could see more widespread use adopted is if there's a big resurgence in COVID cases because of a new wave, criterion one,” he said. “Criterion two is if the new variant is substantially different from what the vaccine was designed for, and then in that case, you might find that very attractive for a more general population.”

Hotez also noted the benefit of ensitrelvir's timing considerations when compared with the much narrower window for initiating the combination therapy nirmatrelvir and ritonavir (Paxlovid; Pfizer).

“I think the big problem that you face with a lot of coronavirus infections, of course, is all the asymptomatic individuals, and you're not aware of exposure,” he said.

References

1. McCrear S. FDA approves oral ensitrelvir for COVID-19 postexposure prophylaxis. AJMC^®. June 1, 2026. Accessed June 17, 2026. https://www.ajmc.com/view/fda-approves-oral-ensitrelvir-for-covid-19-post-exposure-prophylaxis

2. McCrear S. Cicada COVID-19 variant FAQs: symptoms, risk, and prevention. AJMC. June 4, 2026. Accessed June 16, 2026. https://www.ajmc.com/view/cicada-covid-19-variant-faqs-symptoms-risk-and-prevention