XOCOVA offers new post-exposure COVID-19 prevention option for adolescents

Pediatricians now have a new option to consider when counseling adolescents and families following a known COVID-19 exposure. XOCOVA (ensitrelvir), an oral antiviral, is approved in the United States for post-exposure prophylaxis (PEP) of COVID-19 in adults and adolescents aged 12 years and older following contact with an individual with COVID-19. The medication should be initiated as soon as possible and within 72 hours of exposure and is taken once daily for 5 days.

The approval was supported by findings from the global, double-blind, randomized, placebo-controlled phase 3 SCORPIO-PEP trial. The study included 2387 participants aged 12 years and older who had been exposed to a household member with symptomatic COVID-19. In the primary analysis population, XOCOVA reduced the risk of symptomatic COVID-19 through day 10 by 67% compared with placebo. Headache, diarrhea, and cough were the most common adverse events occurring more frequently with XOCOVA than placebo.

For pediatricians, the availability of an oral option for post-exposure prophylaxis introduces new considerations when families call after a household COVID-19 exposure. Because XOCOVA must be started within 72 hours, identifying eligible adolescents and counseling families about when to contact their pediatrician may be important to timely use. Clinicians also need to consider medication interactions and other safety information when determining whether XOCOVA is appropriate for an individual patient. The medication is not approved for children younger than 12 years.

In this Q&A, Charles Vega, MD, FAAFP, health sciences clinical professor at the University of California, Irvine, School of Medicine, discusses what pediatricians should know about COVID-19 post-exposure prophylaxis, which adolescent patients may be appropriate candidates, and how clinicians can counsel families after a known exposure. Vega also addresses how XOCOVA may fit alongside vaccination and other COVID-19 prevention strategies in pediatric practice.

Contemporary Pediatrics: Many parts of the country are seeing a summer increase in COVID-19 activity. What trends are you watching this season, and what should pediatricians know about the continued impact of COVID-19 on children, adolescents, and their families?

Charles Vega, MD, FAAFP: We continue to see COVID-19 activity rise during certain times of year, including summer and winter.¹ The CDC estimates that COVID-19 infections are growing or likely growing in 50 states.²

Contemporary Pediatrics: Some people view COVID-19 as a mild illness now, but we continue to see hospitalizations, complications, and cases of long COVID. Why is it still important to focus on preventing infection, particularly in children and adolescents who may be at higher risk?

Vega: It’s true that COVID-19 continues to affect millions of Americans each year and can have lasting impacts.^3-5 It can become severe, and even when mild or moderate, may worsen existing health conditions or contribute to new ones.^4-6

Anyone can get COVID-19, but some are more likely than others to get very sick, including people who are older, have a weakened immune system, have certain disabilities, or have underlying health conditions.⁷

XOCOVA was studied in a clinical trial that included participants without risk factors for severe COVID‑19 as well as individuals at high risk for developing severe disease. Common risk factors include asthma, diabetes, being overweight, smoking, depression, and an inactive lifestyle.⁹

Adults and adolescents 12 years of age and older may benefit from taking XOCOVA after being exposed to COVID-19. Its use is not limited to people who are immunocompromised or have underlying conditions, but those who are at high risk may benefit from post-exposure prophylaxis with XOCOVA.^8,9 It is not known if XOCOVA is safe and effective in children less than 12 years of age.

Contemporary Pediatrics: XOCOVA is the first FDA-approved oral antiviral for post-exposure prophylaxis. How does having an option to prevent COVID-19 after a known exposure change the conversation pediatricians can have with families?

Vega: I often hear from families who ask what they can do to protect others in their household when one person tests positive for COVID-19. Until now, the best advice we could offer was practicing good hygiene and distancing from an infected person. With XOCOVA, we now have an option to help prevent people 12 years of age and older from getting sick after exposure to COVID-19.⁸ 

After someone is exposed, the virus can begin multiplying before symptoms start. That period between exposure and symptom onset is important because acting quickly could help reduce the risk of developing COVID-19.^10,11

XOCOVA can help prevent COVID-19 when taken within 72 hours of exposure by blocking the virus from multiplying. In a clinical study, XOCOVA reduced the risk of developing symptomatic COVID-19 by 67% through Day 10 versus placebo.⁹

Contemporary Pediatrics: Which pediatric patients or household situations do you think could benefit most from a post-exposure option like XOCOVA? Are there specific scenarios—such as a family member testing positive, travel, or outbreaks in camps or schools—where you see this fitting into clinical practice?

Vega: First, it is important to note that XOCOVA was studied in and approved for people 12 years of age and older, so it is not recommended for younger pediatric patients.

COVID-19 is highly transmissible and up to 47% of people living with an infected individual may develop COVID-19.¹²

Eligible patients living in a variety of settings — from multigenerational households to on-campus housing — could benefit from COVID-19 post-exposure prophylaxis.^8,9,13

The home is not the only place where someone can be exposed to COVID-19. People can also be exposed in indoor environments with inadequate ventilation, during activities that increase respiratory fluids, such as speaking loudly, singing or exercising, during prolonged exposure, and in crowded spaces where face coverings are inconsistently or improperly worn, such as in schools and athletic facilities.¹³

Contemporary Pediatrics: What advice would you give pediatricians about helping families recognize when to act after a COVID-19 exposure, and how can they explain the role of a medication like XOCOVA alongside other preventive measures such as vaccination and staying home when ill?

Vega: Vaccination remains critical for helping to prevent COVID-19, but vaccination may not stop infection completely, particularly with new variants and as immunity wanes over time.^9,14

I will explain to my patients and their families that XOCOVA does not replace vaccines, but it helps to prevent COVID-19 by blocking the virus from multiplying during the critical window between exposure and symptom onset.

XOCOVA is not going to be for every adolescent patient, but it does have the potential to benefit anyone who does not want to get COVID-19, once a healthcare provider has determined that XOCOVA is appropriate for them.

Now, in addition to recommending my patients stay updated with vaccinations, I’ll be talking to their parents and caregivers about XOCOVA, so they are ready to act quickly in the event of an exposure.

References

1. Centers for Disease Control and Prevention. 2026 COVID-19 summer outlook. CDC. 2026. Accessed September 10, 2026. https://www.cdc.gov/cfa-qualitative-assessments/php/data-research/2026covid-19outlook.html

2. Centers for Disease Control and Prevention. Current epidemic trends (based on Rt). CDC. Accessed September 10, 2026. https://www.cdc.gov/cfa-modeling-and-forecasting/rt-estimates/index.html?tab=0

3. Centers for Disease Control and Prevention. Preliminary estimates of COVID-19 burden for 2024-2025. CDC. 2026. Accessed September 10, 2026. https://www.cdc.gov/covid/php/surveillance/burden-estimates.html

4. Centers for Disease Control and Prevention. Long COVID basics. CDC. 2026. Accessed September 10, 2026. https://www.cdc.gov/long-covid/about/index.html

5. Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022;28(3):583-590. doi:10.1038/s41591-022-01689-3

6. Sax PE, Draica F, et al. New onset conditions, exacerbations and worsening of underlying conditions following COVID-19 infection. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); 2026; Denver, CO.

7. Centers for Disease Control and Prevention. About COVID-19. CDC. Accessed August 7, 2026. https://www.cdc.gov/covid/about/index.html

8. XOCOVA (ensitrelvir) [prescribing information]. Shionogi Inc. Accessed July 9, 2026. https://www.shionogi.com/content/dam/shionogi/si/products/pdf/xocova.pdf

9. Hayden FG, Shinkai M, et al. Ensitrelvir for COVID-19 postexposure prophylaxis in household contacts. N Engl J Med. 2026;394(19):1905-1915. doi:10.1056/NEJMoa2509306

10. Kawashima S, Matsui Y, et al. Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally. Biochem Biophys Res Commun. 2023;645:132-136. doi:10.1016/j.bbrc.2023.01.040

11. Kuroda T, Nobori H, et al. Efficacy comparison of 3CL protease inhibitors ensitrelvir and nirmatrelvir against SARS-CoV-2 in vitro and in vivo. J Antimicrob Chemother. 2023;78(4):946-952. doi:10.1093/jac/dkad027

12. Tanaka M, Ruiz C, et al. SARS-CoV-2 transmission dynamics in households with children, Los Angeles, California. Front Pediatr. 2021;9:752993. doi:10.3389/fped.2021.752993

13. United States Environmental Protection Agency. Indoor air and coronavirus (COVID-19). EPA. Accessed September 10, 2026. https://www.epa.gov/indoor-air-quality-iaq/indoor-air-and-coronavirus-covid-19

14. Centers for Disease Control and Prevention. The possibility of COVID-19 after vaccination: breakthrough infections. CDC. Accessed September 10, 2026. https://stacks.cdc.gov/view/cdc/110515