Outpatient and urgent care encounters can create an early opportunity to protect people who were exposed to COVID-19, particularly vulnerable household contacts. Charles P. Vega, MD, discusses the roles of household risk assessment, masking and distancing, vaccination, testing, telehealth, and antiviral postexposure prophylaxis (PEP) in the prevention of COVID-19 after exposure.

Outpatient and urgent care clinicians, along with patients and their loved ones, are the key players involved in early COVID-19 (ie, SARS-CoV-2) prevention after exposure. Clinicians have the know-how, and families often know who in their households are most vulnerable. Household transmission is substantial with the Omicron variant. One meta-analysis estimated a household secondary attack rate of 42.7% for Omicron, so 1 affected family member is very likely to infect another. Those who are at risk for severe COVID-19 include older adults, people with concomitant disease(s), and infants younger than 6 months. It takes a union among clinicians, patients, and families to prevent the worst outcomes.

Most patients with COVID-19 who present in outpatient and urgent care settings are symptomatic. They may also mention, for example, an 84-year-old grandfather at home or a husband with diabetes and heart failure who is becoming symptomatic. We really want to consider the entire household—to extend beyond the patient in front of us and think of others who may be impacted. It is important to talk with the main contact or index person about protecting everybody they encounter. That means distancing and isolating as much as possible, as well as masking. All these basic measures work. Talking to the index patient about protecting people around them can also prompt discussions about vaccination. A vaccine will not protect someone from an exposure already occurring in their household, but it can protect them against a future exposure.

I had not previously been promoting antiviral therapies for COVID-19 PEP because we did not have anything available in that area until very recently (ie, ensitrelvir). Ensitrelvir was US Food and Drug Administration (FDA) approved as a postexposure preventive option only in June 2026. It is not just for high-risk individuals. If a patient is older than 12 years and has had household contact with somebody with COVID-19 within the past 72 hours, they can begin treatment. In the SCORPIO-PEP trial, ensitrelvir reduced transmission by approximately two-thirds and was very well tolerated.

When I think about for whom COVID-19 PEP would be most useful, it is those who are at high risk for severe COVID-19. Age is the clearest risk factor, while diabetes, severe obesity, and chronic dysfunction of a major organ (eg, the brain, lungs, heart, kidney, or liver) also increase the risk of severe disease. I also consider vaccination status. Vaccines can be more protective against more severe illness, so I ask about the last time a patient received a COVID-19 vaccine.

Testing for COVID-19 is very useful, and, while I trust a positive home antigen test, especially when patients are symptomatic, clinical polymerase chain reaction testing remains valuable due to its higher sensitivity. However, home testing can enable a telehealth discussion of transmission prevention and treatment. Time is of the essence with PEP against COVID-19. Many individuals who could benefit from ensitrelvir will be disqualified from taking it because their first exposure to COVID-19 was more than 72 hours ago.

The responsibilities are similar in outpatient and urgent care. In person or by telehealth, I ask who lives with the index patient and whether anyone in the home is at high risk for severe COVID-19. An established index patient may contact me directly, and the acutely ill index patient is often the person who prompts the discussion about whether another household member may benefit from PEP.

Clinicians have historically prescribed antiviral prophylaxis at low rates. One reason may be the many messages about antimicrobial stewardship. Avoiding antibiotic overuse is absolutely important, but antivirals are not antibiotics. The rate of viral resistance in response to antiviral use is much lower. Patients who are at extremely high risk of severe COVID-19, including transplant recipients and those with multiple chronic illnesses, with AIDS, or on immunosuppressive therapy, are not yet receiving PEP for COVID-19. With the recent FDA approval of ensitrelvir, we now have a tool to help prevent COVID-19 after exposure in these vulnerable patients.