Paxlovid Was Most Effective in Older Adults During Omicron Surge, Study Shows

Paxlovid—the antiviral treatment used to prevent serious illness and death from COVID-19—may be most effective for adults over 65, new research shows. But the drug may yield little to no benefit for younger populations.

The claim comes from new research, published last week in the New England Journal of Medicine, to assess the effectiveness of Paxlovid in patients during an Omicron surge in Israel in a population that already had some level of prior COVID immunity.

In examining data from more than 109,000 Israeli patients who were at least 40 years old, researchers found that Paxlovid significantly reduced the rates of hospitalization and death from COVID in people ages 65 and older, compared to those who did not take the drug.

"Among patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received the drug," lead study author Ronen Arbel, PhD, told Health. "This shows that the drug is an important second line of defense for vaccinated patients, and the first line in the unvaccinated patients."

Specifically, of the 42,821 patients over 65 who got COVID, only 11 of those who took at least one dose of Paxlovid were hospitalized, compared to 766 patients who did not take the drug—that's a 73% reduction in risk. Similarly, only two out of 2484 Paxlovid-treated patients died, compared to 158 COVID-related deaths out of 40,337 untreated patients—a 79% reduction in risk.

Despite these significant reductions in risk of hospitalizations and deaths for patients over 65, researchers saw little to no benefit for a younger population treated with Paxlovid.

Paxlovid Is Still Recommended for High-Risk Individuals Under 65

Paxlovid was authorized for emergency use among people ages 12 and older who are at an increased risk of severe COVID-19, which can lead to hospitalization or death.

"Populations who can benefit from treatment with Paxlovid are those who are at least 12 years of age, weigh at least 88 pounds, tested positive for COVID-19, have mild-to-moderate [symptoms], and are at high risk of progression to severe COVID-19," Brigid Groves, PharmD, senior director of practice and professional affairs at the American Pharmacy Association.

According to Groves, the risk factors that put patients at a higher risk of severe COVID, include being older than 65, or having certain medical conditions or a weakened immune system.

While the new research showed that people over 65 reaped the most benefits from taking Paxlovid, the study leaves questions about its effectiveness among younger populations—even those for whom the treatment is recommended.

Though the study saw no benefit for adults ages 40–64 who were approved to take the drug, previous research has shown slightly different results. A 2022 preprint study using data from Massachusetts General Brigham showed that Paxlovid reduced the risk of hospitalization among COVID patients ages 50 and older by 45%.

Pfizer—the pharmaceutical company that makes Paxlovid—also found, in its own research, that the drug lowered the risk of hospitalization or death in unvaccinated COVID patients by 88% among patients who were at least 18 years old. However, Paxlovid's trials took place during the Delta surge.

Because the data, at this point, is still relatively inconclusive, experts suggest treating the study findings as guidelines to confirm the treatment's efficacy in older populations—but not to eliminate its possibility of benefitting a younger high-risk group.

"Our results confirm CDC guidelines to treat high-risk patients, prioritizing those above 65," said Arbel. "It should not be limited, but rather a factor to consider in the risk assessment of patients. Ultimately, it is a clinical decision based on the risk profile and additional clinical considerations by the caring physician."

Currently, the CDC still recommends that high-risk individuals, regardless of age, take Paxlovid to prevent mild-to-moderate cases of COVID-19 from progressing into more serious health issues.

"Eligible patients at high risk of progression to severe COVID-19 are recommended to be treated with Paxlovid to reduce the likelihood of hospitalization and death," said Groves.

Paxlovid Efficacy and COVID-19 Rebound Cases

The new research did not track symptoms or subsequent COVID-19 tests, so it doesn't offer any insights on rebound cases of COVID, or when patients test positive or have a resurgence of symptoms after the illness initially waned.

Although COVID rebounds have been commonly associated with Paxlovid treatment, research shows that rebound cases, though mild and not associated with severe illness, can occur even in patients who haven't taken the antiviral drug.

"Some patients with COVID-19 experience a recurrence of symptoms or a new positive viral test after having previously tested negative," said Groves. "The phenomenon, 'COVID-19 rebound,' occurs independently and regardless of Paxlovid treatment or vaccination status. This brief recurrence of symptoms may be part of the natural progression of SARS-CoV-2 in some patients."

According to the most recent information from the CDC, COVID rebound following a course of Paxlovid does not mean that a patient developed a resistance to Paxlovid.

These COVID rebounds after Paxlovid use also don't negate the drug's effectiveness in reducing hospitalizations and deaths, the CDC said. There's also no data that suggests a longer course of treatment, or a repeat course of treatment, would be more beneficial for COVID rebound cases.