Paxlovid Vindicated for Younger COVID Patients

Nirmatrelvir-ritonavir (Paxlovid) halved hospitalizations for COVID-19 patients, including triply vaccinated individuals and younger adults, a CDC study showed.

People prescribed the antiviral combination within 5 days of diagnosis had a 51% lower hospitalization rate within 30 days after diagnosis than those who did not receive the drug (0.47% vs 0.86%, adjusted HR 0.49, 95% CI 0.46-0.53), reported Melisa M. Shah, MD, of the CDC’s National Center for Immunization and Respiratory Diseases in Atlanta, and colleagues in the Morbidity and Mortality Weekly Report.

The magnitude of benefit was similar for fully vaccinated individuals who had at least three doses of an mRNA vaccine (aHR 0.50, 95% CI 0.45-0.55).

“Paxlovid should be offered to eligible adults irrespective of vaccination status, especially in groups with the highest risk for severe COVID-19 outcomes, such as older adults and those with multiple underlying health conditions,” Shah’s group urged.

Notably, young adults appeared to gain almost as much as older adults, with an adjusted hazard ratio for 30-day admissions after nirmatrelvir/ritonavir prescription of 0.59 (95% CI 0.48-0.71) for those ages 18 to 49, compared with 0.40 (95% CI 0.34-0.48) for 50- to 64-year-olds and 0.53 (95% CI 0.48-0.58) for those 65 and older.

In that youngest age group, the antiviral was associated with numerically but not significantly lower hospitalization rates even among fully vaccinated and boosted individuals (aHR 0.75, 95% CI 0.53-1.06) and those with only one underlying health condition (aHR 0.91, 95% CI 0.58-1.44).

Those findings counter the conclusions of an observational retrospective cohort study from Israel, in which patients ages 40 to 64 had no benefit for hospitalization with the drug compared with untreated patients (aHR 0.74, 95% CI 0.35-1.58), unlike the relative 73% reduction among older adults, leading those researchers to conclude that seniors should be prioritized for use.

Older age is a predominant risk factor in consideration for nirmatrelvir/ritonavir in clinical guidelines for use, but younger adults can meet the same risk level with underlying conditions, Shah’s group noted. The drug is not authorized for use in standard-risk outpatients with COVID-19.

Fully 63.3% of hospitalizations in the current study occurred among persons ages 65 and older.

The study included 699,848 adults from the Cosmos database of electronic medical records from Epic, which covers a population of more than 160 million people in U.S. health systems. Inclusion required an outpatient encounter — whether telemedicine, in-person, urgent care, or emergency department visit — associated with a COVID-19 diagnosis and at least one prior face-to-face encounter recorded in the electronic medical record during the 3 years prior.

The patients were all eligible for nirmatrelvir/ritonavir from April to August of this year, a period during which Omicron remained the dominant variant.

“The initial randomized clinical trial of Paxlovid, which showed an 89% reduction in severe COVID-19 outcomes, was conducted in unvaccinated persons with no previous infection during the period preceding Omicron variant predominance,” Shah and team noted. “This real-world analysis demonstrated that being prescribed Paxlovid is associated with a substantially reduced hospitalization risk among persons with previous immunity from infection or vaccination in the setting of the current circulating Omicron subvariants.”

Of the study population, 28.4% received a nirmatrelvir/ritonavir prescription within 5 days of COVID-19 diagnosis.

While those who were immunocompromised accounted for 9.4% of the study population, and 30.2% of them received the antiviral, results were not broken out for this group in comparison with untreated individuals.

The study also found fewer in-hospital deaths in the nirmatrelvir/ritonavir-treated patients (0.01% vs 0.04% in nonrecipients), although other deaths outside the hospital were not ascertained.

Other limitations of the study included counting prescription as a proxy for use of nirmatrelvir/ritonavir and inability to confirm that patients took the full 5-day course of medication. In addition, dates of diagnosis or test positivity were used to estimate illness onset, asymptomatic COVID-19 infection in the nonrecipient comparison group couldn’t be excluded, and underlying health conditions and immunocompromise had to be approximated using billing and medical record fields.