Ritonavir-boosted nirmatrelvir protects older adults against post-COVID conditions

Treatment with nirmatrelvir/ritonavir helps lower the incidence of post-COVID conditions (PCC) in older adults, according to a large study.

Data from 874,299 patients with COVID-19 who were at least 12 years of age and at high risk of severe illness (ie, older age, underlying medical condition, use of immune-suppressing medication) showed that among adults ≥50 years of age, those who did vs did not receive nirmatrelvir/ritonavir had a lower risk of PCC (≥1 condition: relative risk [RR], 0.91, 95 percent confidence interval [CI], 0.91–0.92; ≥2 conditions: RR, 0.86, 95 percent CI, 0.85–0.87). [IDWeek 2023, abstract 1937]

PCC was defined as new-onset conditions that occurred at least 60 days after index date and not reported within 7–365 days prior.

The risk reduction was seen for most individual PCC conditions, including renal, haematologic and vascular, neurologic and musculoskeletal conditions, among others, reported presenting author Dr Alexandra Dalton of Centers for Disease Control and Prevention in Raleigh, North Carolina, US.

In other age groups, the results were mixed. For example, among adults between 18 and 49 years of age, treatment had no significant effect on PCC risk (≥1 condition: RR, 1.00, 95 percent CI, 0.99–1.01; ≥2 conditions: RR, 0.98, 95 percent CI, 0.96–1.00). Furthermore, the associations with individual PCC conditions varied, such that there was an increased risk of asthma and a decreased risk of a thromboembolic event.

Among adolescents between 12 and 17 years, on the other hand, treatment was positively associated with PCC risk for ≥1 condition (RR, 1.09, 95 percent CI, 1.04–1.15) but not for ≥2 conditions (RR, 1.04, 95 percent CI, 0.95–1.15). The risk increase was notable for a few individual PCC conditions including hypertension, asthma, and type 2 diabetes.

“The differences in the association between [nirmatrelvir/ritonavir] and the occurrence of PCC by age group may be due to differences in baseline health in these age groups,” Dalton explained.

She underscored the need for additional investigations to gain deeper insights into the relationship between acute COVID-19 treatments, such as nirmatrelvir/ritonavir, and PCC. These should answer questions regarding the risk of severe COVID-19 and the occurrence of PCC, additional factors that may clarify the association between treatment and PCC, and clinician prescribing behaviour.

For the current study, Dalton and colleagues used data from a large healthcare and consumer data ecosystem. The analysis included 291,433 patients treated with nirmatrelvir/ritonavir and 582,866 matched untreated patients. Most patient characteristics were similar between the two groups.

Compared with the untreated group, the treated group had a higher proportion of patients without healthcare encounters in the previous year (4.1 percent vs 2.0 percent) and those who were vaccinated against COVID-19 (69.8 percent vs 61.6 percent), as well as a lower proportion of patients with documented prior COVID-19 (9.5 percent vs 14.4 percent).

The large dataset was one of the study’s strengths, with the patients likely to be representative of the US healthcare-seeking population. Nevertheless, Dalton admitted that she and her team were not able to verify the patients’ adherence to treatment and that additional factors influencing nirmatrelvir/ritonavir prescriptions and/or PCC may not have been measured and controlled for.

Furthermore, “PCC definition is broad. Conditions may or may not be due to SARS-CoV-2 infection, and PCC diagnoses are based on a single diagnosis code, which may lead to misclassification,” she said.