Mixed Signals for Paxlovid and Long COVID Risk in CDC Study

Use of nirmatrelvir-ritonavir (Paxlovid) during the acute phase of COVID-19 appeared to significantly reduce the risk of post-COVID conditions (PCCs) in older adults at high risk for severe disease, but may have increased the risk in adolescents, according to a large case-control study from the CDC.

In adults ages 50 and up, the risk of PCCs was lower among those who received nirmatrelvir-ritonavir, with relative risks (RRs) of one or more PCC of 0.91 (95% CI 0.91-0.92) and two or more PCCs of 0.86 (95% CI 0.85-0.87), reported Alexandra Dalton, PhD, of the CDC’s Coronavirus and Other Respiratory Viruses Division, during a late-breaking abstract session at the IDWeek annual meeting.

However, in adolescents ages 12 to 17, the overall risk of PCCs in those who received the antiviral was significant for one or more PCCs, including hypertension, asthma, and type 2 diabetes, but not significant for two or more PCCs:

• One or more PCCs: RR 1.09, 95% CI 1.04-1.15
• Two or more PCCs: RR 1.04, 95% CI 0.95-1.14

For adults ages 18 to 49, the use of nirmatrelvir-ritonavir appeared neutral with regard to PCC risks, with some variation. Dalton pointed to a slightly increased risk of asthma, but a decreased risk of thromboembolic events.

“We saw that the association between Paxlovid and the occurrence of post-COVID conditions by age group is diverse,” Dalton noted. “We think some of this difference may be due to differences in baseline health of the age groups, but this is a very new area of research, and there’s still a lot to be learned.”

The CDC is “already thinking about what future research is going to be needed to help us better understand this relationship,” she said. “For example, what’s the association of acute COVID-19 risk with this treatment? This analysis focused on those who were at higher risk for severe illness, but we haven’t looked at individuals who are not at increased risk, nor did we stratify this current analysis by underlying medical conditions. We also want to understand more about physician prescribing behavior to see how that may be influencing results.”

Nirmatrelvir-ritonavir is recommended for patients who are at high risk of developing severe COVID, including those ages 50 and older, especially those ages 65 and over; those who are unvaccinated; and those with comorbid medical conditions.

A previous study found that the drug reduced the risk of a PCC by about 25% in older adults with risk factors for severe disease compared with those who didn’t receive the drug. “But,” Dalton noted, “that was a VA study, so the results might not be applicable to the larger population.”

For the current study, the researchers extracted data from HealthVerity, a large consumer healthcare database. The team scanned about 4.3 million patient records, eventually including 297,662 high-risk patients who received a nirmatrelvir-ritonavir prescription within 5 days of positive lab results or clinical diagnosis of COVID. The cohort was matched with 582,866 untreated patients. All patients were at least 12 years old and at risk for severe disease due to age, underlying medical issues, or use of immunosuppressive medications.

After matching, the two groups were similar in most respects, Dalton said. However, more treated patients had no healthcare encounters in the previous year (4.1% vs 2%) and were vaccinated against COVID-19 (69.8% vs 61.6%), and fewer had a documented prior COVID infection (9.5% vs 14.4%).

The outcome of interest was a PCC recorded 60 days or more after the index illness date with no history of that condition in the prior year. These conditions were grouped into nine system categories: cardiac, respiratory, renal, hematological and vascular, gastrointestinal, neurologic, mental health, musculoskeletal, diabetes (types 1 and 2), and other.

Dalton noted that she and her team could not verify adherence to the drug, which was a limitation to the study.

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