Paxlovid Linked to Lower Risk of Long COVID

Treating COVID-19 with Paxlovid, a combination of nirmatrelvir with ritonavir, within 5 days of symptom onset was associated with lower risk for developing Post-COVID-19 Conditions (PCC), or Long COVID, in a large Veterans Affairs (VA) cohort study.

In addition to reducing risk of mild to moderate infection becoming severe, and of severe symptoms requiring hospitalization—for which Paxlovid is indicated under Authorization for Emergency Use, and an FDA advisory committee recently recommended full approval—this study found that fewer patients treated with Paxlovid later developed PCC than matched, untreated controls.

"The totality of evidence suggests that improving the uptake and use of nirmatrelvir in the acute phase as a means of not only preventing progression to severe acute disease but also reducing the risk of post-acute adverse health outcomes may be beneficial," declared investigators Yan Xie, PhD, Taeyoung Choi, MPH and Ziyad Al-Aly, MD, Clinical Epidemiology Center, Research and Development Service, VA St Louis Health Care System, St Louis, Missouri.

Using the VA health care databases, Xie and colleagues identified a cohort of 281,793 participants who had tested positive for SARS-CoV-2 between January 3, 2022 and December 31, 2022. Within 5 days of the positive test, 35,717 were treated with nirmatrelvir-ritonavir, and 246,076 who had not received antiviral or antibody treatment within the first 30 days after infection served as the control group.

All participants had at least 1 risk factor for progression to severe COVID-19 illness. Inverse probability weighting was applied to match treated and untreatedfor risk of post-acute outcomes, including hospitalization, death, and a pre-specified set of 13 sequelae consistent with PCC.

Xie and colleagues reported that, compared with the control group, the nirmatrelvir-ritonavir treated group had reduced risk for PCC (RR, 0.74; 95% CI, 0.72-0.77). The event rate at 180 days was 12.99% (12.52-13.49) in the treated group and 17.51% (17.08-17.94) in the untreated controls. This amounted to an absolute risk reduction (ARR) in the treated group at 180 days of 4.51% (4.01-4.99)

In addition to 26% less risk of PCC, treatment was associated with 24% less risk of post-acute hospitalization and 47% less risk of death.The absolute scale of risk reduction amounted to 4.51, 1.72, and 0.65 less cases of PCC, hospitalization, and deaths, respectively, for every 100 treated persons between 30 to 180 days.

A statistically significant reduction in risk with treatment was found with 10 of the 13 pre-specified post-acute sequelae, but not with new-onset diabetes, liver disease or cough. The antiviralwas associated with statistically significant reduction in risk for PCC whether or notparticipants had previously been vaccinated, or had received a booster vaccination; as well as in those with first-time SARS-CoV-2 infection or reinfection.

In an accompanying Editor's Note, Mitchell Katz, MD, NYC Health and Hospitals, New York, NY, suggested that the apparent protective effect might be a function of lessening severity of COVID-19 rather than specific drug effect, and that fewer cases of PCC might arise when illness severity is mitigated by any means.

Although noting that a randomized clinical trial would be the "right study" to determine whether the antiviral reduces risk for Long COVID, Katz conceded, "until we have better data, the available evidence suggests that nirmaltrelvir may prevent PCC."