Paxlovid remains effective in those vaccinated against COVID-19

Israeli researchers have found that paxlovid use in those at risk of COVID-19 progression remains effective even in fully vaccinated patients

The effectiveness of the anti-viral drug paxlovid in preventing the progression of COVID-19 remains even in those who have been adequately vaccinated against the virus according to the results of a real-world study by Israeli researchers.

Paxlovid consists of nirmatrelivir, a protease inhibitor against COVID-19 and ritonavir, which reduces the in vivo metabolism of nirmatrelivir. The published data for the drug (the EPIC-HR trial) suggested that treatment of symptomatic COVID-19 in patients at risk of progression to severe disease, results in an 89% lower risk compared to placebo. Nevertheless, the study was undertaken before omicron became the main circulating variant and therefore the generalisability of the study’s findings are potentially limited. Consequently, for the present study, the Israeli team decided to undertake a large, retrospective cohort study of high-risk COVID-19 patients, to assess the effectiveness of paxlovid at preventing progression to severe COVID-19 and subsequent death during the time when omicron was the predominant strain.

Using a large, national health service database, the researchers identified all adults (18 years and over) who tested positive for COVID-19 but restricted the search to those who would be suitable candidates for treatment with paxlovid, i.e., those who were older than 60 years, with a body mass index (BMI) greater than 30 and with co-morbidities including diabetes, hypertension and cardiovascular disease. However, unlike in the EPIC-HR trial, where those who had been vaccinated were excluded, for the present analysis, researchers included patients, regardless of their vaccination status. The main outcome of the study was a composite of severe COVID-19 or COVID-19-related mortality. For their analysis, the researchers included demographic and co-morbidity data and which were adjusted for in the analysis.

Paxlovid and progression of COVID-19

A total of 4,737 individuals with a mean age of 68.5 years (42.1% male) were treated with paxlovid and compared with 175,614 individuals who tested positive but who did not receive the drug. In total, 77.8% of those given paxlovid had adequate COVID-19 vaccination compared to 75% of those in the non-paxlovid group.

Overall, the primary outcome occurred in 39 individuals receiving paxlovid compared to 903 in those not given the drug. Paxlovid was therefore associated with a significantly lower risk of severe COVID-19 or mortality (hazard ratio, HR = 0.54, 95% CI 0.39 – 0.75). Moreover, among the whole cohort, having adequate COVID-19 vaccination, was also associated with a significantly lower risk of the primary outcome (HR = 0.20, 95% CI 0.17 – 0.22).

When the analysis was restricted to those diagnosed with COVID-19 when omicron was the main circulating variant, paxlovid was also associated with a greater reduction in the primary endpoint (HR = 0.43, 95% CI 0.64 – 0.85). Interestingly, among those given paxlovid and who were adequately vaccinated, there was still a significant reduction in the primary outcome (HR = 0.62, 95% CI 0.39 – 0.98) as well as among those not vaccinated (HR = 0.52, 95% CI 0.32 – 0.82).

The authors concluded that their study had demonstrated that in a real-world setting and during the period of time when omicron was the dominant variant, paxlovid was associated with a significant reduction in progression of COVID-19 and COVID-19-related mortality.

Najjar-Debbiny R et al. Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients Clin Infect Dis 2022