Paxlovid shows greatest benefit in severely immunocompromised patients with COVID-19

A new study in British Columbia has examined the association of nirmatrelvir and ritonavir (Paxlovid) with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection. The investigators argue that postmarket analysis of individuals who receive Paxlovid is essential because these individuals may differ substantially from those included in published clinical trials. The cohort study, conducted from February 1, 2022 to February 3, 2023, included patients who belonged to one of four higher-risk groups of individuals who received priority for COVID-19 vaccination in B.C.: Clinically extremely vulnerable people who were severely immunocompromised Clinically extremely vulnerable people who were moderately immunocompromised Clinically extremely vulnerable people who were not immunocompromised, but had medical conditions associated with a high risk for complications from COVID-19 Other higher-risk individuals who were not in a clinically extremely vulnerable group, such as those older than 70 years who were unvaccinated. Patients with COVID-19 who received Paxlovid were matched to patients in the same vulnerability group; control group participants were of the same sex, age and propensity score for Paxlovid treatment, and were also infected within one month of the individual treated with Paxlovid. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days of an individual’s cohort entry date. Results showed the following: A total of 6,866 individuals were included in the study; 56.6% were female and the median age was 70 years. Overall, vaccination was greater than 90% in the three clinically extremely vulnerable groups, but less than 80% in other higher-risk individuals who were not in a clinically extremely vulnerable group. Compared with unexposed controls, treatment with Paxlovid was associated with statistically significant relative reductions in death/emergency hospitalization in the severely immunocompromised group (560 patients; risk difference [RD], −2.5%, 95%CI, −4.8% to −0.2%) and in the moderately immunocompromised group (2,628 patients; RD, −1.7%; 95%CI, −2.9% to −0.5%). In patients who were not immunocompromised, but had medical conditions associated with a high risk for complications from COVID-19, the RD was −1.3%, but the findings were not statistically significant (2,100 patients; 95%CI, −2.8% to 0.1%). In other higher-risk individuals who were not in a clinically extremely vulnerable group (e.g., those ≥ 70 years who were unvaccinated), treatment was associated with a nominally higher risk of death/emergency hospitalization (RD, 1.0%), but the findings were not statistically significant (1,578 patients; 95%CI, −0.9% to 2.9%). The authors conclude that a stratified analysis of individuals according to vulnerability to complications from COVID-19 is crucial to understanding which individuals should receive Paxlovid. In their cohort study, Paxlovid treatment was associated with a reduced risk of COVID-19 hospitalization or death in clinically extremely vulnerable individuals, with the greatest benefit seen in severely immunocompromised individuals. However, no reduction in death/emergency hospitalization was seen in lower-risk individuals, including those aged 70 years or older who were not moderately or severely immunocompromised. The authors note that Omicron was the main circulating COVID-19 variant during the study period; therefore, their study results may not be applicable to other variants, past or future. Reference 1. Dormuth CR, Kim JD, Fisher A, et al. Nirmatrelvir-ritonavir and COVID-19 mortality and hospitalization among patients with vulnerability to COVID-19 complications. JAMA Network Open 2023;6(10):e2336678. Published online October 2, 2023. (accessed October 3, 2023).

Paxlovid shows greatest benefit in severely immunocompromised patients with COVID-19

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