Nirmatrelvir, an inhibitor of the main protease of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has demonstrated a significant decrease in the risk of progression to severe disease in symptomatic high-risk patients infected with the B.1.617.2 (delta) variant of SARS-CoV-2. The effectiveness of nirmatrelvir against the B.1.1.529 variant (omicron) is unknown.
The study included all Clalit Health Services members, 40 years of age and older, with confirmed infection of SARS-CoV-2 during the omicron surge that were defined as high-risk for severe disease. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association between nirmatrelvir treatment and hospitalizations and deaths due to Covid-19, with adjustment for individual sociodemographic factors, coexisting conditions, and prior Covid-19 immunity status.
109,213 participants were eligible for nirmatrelvir therapy during the two-month study period. Among the 42,819 eligible patients aged 65 years and above, 2,504 were treated with nirmatrelvir. Hospitalizations due to Covid-19 occurred in 14 out of the treated and 762 of the untreated patients: adjusted HR 0.33 (95% CI, 0.19 to 0.55). Death due to Covid-19 occurred in 2 treated and 151 untreated patients; adjusted HR: 0.19 (95% CI, 0.05 to 0.76). Among the 66,394 eligible patients 40 to 64 years of age, 1,435 were treated with nirmatrelvir. Hospitalizations due to Covid-19 occurred in 9 treated and 334 untreated patients: adjusted HR 0.78 (95% CI, 0.40 to 1.53). Death due to Covid-19 occurred in 1 treated and 13 untreated patients; adjusted HR: 1.64 (95% CI, 0.40 to 12.95).
Nirmatrelvir therapy was associated with a 67% reduction in Covid-19 hospitalizations and an 81% reduction in Covid-19 mortality in patients 65 years and above. However, no significant benefit in avoidance of severe Covid-19 outcomes was shown in younger adults.