Nirmatrelvir Use and Severe Covid-19 Outcomes during the Omicron Surge
Ph.D Ronen Arbel, Yael Wolff Sagy, Ph.D Moshe Hoshen, Erez Battat, M.D Gil Lavie, Ruslan Sergienko, Ph.D Michael Friger, M.D Jacob G Waxman, M.D Noa Dagan, Ran Balicer, Yatir Ben-Shlomo, B.Sc Alon Peretz, M.D Shlomit Yaron, M.D Danielle Serby, M.Sc Ariel Hammerman, Ph.D Doron Netzer
New England Journal of Medicine, doi:10.1056/nejmoa2204919
BACKGROUND The oral protease inhibitor nirmatrelvir has shown substantial efficacy in highrisk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding the effectiveness of nirmatrelvir in preventing severe coronavirus disease 2019 (Covid-19) outcomes from the B.1.1.529 (omicron) variant are limited.
METHODS We obtained data for all members of Clalit Health Services who were 40 years of age or older at the start of the study period and were assessed as being eligible to receive nirmatrelvir therapy during the omicron surge. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of nirmatrelvir treatment with hospitalization and death due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions, and previous SARS-CoV-2 immunity status.
RESULTS A total of 109,254 patients met the eligibility criteria, of whom 3902 (4%) received nirmatrelvir during the study period. Among patients 65 years of age or older, the rate of hospitalization due to Covid-19 was 14.7 cases per 100,000 person-days among treated patients as compared with 58.9 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 to 0.49). The adjusted hazard ratio for death due to Covid-19 was 0.21 (95% CI, 0.05 to 0.82). Among patients 40 to 64 years of age, the rate of hospitalization due to Covid-19 was 15.2 cases per 100,000 person-days among treated patients and 15.8 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.74; 95% CI, 0.35 to 1.58). The adjusted hazard ratio for death due to Covid-19 was 1.32 (95% CI, 0.16 to 10.75).
CONCLUSIONS Among patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received nirmatrelvir than among those who did not. No evidence of benefit was found in younger adults.
References
Arbel, Hammerman, Sergienko, BNT162b2 vaccine booster and mortality due to Covid-19, N Engl J Med
Arbel, Sergienko, Friger, Effectiveness of a second BNT162b2 booster vaccine against hospitalization and death from COVID-19 in adults aged over 60 years
Callaway, Ledford, How bad is omicron? What scientists know so far, Nature
Dagan, Barda, Kepten, BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting, N Engl J Med
Hammond, Leister-Tebbe, Gardner, Oral nirmatrelvir for highrisk, nonhospitalized adults with Covid-19, N Engl J Med
Li, Wang, Lavrijsen, SARS-CoV-2 omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination, Cell Res
Lévesque, Hanley, Kezouh, Suissa, Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes, BMJ
Rubin, Baden, Morrissey, Audio interview: understanding the omicron variant of SARS-CoV-2, N Engl J Med
Rubin, Baden, The potential of intentional drug development, N Engl J Med
Takashita, Kinoshita, Yamayoshi, Efficacy of antibodies and antiviral drugs against Covid-19 omicron variant, N Engl J Med
Takashita, Kinoshita, Yamayoshi, Efficacy of antiviral agents against the SARS-CoV-2 omicron subvariant BA.2, N Engl J Med
Vangeel, Chiu, Jonghe, Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 omicron and other variants of concern, Antiviral Res
