Nirmatrelvir-ritonavir combination reduces hospitalization and mortality in COVID-19

1. In this retrospective cohort study, treatment with nirmatrelvir plus ritonavir was associated with a reduced risk of hospitalization within 14 days or death within 28 days of SARS-CoV-2 infection. 

2. Prescription of nirmatrelvir plus ritonavir was less likely in Hispanic/Latinx or Black individuals as compared to White individuals.

Evidence Rating Level: 2 (Good)

Study Rundown: Nirmatrelvir plus ritonavir was granted emergency use authorization in the United States for individuals with mild to moderate coronavirus disease 2019 (COVID-19). Yet, there remains a gap in the literature regarding the impact of this therapeutic combination on hospitalization and mortality outcomes in the short term following infection. This retrospective cohort study aimed to compare outcomes of COVID-19 patients receiving nirmatrelvir plus ritonavir versus usual care. A small percentage of individuals were hospitalized within 14 days or died within 28 days of a SARS-CoV-2 infection in those who received nirmatrelvir plus ritonavir. Similarly, a small percentage of individuals who did not receive the treatment were hospitalized within 14 days or died within 28 days of a SARS-CoV-2 infection. The incidence was low in both groups. However, nirmatrelvir plus ritonavir was associated with increased protectivity in those who were incompletely vaccinated, received a vaccine dose more than 20 weeks prior, or were unvaccinated. Treatment with nirmatrelvir plus ritonavir was associated with a reduced risk of both hospitalization and death as compared to those who did not receive treatment. The strength of this observational study was the large study population that was incorporated. A potential limitation of this study is the low adherence to treatment, which may lead to underestimating its benefits.

Click to read the study in the Annals of Internal Medicine

Relevant Reading: Evaluating the performance of Centers for Disease Control and Prevention COVID-19 community levels as leading indicators of COVID-19 mortality

In-Depth [retrospective cohort study]: This population-based cohort study examined the effectiveness of nirmatrelvir plus ritonavir in preventing hospitalization within 14 days or death within 28 days of SARS-CoV-2 infection. Individuals aged 50 years or older in Massachusetts or New Hampshire were included. In anticipation of bias in the prescription of nirmatrelvir plus ritonavir, an inverse probability-weighted design was used. Nirmatrelvir plus ritonavir was more likely to be prescribed to patients with older age, more comorbidities, full vaccination, and recent receipt of vaccine dose. From the multivariate logistic model, outpatients reporting Hispanic or Latinx ethnicity (adjusted odds ratio, 0.77; 95% Confidence Interval [CI], 0.68 to 0.86) or Black race (adjusted odds ratio, 0.53; 95% CI, 0.46 to 0.62) were less likely to be prescribed nirmatrelvir plus ritonavir compared to those of White race. A total of 69 (0.55%) of those treated with nirmatrelvir plus ritonavir and 310 (0.97%) experienced the primary composite end point of hospitalization within 14 days or death within 28 days of SARS-CoV-2 infection. The adjusted risk ratio for nirmatrelvir plus ritonavir was 0.56 (95% CI, 0.42 to 0.75). The estimated effect of treatment was not impacted after excluding individuals who received one or more outpatient therapy for COVID-19. The risk reduction was observed across subgroups based on age, comorbidity scores, and body mass index. However, an 81% risk reduction was seen in the subgroup of unvaccinated persons for the primary outcome. In secondary analyses, treatment was associated with fewer hospitalizations (adjusted risk ratio, 0.60; 95% CI, 0.44 to 0.81) and fewer deaths (adjusted risk ratio, 0.29; 95% CI, 0.12 to 0.71). In summary, nirmatrelvir plus ritonavir may improve the short-term management of COVID-19 patients.

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