Efficacy of Nirmatrelvir/ritonavir in reducing the risk of severe outcome in patients with SARS-CoV-2 infection: a real-life full-matched case-control study (SAVALO Study)

Abstract

Background Ritonavir-boosted nirmatrelvir (N/r) is an antiviral which targets the main viral protease, administered to prevent the progression of SARS-CoV-2 infection in patients at high risk for severe COVID-19. We present a real-life case-control study evaluating the efficacy of N/r therapy in SARS-CoV-2 omicron variants positive outpatients in Campania region, Italy, with the aim of assessing the occurrence of three outcomes (hospital admission, admission in ICU and death) in cases and controls. Methods We enrolled SARS-CoV-2 positive subjects that came to our attention in Early antiviral treatment ambulatory of Infectious Disease ward of University Federico II of Naples, Italy from January 1^st, 2022, to December 31^st, 2022, during the first five days from symptoms occurrence. Patients were enrolled as cases or controls if they were treated with N/r or not treated at all, respectively. Results 1064 patients were included (cases: 423, controls: 1184). Cases showed a lower mortality compared with controls while no differences were observed for other outcomes. Vaccinated patients showed a lower mortality compared with non-vaccinated ones (0.5% vs 7.8%, p<0.001). After full-matching propensity score, N/r reduced hospitalization rate only in unvaccinated patients. In contrast N/r significantly reduced mortality regardless of vaccination status. Conclusions Treatment with N/r has proven effective in reducing mortality among outpatients with SARS-CoV-2 infection during several omicron variant surges. The beneficial effect of N/r treatment in reducing progression is more pronounced in unvaccinated patients.