Nirmatrelvir-ritonavir for Treating COVID-19 Patients: A Case-Control Study

Aims: To compare the efficacy of nirmatrelvir/ritonavir versus symptomatic management in reducing mortality, and clinical severity, and increasing clinical improvement among patients with COVID-19. Study design: A multicentre, retrospective, and case-control study was conducted, with a 3:1 matching ratio (three controls per case). Place and Duration of Study: Hospital and Ambulatory Care Medical Units. The study was conducted from October 1st, 2024 to January 31st, 2025, with COVID-19 Mexican patients attending an outpatient consultation at several units in Puebla State, Mexico, from September 29th, 2022 to June 3rd, 2023. Methodology: Data on health and sociodemographic variables were collected through a retrospective design, using the SINOLAVE system. Results: We included 5,228 patients with COVID-19 (3,921 controls and 1,307 cases). The average age was 41.19 (SD=15.17, median age=39 [IQR=29-51]). Common factors associated with severe COVID-19 disease, mortality, and clinical improvement were: nirmatrelvir/ritonavir ([severity OR=0.080; 95%CI 0.019-0.343, p=0.001], [mortality OR=0.058; 95%CI 0.008-0.425, p=0.005], [clinical improvement OR=16.458; 95%CI 2.221-121.944, p=0.006]), and age ([severity OR=1.065; 95%CI 1.042-1.089, p<0.001], [mortality OR=1.087; 95%CI 1.063-1.111, p<0.001], [clinical improvement OR=0.921; 95%CI 0.901-0.941, p<0.001]). Other factors associated with COVID-19 severity were: headache (OR=2.941; 95%CI 1.231-7.029, p=0.015), profound weakness (OR=0.196; 95%CI 0.049-0.784, p=0.021), dyspnoea (OR=4372.92; 95% CI 1522.538-12559.587, p<0.001), coryza (OR=13.539; 95%CI 1.816-100.932, p=0.011), anosmia (OR=0.041; 95%CI 0.007-0.253, p=0.001), and diabetes (OR=5.823; 95%ci 2.091-16.217, p=0.001). Additionally, sex was another factor associated with COVID-19 mortality (OR=2.664; 95%CI 1.441-4.925, p=0.002) and clinical improvement (OR=0.449; 95%CI 0.248-0.813, p=0.008). In contrast, employment (OR=2.431; 95%CI 1.165-5.073, p=0.018), sudden onset (OR=0.374; 95%CI 0.203-0.690, p=0.002), painful swallowing (OR=5.733; 95%CI 3.179-10.339, p<0.001) and Chronic Obstructive Pulmonary Disease (COPD) (OR=0.301; 95%CI 0.100-0.908, p=0.033) are associated with clinical improvement. Conclusion: Nirmatrelvir/ritonavir can significantly reduce the risk of mortality and severity of COVID-19, and increase the clinical improvement in patients with COVID-19. In addition, older age, headache, dyspnoea, coryza, and diabetes were associated with severe COVID-19, while profound weakness, and anosmia were linked to a lower risk. Clinical improvement was associated with younger age, female sex, employment, and painful swallowing, meanwhile sudden onset and COPD reduced the likelihood of improvement. Mortality risk increased with older age and male sex, whereas employment was protective factor.