ABSTRACT
Background: Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ³ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ≥ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Methods: We performed a retrospective cohort study of hospitalized and non-hospitalized patients with a confirmed diagnosis of COVID-19 in Hong Kong, China, for an observation period from 1 January 2022 to 31 December 2022 (during the omicron BA.2 and BA.5 variant wave). Adult COVID-19 patients (age ≥ 18 years) were selected from medical records held by the Hospital Authority of Hong Kong. We included all patients with COVID-19 regardless of disease severity at baseline having chronic kidney disease (CKD) stage 4 or above (i.e with eGFR < 30 ml/min per 1.73m2) with or without dialysis who receive either nirmatrelvir/ritonavir or molnupiravir. Outcomes at day 90 post-treatment of each treatment arm (nirmatrelvir/ritonavir v.s. molnupiravir) were analyzed and compared. All-cause mortality, respiratory outcomes including mechanical ventilation and non-invasive ventilation, cardiovascular events including myocardial infarction and ischemic stroke, and hepatic complications including elevated liver enzymes were analyzed. Time-to-event analysis was performed for the designated outcomes using univariate and multivariate Cox proportional hazard model regression for unadjusted and adjusted hazard ratios (HR).Findings: We included 454 and 5,880 CKD stage 4 or above patients receiving nirmatrelvir/ritonavir and molnupiravir respectively from public clinics and hospitals managed by the Hospital Authority in Hong Kong during the period. At 90 days, 662 (10.4%) patients of the combined cohort experienced all-cause mortality. Nirmatrelvir/ritonavir group had significant lower all-cause mortality than molnupiravir group (6.82% vs 10.7%) with unadjusted HR of 0.67 (95% CI 0.472 - 0.97, p=0.0337*). After adjusting for sex, age, hypertension, diabetes mellitus, history of myocardial infarction and dialysis in multi-variate analysis, nirmatrelvir/ritonavir group was still associated with superior 90-day survival with adjusted HR of 0.60 (95% CI 0.48 - 0.992, p = 0.0452*). Composites of mechanical and non-invasive ventilation rate were similar in nirmatrelvir/ritonavir and molnupiravir groups (0.96% vs 1.10%, p=0.651). Nirmatrelvir/ritonavir group had higher proportion of patients who received non-invasive ventilation (1.10% vs 0.42%, p = 0.0383*) and trended towards fewer patients requiring mechanical ventilation although statistical significance was not reached (0% vs 0.59%, p = 0.996). There were no significant differences in rate of myocardial infarction (0.88% vs 2.14%, p = 0.0844) and ischemic stroke (0.22% vs 0.61%, p = 0.34) between nirmatrelvir/ritonavir and molnupiravir groups. Hepatic impairment, defined by elevated alanine aminotransferase concentration ≥ 2X upper limit of normal (ULN), was present in 1.45% and 0.94% of patients in nirmatrelvir/ritonavir and molnupiravir groups respectively (p=0.523).Interpretation: Nirmatrelvir/ritonavir is safe and efficacious when compared to molnupiravir in patients with advanced kidney disease.Funding: Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong Special Administrative Region, China and Mr. Lee Won Keung Donation Fund.Declaration of Interest: The authors report no conflict of interest.Ethical Approval: The study was approved by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster. Informed consent from individual patient was waived as the study involved analysis of anonymized data from hospital registry only. The study was performed in compliance with the Declaration of Helsinki.