Safety and Efficacy of Nirmatrelvir/Ritonavir in Advanced Kidney Disease (preprint)

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.

Invasive pneumococcal disease, pneumococcal pneumonia and all-cause pneumonia in Hong Kong during the COVID-19 pandemic compared with the preceding 5 years: a retrospective observational study

ObjectivesTo compare the incidence and severity of invasive pneumococcal diseases (IPDs), pneumococcal pneumonia and all-cause pneumonia during the COVID-19 pandemic period with universal masking and social distancing with that of previous 5 years.DesignRetrospective observational study on incidence of IPDs, pneumococcal pneumonia and all-cause pneumonia between January 2015–December 2019 and March 2020–March 2021. January–February 2020 was excluded from analysis as it was treated as a transitional period between normal time and pandemic.SettingEpisode-based data by retrieval of hospitalisation records from the Hospital Authority’s territory-wide electronic medical record database in Hong Kong.ParticipantsHospitalised patients with IPD (n=742), pneumococcal pneumonia (n=2163) and all-cause pneumonia (including COVID-19 pneumonia, n=453 999) aged 18 years or above. Control diagnoses were included to assess confounding from health-seeking behaviours.Primary and secondary outcomesPrimary outcome is the incidence of diseases between two periods. Secondary outcomes include disease severity surrogated by length of stay and mortality.ResultsMonthly average number of IPD, pneumococcal pneumonia and all-cause pneumonia hospitalisation significantly decreased by 88.9% (95% CI 79.8% to 98.0%, p<0.0005), 72.5% (95% CI 65.9% to 79.1%, p<0.0005) and 17.5% (95% CI 16.8% to 18.2%, p<0.0005), respectively. Changes in trend from January 2015–December 2019 to March 2020–March 2021 were −70% (95% CI −87% to −35%, p=0.0025), –43% (95% CI −59% to −19%, p=0.0014) and −11% (95% CI −13% to −10%, p<0.0005), respectively. Length of stay for IPD and pneumococcal pneumonia episodes were insignificantly different in the two periods. No reductions in hospitalisations for control diagnoses were observed.ConclusionsIncidence of IPD, pneumococcal pneumonia and all-cause pneumonia decreased during the COVID-19 pandemic. This was observed with universal masking and social distancing. We postulated this is related to reduced transmission of respiratory viruses and bacteria.

Border Restriction as a Public Health Measure to Limit Outbreak of Coronavirus Disease 2019 (preprint)

Background: Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease.Methods: A novel metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration was applied to investigate the effect of border restriction between Hong Kong and mainland China on the epidemiological characteristics of COVID-19 in Hong Kong. Isolation facilities occupancy was also studied.Results: At R0 is set to be inversely correlated with temperature of 2.2, the cumulative COVID-19 cases in Hong Kong can be reduced by 13.99% (from 29,163 to 25,084) with complete border closure. At an in-patient mortality of 1.4%, the number of deaths can be reduced from 408 to 351 (57 lives saved). However, border closure alone was insufficient to prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary. Conclusions: As a public health measure to tackle COVID-19, border restriction is effective in reducing cumulative cases and mortality.

Border Restriction as a Public Health Measureto Limit Outbreak of Coronavirus Disease 2019 (COVID-19) (preprint)

Background: Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease. Method: A novel metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration was applied to investigate the effect of border restriction between Hong Kong and mainland China on the epidemiological characteristics of COVID-19 in Hong Kong. Isolation facilities occupancy was also studied. Results: At R0 of 2.2, the cumulative COVID-19 cases in Hong Kong can be reduced by 13.99% (from 29,163 to 25,084) with complete border closure. At an in-patient mortality of 1.4%, the number of deaths can be reduced from 408 to 351 (57 lives saved). However, border closure alone was insufficient to prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary. Conclusion: As a public health measure to tackle COVID-19, border restriction is effective in reducing cumulative cases and mortality.