ABSTRACT
BackgroundPatients on kidney replacement therapy (KRT; dialysis and kidney transplantation) are at the highest risk of severe outcomes from COVID-19. Due to limited inclusion of patients on KRT in clinical trials, information is limited on the effectiveness of sotrovimab (a neutralising monoclonal antibody). We sought to address this by comparing its effectiveness against molnupiravir (an antiviral) in preventing severe COVID-19 outcomes in non-hospitalised adults with symptomatic COVID-19. MethodsWith the approval of NHS England we used routine clinical data from 24 million patients in England linked to the UK Renal Registry (UKRR) to identify patients on KRT, and data on antiviral treatments, COVID-19 test results, hospitalisation events and death from the OpenSAFELY-TPP data resource. Cox proportional hazards models (stratified for region) were used to estimate hazard ratios of sotrovimab vs. molnupiravir with regards to COVID-19 related hospitalisation or deaths in the subsequent 28 days (as the primary outcome). Further analyses were conducted using propensity score weighting (adjusted for region) and to investigate robustness of results with regards to different time periods, missing data, and adjustment variables. We also conducted a complementary analysis using data from patients in the Scottish Renal Registry (SRR) treated with sotrovimab or molnupiravir, following similar analytical approaches. ResultsAmong the 2367 renal patients treated with sotrovimab (n=1852) or molnupiravir (n=515) between December 16, 2021 and August 1, 2022 in England, 38 cases (1.6%) of COVID-19 related hospitalisations/deaths were observed during the 28 days of follow-up after treatment initiation, with 21 (1.1%) in the sotrovimab group and 17 (3.3%) in the molnupiravir group. In multiple-adjusted analysis sotrovimab was associated with substantially lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (hazard ratio, HR=0.35, 95% CI: 0.17 to 0.71; P=0.004), with results remaining robust in sensitivity analyses. In the SRR cohort, there were 19 cases (1.9%) of COVID-19 related hospitalisations/deaths during the 28 days of follow-up after treatment initiation of sotrovimab (n=723) or molnupiravir (n=270). In multiple-adjusted analysis, sotrovimab showed a trend toward lower risk of 28-day COVID-19 related hospitalisation/death than treatment with molnupiravir (HR=0.39, 95% CI: 0.13 to 1.21; P=0.106). In both datasets, sotrovimab had no evidence of association with other hospitalisation/death compared with molnupiravir (HRs ranging from 0.73-1.29; P>0.05). ConclusionsIn routine care of non-hospitalised patients with COVID-19 on kidney replacement therapy, those who received sotrovimab had substantially lower risk of severe COVID-19 outcomes than those receiving molnupiravir.
ABSTRACT
BackgroundPatients with kidney failure requiring kidney replacement therapy (KRT) are at high risk of complications and death following SARS-CoV-2 infection with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on incidence of infection, hospitalization and death of COVID-19 infection. MethodsStudy design was an observational data linkage cohort study. Multiple healthcare datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland, from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses and vaccine effectiveness were calculated. ResultsAs of 19th September 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness against infection and hospitalization was 33% (95% CI 0-52) and 38% (95% CI 0-57) respectively. 9.2% of fully vaccinated individuals died within 28 days of a SARS-CoV-2 positive PCR test (7% dialysis patients and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated Scottish population being admitted to hospital or dying death due to COVID19 during that period. ConclusionsThese data demonstrate a primary vaccine course of two doses has limited impact on COVID-19 infection and its complications in patients treated with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required.
ABSTRACT
IntroductionInfection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving renal replacement therapy (RRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing RRT in Scotland. MethodsStudy design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed. ResultsDuring the period 1st March 2020 to 31st May 2020, 110 patients receiving RRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent RRT population. Of those affected, 87 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients. ConclusionThe rate of detected SARS-CoV-2 in people receiving RRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection.
