Clinical Outcomes and Vaccine Effectiveness for SARS-CoV-2 Infection in People Attending Advanced CKD Clinics: A Retrospective Provincial Cohort Study.

BACKGROUND: People with advanced CKD are at high risk of mortality and morbidity from coronavirus disease 2019 (COVID-19). We measured rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes in a large population attending advanced CKD clinics during the first 21 months of the pandemic. We examined risk factors for infection and case fatality, and we assessed vaccine effectiveness in this population. METHODS: In this retrospective cohort study, we analyzed data on demographics, diagnosed SARS-CoV-2 infection rates, outcomes, and associated risk factors, including vaccine effectiveness, for people attending a province-wide network of advanced CKD clinics during the first four waves of the pandemic in Ontario, Canada. RESULTS: In a population of 20,235 patients with advanced CKD, 607 were diagnosed with SARS-CoV-2 infection over 21 months. The case fatality rate at 30 days was 19% overall but declined from 29% in the first wave to 14% in the fourth. Hospitalization and intensive care unit (ICU) admission rates were 41% and 12%, respectively, and 4% started long-term dialysis within 90 days. Significant risk factors for diagnosed infection on multivariable analysis included lower eGFR, higher Charlson Comorbidity Index, attending advanced CKD clinics for more than 2 years, non-White ethnicity, lower income, living in the Greater Toronto Area, and long-term care home residency. Being doubly vaccinated was associated with lower 30-day case fatality rate (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.03 to 0.52). Older age (OR, 1.06 per year; 95% CI, 1.04 to 1.08) and higher Charlson Comorbidity Index (OR, 1.11 per unit; 95% CI, 1.01 to 1.23) were associated with higher 30-day case fatality rate. CONCLUSIONS: People attending advanced CKD clinics and diagnosed with SARS-CoV-2 infection in the first 21 months of the pandemic had high case fatality and hospitalization rates. Fatality rates were significantly lower in those who were doubly vaccinated. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN10560922.mp3.

Effectiveness of Three Doses of mRNA COVID-19 Vaccines in the Hemodialysis Population during the Omicron Period.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine effectiveness studies in the hemodialysis population have demonstrated that two doses of mRNA COVID-19 vaccines are effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe complications when Alpha and Delta were predominant variants of concern. Vaccine effectiveness after a third dose versus two doses for preventing SARS-CoV-2 infection and severe COVID-19 in the hemodialysis population against Omicron is not known. METHODS: We conducted a retrospective cohort study in Ontario, Canada, between December 1, 2021, and February 28, 2022, in the maintenance hemodialysis population who had received two versus three doses of mRNA COVID-19 vaccines. COVID-19 vaccination, SARS-CoV-2 infection, and related hospitalization and death were determined from provincial databases. The primary outcome was the first RT-PCR confirmed SARS-CoV-2 infection, and the secondary outcome was a SARS-CoV-2-related severe outcome, defined as either hospitalization or death. RESULTS: A total of 8457 individuals receiving in-center hemodialysis were included. At study initiation, 2334 (28%) individuals received three doses, which increased to 7468 (88%) individuals by the end of the study period. The adjusted hazard ratios (aHR) for SARS-CoV-2 infection (aHR, 0.58; 95% confidence interval [CI], 0.50 to 0.67) and severe outcomes (hospitalization or death) (aHR, 0.40; 95% CI, 0.28 to 0.56) were lower after three versus two doses of mRNA vaccine. Prior infection, independent of vaccine status, was associated with a lower risk of reinfection, with an aHR of 0.44 (95% CI, 0.27 to 0.73). CONCLUSIONS: Three-dose mRNA COVID-19 vaccination was associated with lower incidence of SARS-CoV-2 infection and severe SARS-CoV-2-related outcomes during the Omicron period compared with two doses.

Early Experience with Modified Dose Nirmatrelvir/Ritonavir in Dialysis Patients with Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir/ritonavir was approved for use in high-risk outpatients with coronavirus disease 2019 (COVID-19). However, patients with severe CKD were excluded from the phase 3 trial, and the drug is not recommended for those with GFR <30 ml/min per 1.73 m 2 . On the basis of available pharmacological data, we developed a modified low-dose regimen of nirmatrelvir/ritonavir 300/100 mg on day 1, followed by 150/100 mg daily from day 2 to 5. In this study, we report our experience with this modified dose regimen in dialysis patients in the Canadian province of Ontario. METHODS: We included dialysis patients who developed COVID-19 and were treated with the modified dose nirmatrelvir/ritonavir regimen during a 60-day period between April 1 and May 31, 2022. Details of nirmatrelvir/ritonavir use and outcomes were captured manually, and demographic data were obtained from a provincial database. Data are presented with descriptive statistics. The principal outcomes we describe are 30-day hospitalization, 30-day mortality, and required medication changes with the modified dose regimen. RESULTS: A total of 134 dialysis patients with COVID-19 received nirmatrelvir/ritonavir during the period of study. Fifty-six percent were men, and the mean age was 64 years. Most common symptoms were cough and/or sore throat (60%). Medication interactions were common with calcium channel blockers, statins being the most frequent. Most patients (128, 96%) were able to complete the course of nirmatrelvir/ritonavir, and none of the patients who received nirmatrelvir/ritonavir died of COVID-19 in the 30 days of follow-up. CONCLUSIONS: A modified dose of nirmatrelvir/ritonavir use was found to be safe and well tolerated, with no serious adverse events being observed in a small sample of maintenance dialysis patients.

Vaccine Effectiveness Against SARS-CoV-2 Infection and Severe Outcomes in the Maintenance Dialysis Population in Ontario, Canada.

BACKGROUND: Vaccination studies in the hemodialysis population have demonstrated decreased antibody response compared with healthy controls, but vaccine effectiveness for preventing SARS-CoV-2 infection and severe disease is undetermined. METHODS: We conducted a retrospective cohort study in the province of Ontario, Canada, between December 21, 2020, and June 30, 2021. Receipt of vaccine, SARS-CoV-2 infection, and related severe outcomes (hospitalization or death) were determined from provincial health administrative data. Receipt of one and two doses of vaccine were modeled in a time-varying cause-specific Cox proportional hazards model, adjusting for baseline characteristics, background community infection rates, and censoring for non-COVID death, recovered kidney function, transfer out of province, solid organ transplant, and withdrawal from dialysis. RESULTS: Among 13,759 individuals receiving maintenance dialysis, 2403 (17%) were unvaccinated and 11,356 (83%) had received at least one dose by June 30, 2021. Vaccine types were BNT162b2 (n=8455, 74%) and mRNA-1273 (n=2901, 26%); median time between the first and second dose was 36 days (IQR 28-51). The adjusted hazard ratio (HR) for SARS-CoV-2 infection and severe outcomes for one dose compared with unvaccinated was 0.59 (95% CI, 0.46 to 0.76) and 0.54 (95% CI, 0.37 to 0.77), respectively, and for two doses compared with unvaccinated was 0.31 (95% CI, 0.22 to 0.42) and 0.17 (95% CI, 0.1 to 0.3), respectively. There were no significant differences in vaccine effectiveness among age groups, dialysis modality, or vaccine type. CONCLUSIONS: COVID-19 vaccination is effective in the dialysis population to prevent SARS-CoV-2 infection and severe outcomes, despite concerns about suboptimal antibody responses.

Acute kidney injury requiring renal replacement therapy in people with COVID-19 disease in Ontario, Canada: a prospective analysis of risk factors and outcomes.

BACKGROUND: Severely ill people with coronavirus disease 2019 (COVID-19) are at risk of acute kidney injury treated with renal replacement therapy (AKI-RRT). The understanding of the risk factors and outcomes for AKI-RRT is incomplete. METHODS: We prospectively collected data on the incidence, demographics, area of residence, time course, outcomes and associated risk factors for all COVID-19 AKI-RRT cases during the first two waves of the pandemic in Ontario, Canada. RESULTS: There were 271 people with AKI-RRT, representing 0.1% of all diagnosed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. These included 10% of SARS-CoV-2 admissions to intensive care units (ICU). Median age was 65 years, with 11% <50 years, 76% were male, 47% non-White and 48% had diabetes. Overall, 59% resided in the quintile of Ontario neighborhoods with the greatest ethnocultural composition and 51% in the two lowest income quintile neighborhoods. Mortality was 58% at 30 days after RRT initiation, and 64% at 90 days. By 90 days, 20% of survivors remained RRT-dependent and 31% were still hospitalized. On multivariable analysis, people aged >70 years had higher mortality (odds ratio 2.4, 95% confidence interval 1.3, 4.6). Cases from the second versus the first COVID-19 wave were older, had more baseline comorbidity and were more likely to initiate RRT  >2 weeks after SARS-CoV-2 diagnosis (34% versus 14%; P < 0.001). CONCLUSIONS: AKI-RRT is common in COVID-19 ICU admissions. Residency in areas with high ethnocultural composition and lower socioeconomic status are strong risk factors. Late-onset AKI-RRT was more common in the second wave. Mortality is high and 90-day survivors have persisting high morbidity.

Acute kidney injury requiring renal replacement therapy in people with COVID-19 disease in Ontario, Canada: a prospective analysis of risk factors and outcomes

Background Severely ill people with COVID-19 are at risk of acute kidney injury treated with renal replacement therapy (AKI-RRT). Understanding of risk factors and outcomes for AKI-RRT is incomplete. Methods We prospectively collected data on the incidence, demographics, area of residence, time course, outcomes, and associated risk factors for all COVID-19 AKI-RRT cases during the first 2 waves of the pandemic in Ontario, Canada Results There were 271 people with AKI-RRT, representing 0.1% of all diagnosed SARS-CoV-2 cases. These included 10% of SARS-CoV-2 admissions to intensive care units (ICU). Median age was 65 years, with 11% under 50, 76% were male, 47% non-white, and 48% had diabetes. Overall, 59% resided in the quintile of Ontario neighborhoods with the greatest ethnocultural composition and 51% in the 2 lowest income quintile neighborhoods. Mortality was 58% at 30 days after RRT initiation, and 64% at 90 days. By 90 days, 20% of survivors remained RRT-dependent and 31% were still hospitalized. On multivariable analysis, people aged over 70 had higher mortality (odds ratio (OR) 2.4, 95% CI: 1.3, 4.6). Cases from the second versus the first COVID-19 wave were older, had more baseline co-morbidity, and were more likely to initiate RRT over 2 weeks after SARS-CoV-2 diagnosis (34% vs 14%, p < 0.001). Conclusions AKI-RRT is common in COVID-19 ICU admissions. Residency in areas with high ethnocultural composition and lower socioeconomic status are strong risk factors. Late onset AKI-RRT was more common in the second wave. Mortality is high and 90-day survivors have persisting high morbidity. Graphical Graphical

COVID-19 chez les patients ontariens sous dialyse à long terme.

CONTEXTE: Les patients sous dialyse à long terme pourraient avoir un risque accru d'infection par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2), et de maladie et de mortalité associées. Nous avons voulu décrire l'incidence, les facteurs de risque et les issues de l'infection chez ces patients en Ontario (Canada). MÉTHODES: Nous avons utilisé des ensembles de données reliées pour comparer les caractéristiques de la maladie et la mortalité chez les patients sous dialyse à long terme en Ontario qui ont testé positif pour le SRAS-CoV-2 et ceux qui n'ont pas développé d'infection, entre le 12 mars et le 20 août 2020. Nous avons recueilli des données sur l'infection par le SRAS-CoV-2 de manière prospective. Nous avons évalué les facteurs de risque d'infection et de mortalité par des analyses de régression logistique multivariées. RÉSULTATS: Pendant la période à l'étude, 187 patients dialysés sur 12 501 (1,5 %) ont reçu un diagnostic d'infection par le SRAS-CoV-2. Parmi eux, 117 (62,6 %) ont été hospitalisés, et le taux de mortalité était de 28,3 %. Les facteurs prédictifs significatifs associés à l'infection incluaient l'hémodialyse dans un centre plutôt que la dialyse à domicile (rapport de cotes [RC] 2,54; intervalle de confiance [IC] à 95 % 1,59­4,05), le fait de vivre dans un établissement de soins de longue durée (RC 7,67; IC à 95 % 5,30­11,11), le fait d'habiter la région du Grand Toronto (RC 3,27; IC à 95 % 2,21­4,80), les ethnicités Noire (RC 3,05; IC à 95 % 1,95­4,77), du sous-continent indien (RC 1,70; IC à 95 % 1,02­2,81) et autres non blanches (RC 2,03; IC à 95 % 1,38­2,97) et les quintiles de revenu inférieurs (RC 1,82; IC à 95 % 1,15­2,89). INTERPRÉTATION: Les patients sous dialyse à long terme sont exposés à un risque accru d'infection par le SRAS-CoV-2 et de mortalité due à la maladie à coronavirus 2019. Il faudra travailler à éliminer les facteurs de risque d'infection et vacciner ces patients en priorité.

COVID-19 in patients undergoing long-term dialysis in Ontario.

BACKGROUND: Patients undergoing long-term dialysis may be at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of associated disease and mortality. We aimed to describe the incidence, risk factors and outcomes for infection in these patients in Ontario, Canada. METHODS: We used linked data sets to compare disease characteristics and mortality between patients receiving long-term dialysis in Ontario who were diagnosed SARS-CoV-2 positive and those who did not acquire SARS-CoV-2 infection, between Mar. 12 and Aug. 20, 2020. We collected data on SARS-CoV-2 infection prospectively. We evaluated risk factors for infection and death using multivariable logistic regression analyses. RESULTS: During the study period, 187 (1.5%) of 12 501 patients undergoing dialysis were diagnosed with SARS-CoV-2 infection. Of those with SARS-CoV-2 infection, 117 (62.6%) were admitted to hospital and the case fatality rate was 28.3%. Significant predictors of infection included in-centre hemodialysis versus home dialysis (odds ratio [OR] 2.54, 95% confidence interval [CI] 1.59-4.05), living in a long-term care residence (OR 7.67, 95% CI 5.30-11.11), living in the Greater Toronto Area (OR 3.27, 95% CI 2.21-4.80), Black ethnicity (OR 3.05, 95% CI 1.95-4.77), Indian subcontinent ethnicity (OR 1.70, 95% CI 1.02-2.81), other non-White ethnicities (OR 2.03, 95% CI 1.38-2.97) and lower income quintiles (OR 1.82, 95% CI 1.15-2.89). INTERPRETATION: Patients undergoing long-term dialysis are at increased risk of SARS-CoV-2 infection and death from coronavirus disease 2019. Special attention should be paid to addressing risk factors for infection, and these patients should be prioritized for vaccination.