Abstract Background and Aims The effect of vaccinations against SARS-CoV-2 on risk of infection and subsequent adverse outcomes in patients with kidney dysfunction beyond end-stage kidney disease remains uncertain. Based on nationwide data from multiple health care registers, the study aims to evaluate vaccination effect on rates of SARS-CoV-2 infection and subsequent risk of associated mortality in patients with kidney disease beyond end-stage kidney disease. Method A population-based retrospective cohort study on all Danish residents ≥18 years with an eGFR ≤90 ml/min/1.73 m2 identified between February 1st 2021 and June 27th 2022 corresponding to predominance of Alpha-, Delta-, and Omicron-variant. Outcomes compared based on vaccination state (unvaccinated, vaccinated, and booster vaccinated) across predefined eGFR categories (eGFR 60-90 mL/min/1.73 m2; eGFR 45-59 mL/min/1.73 m2, eGFR 30-44 mL/min/1.73 m2; eGFR <30 mL/min/1.73 m2). Risk of infection reported as age- and gender-standardized rate ratios of positive SARS-CoV-2 PCR and subsequent risk of death reported as age- and gender standardized 30-day mortality risk. Standardized risks computed based on hazards obtained in multiple cause-specific Cox regression models. Results A total of 982,047 adults with eGFR ≤90 ml/min/1.73 m2 identified. Gender distribution was 43.9% male, median age was 71 [IQR 61–78] years, median eGFR 75 [IQR 63-84], and 13.1% diabetes. Population rates of vaccination were 3.5%, 80.1%, and 95.4% for Alpha-, Delta-, and Omicron-variant, with 66.2% booster vaccinated at Omicron-variant baseline (Pfizer BionTech 88.3%, Moderna 9.4%, other vaccinations 2.3%). In total 359,428 SARS-CoV-2 infections were identified (Alpha: n = 7,861, Delta: n = 27,868, Omicron: n = 323,699), corresponding to a crude rate of positive SARS-CoV-2 PCR test of 629.0 per 100,000 person-weeks overall. Vaccination and booster vaccination were associated with progressively lower rate of SARS-CoV-2 infection. Age- and gender-standardized rate ratios are shown in Fig. 1. Overall, mean 30-day risks of death were 7.1‰ [95% CI 6.7-7.6], 3.8‰ [95% CI 3.5-4.0], and 1.4‰ [95% CI 1.3-1.4] in unvaccinated, vaccinated, and booster vaccinated persons, respectively. Vaccination and booster vaccination were associated with benefit on 30-day mortality across all strata of eGFR despite progressive increase in risk of death observed with declining kidney function. Age- and gender standardized 30-day mortality rates following a positive PCR for SARS-CoV-2 across granular eGFR are shown in Fig. 2. Conclusion Based on comprehensive nationwide data covering Alpha-, Delta-, and Omicron-variant predominance in Denmark, vaccination and booster vaccination against COVID-19 were associated with lower rates of SARS-CoV-2 infection and benefit on subsequent risk of 30-day mortality across all strata of eGFR.
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