Associations of Pre-Pandemic CKD With Acute and Post-Acute COVID-19: The C4R Study.

Publication date: Jun 26, 2026

While kidney failure is associated with severe COVID-19, data on early-stage chronic kidney disease (CKD) and its relationship to acute and post-acute COVID-19, as well as post-vaccination antibody responses, are limited. We evaluated pre-pandemic CKD stage in relation to these outcomes. Prospective cohort. Adults in nine US population-based studies established since 1971, with pre-pandemic CKD measurements and follow-up for COVID-19 outcomes. CKD stages (low CKD stage [reference], moderate CKD stage, high CKD stage, and very high CKD stage) defined by creatinine-based eGFR and urinary albumin-to-creatinine ratio. (i) COVID-19 hospitalization or death (self-report/medical records, 2020‒2023); (ii) RECOVER Long COVID Research Index score ≥11 (LCRI-positivity by questionnaires, 2023‒2024); (iii) post-vaccination anti-Spike 1 (S1) IgG levels (dried blood spots, 2021‒2022). Cause-specific hazards for severe COVID-19, logistic regression for LCRI-positivity, and generalized additive models for anti-S1 IgG. Among 26,039 participants, CKD stage was low in 81. 7%, moderate in 13. 0%, high in 3. 6%, and very high in 1. 7%. Over a median 550-day follow-up (P25-P75: 314‒636), 734 had severe COVID-19; 12. 1% of infected (669/5,527) were classified as LCRI-positive; and 3. 1% (82/2,679) were anti-S1 IgG antibody non-reactive. A more severe CKD stage was associated with a greater risk for severe COVID-19: the HR for moderate stage CKD was 1. 27 (95% CI, 1. 03‒1. 56), for high stage CKD, 2. 33 (1. 77‒3. 06), and for very high stage CKD, 2. 72 (1. 88‒3. 92). Higher CKD stages were associated with lower anti-S1 IgG levels: ‒12. 00% (95% CI: ‒21. 14% to ‒1. 78%) for moderate stage CKD, ‒27. 03% (95% CI, ‒40. 00% to ‒11. 25%) for high stage CKD, and ‒48. 9% (95% CI, ‒61. 60% to ‒32. 01%) for very high stage CKD. A higher prevalence of LCRI positivity was observed only among infected individuals with very high stage CKD (OR=2. 20; 95% CI: 1. 16‒4. 18). Some outcomes were self-reported. Higher CKD stages were associated with a greater risk for severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed between CKD stage and LCRI-positivity except in individuals with very high stage CKD. Chronic kidney disease, kidney dysfunction, SARS-CoV-2 infection, severe COVID-19, Long COVID, anti-S1 IgG antibody, Prospective cohort.

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