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Associations of Pre-Pandemic CKD With Acute and Post-Acute COVID-19: The C4R Study
Yuni Choi1, David R Jacobs2, Holly J Kramer3
1Division of General Medicine, Columbia University Medical Center, New York, New York.
Insights
Individuals with higher stages of chronic kidney disease (CKD) faced increased severe COVID-19 risk and diminished anti-Spike 1 (S1) IgG antibody responses. Long COVID risk was elevated only in very high stage CKD patients.
Area of Science:
- Nephrology
- Infectious Diseases
- Immunology
Background:
- Kidney failure is linked to severe COVID-19, but early-stage chronic kidney disease (CKD) impacts on acute/post-acute COVID-19 and vaccine response are unclear.
- This study investigates pre-pandemic CKD stage's association with COVID-19 severity, Long COVID, and post-vaccination antibody levels.
Purpose of the Study:
- To assess the relationship between pre-pandemic chronic kidney disease (CKD) stage and COVID-19 outcomes.
- To evaluate the impact of CKD on severe COVID-19, Long COVID prevalence, and anti-SARS-CoV-2 antibody response post-vaccination.
Main Methods:
- A prospective cohort study included 26,039 adults from nine US-based studies with pre-pandemic CKD measurements.
- CKD stages were defined using estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio.
- Outcomes included severe COVID-19 (hospitalization/death), Long COVID (RECOVER Long COVID Research Index score ≥11), and anti-Spike 1 (S1) IgG antibody levels.
Main Results:
- Higher CKD stages correlated with increased risk of severe COVID-19 (HRs ranging from 1.27 to 2.72).
- Advanced CKD stages were associated with significantly lower anti-S1 IgG antibody levels (up to -48.9% reduction).
- Increased Long COVID prevalence was observed only in infected individuals with very high stage CKD (OR=2.20).
Conclusions:
- Pre-pandemic chronic kidney disease stage is a significant risk factor for severe COVID-19.
- CKD negatively impacts anti-SARS-CoV-2 vaccine antibody response.
- Long COVID risk is elevated in severe CKD, warranting further investigation.
Rationale & Objective:
Kidney failure is associated with severe COVID-19, but data on early stage chronic kidney disease (CKD) and its relationship to acute and post-acute COVID-19 as well as postvaccination antibody responses are limited. We evaluated pre-pandemic CKD stage in relation to these outcomes.
Study Design:
Prospective cohort.
Setting & Participants:
Adults in 9 US population-based studies established since 1971, with pre-pandemic CKD measurements and follow-up for COVID-19 outcomes.
Exposure:
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-creatinine ratio.
Outcome:
(1) COVID-19 hospitalization or death (self-report/medical records, 2020-2023); (2) RECOVER Long COVID Research Index score ≥11 (LCRI-positivity by questionnaires, 2023-2024); (3) post-vaccination anti-spike 1 (S1) IgG levels (dried blood spots, 2021‒2022).
Analytical Approach:
Cause-specific hazards for severe COVID-19, logistic regression for LCRI positivity, and generalized additive models for anti-S1 IgG.
Results:
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 period (IQR, 314-636), 734 had severe COVID-19; 12.1% of infected patients (669 of 5,527) were classified as LCRI positive; and 3.1% (82 of 2,679) were anti-S1 IgG antibody nonreactive. 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 (odds ratio, 2.20 [95% CI, 1.16-4.18]).
Limitations:
Some outcomes were self-reported.
Conclusions:
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.
Plain-Language Summary:
Chronic kidney disease (CKD) affects approximately 1 in 7 US adults, yet its impact on COVID-19 outcomes, particularly in early stage CKD, remains incompletely understood. We analyzed pre-pandemic CKD stage data from 9 population-based US cohorts to assess their associations with the risk of severe COVID-19, symptom-defined long COVID, and postvaccination anti-spike 1 IgG levels. More advanced stages of CKD had a stronger relationship with severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed with symptom-defined long COVID, although its prevalence was higher among individuals with very high stage CKD. These findings suggest an altered vaccine-induced immunity and increased susceptibility to both acute and post-acute COVID-19 outcomes among persons with advanced CKD. Adults with advanced CKD may benefit from targeted preventive measures.
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