Abstract
Abstract Background and Aims The impact of “long COVID-19” on “short-term” or “long-term” influence on kidney function change remains unknown. We aimed to investigate the causal association between COVID-19 and subsequent kidney outcomes. Method 10121 participants exposed to COVID-19 were matched up to 3 unexposed controls by age, sex, Townsend deprive index and severity of COVID-19 from UK Biobank. Using conditional and time-varying Cox proportional hazard regression, we first investigated the association between the SARS-CoV-2 infection and incidence of acute kidney disorder and chronic kidney disease (CKD). One-sample mendelian randomization (MR) using polygenetic risk score (PRS) of COVID-19 as instrumental variable was performed. Then, we extended the finding with two-sample MR analyses using GWAS summary statistics from UKB as outcomes, and GWAS of COVID-19 severity, hospitalization and susceptibility from the COVID-19 Host Genetics Initiative (r7) database as exposures. Results In observational study, we observed time-varying effects of COVID-19 on the risk of acute kidney disorder incidence, with the highest hazard effect in the second week (HR 12.77, 95% CI: 5.93-27.70) and disappearing in the fourth week (HR 2.28, 95% CI: 0.75-6.93). In subgroup analysis, this time-varying effects were only found in patients with moderate and severe COVID-19, but not mild COVID-19 patients. No association was observed between SARS-CoV-2 infection and the risk of incident CKD. Subsequent individual-level MR showed that COVID-19 severity, hospitalization and susceptibility were significantly associated with increased risk of acute kidney disorder, but not CKD. Two-sample MR indicated that none of the COVID-19 phenotypes were associated with these two diseases nor other kidney traits. Conclusion COVID-19 had “short-term” effects on the risk of subsequent acute kidney disorder incidence, and the hazard effects were only observed in moderate or severe but not mild COVID-19 patients.
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