Plasma aldosterone is low in patients hospitalized with COVID-19 and not associated with changes in serum potassium levels: post-hoc observational analyses of clinical trial data

Simon Krenn^1,2,3Sebastian Hödlmoser^2,4,5Amelie Kurnikowski^2,3Patrick Jorge³Farsad Alexander Eskandary³Georg Heinze⁴Manfred Hecking^3*Roman Reindl-Schwaighofer³

• ¹AIT Austrian Institute of Technology, Center for Health & Bioresources, Medical Signal Analysis, Vienna, Austria
• ²Medical University of Vienna, Center for Public Health, Department of Epidemiology, Vienna, Austria
• ³Medical University of Vienna, Department of Medicine III, Division of Nephrology and Dialysis, Vienna, Austria
• ⁴Medical University of Vienna, Center for Medical Data Science, Section for Clinical Biometrics, Vienna, Austria
• ⁵Medical University of Vienna, Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Vienna, Austria

Background: Hypokalemia is common in patients hospitalized with Corona Virus Disease 2019 (COVID-19) and associated with mortality, progression and severity of disease. Increased aldosterone levels were previously suggested to be a main cause of potassium loss in this population. We aimed to assess effects of the latest morning plasma aldosterone levels on changes in serum potassium during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods: We used dynamic generalized estimating equations (GEEs) on longitudinal data (3 weeks) from an adequately sized (159 patients) platform trial evaluating therapeutics for COVID-19 during the first wave of infections in Vienna, Austria. We adjusted for important confounding variables (GEE A, 106 patients), conducted sensitivity analyses by including medications with potential to confound the analysis (GEE B, 82 patients) and by modelling an exponential decay of effects on potassium over time (GEE C, 82 patients). Further, we explored the relationship descriptively. Results: The median potassium concentration was 3.8 [quartile 1: 3.5, quartile 3: 4.0] mmol/L, and hypokalemia (<3.5 mmol/L) was present in 15.7% of patients at first blood draw compared to 21.6% throughout the three-week observation period. The median aldosterone concentration was 45.0 [20.0, 104.0] pmol/L and was below the lower limit of quantitation (20 pmol/L) in 32.4% of samples. Aldosterone did not associate with changes in potassium neither in GEE A (base-10 logarithm of aldosterone, β: -0.008 [95% CI: -0.074, 0.057], p-value: 0.805), in GEE B (β: 0.013, [-0.064, 0.090], p-value: 0.739) nor in GEE C (β: 0.001 [-0.078, 0.075], p-value: 0.971). Conclusion: Aldosterone levels were low and did not associate with potassium changes in patients hospitalized with COVID-19 during the first wave of the SARS-CoV-2 pandemic.