Martin Wiegand1, David J Halsall2, Sarah L Cowan2, Kevin Taylor2, Robert J B Goudie1, Jacobus Preller2, Mark Gurnell2,3. 1. MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK. 2. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 3. Wellcome-MRC Institute of Metabolic Science, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
Abstract
Objective: Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography-tandem mass spectrometry (LCMSMS) to address this uncertainty. Design: All patients admitted to Cambridge University Hospitals with COVID-19 between 10 March 2020 and 13 May 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion. Methods: Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay. Results: Using LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Diasorin LIAISON®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 (95% CI -34.4 to 54.1) + slope 3.16 (95% CI 2.09-4.15) pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 (95% CI -31.9 to -4.3) and slope 1.0 (95% CI 0.89-1.02) pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels > 744 nmol/L (P = 0.005). Conclusion: When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.
Objective: Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography-tandem mass spectrometry (LCMSMS) to address this uncertainty. Design: All patients admitted to Cambridge University Hospitals with COVID-19 between 10 March 2020 and 13 May 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion. Methods: Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay. Results: Using LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Diasorin LIAISON®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 (95% CI -34.4 to 54.1) + slope 3.16 (95% CI 2.09-4.15) pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 (95% CI -31.9 to -4.3) and slope 1.0 (95% CI 0.89-1.02) pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels > 744 nmol/L (P = 0.005). Conclusion: When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.
Entities:
Keywords:
COVID-19; SARS-CoV-2; renin-angiotensin-aldosterone system
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