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. 2022 Oct 14;11(11):e220190.
doi: 10.1530/EC-22-0190. Print 2022 Nov 1.

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Martin Wiegand  1 , David J Halsall  2 , Sarah L Cowan  2 , Kevin Taylor  2 , Robert J B Goudie  1 , Jacobus Preller  2 , Mark Gurnell  2   3
Affiliations

Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay

Martin Wiegand et al. Endocr Connect. .

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.

Keywords: COVID-19; SARS-CoV-2; renin-angiotensin-aldosterone system.

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Figures

Figure 1
Figure 1
Histograms of the first available result: (A) aldosterone, measured using LCMSMS, (B) cortisol and (C) renin.
Figure 2
Figure 2
Scatter plots of paired aldosterone, cortisol and renin results, with linear regression lines shown. (A) Aldosterone (measured using LCMSMS) against cortisol. (B) Aldosterone (LCMSMS) against renin (two extreme outliers are outside the plotting region; see Supplementary Fig. 1 for zoomed-out version).
Figure 3
Figure 3
Kaplan–Meier survival plot for 28-day survival in steroid naive patients after first positive test, stratified by the first cortisol result after the test. The 95% CIs are shown by shading.
Figure 4
Figure 4
Comparison of aldosterone measured by LCMSMS and CLIA with Passing–Bablok regression line (solid black) shown. The dotted grey line indicates the y = x identity line.
See this image and copyright information in PMC

References

    1. UK Government. Coronavirus (COVID-19) in the UK: deaths. London, UK: UK Health Security Agency, 2022. (available at: https://coronavirus.data.gov.uk/details/deaths?areaType=overview&areaNam...)
    1. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CLet al.A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020579270–273. (10.1038/s41586-020-2012-7) - DOI - PMC - PubMed
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche Aet al.SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020181 271.e8–280.e8. (10.1016/j.cell.2020.02.052) - DOI - PMC - PubMed
    1. Santos RA, Ferreira AJ, Verano-Braga T, Bader M. Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin-angiotensin system. Journal of Endocrinology 2013216R1–R17. (10.1530/JOE-12-0341) - DOI - PubMed
    1. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. New England Journal of Medicine 20203821653–1659. (10.1056/NEJMsr2005760) - DOI - PMC - PubMed

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