Endocrine Abstracts

Background: SARS-CoV-2 targets membrane-bound angiotensin-converting enzyme 2 (ACE2) to achieve cellular entry. Resultant loss of ACE2 function may lead to unregulated activation of the renin-angiotensin-aldosterone system (RAAS), contributing to the pathogenesis of hypertension and triggering a proinflammatory cascade. However, evidence to support this is conflicting, with either no change or an increase in the concentration of circulating aldosterone reported in patients with COVID-19.

Patients & Methods: Blood aldosterone concentrations from 126 steroid-naive patients, collected within three days of the patient’s first positive SARS-CoV-2 PCR test, were analysed by liquid chromatography tandem mass-spectrometry (LC-MSMS). Cortisol was determined by immunoassay (Siemen’s Centaur®).

Results: In contrast to previous reports, aldosterone was undetectable by LC-MSMS in more than half of the patients studied. Given this discrepancy, aldosterone measurement was repeated in a commonly used clinical immunoassay (Liaison Diasorin®). The immunoassay over-estimated aldosterone compared to the LC-MSMS assay, suggesting assay interference as a possible explanation of this discordance. Solvent extraction prior to immunoassay improved the agreement between methods and reduced random noise (Pearson R² 0.96 c.f. 0.60) consistent with a water-soluble interference in the direct immunoassay. The magnitude of this interference did not obviously correlate with markers of kidney or liver function. As previously observed, blood cortisol concentrations were often increased and provided prognostic information in terms of overall 28-day mortality in this patient group with 44% of patients with serum cortisol >744nmol/l dying compared to 11% of patients in the low cortisol group (P = 0.005 log-rank test for difference in survival curves). Raised cortisol concentration may contribute to the paradoxical suppression of RAAS prevalent in this patient group due to cross-talk at the mineralocorticoid receptor; however no obvious negative correlation between circulating cortisol and aldosterone was apparent.

Conclusions: This study does not support the hypothesis that SARS-CoV-2 infection leads to aldosterone excess