Alterations in cortisol and interleukin-6 secretion in patients with COVID-19 suggestive of neuroendocrine-immune adaptations

Maria P Yavropoulou; Maria G Filippa; Aimilia Mantzou; Fotinie Ntziora; Maria Mylona; Maria G Tektonidou; Nikolaos I Vlachogiannis; Dimitrios Paraskevis; Gregory A Kaltsas; George P Chrousos; Petros P Sfikakis

doi:10.1007/s12020-021-02968-8

Alterations in cortisol and interleukin-6 secretion in patients with COVID-19 suggestive of neuroendocrine-immune adaptations

Endocrine. 2022 Feb;75(2):317-327. doi: 10.1007/s12020-021-02968-8. Epub 2022 Jan 18.

Affiliations

¹ 1st Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece. myavropoulou@med.uoa.gr.
² 1st Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
³ University Research Institute of Maternal and Child Health and Precision Medicine Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
⁴ Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
⁵ University Research Institute of Maternal and Child Health and Precision Medicine and UNESCO Chair on Adolescent Health Care, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.

^# Contributed equally.

Abstract

Purpose: The beneficial effect of glucocorticoids in coronavirus disease (COVID-19) is established, but whether adrenal cortisol secretion is impaired in COVID-19 is not fully elucidated. In this case-control study, we investigated the diurnal free bioavailable salivary cortisol secretion in COVID-19 patients.

Methods: Fifty-two consecutive COVID-19 patients-before dexamethasone treatment in cases required-recruited between April 15 to June 15, 2021, (NCT04988269) at Laikon Athens University-Hospital, and 33 healthy age- and sex-matched controls were included. Diurnal salivary cortisol (8 a.m., 12, 6, and 10 p.m.), plasma adrenocorticotropin (ACTH) and aldosterone, and serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels were assessed. Diurnal salivary dehydroepiandrosterone (DHEA) and IL-6 were also assessed in subgroups of patients.

Results: Median CRP and IL-6 measurements were about sixfold higher in patients than controls (both p < 0.001) Morning salivary cortisol levels did not differ between the two groups, but patients exhibited higher median levels of evening and nocturnal salivary cortisol compared to controls [0.391 (0.054, 0663) vs. 0.081 (0.054, 0.243) μg/dl, p < 0.001 and 0.183 (0.090, 0.834) vs. 0.054 (0.054, 0.332) μg/dl, p < 0.001, respectively], resulting in higher time-integrated area under the curve (AUC) (4.81 ± 2.46 vs. 2.75 ± 0.810, respectively, p < 0.001). Circulating ACTH, DHEA, and aldosterone levels were similar in patients and controls. Serum IL-6, but not ACTH levels, was strongly correlated with nocturnal cortisol salivary levels (ρ = 0.555, p < 0.001) in patients.

Conclusions: Increased evening and nocturnal but not morning cortisol secretion may occur in even clinically mild COVID-19. In the context of acute viral infection (COVID-19), IL-6 may partially replace ACTH as a stimulus of the glucocorticoid-secreting adrenal zona-fasciculata without influencing the secretion of DHEA and aldosterone.

Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04988269?term=yavropoulou&draw=2&rank=3 (NCT04988269).

Keywords: Adrenocorticotropin; Aldosterone; Diurnal salivary cortisol; Diurnal salivary dehydroepiandrosterone; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Case-Control Studies
Humans
Hydrocortisone
Interleukin-6*
SARS-CoV-2

Substances

Interleukin-6
Hydrocortisone

Associated data

ClinicalTrials.gov/NCT04988269