Alterations in Cortisol and Interleukin-6 secretion in patients with COVID-19 suggestive of Neuroendocrine-immune adaptations
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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).
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A disturbed circadian cortisol rhythm with abnormally high afternoon and night cortisol levels was found in patients with even mild or moderate COVID-19 compared with healthy controls.
“Indeed, a disturbed circadian cortisol rhythm with abnormally high afternoon and night cortisol levels was found in patients with even mild or moderate COVID-19 compared with healthy controls.21”
From Diurnal production of cortisol and prediction of treatment response in rheumatoid arthritis: a 6-month, real-life prospective cohort study (2024) · cites this paper as [21]
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Yavropoulou, M. P., Filippa, M. G., Vlachogiannis, N. I., Fragoulis, G. E., Laskari, K., Mantzou, A., Panopoulos, S., Fanouriakis, A., Bournia, V.-K., Evangelatos, G., et al. (2024) · RMD Open · doi:10.1136/rmdopen-2023-003575 · Cited by 13 · see citing works
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- Authors
- Yavropoulou, M. P., Filippa, M. G., Mantzou, A., Ntziora, F., Mylona, M., Tektonidou, M. G., Vlachogiannis, N. I., Paraskevis, D., Kaltsas, G. A., Chrousos, G. P., & Sfikakis, P. P.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Yavropoulou, Maria P.
- ORCID
- Venue
- Endocrine
- Published
- 2022-01-18
- Volume
- 75
- Issue
- 2
- Pages
- 317-327
- ISSN
- 0969-711X (ISSN-L)
- 1355-008X
- 1559-0100
- PMC
- PMC8765492
- OpenAlex
- W4225443060
- Cited by
- 33
- References
- 47
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 7 · 2022: 10
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine (publishedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National and Kapodistrian University of Athens
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- COVID-19 pandemic, salivary cortisol, diurnal cortisol rhythm, interleukin-6, neuroendocrine-immune interaction, ACTH, aldosterone, dehydroepiandrosterone, C-reactive protein, glucocorticoids, dexamethasone, adrenal function, cytokine storm
- MeSH terms
- COVID-19, SARS-CoV-2, Humans, Hydrocortisone, Interleukin-6, Case-Control Studies
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