Assessment of Diurnal Salivary Cortisol Production in COVID-19

Study Overview
=================
Brief Summary
-----------------
In the year of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic several studies have focused on the effect of the COVID-19 on the adrenal cortex, demonstrating conflicting results. Herein, researchers sought to investigate the adrenal response in patients with COVID-19by assessing the diurnal rhythm of salivary cortisol and the adrenal androgen dehydroepiandrosterone (DHEA), as well as the plasma levels of aldosterone and adrenocorticotropic hormone (ACTH) in consecutive patients before the possible therapeutic administration of dexamethasone. To elucidate the potential association between the magnitude of individual immune response and the adrenal cortex response we included serum measurements of interleukin - 6 (IL-6).

Detailed Description
-----------------
All adult consecutive patients that visited the emergency department of the LAIKO General Hospital of Athens from May to July 2021 due to confirmed COVID-19 and related symptomatology were eligible for the study. Age and gender matched healthy individuals without COVID-19 who had never been treated with GCs and fulfilled the exclusion criteria were also recruited from the Hospital's personnel and included in the analysis as Controls. Blood samples were obtained immediately upon admission for the measurements of ACTH, IL-6 and aldosterone, which were performed by electrochemiluminescence assays on the cobas e 801 immunoassay analysers (Roche Diagnostics GmbH). Salivary samples for free cortisol and DHEAS were obtained during the next day using the Salivette (Sarstedt, Nümbrecht, Germany) at different time points 0800, 12.00, 18.00, and 22.00. Within 24h after saliva collection the salivettes were centrifuged at 2400 g for 20 min in 4 °C and aliquots were stored at -80 °C and analyzed by an Immunochemiluminescence assay in a Roche COBAS E411 analyzer.

Official Title
-----------------
COVID-19, Interleukin - 6 and Diurnal Salivary Cortisol

Conditions
-----------------
COVID-19, Adrenal Insufficiency, Adrenal Hyperfunction

Intervention / Treatment
-----------------
* Diagnostic Test: Blood sampling
* Diagnostic Test: Saliva sampling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients that visited the Emergency Department of LAIKO General Hospital of Athens, Greece from May to July 2021 due to confirmed COVID-19 and related symptomatology Exclusion Criteria: (i) pre-existing hypoadrenalism or concurrent systemic glucocorticoid treatment (ii) patients with chronic kidney disease stage 3b and above, (iii) patients with advanced metastatic disease.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients (Cases)<br>Adult consecutive patients that visited the Emergency Department of LAIKO General Hospital of Athens, Greece from May to July 2021 due to confirmed COVID-19 and related symptomatology. Blood sampling on the day of admission (one time point) and saliva sampling at 4 different time points (0.800, 12.00, 18.00,22.00) the next day (all sampling in one day). | Diagnostic Test: Blood sampling<br>* Assessment of circulating levels of plasma ACTH, plasma aldosterone and serum interleukin -6 levels at day 1<br>Diagnostic Test: Saliva sampling<br>* Assessment of diurnal variation of cortisol and DHEA levels in the saliva at 4 different time points during the day (0.800, 12.00, 18.00, 22.00) at day 2.<br>|
| Healthy Controls<br>Age and gender matched healthy individuals without COVID-19. Blood sampling (at day 1) and saliva sampling at different time points (0.800, 12.00, 18.00,22.00) the next day (all sampling in one day-day 2). | Diagnostic Test: Blood sampling<br>* Assessment of circulating levels of plasma ACTH, plasma aldosterone and serum interleukin -6 levels at day 1<br>Diagnostic Test: Saliva sampling<br>* Assessment of diurnal variation of cortisol and DHEA levels in the saliva at 4 different time points during the day (0.800, 12.00, 18.00, 22.00) at day 2.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diurnal variation of cortisol levels in the saliva (mcg/dL) | Saliva sampling was performed at 4 different time points during one day (08.00, 12.00, 18.00, 22.00). | One day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single hormone assessment of plasma ACTH levels (pg/mL) | Blood sampling was performed on the day of Hospital admission at one time point | One day | 
| Diurnal variation of dehydroepiandrosterone (DHEA) levels (pg/mL) in the saliva | Saliva sampling was performed at 4 different time points during one day (08.00, 12.00, 18.00, 22.00). | One day | 
| Single hormone assessment of plasma aldosterone levels (pmol/L) | Blood sampling was performed on the day of Hospital admission at one time point | One day | 
| Single hormone assessment of serum Interleukin-6 levels (IL-6) (pg/mL) | Blood sampling was performed on the day of Hospital admission at one time point | One day | 
| Single hormone assessment of serum C-reactive protein levels (CRP) (mg/L) | Blood sampling was performed on the day of Hospital admission at one time point | One Day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SARS-CoV-2 infection, Adrenal Cortex, Salivary Cortisol, Salivary DHEA, Aldosterone, ACTH, Interleukin 6, Circadian Rythm