Alterations in Cortisol and Interleukin-6 Secretion in Patients With COVID-19 Suggestive of Neuroendocrine-Immune Adaptations

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- recruited between April 15th -June15th-2021, (NCT04988269) at Laikon Athens University-Hospital, and 33 healthy age- and sex-matched controls were included. Diurnal salivary cortisol (8am, 12, 6, and 10pm), 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.ResultsMedian CRP and IL-6 measurements were about 6-fold 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, 0,663) 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 (rho=0.555, p<0.001) in patients.ConclusionIncreased evening and nocturnal but not morning cortisol secretion 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.

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Cortisol secretion pattern in overweight/obese and normal-weight infants: a cross-sectional study

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0273 ◽

2020 ◽

Vol 33 (2) ◽

pp. 241-246

Author(s):

Ana Cristina Resende Camargos ◽

Pedro Henrique Scheidt Figueiredo ◽

Sueli Ferreira da Fonseca ◽

Mariana Aguiar de Matos ◽

Katherine Simone Caires Oliveira ◽

...

Keyword(s):

Salivary Cortisol ◽

Area Under The Curve ◽

Cross Sectional Study ◽

Normal Weight ◽

Control Group ◽

Cortisol Secretion ◽

Cross Sectional ◽

Increased Risk ◽

Highly Sensitive ◽

Cortisol Levels

AbstractBackgroundThe salivary circadian diurnal cortisol plays an important role in growth and development. Inappropriate levels may induce changes associated with an increased risk of obesity later in life. It is unknown if there are differences in cortisol secretion pattern between overweight/obese infants when compared with theirs peers in infancy. Thus, this study aimed to compare the salivary cortisol secretion pattern in overweight/obese and normal-weight infants.MethodsThirty-three (overweight/obese = 17 and normal weight = 16) infants between 6 and 24 months of age had saliva samples collected upon awakening (T1), 30 min after waking (T2), at 12:00 am or before the baby’s meal (T3), and prior to bedtime (T4). Highly sensitive enzyme immunoassays were used for cortisol analyses.ResultsSalivary cortisol levels were similar between the groups: T1 (p = 0.22; 95% confidence interval [CI]: −5.65, 1.37), T2 (p = 0.24; 95% CI: −8.23, 2.17), T3 (p = 0.95; 95% CI: −3.16, 2.96), and T4 (p = 0.81; 95% CI: −1.39, 1.08); and no differences were observed between area under the curve (AUC) (p = 0.80; 95% CI: −4.58–13.66). The cortisol level reduced in T4 (95% CI: 1.35–2.96) compared to T1 (95% CI: 5.15–8.49) and T2 in the overweight/obese group (p < 0.001; 95% CI: 6.02–11.04). In the normal-weight group, the cortisol reduced in T3 (95% CI: 2.86–8.18) compared to T1 (95% CI: 5.64–12.28) and decreased until T4 (p = 0.001; 95% CI: 1.25–3.37).ConclusionsThe overweight/obese infant group presented a different pattern of cortisol secretion, although cortisol levels did not differ between the control group.

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Salivary cortisol in a middle-aged community sample: results from 990 men and women of the KORA-F3 Augsburg study

Acta Endocrinologica ◽

10.1530/eje-10-0491 ◽

2010 ◽

Vol 163 (3) ◽

pp. 443-451 ◽

Cited By ~ 29

Author(s):

Florian Lederbogen ◽

Christine Kühner ◽

Clemens Kirschbaum ◽

Christa Meisinger ◽

Josefine Lammich ◽

...

Keyword(s):

Social Support ◽

Salivary Cortisol ◽

Perceived Social Support ◽

Community Sample ◽

Area Under The Curve ◽

Smoking Habits ◽

Cortisol Secretion ◽

Middle Aged ◽

Scientific Medicine ◽

Cross Sectional

ObjectiveAnalysis of salivary cortisol concentrations and derived indices is increasingly used in clinical and scientific medicine. However, comprehensive data on these parameters in the general population are scarce. The aim of this study was to evaluate the concentrations of salivary cortisol in a large middle-aged community sample and to identify major factors associated with altered hormone levels.DesignWe conducted a cross-sectional study within the Cooperative Health Research in the Region of Augsburg (KORA)-F3 study. A total of 1484 participants aged 50–69 years (52% women) had agreed to provide four saliva samples during a regular weekday.MethodsWe measured salivary cortisol concentrations at wake-up (F0), ½ h (F½), 8 h (F8), and 14 h (F14) after waking. We calculated cortisol awakening response (CAR), slope, and area under the curve (AUCG) of the circadian cortisol secretion. Sociodemographic and clinical characteristics were evaluated by interview and questionnaires, sampling conditions by protocol. In total, 1208 participants returned saliva samples, exclusion criteria left 990 subjects for final analyses.ResultsSalivary cortisol levels were (means±s.d.) F0=13.7±7.6, F½=20.5±9.8, F8=5.4±3.3, and F14=2.0±1.8 nmol/l. Earlier sampling times were associated with higher CAR and smaller slope. Cortisol secretion was also influenced by gender and smoking habits. Higher perceived social support was associated with lower AUCG and smaller slope.ConclusionsWe provide data on salivary cortisol concentrations in a large middle-aged community sample. Gender, sampling time, smoking habits, and perceived social support appeared as determinants of cortisol secretion.

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Two variants of the Nutritional Risk in the Critically Ill Score as predictors of mortality in Intensive Care Unit patients at a Brazilian University Hospital

Revista de Nutrição ◽

10.1590/1678-9865202033e190031 ◽

2020 ◽

Vol 33 ◽

Author(s):

Amanda Forte dos Santos SILVA ◽

Audrey Machado dos REIS ◽

Julia MARCHETTI ◽

Oellen Stuani FRANZOSI ◽

Thais STEEMBURGO

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Critically Ill ◽

Interleukin 6 ◽

Characteristic Curve ◽

University Hospital ◽

Nutritional Risk ◽

C Reactive Protein ◽

Predictors Of Mortality ◽

Reactive Protein

ABSTRACT Objective To evaluate the agreement between the modified version of the Nutritional Risk in the Critically Ill Score (without Interleukin-6) and a variant composed of C-Reactive Protein as well as its capacity to predict mortality. Methods A prospective cohort study was carried out with 315 patients in an Intensive Care Unit of a university hospital from October 2017 to April 2018. The agreement between the instruments was evaluated using the Kappa test. The predictive capacity for estimating mortality was assessed with the Receiver Operating Characteristic curve. Results The critical patients involved in the study had a mean age of 60.8±16.3 years and 53.5% were female. Most patients had C-Reactive Protein levels ?10mg/dL (n=263, 83.5%) and their admission in the Intensive Care Unit was medical (n=219, 69.5%). The prevalence of mortality was observed in 41.0% of the evaluated patients. The proportions at high nutritional risk according to Nutritional Risk in the Critically Ill without Interleukin-6 and with C-Reactive Protein were 57.5% and 55.6%, respectively. The tools showed strong and significant agreement(Kappa=0.935; p=0.020) and satisfactory performances in predicting mortality (area under the curve 0.695 [0.636-0.754] and 0.699 [0.640-0.758]). Conclusion Both versions of the Nutritional Risk in the Critically Ill tool show a satisfactory agreement and performance as predictors of mortality in critically ill patients. Further analysis of this variant and the association between nutrition adequacy and mortality is needed.

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The Diagnostic Performance of Interleukin-6 and C-Reactive Protein for Early Identification of Neonatal Sepsis

Diagnostics ◽

10.3390/diagnostics10110978 ◽

2020 ◽

Vol 10 (11) ◽

pp. 978

Author(s):

Belay Tessema ◽

Norman Lippmann ◽

Anja Willenberg ◽

Matthias Knüpfer ◽

Ulrich Sack ◽

...

Keyword(s):

Interleukin 6 ◽

Neonatal Sepsis ◽

Diagnostic Performance ◽

University Hospital ◽

C Reactive Protein ◽

Clinical Sepsis ◽

Reactive Protein ◽

Increased Sensitivity ◽

And Performance ◽

Culture Negative

Interleukin-6 (IL-6) and C-reactive protein (CRP) are being used for diagnosis of sepsis. However, studies have reported varying cut-off levels and diagnostic performance. This study aims to investigate the optimal cut-off levels and performance of IL-6 and CRP for the diagnosis of neonatal sepsis. The study was conducted at the University Hospital of Leipzig, Germany from November 2012 to June 2020. A total of 899 neonates: 104 culture proven sepsis, 160 clinical sepsis, and 625 controls were included. Blood culture was performed using BacT/ALERT 3D system. IL-6 and CRP were analyzed by electrochemiluminescent immunoassay and immunoturbidimetric assay, respectively. Data were analyzed using SPSS 20 statistical software. Among neonates with proven sepsis, the optimal cut-off value of IL-6 was 313.5 pg/mL. The optimal cut-off values for CRP in 5 days serial measurements (CRP1, CRP2, CRP3, CRP4, and CRP5) were 2.15 mg/L, 8.01 mg/L, 6.80 mg/L, 5.25 mg/L, and 3.72 mg/L, respectively. IL-6 showed 73.1% sensitivity, 80.2% specificity, 37.6% PPV, and 94.8% NPV. The highest performance of CRP was observed in the second day with 89.4% sensitivity, 97.3% specificity, 94.5% PPV, and 98.3% NPV. The combination of IL-6 and CRP showed increase in sensitivity with decrease in specificity. In conclusion, this study defines the optimal cut-off values for IL-6 and CRP. The combination of IL-6 and CRP demonstrated increased sensitivity. The CRP 2 at cut-off 8.01 mg/L showed the highest diagnostic performance for identification of culture negative clinical sepsis cases. We recommend the combination of IL-6 (≥313.5 pg/mL) and CRP1 (≥2.15 mg/L) or IL-6 (≥313.5 pg/mL) and CRP2 (≥8.01 mg/L) for early and accurate diagnosis of neonatal sepsis. The recommendation is based on increased sensitivity, that is, to minimize the risk of any missing cases of sepsis. The CRP2 alone at cut-off 8.01 mg/L might be used to identify clinical sepsis cases among culture negative sepsis suspected neonates in hospital settings.

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Diagnostic accuracy of three biomarkers in identifying serious bacterial infections in children younger than 36 months with fever without source / Acurateţea diagnostică a trei biomarkeri în identificarea infecţiilor bacteriene severe la copiii cu vârsta sub 36 luni cu febră fără focar

Revista Romana de Medicina de Laborator ◽

10.1515/rrlm-2015-0032 ◽

2015 ◽

Vol 23 (3) ◽

pp. 313-322

Author(s):

Diana Aniela Moldovan ◽

Maria Despina Baghiu ◽

Alina Balas ◽

Emese Rozalia Fabian-Frast ◽

Cristian Boeriu

Keyword(s):

Emergency Department ◽

Diagnostic Accuracy ◽

Interleukin 6 ◽

Bacterial Infections ◽

Screening Tool ◽

University Hospital ◽

C Reactive Protein ◽

Reactive Protein ◽

Serious Bacterial Infections ◽

Better Than

Abstract Objectives: Our study aimed to evaluate and compare the accuracy of C-reactive protein, Procalcitonin and Interleukine-6 in identifying serious bacterial infections (SBI) in children with fever without source. Methods: 139 children, aged 7 days to 36 months, addressing the Emergency Department from a Romanian university hospital, were prospectively enrolled during 2013. C-reactive protein, Procalcitonin and Interleukin-6 were determined for every patient. SBI diagnosis was based on cultures results and chest radiographs. Results: 31 patients (22.3%) had SBI. C-reactive protein [AUC: 0.87 (95%CI: 0.81-0.92)] and Procalcitonin [AUC: 0.83 (95%CI: 0.76-0.89)] proved strong prediction value for SBI and performed better than Interleukin-6 [AUC: 0.77 (95%CI: 0.69-0.84)]. For the group of children with the duration of fever less than 8 hours, Interleukin- 6 was the best predictor [AUC: 0.88 (0.76-0.95)]. Conclusions: Both C-reactive protein and Procalcitonin are strong and similar predictors for SBI, and Interleukin- 6 might be a better SBI screening tool for children with shorter duration of fever.

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Relationship between Meditation and Waking Salivary Cortisol Secretion among Long-Term MBSR Instructors

Complementary Medicine Research ◽

10.1159/000493124 ◽

2019 ◽

Vol 26 (2) ◽

pp. 101-109 ◽

Cited By ~ 1

Author(s):

Sara Wagner Robb ◽

Alyson Haslam ◽

Michael D. Wirth ◽

Jennifer L. Gay ◽

Lauren Middleton ◽

...

Keyword(s):

Stress Response ◽

Perceived Stress ◽

Stress Reduction ◽

Salivary Cortisol ◽

Area Under The Curve ◽

Cortisol Response ◽

Cortisol Secretion ◽

Meditation Practice ◽

Mindfulness Based Stress Reduction

Background: A potential relationship between long-term meditation practice and stress reduction remains virtually unexplored. The purpose of this study was to characterize stress using salivary waking cortisol in a group of long-term meditators with training in the Mindfulness-Based Stress Reduction (MBSR) program. Materials and Methods: Four salivary cortisol samples were collected from meditators (n = 84) during the first hour of awakening. The waking cortisol rhythm was summarized using cortisol area under the curve (AUC) with respect to increased secretion above baseline (AUCI) and cortisol AUC above ground (above zero, AUCG); data on meditation duration and depth, perceived stress, and other covariates were collected via self-reported questionnaire. Results: Individuals in the highest quartile of years meditating (> 26 years) had statistically significantly elevated AUCG values (p = 0.01) as compared to individuals in the lowest quartile of years meditating (≤10 years). This relationship was more pronounced among individuals waking at or before 6: 30 a.m. Conclusions: Overall, an increasing number of years of meditation practice was related to a higher waking cortisol response. These intriguing findings warrant additional exploration, as the stress response can be complex.

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The Role of C-reactive Protein in the Prediction of the Clinical Severity of Acute Diverticulitis

The American Surgeon ◽

10.1177/000313481408000423 ◽

2014 ◽

Vol 80 (4) ◽

pp. 391-395 ◽

Cited By ~ 14

Author(s):

Aristotelis Kechagias ◽

Tero Rautio ◽

Georgios Kechagias ◽

Jyrki Mäkelä

Keyword(s):

Acute Diverticulitis ◽

Characteristic Curve ◽

Area Under The Curve ◽

Clinical Severity ◽

University Hospital ◽

C Reactive Protein ◽

Mild Disease ◽

Reactive Protein ◽

Hinchey Classification ◽

Independent Risk Factors

The aim of this study is to investigate the value of C-reactive protein (CRP) and of other laboratory parameters obtained during the initial evaluation of the patient in the prediction of the clinical severity of acute diverticulitis. The records of patients treated for acute diverticulitis at the Oulu University Hospital from December 2006 to December 2008 were retrospectively reviewed. Mild disease was defined when conservative treatment was successful. Severe acute diverticulitis was considered when percutaneous drainage of an abscess and/or surgery was necessary. From the 182 patients considered for analysis, 158 (87%) had mild disease, whereas 24 (13%) had severe. CRP ( P = 0.034) and the Hinchey classification ( P = 0.006) were shown to be independent risk factors for severe acute diverticulitis in the logistic regression analysis. The receiver operating characteristic curve showed that a CRP cutoff value of 170 mg/L significantly discriminated severe from mild diverticulitis (87.5% sensitivity, 91.1% specificity, area under the curve 0.942, P < 0.00001). CRP is a useful tool in the prediction of the clinical severity of acute diverticulitis. A mild episode is very likely in patients with CRP less than 170 mg/L. Those with higher CRP values have a greater probability to undergo surgical treatment or at least a percutaneous intervention.

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