927 – Hormonal Dysregulation in Long COVID: Exploring the Salivary Cortisol Profile
Marta Camici, Marta Franco, Lorenzo Talamanca, Manuela Petino, Jessica Paulicelli, Liliana Scarnecchia, Alessandra Vergori, Stefano Curcio, Roberto Baldelli, Paolo Zuppi, Andrea Antinori
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Background
While reduced morning serum cortisol (SC) is common in long COVID (LC) patients, measuring salivary cortisol throughout the day better reflects dynamic secretion and may offer greater sensitivity than SC. This study investigates this relationship, alongside hormonal dysregulation and LC predictors.
Methods
This prospective, single-center, case-control study at a LC-clinic in Rome included 96 participants assessed at least 28 days post-positive SARS-CoV-2 PCR test. LC was defined as at least one new or persisting symptom, with severe LC defined as four or more of fatigue, concentration/memory deficits, poor exercise tolerance, dyspnea, arthralgia, or dysautonomia. Fatigue, assessed using the Fatigue Assessment Scale (FAS) at baseline and 12 weeks, was defined as FAS ≥ 22 (severe: FAS ≥ 35).
Two weeks post-BL, blood samples for hormonal assessment and salivary cortisol samples (8:00 AM, 3:00 PM, 11:00 PM) were collected. Patients with SC <15 µg/dL underwent a 1 µg ACTH stimulation test to assess for adrenal insufficiency. Salivary cortisol data from a control group (healthy, COVID-19-free for 4+ months) were also analyzed.
Results
Of 96 patients, 60% were female, all white, mean age 58 ± 15 yrs, 61% had >3 comorbidities, 42% had prior COVID-19, and the mean SARS-CoV-2 vaccine doses received was 2.9 ± 1. 62.5% exhibited FAS scores ≥ 22.
LC was present in 86% of participants, with 80% experiencing moderate and 20% severe symptoms. 13.5% were asymptomatic post-COVID (APC).
Altered FAS was strongly associated with both LC presence and severity (p<0.0001), and negatively impacted daily life (p<0.001).
Vaccination was found to be protective (p=0.03), while psychiatric comorbidities increased LC risk (p=0.04). One LC patient (1.2%) had adrenal insufficiency requiring replacement therapy.
Morning salivary cortisol was higher in controls than in both APC and LC groups (p=0.005), while afternoon/evening cortisol was lower (Figure 1).
Although morning SC did not differ between groups, median ACTH was higher in LC than APC (26 pg/ml vs 13 pg/ml; p<0.001).
No differences were observed between groups for testosterone, DHEAS, TSH, ft3, or ft4. Median TSH was higher in the pathological FAS group (2.07 mU/L vs 1.58 mU/L; p=0.004).
Conclusions
This study reveals a disrupted circadian cortisol rhythm in individuals post-COVID-19, marked by lower daytime and higher evening/nighttime cortisol levels, potentially correlating with disease severity. Elevated ACTH levels in LC may suggest adrenal impairment.
Link (Conference on Retroviruses and Opportunistic Infections) [Abstract Only]
Marta Camici, Marta Franco, Lorenzo Talamanca, Manuela Petino, Jessica Paulicelli, Liliana Scarnecchia, Alessandra Vergori, Stefano Curcio, Roberto Baldelli, Paolo Zuppi, Andrea Antinori
[Line breaks added]
Background
While reduced morning serum cortisol (SC) is common in long COVID (LC) patients, measuring salivary cortisol throughout the day better reflects dynamic secretion and may offer greater sensitivity than SC. This study investigates this relationship, alongside hormonal dysregulation and LC predictors.
Methods
This prospective, single-center, case-control study at a LC-clinic in Rome included 96 participants assessed at least 28 days post-positive SARS-CoV-2 PCR test. LC was defined as at least one new or persisting symptom, with severe LC defined as four or more of fatigue, concentration/memory deficits, poor exercise tolerance, dyspnea, arthralgia, or dysautonomia. Fatigue, assessed using the Fatigue Assessment Scale (FAS) at baseline and 12 weeks, was defined as FAS ≥ 22 (severe: FAS ≥ 35).
Two weeks post-BL, blood samples for hormonal assessment and salivary cortisol samples (8:00 AM, 3:00 PM, 11:00 PM) were collected. Patients with SC <15 µg/dL underwent a 1 µg ACTH stimulation test to assess for adrenal insufficiency. Salivary cortisol data from a control group (healthy, COVID-19-free for 4+ months) were also analyzed.
Results
Of 96 patients, 60% were female, all white, mean age 58 ± 15 yrs, 61% had >3 comorbidities, 42% had prior COVID-19, and the mean SARS-CoV-2 vaccine doses received was 2.9 ± 1. 62.5% exhibited FAS scores ≥ 22.
LC was present in 86% of participants, with 80% experiencing moderate and 20% severe symptoms. 13.5% were asymptomatic post-COVID (APC).
Altered FAS was strongly associated with both LC presence and severity (p<0.0001), and negatively impacted daily life (p<0.001).
Vaccination was found to be protective (p=0.03), while psychiatric comorbidities increased LC risk (p=0.04). One LC patient (1.2%) had adrenal insufficiency requiring replacement therapy.
Morning salivary cortisol was higher in controls than in both APC and LC groups (p=0.005), while afternoon/evening cortisol was lower (Figure 1).
Although morning SC did not differ between groups, median ACTH was higher in LC than APC (26 pg/ml vs 13 pg/ml; p<0.001).
No differences were observed between groups for testosterone, DHEAS, TSH, ft3, or ft4. Median TSH was higher in the pathological FAS group (2.07 mU/L vs 1.58 mU/L; p=0.004).
Conclusions
This study reveals a disrupted circadian cortisol rhythm in individuals post-COVID-19, marked by lower daytime and higher evening/nighttime cortisol levels, potentially correlating with disease severity. Elevated ACTH levels in LC may suggest adrenal impairment.
Link (Conference on Retroviruses and Opportunistic Infections) [Abstract Only]
