Opinion Is Low Cortisol a Marker of Long COVID?, 2024, Alaedini et al.

SNT Gatchaman · Mar 24, 2024

Is Low Cortisol a Marker of Long COVID?
Armin Alaedini; Stafford Lightman; Gary P. Wormser

Cortisol is the primary glucocorticoid hormone produced by the adrenal glands, playing a critical role in multiple physiological processes, including metabolism, immune response regulation, cardiovascular regulation, and the body's stress response1. The secretion of cortisol is closely regulated by the hypothalamus-pituitary-adrenal (HPA) axis. The process is initiated by the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which stimulates the production of adrenocorticotropic hormone (ACTH) by the pituitary gland.

Link | PDF (The American Journal of Medicine) [Open Access]

SNT Gatchaman · Mar 24, 2024

@Hutan FYI. In reference to Distinguishing features of Long COVID identified through immune profiling (2023, Nature) and Cytokines IL1β, IL6, TNFα and serum cortisol levels may not constitute reliable biomarkers to identify individuals with post-acute sequelae of COVID-19 (2024, Therapeutic Advances in Neurological Disorders)

The levels of cortisol in the body are very dynamic, following a distinct circadian pattern throughout the day. Levels typically increase in the first half hour after awakening by up to 60%, in what has been called the cortisol awakening response, followed by a sharp drop over the next few hours, reaching their lowest point in the evening. Underlying this circadian rhythm, cortisol also exhibits ultradian fluctuations in a pulsatile pattern with several peaks and troughs throughout the day that change in amplitude.
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Because of these fluctuations and the wide and rapid changes in circulating levels, reliable and reproducible evaluation of cortisol secretion is not trivial. Such assessment cannot be based on only a single measurement, but rather requires the collection of multiple blood, saliva, or urine samples throughout the day. Any single measurement would also ideally need to account for the time elapsed since awakening and not necessarily just the time of day. In assessing the difference in cortisol output between groups, multiple measurements in blood or saliva samples are usually used to analyze the change from baseline, the size of the cortisol awakening response, or the elevation and slope of the diurnal curve.
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Surprisingly, none of these approaches was taken in either of the two cited studies of cortisol levels in long COVID. Both studies conducted a single measurement in blood plasma or serum, taking note of the time of day, but not the time since awakening, for the sample collection. More importantly, no attempt was made to take serial samples to overcome the problem associated with the very rapid changes occurring due to ultradian rhythmicity. Considering the dramatic ultradian and diurnal cortisol oscillations, meaningful interpretation of the reported cortisol levels in these two studies is simply not possible. The issue is further compounded by the potential association of long COVID with sleep disturbances, including earlier than average awakening times, which could significantly shift the cortisol diurnal curve, giving the appearance of uniformly lower circulating
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SNT Gatchaman · Mar 24, 2024

I think the Yale team now has multiple time-point saliva assessments underway. IIRC something like 10-15 spit samples per day for 3 days.

Hutan · Mar 24, 2024

Surprisingly, none of these approaches was taken in either of the two cited studies of cortisol levels in long COVID. Both studies conducted a single measurement in blood plasma or serum, taking note of the time of day, but not the time since awakening, for the sample collection. More importantly, no attempt was made to take serial samples to overcome the problem associated with the very rapid changes occurring due to ultradian rhythmicity. Considering the dramatic ultradian and diurnal cortisol oscillations, meaningful interpretation of the reported cortisol levels in these two studies is simply not possible. The issue is further compounded by the potential association of long COVID with sleep disturbances, including earlier than average awakening times, which could significantly shift the cortisol diurnal curve, giving the appearance of uniformly lower circulating
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I'll resist the temptation to find an appropriate gif, but,

Eddie · Mar 24, 2024

SNT Gatchaman said: ↑

I think the Yale team now has multiple time-point saliva assessments underway. IIRC something like 10-15 spit samples per day for 3 days.
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Yeah that's about right from what I remember. I gave my samples about a year ago when I was still living in NYC. I'm surprised a preprint hasn't come out yet but maybe I was one of the first participants.

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Opinion Is Low Cortisol a Marker of Long COVID?, 2024, Alaedini et al.

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Opinion Is Low Cortisol a Marker of Long COVID?, 2024, Alaedini et al.

SNT Gatchaman Senior Member (Voting Rights)

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