Striking Drop in Stress Hormone Predicts Long Covid in Study


Senior Member
  • Cortisol could be used with other biomarkers for diagnosis
  • Research identifies three potential causes of chronic symptoms
Striking decreases in the stress hormone cortisol were the strongest predictor for who develops long Covid in new research that identified several potential drivers of the lingering symptoms afflicting millions of survivors.

Levels of cortisol in the blood of those with the so-called post Covid-19 condition were roughly half those found in healthy, uninfected people or individuals who fully recovered from the pandemic disease, researchers at Yale School of Medicine in Connecticut and the Icahn School of Medicine at Mount Sinai in New York found.

No one knows yet what causes the constellation of symptoms, often termed long Covid, that afflict some 10% to 20% of people after the acute phase of infection from SARS-CoV-2, the virus that causes Covid-19. The US government is spending more than $1 billion to learn why it occurs and to devise strategies to treat and prevent the condition.

One avenue for research is the endocrine system, which produces hormones like cortisol that affect every part of the body, including inflammation and metabolism. Cortisol helps control mood, motivation, and fear. Low levels can cause fatigue, muscle weakness, gastrointestinal upsets and hypotension, according to the Mayo Clinic.

Low cortisol has been reported in people with myalgic encephalomyelitis, or chronic fatigue syndrome, and boosting it with hydrocortisone treatment has provided a modest improvement in symptoms, researchers Akiko Iwasaki, David Putrino and their co-authors wrote in the study, released ahead of peer-review and publication on Aug. 10.


Senior Member
U.S., Earth
Thanks for posting! In addition to finding low cortisol in Long Covid, the researchers also found increased EBV antibodies in patients with Long Covid, which is more evidence that EBV is reactivated by the coronavirus.

Unfortunately, the Bloomberg article is paywalled, but here's a good Science article that also discusses this research:

Blood abnormalities found in people with Long Covid

And here's the actual study (preprint) from Akiko Iwasaki, David Putrino, and others:

Distinguishing features of Long COVID identified through immune profiling (Klein et al, 2022)
SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID13. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions13; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear.

Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID.

Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus.

Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups.

Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.
(emphasis and spacing added)