Low levels of a stress hormone called cortisol can also indicate the lingering symptoms post a COVID infection, according to a study not peer-reviewed yet.

Long COVID is defined as having new or ongoing symptoms four weeks or more after the start of the disease. Symptoms include fatigue, shortness of breath, loss of concentration and joint pain. The symptoms can adversely affect day-to-day activities, and in some cases can be severely limiting.

Researchers from Yale University in the US included 215 individuals, including 99 with long COVID, in an exploratory, cross-sectional study using machine learning methods to identify key immunological features distinguishing long COVID.

The results posted online on a pre-print website showed that among participants with long COVID, the most striking was levels of cortisol in the blood. It was roughly half of those found in healthy or convalescent controls. Low levels of cortisol are known to cause weakness, fatigue, and low blood pressure.

"Based on machine learning, cortisol levels alone were the most significant predictor for long COVID classification," wrote Akiko Iwasaki, from the Department of Immunobiology, at Yale School of Medicine along with other researchers in the paper.

Prior reports have associated low cortisol levels during the early phase of COVID-19 in patients that develop respiratory long COVID symptoms.

Low cortisol has also been reported in people with myalgic encephalomyelitis, or chronic fatigue syndrome, and boosting it with hydrocortisone treatment has provided a modest improvement in symptoms, Iwasaki said.

Analysis of circulating immune mediators and various hormones also revealed pronounced differences, but levels of cortisol were 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 the accurate classification of long COVID, with decreased levels of cortisol being the most significant individual predictor.

"Thus, our current finding of persistently decreased cortisol production in participants with long COVID more than a year following acute infection warrants expanded investigation," Iwasaki said.