Low cortisol, coupled with increased levels of two proteins could potentially be used in a set of biomarkers to objectively identify those with long Covid.

New research found that the stress hormone, cortisol was the strongest predictor of who develops long Covid. The research also identified several potential drivers of the lingering symptoms afflicting millions of survivors. Levels of cortisol in the blood of those with the 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. According to the Mayo Clinic, cortisol helps control mood, motivation, and fear.

Low levels can cause fatigue, muscle weakness, gastrointestinal upsets and hypotension. 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 August 10.

No one knows yet what causes the constellation of symptoms, often termed long Covid, that afflict some 10 per cent to 20 per cent of people after the acute phase of infection from SARS-CoV-2, the virus that causes COVID-19. One avenue for research is the endocrine system, which produces hormones like cortisol that affect every part of the body, including inflammation and metabolism.

The Yale-Mount Sinai group used comprehensive immune "phenotyping," patient surveys and machine learning to identify differences in people with and without long Covid following infection during the pandemic's first wave in 2020. Fatigue, "brain fog," and problems with the autonomic nervous systems were the most common ailments debilitating sufferers more than a year later.

Data from the group points to remnants of the virus persisting in the body, reactivation of latent herpesviruses and chronic inflammation as potential causes, Iwasaki, a professor of immunobiology and molecular, cellular, and developmental biology at Yale, said in a series of Twitter posts. "Long Covid group reported significant increases in the intensity of symptoms and dramatically worsened quality of life.

Survey outcomes put together into a single classification metric "Long COVID Propensity Score or LCPS" demonstrated significant diagnostic potential," the author tweeted. Low cortisol, coupled with increased levels of two proteins -- IL-8 and galectin-1 -- could potentially be used in a set of biomarkers to objectively identify those with long Covid, the authors said.

The study involved 215 people, including 99 with long Covid. Forty were part of a healthy, uninfected control group, while the remainder had been infected but fully recovered. Although the study was small and exploratory in nature, it will help inform the development of strategies to diagnose and treat long Covid, she said. "We hope that our study will be informative to others working in the field. We need validation across cohorts.

We also hope that these data will help those who are still sceptical understand that long COVID is real, and it has a biological basis," the author said.

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