Long COVID Associated With Hormonal, Immune Differences


A new study from Yale School of Medicine and Icahn School of Medicine at Mount Sinai found that patients with long COVID had increased antibodies that help fight different viruses and lower levels of cortisol.

Nearly 1 in 5 people who had an infection with COVID-19 suffer from long COVID, according to data from the CDC.1 Symptoms of long COVID include brain fog, confusion, pain, and extreme fatigue, but the biological processes associated with the development of the condition have not been understood.

However, new research published in the journal Nature has found that patients with long COVID have clear differences in immune and hormone function compared to those who don’t have the condition.2

“These findings are important—they can inform more sensitive testing for long COVID patients and personalized treatments for long COVID that have, until now, not had a proven scientific rationale,” David Putrino, PhD, an author on the study, said in a release.3

A team of researchers from Yale School of Medicine and Icahn School of Medicine at Mount Sinai conducted a cross-sectional study to identify biological features associated with long COVID. Data was gathered from Mount Sinai Hospital, Mount Sinai Union Square, and Yale School of Medicine between January 2021 and June 2022.

Investigators analyzed blood samples using machine learning from 273 patients who were divided into 3 groups: those who had long COVID symptoms for an average of 1 year, those who had COVID-19 but made a full recovery, and those who had not been infected with COVID-19. Participants also completed a questionnaire about symptoms, medical history, and health-related quality of life.

The machine learning algorithm was able to identify patients with and without long COVID with 96% accuracy based on differences between circulating immune cells and hormonal dysfunction in the blood samples.

Investigators found that patients with long COVID had abnormal T cell activity and increased antibodies that help fight different viruses, particularly the Epstein-Barr virus. Patients with long COVID were also seen to have lower levels of cortisol.

“This work is so exciting because it is one of the first to show us clear, measurable differences in blood biomarkers of people with long COVID compared with people who recovered fully from an acute infection and a group of people who have never been infected with SARS-CoV-2,” said Putrino. “This is a decisive step forward in the development of valid and reliable blood testing protocols for long COVID.”

1. Nearly One in Five American Adults Who Have Had COVID-19 Still Have “Long COVID.” News Release. CDC. June 22, 2022. Accessed September 25, 2023. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220622.htm
2. Klein J, Wood J, Jaycox J, et al. Distinguishing features of Long COVID identified through immune profiling. Nature (2023). https://doi.org/10.1038/s41586-023-06651-y
3. People with long COVID have distinct hormonal and immune differences from those without this condition. News Release. Mount Sinai. September 25, 2023. Accessed September 25, 2023. https://www.mountsinai.org/about/newsroom/2023/people-with-long-covid-have-distinct-hormonal-and-immune-differences-from-those-without-this-condition

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