Distinct immune, hormone responses shed light on mysteries of long COVID: search of treatments for a lingering sickness that is both debilitating and puzzling

People who have experienced brain fog, confusion, pain, and extreme fatigue for months or longer after being infected with the COVID-19 virus exhibit different immune and hormonal responses to the virus than those not diagnosed with long COVID, according to a new study by researchers at Yale School of Medicine and Icahn School of Medicine at Mount Sinai.

An estimated 7.5% of people infected with the SARS-CoV-2 virus in the U.S. later suffer from long COVID.

“If you are a doctor doing routine lab work on these patients, you are not going to find these signals,” said Akiko Iwasaki, co-senior author of the paper.

For the study, researchers analyzed blood samples from 268 people who had either experienced long COVID symptoms for an average of one year; had been infected with COVID-19 but had fully recovered; or had no known prior infections.

The researchers observed significant differences between the circulating antibodies and other immune system cells among those with long COVID and the other groups of patients.

Among those who had exhibited long COVID researchers also found increased circulation of antibodies that help the body fight non-COVID-19 viruses, particularly those known to defend against Epstein-Barr virus, a human herpesvirus that has been linked with many cancers. In addition, these patients had markedly lower levels of cortisol, a steroid hormone released by the adrenal glands in times of stress.

While these findings reveal key biological processes associated with long COVID, the complexity of individual responses means developing therapies to treat the ailment will be difficult, the authors say.

“There is no ‘silver bullet’ for treating long COVID, because it is an illness that infiltrates complex systems such as the immune and hormonal regulation,” said co-senior author David Putrino.

The new insights, however, provide important clues that may help in developing new diagnostics and therapies, Iwasaki said.

“Once we have more information on these signals, we can start to think about designing the right trials to treat this condition,” she said.

Though Covid-19 itself is no longer deemed a global emergency by the World Health Organization, many infections have been followed by a malady called “long Covid”. This disorder is taking a particularly hard toll on otherwise healthy women.

‘There is no proven treatment for long Covid,’ said Tacconelli, a professor of infectious diseases at the University of Verona in Italy.

Long Covid has a lengthy list of symptoms and scientists struggle to understand why some people suffer ill health well after they’ve overcome the coronavirus. Nonetheless, various elements are becoming clearer as doctors look at large groups of patients.

‘There is no one long Covid,’ said Tacconelli. ‘It includes several diseases.’