Immune and hormonal characteristics of COVID-19

Some people may experience chronic symptoms for months or years after an acute viral infection. Long COVID, a syndrome that develops in some people after acute SARS-CoV-2 infection, is a prominent recent example. More than 200 COVID-19 symptoms have been recorded. Typical symptoms include extreme fatigue, cognitive impairment, post-exertion malaise and respiratory problems. Studies show that approximately one in eight survivors of acute SARS-CoV-2 infection go on to experience persistent symptoms. The process that causes COVID-19 remains unclear.

To elucidate the biology behind COVID-19, an NIH-funded research team (in part through the RECOVER Initiative) conducted a study of more than 250 people. Participants included people infected with SARS-CoV-2 and those without infection. Among those infected, some have COVID-19 and some do not. The researchers measured the levels of various immune cells and markers in the participants’ blood. They also measured antibody responses against SARS-CoV-2 and a range of other viruses.The result appears in nature

The team found significant differences in the immune cells of participants with and without COVID-19. People with COVID-19 have higher levels of cells called nontraditional monocytes and activated B lymphocytes. They had lower levels of type 1 conventional dendritic cells and central memory T cells. These differences did not depend on age, sex, or body mass index. Participants with long COVID-19 also had varying levels of immune signaling molecules.

Participants with COVID-19 had a much stronger antibody response to the SARS-CoV-2 spike protein than those without COVID-19. They also had a stronger response to an unrelated virus, Epstein-Barr virus (EBV). EBV is a common herpes virus that causes mononucleosis. After infection, it remains latent in the body and can sometimes reactivate. Higher levels of EBV antibodies indicate recent reactivation of the virus.

When researchers used machine learning to determine which characteristics best predicted long-term COVID-19 status, they found that the strongest predictor was the stress hormone cortisol. People with long COVID had much lower cortisol levels than those without the infection. Other strong predictors of developing COVID-19 include elevated levels of a protein called galectin-1, elevated antibodies against EBV, and reduced levels of certain immune cells.

These findings identify potential biomarkers that could help diagnose COVID-19. They also suggest possible mechanisms leading to long-lasting COVID-19. These include persistence of SARS-CoV-2 components in the body, reactivation of latent EBV, and chronic inflammation.

“These findings are important,” said co-senior author Dr. David Putrino of the Icahn School of Medicine at Mount Sinai. “They could provide more sensitive testing for patients with COVID-19 and inform personalized treatments for COVID-19, for which to date there is no proven scientific rationale. A decisive step for reliable blood testing solutions. “

Another senior author, Dr. Akiko Iwasaki of Yale School of Medicine, said: “These findings tell us something about the underlying disease pathogenesis of COVID-19 and suggest potential avenues for treatment.”

—Dr. Brian Doctorow