How Long Haul Covid Alters the Immune System

By Liz Szabo, Kaiser Health News

There’s a reason soldiers go through basic training before heading into combat: Without careful instruction, green recruits armed with powerful weapons could be as dangerous to one another as to the enemy.

The immune system works much the same way. Immune cells, which protect the body from infections, need to be “educated” to recognize bad guys — and to hold their fire around civilians.

In some Covid-19 patients, this education may be cut short. Scientists say unprepared immune cells appear to be responding to the coronavirus with a devastating release of chemicals, inflicting damage that may endure long after the threat has been eliminated.

“If you have a brand-new virus and the virus is winning, the immune system may go into an ‘all hands on deck’ response,” said Dr. Nina Luning Prak, co-author of a January study on Covid and the immune system. “Things that are normally kept in close check are relaxed. The body may say, ‘Who cares? Give me all you’ve got.’”

While all viruses find ways to evade the body’s defenses, a growing field of research suggests that the coronavirus unhinges the immune system more profoundly than previously realized.

Some Covid survivors have developed serious autoimmune diseases, which occur when an overactive immune system attacks the patient, rather than the virus. Doctors in Italy first noticed a pattern in March 2020, when several Covid patients developed Guillain-Barré syndrome, in which the immune systems attacks nerves throughout the body, causing muscle weakness or paralysis.

As the pandemic has surged around the world, doctors have diagnosed patients with rare, immune-related bleeding disorders. Other patients have developed the opposite problem, suffering blood clots that can lead to stroke.

All these conditions can be triggered by “autoantibodies” — rogue antibodies that target the patient’s own proteins and cells. In a report published in October, researchers even labeled the coronavirus “the autoimmune virus.”

Although doctors are researching ways to overcome immune disorders in Covid patients, new treatments will take time to develop. Scientists are still trying to understand why some immune cells become hyperactive — and why some refuse to stand down when the battle is over.

Key immune players called “helper T cells” typically help antibodies mature. If the body is invaded by a pathogen, however, these T cells can switch jobs to hunt down viruses, acting more like “killer T cells,” which destroy infected cells. When an infection is over, helper T cells usually go back to their old jobs.

In some people with severe Covid, however, helper T cells don’t stand down when the infection is over, said James Heath, a professor and president of Seattle’s Institute for Systems Biology.

About 10% to 15% of hospitalized Covid patients Heath studied had high levels of these helper T cells, which were still looking for the enemy long after it had been eliminated. He’s now studying whether these overzealous T cells might inflict damage that leads to chronic illness or symptoms of autoimmune disease.

“These T cells are still there months later and they’re aggressive,” Heath said. “They’re on the hunt.”

Friendly Fire

Covid appears to confuse multiple parts of the immune system. In some patients, Covid triggers autoantibodies that target the immune system itself, leaving patients without a key defense against the coronavirus.

In October, a study published in Science led by Rockefeller University’s Jean-Laurent Casanova showed that about 10% of Covid patients become severely ill because they have antibodies against an immune system protein called interferon.

Disabling interferon is like knocking down a castle’s gate. Without these essential proteins, invading viruses can overwhelm the body and multiply wildly.

New research shows that the coronavirus may activate preexisting autoantibodies, as well as prompt the body to make new ones. In the January study, half of the hospitalized Covid patients had autoantibodies, compared with fewer than 15% of healthy people.

Other research has produced similar findings. In a study out in December, researchers found that hospitalized Covid patients harbored a diverse array of autoantibodies.

While some patients studied had antibodies against virus-fighting interferons, others had antibodies that targeted the brain, thyroid, blood vessels, central nervous system, platelets, kidneys, heart and liver, said Dr. Aaron Ring, assistant professor of immunology at Yale School of Medicine.

Similarities With Lupus

Some patients had antibodies associated with lupus, a chronic autoimmune disorder that can cause pain and inflammation in any part of the body. Covid patients rife with autoantibodies tended to have the severest disease, said Ring, who was surprised at the level of autoantibodies in some patients.

“They were comparable or even worse than lupus,” Ring said.

Researchers would like to know if lingering autoantibodies contribute to the symptoms of “long Covid,” which afflicts one-third of covid survivors up to nine months after infection, according to a new study in JAMA Network Open.

“Long haulers” suffer from a wide range of symptoms, including debilitating fatigue, shortness of breath, cough, chest pain and joint pain. Other patients experience depression, muscle pain, headaches, intermittent fevers, heart palpitations and problems with concentration and memory, known as brain fog.

Less commonly, some patients develop an inflammation of the heart muscle, abnormalities in their lung function, kidney issues, rashes, hair loss, smell and taste problems, sleep issues and anxiety.

The National Institutes of Health has announced a four-year initiative to better understand long Covid, using $1.15 billion allocated by Congress.

Ring said he’d like to study patients over time to see if specific symptoms might be explained by lingering autoantibodies.

“We need to look at the same patients a half-year later and see which antibodies they do or don’t have,” he said. If autoantibodies are to blame for long Covid, they could “represent an unfortunate legacy after the virus is gone.”

Kaiser Health News is a nonprofit news service covering health issues. It is not affiliated with Kaiser Permanente.