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.

Rheumatoid Arthritis Drug Linked to Overdoses

Pat Anson, Editor

A drug that’s long been used to treat rheumatoid arthritis and other autoimmune diseases has been linked to dozens of deaths in the U.S. and Australia, mainly because patients have taken it daily rather than the recommended weekly dose, according to a new study published in the Medical Journal of Australia.

Methotrexate was originally developed and is still used for chemotherapy because of its ability to stop the growth and spread of tumors. Because it is also effective as an immune system inhibitor, low doses of methotrexate became a front line therapy for rheumatoid arthritis in the 1950’s. It is also used to treat psoriasis, lupus, sarcoidosis, and inflammatory bowel diseases such as Crohn’s.

Researchers say methotrexate is safe when taken once or twice a week, but the drug is so potent that accidental daily dosing can be lethal.

“The unusual dosing schedule of low dose methotrexate is associated with a risk that it will be prescribed, dispensed or administered daily instead of weekly,” said lead author Rose Cairns, PhD, of the NSW Poisons Information Centre in Australia.

“Used appropriately, methotrexate is considered safe and efficacious; accidental daily dosing, however, can potentially be lethal. Higher or more frequent doses can result in gastro-intestinal mucosal ulceration, hepatotoxicity, myelosuppression, sepsis and death.”

In a review of medication errors in Australia from 2004 to 2014, researchers linked methotrexate to 22 deaths, including seven cases in which erroneous daily dosing was documented. One patient took methotrexate for 10 consecutive days. Reasons for the errors included patient misunderstanding and incorrect packaging of the drug by pharmacists.

A similar study of medication errors in the U.S. over a 4 year period identified over 100 methotrexate dosing errors that resulted in 25 deaths. Over a third (37%) of the errors were attributed to the prescriber, 20% to the patient, 19% to pharmacists, and 18% to administration by a health care professional.

The researchers also found a “worrying increase” in the number of medication errors just in the past year.

“It is difficult to explain this increase, but the risk of methotrexate medication error may be increasing as the population ages. Older people may be at increased risk because of a range of problems that includes confusion, memory difficulties, and age-related decline in visual acuity,” said Cairns.

Cairns and her colleagues say more needs to be done by drug makers and health professionals to reduce the risk of methotrexate overdosing, such as clearer labeling, smaller sized packages, and distinctly colored tablets.

"Methotrexate use is likely to continue increasing as Australia's population ages, so that additional measures are needed to prevent these errors," the authors concluded.

Miss Understood: Judged and Defeated

By Arlene Grau, Columnist

I like to think of myself as the type of person who always gets back up no matter how hard I get knocked down. It may not always be as quick as I'd like, but I find my courage and strength through every circumstance. Recently, I got hit with a big blow and I haven't figured out how to get back on my feet and keep fighting.

I had my disability case heard by a judge in May. I knew it could go either way, but I  felt like my lawyer had prepared a really good case and I had a chance.

My lawyer started to present my case to the judge, but as soon as he stated my disabilities the judge took one look at me and asked me how I knew I had Lupus and rheumatoid arthritis. I told him I had countless lab tests done, physical exams, two skin biopsies (I showed him the scars), x-rays, MRI's, and CAT scans.

The judge then asked my lawyer for “proof” showing that I do in fact have these diseases, because letters from my doctors won't do. People have been known to pay doctors to write them, he said.

I was amazed at what was happening. I understand why the judge was saying that, because there is so much fraud going on in disability cases. But I think it would be very hard to fake everything I have. I even showed him the scar I have on my wrist from surgery needed to repair the damage caused by arthritis. My lawyer showed him the file backing up my story, but he still looked like he didn't believe a word I said.

My lawyer was able to provide lab results showing that I am in fact positively diagnosed with rheumatoid arthritis and Lupus. But when he tried to explain them, the judge’s response was, "I'm not a doctor, I can't read these and confirm that."

In the end, the ruling was that my case would continue on another day --- when a rheumatologist provided by the state can either come in or phone in to confirm or deny that I am diagnosed with what I have.

It only took the judge about 10 minutes to decide he didn't want to hear my case. He didn't believe that I was sick, even with the proof documented right in front of him.  One was a lab summary with a footnote from one of the doctors where I was hospitalized, explaining that I was there because I was having an arthritis and Lupus flare.

All he had to do was read it, but he refused.

To date, I've been without disability benefits for 26 months and it has been the most stressful two years of my life. Even with the insurance that I'm paying for, I'm responsible for 10% of the cost of my health care.  My medical expenses are ridiculously high because I need infusions, biweekly blood work, MRI's, etc. -- along with weekly visits to my rheumatologist and monthly visits to see my pain specialist.

Right now I feel so defeated. No matter what I wanted to do or say, I had to sit there quietly and let that man judge me and rule over me with all his ignorant power.

I've come so far when it comes to dealing with people who refuse to understand my diseases or learn about them. But then my trial brought me back to a place where I don't want to be. Being judged by others is never fun. When you're being accused of such a big lie and your character is poked at, you can't help but get hurt and take it personal.

Someone once told me that they might deny me because I can't be 29 and disabled. My response to them was does a five year old child ask to be given leukemia? Does a 23 year old ask to be given breast cancer? Of course not. But sometimes those are the cards we're dealt.

I was two weeks shy of my 23rd birthday when I was diagnosed with RA and fibromyalgia. I was still able to work hard for another 5 years, until they started to take a toll on my body.

Just because the name isn't cancer doesn't mean it isn't a serious disease.

I wish this judge would hear the story of my journey with RA, Lupus and fibromyalgia so he could get a better understanding of just how advanced they're getting. But instead all he sees is the person delivering the information: A young, seemingly healthy, able body.

Frauds have ruined the system for those of us who truly need and deserve it.

Arlene Grau lives in southern California. She suffers from rheumatoid arthritis, fibromyalgia, lupus, migraine, vasculitis, and Sjogren’s disease.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.