According to a new study published by Stanford Medicine today in the journal Nature Communications, hospitalized COVID-19 patients are substantially more likely to have autoantibodies — antibodies directed at their own tissues or substances their immune cells secrete into the blood — than people without COVID-19.
“If you get sick enough from COVID-19 to end up in the hospital, you may not be out of the woods even after you recover,” stated PJ Utz, M.D., professor of immunology and rheumatology at Stanford Medicine, in a press release issued on September 14, 2021.
The researchers identified and measured levels of antibodies targeting the SARS-C0V-2 coronavirus, autoantibodies, and antibodies directed against cytokines, proteins that immune cells secrete to communicate with one another and coordinate their overall strategy.
The scientists found that upward of 60% of all hospitalized COVID-19 patients, compared with about 15% of healthy controls, carried anti-cytokine antibodies.
This could be the result of immune-system overdrive triggered by a virulent, lingering infection. In the fog of war, 'the abundance of cytokines may trip off the erroneous production of antibodies targeting them,' said Utz, a member of Stanford Bio-X, the Stanford Institute for Immunity, Transplantation, and Infection, and the Stanford Maternal and Child Health Research Institute.
If any of these antibodies block a cytokine’s ability to bind to its appropriate receptor, the intended recipient immune cell may not get activated. That, in turn, might buy the coronavirus more time to replicate and lead to a much worse outcome.
“Within a week after checking in at the hospital, about 20% of these patients had developed new antibodies to their own issues that weren’t there the day they were admitted,” Utz said. “In many cases, these autoantibody levels were similar to what you’d see in a diagnosed autoimmune disease.”
In some cases, the presence of those newly detected autoantibodies may reflect an increase, driven by the immune response, of antibodies that had been flying under the radar at low levels, Utz said. It could be that inflammatory shock to the systems of patients with severe COVID-19 caused a jump in previously undetectable, and perhaps harmless, levels of autoantibodies these individuals may have been carrying before infection.
In other cases, autoantibody generation could result from exposure to viral materials that resemble our own proteins, Utz said.
“It’s possible that in the course of a poorly controlled SARS-CoV-2 infection — in which the virus hangs around for too long while an intensifying immune response continues to break viral particles into pieces — the immune system sees bits and pieces of the virus that it hadn’t previously seen,” he said.
“If any of these viral pieces too closely resemble one of our own proteins, this could trigger autoantibody production.”
The finding bolsters the argument for vaccination, he added.
Vaccines for COVID-19 contain only a single protein — SARS-CoV-2’s so-called spike protein — or the genetic instructions for producing it. Thus, with vaccination, the immune system is never exposed to — and potentially confused by the numerous other novel viral proteins generated during infection.
In addition, vaccination is less intensely inflammatory than an actual infection, Utz said, so there’s less likelihood that the immune system would be confused into generating antibodies to its own signaling proteins or to the body’s own tissues.
“Patients who, in response to vaccination, quickly mount appropriate antibody responses to the viral spike protein should be less likely to develop autoantibodies,” he said.
Indeed, a recent study in Nature to which Utz contributed showed that, unlike SARS-CoV-2 infection, the Cominraty COVID-19 vaccine produced by Pfizer-BioNTech doesn’t trigger any detectable generation of autoantibodies among recipients.
“If you haven’t been vaccinated and are telling yourself, ‘Most people who get COVID get over it and are OK,’ remember that you can’t know in advance that when you get COVID-19, it will be a mild case,” Utz said.
“If you do get a bad case, you could be setting yourself up for a lifetime of trouble because the virus may trip off autoimmunity."
"We can’t say yet that you’ll definitely get an autoimmune disease — we haven’t studied any patients long enough to know whether these autoantibodies are still there a year or two later, although we hope to study this — but you certainly might. So I wouldn’t want to take that chance.”
Utz intends to study blood samples from SARS-CoV-2-infected people who are asymptomatic or who’ve had mild COVID-19 symptoms. That could help determine whether the massive hyperactivation of the immune system, which doesn’t occur in mildly symptomatic or asymptomatic people, is what causes trouble or whether the mere molecular resemblance of SARS-CoV-2 proteins is enough to trigger autoantibody generation.
Note: Various other Stanford researchers participated in this study. And researchers at the University of Pennsylvania, Philipps Marburg University, the University of Tennessee, Oklahoma Medical Research Foundation, and Kaiser Permanente Northern California contributed to the work.
The study was supported by the National Institutes of Health and numerous other funders. For more news about the school, please visit http://med.stanford.edu/school.html.