The clues were there early on in the pandemic: seemingly moderate COVID-19 cases abruptly going critical. By spring, it was becoming apparent that the SARS-CoV-2 virus was in some cases triggering an immune response, a "Cytokine storm," so severe it caused more damage than the infection itself.
And then, there were the after-effects that lingered in many otherwise recovered patients, including such symptoms as fatigue, muscle ache, "brain fog"--a catalogue familiar to many who suffer from lupus and other auto-immune diseases.
To students of medical history, including Stanford University Immunologist and Prof. PJ Utz, MD, the long hauler phenomenon brings to mind the century-old Spanish Flu epidemic, and it's mysterious after effects.
"Some of which sound as if they are auto-immune in nature. And COVID just happens to be a very bad virus that activates the immune system in ways we don't fully understand, and seems to be contributing to some of these long-lasting effects," said Dr. Utz.
It became the focus of research by Dr. Utz, colleagues, and other teams around the world, probing records and lab work detailing the course of COVID in 147 hospitalized patients. Among the components of the immune system, the investigators looked at levels of a class of antibodies known as autoantibodies, which interact with the body's own proteins, as if unable to distinguish friend from foe.
"I think about antibodies as this universe of proteins that are there to protect us," explained Dr. Utz. "But sometimes, if they're autoantibodies, instead of attacking something outside us, it attacks ourselves… and they can be deadly. There are lots of examples of autoantibodies that directly cause disease."
The study, now in preprint awaiting peer review and brought to general public attention by a Medscape article, found certain autoantibodies in about half of the patients, compared to under 15% in healthy controls. Further, it was found that levels grew rapidly in one subset of patients, who had minimal autoantibodies when first hospitalized with COVID-19.
"That suggests that this virus has the capacity to cause new autoantibodies to form"--PJ Utz, MD
"If you look at them a week later or two weeks later, all of a sudden now they have autoantibodies that weren't there 7 to 14 days earlier," said Dr. Utz. "That suggests that this virus has the capacity to cause new autoantibodies to form."
Among the questions this raises, the most relevant to surviving patients in this group is whether they will come down with an autoimmune disease. Is this a cause of the COVID long hauler syndrome?
These are questions Dr. Utz is not prepared to answer without additional research and follow-up.
But he notes that other researchers have found pathways by which elements of the immune system can sabotage the body's response to COVID. He cited a study of nearly a thousand severe COVID cases by Paul Bastard, PhD and Jean Laurent Casanova, MD, focusing on interferon, an immune system hormone that plays a key role in ridding the body of viruses. They identified a blocking antibody that hampers interferons, and thereby leaves the body more vulnerable to the disease worsening. Not everyone has this blocking antibody. Bastard and Casanova concluded that of the more severe cases, its presence was the cause for 2-3% of those cases in women, and some 12% of those in men.
Which brings us back to the findings of Dr. Utz and his collaborators that some patients with initially undetectable autoantibodies can have significant levels within a week. Why does the body produce enemies against itself?
"It may be that people have very low levels, or they can induce them by the virus. Which came first, the chicken or the egg?"