What are “rogue” antibodies and what do they have to do with severe COVID-19?

Since the COVID-19 pandemic began, scientists have been trying to understand what makes each other react so differently to the disease.

Why do some people get so much sicker than others? And why does it affect different organs of the body, potentially for prolonged periods, when it is prolonged COVID-19?

There is now growing evidence that some of these processes could be related to the production of “rogue” antibodies known as autoantibodies.

Antibodies normally fight infection, but autoantibodies mistakenly target the body’s own cells, tissues, or organs.

But what is their role in covid and how could they drive the severity of the disease?

When the body attacks itself

Even healthy people produce autoantibodies, but usually not in large enough amounts to cause significant damage to the immune system.

However, in patients with covid-19 it has been found that not only damage the immune system, but also healthy brain tissue, blood vessels, platelets, liver and gastrointestinal tract, according to researchers at Yale University in Connecticut (United States).

In covid-19 infections, autoantibodies can target “Dozens of immune pathways”Aaron Ring, associate professor of immunobiology at Yale School of Medicine, told the BBC.

In a recent study published in the journal Nature, his team examined the blood of 194 patients who contracted the virus to varying degrees of severity, and found “marked increases” in autoantibody activity, compared to uninfected individuals.

The more autoantibodies that are detected, the more severe the disease will be experienced by patients.

“It is a double-edged sword. Antibodies are crucial to defend ourselves against infections, but some COVID-19 patients also develop antibodies that damage their own cells and tissues, “said the scientist.

Blocking the immune response to COVID-19

Dr. Ring’s study was based on earlier work led by Dr. Jean-Laurent Casanova at the Rockefeller University in New York, United States.

Casanova’s laboratory has been studying genetic variations that affect a person’s ability to fight infection.

His research highlights the role of autoantibodies that attack some of the proteins responsible for fighting viral infections and blocking virus replication (so-called type 1 interferons).

In October 2020, Dr. Casanova’s team reported in the magazine Science that he had found those autoantibodies in approximately 10% of nearly 1,000 severe COVID-19 patients.

A crucial detail: about 95% of them were mens, which could explain why they are the ones who mostly develop severe COVID-19.

Last month they reported in the magazine Science Immunology the findings of a larger study, with analyzes of 3,600 patients admitted to hospital with severe COVID-19.

They found autoantibodies against type 1 interferons in the blood of the 18% of people who had died from the disease.

More than 20% of patients older than 80 years with severe covid had these autoantibodies, compared with 9.6% among those under 40 years of age.

Dr Casanova said the findings provided “compelling evidence” that the “disruption” caused by rogue antibodies “is often the cause of the life-threatening covid-19.”

Autoantibodies, autoimmune disease and prolonged covid

Other studies are finding links between autoantibodies and COVID-19-related medical conditions that continue even after the virus has been cleared from the body.

In a study published this month in Nature Communications, researchers from Stanford University, in California (United States), found that at least one in five people admitted to hospital with COVID-19 developed autoantibodies in the first week of admission.

For about 50 patients, they had blood samples drawn on different days, including the day they were first admitted.

“Within a week after checking into the hospital, about 20% of these patients had developed new antibodies against their own tissues that were not there on the day they were admitted,” said lead researcher PJ Utz, professor of immunology and rheumatology. at Stanford University School of Medicine.

Professor Utz said this could also explain why some symptoms persist for months even after the disease has cleared up, in the condition known as long-lasting covid.

“If you get sick enough from COVID-19 to end up in the hospital, you may not be out of danger even after you recover.”

In the UK, researchers from Imperial College London found autoantibodies in long-term COVID-19 patients, which were absent in people who recovered quickly from the virus or did not test positive.

Professor Danny Altmann, who heads the research group, told the BBC that the team is working to find out if it can be diagnose long-term covid by identifying newly created autoantibodies.

The research is still in an early stage, but could result in a test simple enough to be used in the doctor’s office.

“We hope not only to advance towards a diagnosis, but also in therapeutic insights: that this illuminates specific mechanisms and treatments,” said Altmann.

For experts, these findings also justify vaccination.

In a poorly controlled viral infection, the virus remains for a long time, while an intensifying immune response continues to break the viral particles into pieces, confusing the immune system, said Professor Utz.

However, vaccines contain only a spike protein or genetic instructions to make it, so the immune system not exposed to the same frenzied activity which could lead to the production of autoantibodies.

Thats not all

But while the advances in this field are exciting, scientists caution that the immune response to covid is complex and autoantibodies are not everything.

Another mechanism that is being investigated is overactive immune response that happens in some cases.

The production of proteins called cytokines (also called cytokines) can reach dangerous levels and cause damage to the body’s own cells, called cytokine storms.

We still don’t understand exactly what happens in our cells when the virus enters our bodies; it is the outcome of that battle that determines the severity and, ultimately, mortality of the disease.

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