COVID-19 Triggers Auto-Immune Illnesses Related Antibodies

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According to a study in the journal npj Aging, the production of auto-antibodies naturally rises with age and SARS-CoV-2 infection can aggravate the development of auto-antibodies related to auto-immune illnesses, which may assist to explain why aging raises the risk of developing severe COVID-19. The study also uncovered some of the elements that link blood clotting issues like thrombosis with the severe form of the disease.

“These findings open the door to a better understanding of many pathological events associated with COVID-19, ranging from memory loss to sudden death from acute thrombosis. The hyperinflammation typical of severe COVID-19 and the increase in auto-antibodies produce blood clotting, resulting in the need to reconstruct tissue and recruit a coagulation cascade. Thrombosis and inflammation are closely correlated. Our study is one more confirmation of this important link,” Otávio Cabral-Marques, a professor at the University of São Paulo’s Medical School (FM-USP) in Brazil and last author of the article, told Agência FAPESP.

On the study, researchers from Germany and the United States worked together.

According to Cabral-Marques, another intriguing finding of the study is that the rise in auto-antibody levels, which are immune proteins that may adversely react with a person’s own tissues or organs, in severe COVID-19 instances may also apply to other illnesses.

“It’s not exclusive to SARS-CoV-2. Other pathogens also raise levels of auto-antibodies, so that they can serve as markers or therapeutic targets to save the lives of patients with almost terminal sepsis, for example,” Cabral-Marques said.

The study includes the analysis of auto-antibody data for 159 COVID-19 patients (71 mild, 61 moderate, and 27 severe), as well as 72 healthy people who served as the control group. “When we cross-referenced the data using artificial intelligence techniques, we discovered two main auto-antibodies that were exacerbated in patients with severe symptoms. They were precisely the auto-antibodies associated with blood clotting and thrombocytopenia [low blood platelet count, heightening the risk of hemorrhage],” said Dennyson Leandro M. Fonseca, first author of the article.

The production of blood clots and netosis, an immune system mechanism involving controlled cell death via the formation of neutrophil extracellular traps (NETs), which are networks of DNA that attach to dangerous bacteria, are two effects of high levels of these auto-antibodies, according to him. NETs may occasionally act as indicators of alveolar inflammation and cause tissue damage.

“When we divided the data into younger and older patients, we found that although this mechanism may occur in under-50s, it makes the elderly more susceptible to severe COVID-19. This explains why old age is one of the main risk factors for COVID-19,” he said.

As previously mentioned, a slight rise in the formation of auto-antibodies is a normal aspect of aging, but the researchers found that SARS-CoV-2 infection worsens levels of auto-antibodies in severe cases.

According to earlier research, interferon-targeting autoantibodies are present in the general population and significantly rise in COVID-19 patients beyond the age of 50. The research published in npj Aging expands the categories of aging-related auto-antibodies and reveals that their effects vary with age and COVID-19 severity.

A significant age-related increase in auto-antibodies against 16 targets, including the amyloid peptide, catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor A, and platelet glycoprotein, was found in severe COVID-19 patients, according to the study’s findings.

This discovery provides new avenues for validation of the action mechanism of auto-antibodies and broadens the pool of targets, providing a more comprehensive picture of the underlying pathophysiology of COVID-19 disease progression with the advance of aging and permitting more suitable interventions,” Cabral-Marques said.

Systemic issue

Due to a confluence of auto-inflammatory and auto-immune reactions, severe COVID-19 is known to cause significant organ damage. In addition to other harm to the lungs, kidneys, and nervous system, this process can cause myopathy (muscle diseases), vasculitis (blood vessel inflammation), arthritis (joint inflammation), anti-phospholipid syndrome (APS) linked to deep vein thrombosis, pulmonary embolism, and stroke, as well as other blood vessel and joint inflammation.

In post-COVID syndrome, immunological dysregulation is also common and results in a variety of symptoms, including exhaustion, vascular dysfunction, pain, neurological manifestations, and neuropsychiatric issues.

The “cytokine storm,” the most well-known inflammatory reaction linked to COVID-19, is essentially a heightened release of cytokines, which alert the immune system to the need to send more defense cells to the infection site. This causes inflammation to worsen and other signaling systems to become dysregulated. Another is the overactivity of macrophages, immune system cells that encourage the formation of autoantibodies.

What happens first?

The severity of COVID-19 or the increase in auto-antibody levels is not yet clear to the article’s writers.

“We analyzed these two directions statistically and believe they’re both mutual and bidirectional,” Fonseca said. “Auto-antibodies may interact, in conjunction with other immune system molecules, in a highly complex network that underlies immunopathological processes in severe COVID-19, or they may be boosted by health problems associated with aging and make the disease progress to a severe condition.”

According to him, severe COVID-19 produces a milieu in the body that includes tissue injury (acute respiratory distress syndrome), a cytokine storm, and hyperactivated macrophages, all of which encourage the creation of auto-antibodies. With various metabolites, cytokines, and chemokines that are naturally dysregulated in aged people as part of immunosenescence, this environment could then enable auto-antibodies to act synergistically, increasing susceptibility to infections and auto-immune illnesses.

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