What are the “treacherous” antibodies linked to the death of COVID-19

The pathology of the novel coronavirus has been largely attributed to a hyperinflammatory response with no clear indication of the underlying mechanism. Autoimmunity has been shown to play an important role in the pathogenesis of several conditions associated with COVID-19, such as Guillain-Barré syndrome, autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune encephalitis and Kawasaki disease. In addition, recent studies of hospitalized patients with COVID-19 showed the majority to have symptoms positive to some of the most commonly tested antibodies. Some patients with COVID-19 have also reported persistent symptoms, many of which could be characterized as rheumatologic in origin.

It is not known how some patients who contract the SARS-CoV-2 virus may be asymptomatic while others die from severe respiratory failure.

Reports of deaths from COVID-19 show significant lung damage. In addition, systemic thrombosis in the arterial, venous and small vessel circulation contributes to mortality in patients with COVID-19. It is believed that this is due to inflammatory factors. However, Given the high levels of antibodies in COVID-19 patients, this thrombosis could also be favored by auto-immunity. In other diseases, we know that they can appear post-infectious autoantibodies, even transient, and cause a substantial increase in the severity of the disease, including post-viral thrombosis.

Normally, antibodies attack pathogens to defend the body against attack, but sometimes stubborn antibodies block body components such as immune cells. Now, a new study posted on medrRxic, adds research linking these “autoantibodies” to a worse prognosis in people with COVID-19.

The team, led by Ana Rodriguez and David Lee of the Grossman School of Medicine at New York University, studied levels of autoantibodies in the blood serum of people who have had to be hospitalized for coronavirus.

The researchers were particularly interested in autoantibodies against annexin A2 protein, which helps stabilize the structure of the cell membrane. It also plays a role in ensuring the integrity of the tiny blood vessels in the lungs. Blockage of annexin A2 leads to lung damage, a hallmark of COVID-19.

“Our study – explains Rodríguez – finds Evidence of higher levels of IgG antibodies to annexin A2 among patients who die from COVID-19. Although comparisons of antibody levels stratified by disease severity are not significantly different in magnitude, the differences between fatal cases and non-critical or critically ill cases were statistically significant ”.

More importantly, the researchers cite in their study, Anti-annexin A2 antibody levels strongly predicted mortality after controlling for patient risk factors and spikes in key laboratory markers associated with severe COVID-19.

Previously, severe COVID-19 had been largely attributed to a cytokine storm, but this assumption has been questioned given that the levels of cytokines in COVID-19 are not as high as one might expect. wait in case of serious lung injury. “Therefore -suggests Rodríguez-, the underlying cause of severe COVID-19 remains to be explained. Several recently published studies have shown that autoimmunity may play a key role in the pathophysiology of COVID-19, including the presence of autoantibodies against type I interferons in a subset of critically ill patients. “

By analyzing the response of the adaptive immune system, a study Fundamental demonstrated elevated levels of extrafollicular B cell activation in patients with severe COVID-19. Although these patients developed high peak anti-SARS-CoV-2 antibodies, they performed poorly. Other studies have also shown higher levels of anti-pico antibodies in severe COVID-19 patients compared to those who have recovered, but these results have been largely attributed to a response to higher viral loads in critically ill patients.

“Although this explanation is plausible – according to Rodroguez-, Some studies have suggested that the viral load may in fact be similar when asymptomatic and symptomatic COVID-19 cases are compared. In addition, there appears to be a lag between when the SARS-CoV-2 virus can be grown in the respiratory tract (during the first week of illness) and the onset of severe respiratory distress (during of the second week) “- The timing of these clinical manifestations can be of critical importance in defining the pathophysiology of severe COVID-19.

“In our analyzes – the research cites – we found that anti-annexin A2 antibody levels were strongly associated with mortality after controlling for patient factors. Even when we included the maximum laboratory abnormalities during hospitalization for these COVID-19 patients, we found that anti-annexin A2 antibody levels were an independent predictor of death. “

Like many other coronaviruses, SARS-CoV-2 can induce mild to moderate viral syndrome or not cause any symptoms. However, others patients die from COVID-19 even without a medical history or other risk factors.

The clinical course of severe COVID-19 has been characterized by a second phase of the disease that occurs approximately 7 to 10 days after the onset of symptoms. The timing of this respiratory distress appears to coincide with the development of the adaptive immune response. Additionally, an initial autoimmune injury can cause cellular damage. “If any of these autoimmune phenomena becomes more chronic, it may explain the long-term symptoms that some patients have experienced. “says Rodríguez.

The study thus confirmed that the level of anti-annexin A2 antibodies is, on average, higher in people who died of COVID-19 than in those who survived, a statistically significant difference.

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