Severe Covid-19: antibodies that are both protective and concomitant

Thought to be protective, the antibodies our bodies produce after being infected with Covid-19 could very well be double-edged swords, researchers from Boston Children’s Hospital (USA) conclude. Their work published in the journal Natureshow that these antibodies are likely responsible for the immune escape causing the deadly “cytokine storm” in critically ill patients.

Monocytes, those immune cells that we thought weren’t affected by Covid-19.

Like cavalry carrying chained enemies on their horses, the antibodies produced by our immune systems carry viruses with them by attaching themselves to them. They then deliver them to the large immune cells responsible for consuming and destroying everything. These cells are, in particular, monocytes and their tissue form, macrophages. These cells, respectively, do not carry ACE2 molecules on their surface or carry them in small quantities, these receptors serve as an entry point for the Covid-19 virus to infect. For this reason, their infection with the famous coronavirus still goes unnoticed. However, it looks like SARS-CoV-2, the Covid-19 virus, has found a way to get in through the window.

By studying fresh blood from 22 patients hospitalized with severe Covid-19 compared with fresh blood from 19 healthy donors, US researchers made a surprising observation. “About 6% of blood monocytes from patients hospitalized with Covid-19 are infected with SARS-CoV-2.they say in their article.This is an important number in the context of the study, as dying cells are rapidly eliminated from the body.“explains Judy Lieberman, first author, in a press release. In the lungs it is “about 10% of monocytes and 8% of lung macrophages of patients (which) were infected“.

Suicide of infected monocytes involved in fatal immune escape

According to scientists, the window through which the virus entered will be called CD16. It is a receptor located on the surface of about 10% of monocytes and is present in all infected people. It is to this CD16 that virus-loaded antibodies can cling. Once the antibodies are fixed, the monocytes do their job: they engulf the antibody-virus complex to destroy it. “Cells with the CD16 receptor then engulf the virus.“concludes Judy Lieberman. Except that these cells are trained soldiers: when they feel infected, they commit suicide. To do this, they activate proteins contained in them called “inflammasomes”. Similar to the cyanide pill in a movie spy’s molar, activated the inflammasome causes cell death through a process called “pyroptosis”.

Antibodies, facilitators of immune escape

It’s a double edged sword“, the researchers note. Because if, on the one hand, this effective suicide prevents the virus from multiplying in infected cells and therefore from spreading, it also triggers “powerful immune signaling‘, they point out. This alarm is the cytokines released after the activation of the inflammasome, which allow the mobilization and activation of immune cells in the direction of the foci of infection. “Inflammatory mediators released by pyroptotic monocytes and macrophages can cause a cytokine storm.“, scientists warn. Cytokines are molecules that serve as an alarm signal for immune cells, which, after being activated by cytokines, produce other cytokines. It is this excitement, although effective in most cases, that is the reason when it gets out of hand over deaths due to Covid-19.

Thus, antibody production may be indirectly involved in this fatal cytokine storm, causing infection and therefore suicide of certain monocytes. “It is perhaps no coincidence that the clinical deterioration of patients coincides in time with the detection of antibodies.against Covid-19, American researchers note. “In fact, some recent studies show that higher antibody levels are correlated with disease severity.“.

Vaccine antibodies do not affect

But what about a vaccine whose mode of action is precisely to produce antibodies to mimic infection? The antibodies produced by the vaccinated do not seem to have the ability to infect monocytes, although their levels were twice as high as those of the patients, the study clarifies. “Overwhelming evidence shows that the neutralizing antibodies produced by the vaccine prevent infection and improve the clinical outcome of infections that do occur, suggesting that (his) antibodies (…) are very helpful.“. Thus, it is possible that antibodies generated by vaccines have other properties that have yet to be elucidated.

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