Dangerous antibody found in patients with severe Covid-19

Scientists warn that plasma transfusion of patients with severe Covid-19 forms can harm other patients, so some elements should be removed from their blood serum.

A team from the Netherlands reported that antibodies found in the blood serum of critically ill patients with Covid-19 and able to bind to the coronavirus S-protein induce a hyper-inflammatory response. Subsequently, this violates the integrity of the pulmonary endothelial barrier (a single layer of flat cells of mesenchymal origin) and causes microvascular thrombosis. The findings of the scientists are presented in an article on bioRxiv.org preprints site (the publication has not yet been reviewed).

“The excessive inflammatory ability of IgG antibodies that bind to the spike protein SARS-CoV-2 is associated with changes in the glycosylation (enzymatic process) of the IgG Fc fragment. <...> This explains why, at the moment when adaptive immunity is turned on, the health status of many patients deteriorates sharply. <...> However, the hyperinflammatory response induced by such an IgG antibody can be specifically neutralized in vitro with the active component of fostamatinib, an approved therapeutic low molecular weight spleen tyrosine kinase inhibitor, ”the researchers write.

The fact that coronavirus disease causes large-scale lesions of the endothelium and leads to blood clots, scientists reported earlier. However, they continue to find out the reasons for this.

The subject of study in a new work was IgG antibodies found in blood samples of critically ill Covid-19. To begin with, the authors examined the plasma of 33 patients who were in intensive care units, but either did not suffer from a coronavirus infection, or were ill, but still did not develop IgG antibodies, or were ill and already had IgG. Then these globular proteins were added in vitro to the medium with immune cells from the lungs and other organs.

“In Covid-19 patients, high IgG titers are associated with the severity of the disease. To determine whether the titers of these antibodies correlate with a stronger cytokine response by macrophages (cells in the body that are capable of actively capturing and digesting bacteria, debris of dead cells and other particles that are foreign or toxic to the body. – Ed.), We analyzed the data for the production of cytokines for all samples that, after application with IgG titers, did indicate that the macrophage hyperinflammatory response was associated with these antibodies. Subsequently, this was confirmed after analysis of four serum samples with different titers by successive dilutions that showed a dose-dependent induction of pro-inflammatory cytokines, ”the authors said.

Thus, scientists ascertain, their data demonstrated that IgG antibodies from the blood plasma of seriously ill patients with coronavirus, capable of binding to the S-protein (it forms the “corona”) of SARS-CoV-2, cause a strong pro-inflammatory response (otherwise immunosuppressive) human macrophages M2. This negative process is characterized by the active production of classical mediators of the cytokine storm, such as IL-1β, IL-6, IL-8, and TNF, that is, uncontrolled inflammation, which leads to damage to one’s own tissues, and “suicide” of the body.

In turn, disruptions in the work of macrophages – and they are present in almost every organ and tissue and play the role of the first line of immune defense against pathogens – further contribute to the formation of blood clots and interfere with the functioning of blood vessels. As for the component of fostamatinib (R406), an oral drug for the treatment of immune thrombocytopenia, a selective low molecular weight Syk kinase inhibitor, it was possible to block the production of immune cell enzymes responsible for the production of pro-inflammatory signaling molecules in macrophages.

According to the author of the article, doctors should take into account not only the use of components of drugs such as fostamatinib but also take into account that transfusion of blood plasma after coronavirus disease (especially severe forms) can harm recipients. Probably, IgG antibodies binding to the spike SARS-CoV-2 protein should be removed from the serum of such donors.