An international group of researchers found, in the blood serum of patients infected with SARS-CoV-2, a set of molecules normally present in autoimmune diseases and that can signal the severity of covid-19. The study was published on the medRxiv platform, in an article that has not yet been peer reviewed. In the future, the results may serve as a subsidy to treat severe cases of the disease or even to prevent the evolution of the clinical condition.
“A number of studies have shown that these molecules that promote systemic autoimmune diseases, known as autoantibodies, also appear in covid-19. We found those associated with healthy people and others whose levels increase with the severity of the covid-19 clinical picture. It was possible to detect, for example, autoantibodies against two molecules with increased levels days before the patient needed oxygen. With this, we hope to be able to prevent the worsening of the cases”, explains Otávio Cabral Marques, a researcher at the Institute of Biomedical Sciences at the University of São Paulo (ICB-USP) and the first author of the article.
Marques coordinates a project financed by FAPESP (Research Support Foundation of the State of São Paulo) dedicated to understanding how the immune system responds to covid-19. The work is signed by researchers from Brazil, Germany, the United States and Israel.
The group analyzed the blood serum of 246 volunteers recruited from Jewish communities in six US states who had not received any vaccine. Of these, 169 tested positive for covid-19 on RT-PCR tests, while the other 77 tested negative and had no symptoms. The infected group was subdivided into mild, moderate and severe conditions.
Computational tools have shown an association between antibodies and molecules of the renin-angiotensin system that, among other functions, produce the protein ACE2 (Angiotensin 2 Converting Enzyme, its acronym in English), to which the virus connects to infect the human cell. The researchers also found antibodies that targeted so-called G protein-coupled receptors (known by the acronym GPCR), which have functions related to inflammation and coagulation, among others.
Moderate and severe cases had the highest levels of autoantibodies, while blood serum from healthy people with mild conditions recorded considerably lower levels.
Autoantibodies against 11 molecules were the most significant to define the severity of cases. Two of them, known by the acronyms anti-CXCR3 and anti-AT1R, for example, were detected in patients who a few days after blood collection for the study needed supplemental oxygen.
CXCR3, against which the first one is directed, is a receptor expressed in activated T lymphocytes, some of them being memory immune cells. The receptor controls the migration of these lymphocytes to a site of inflammation and helps fight infection. AT1R, in turn, has a regulatory role in the circulatory system. The antibody that works against it increases damage to the endothelium, the inner part of blood vessels.
Among those autoantibodies that are most related to the severity of cases, the researchers draw attention to the presence of the antibody against the receptor known as STAB1. With a “trash” function, the STAB1 eliminates cell debris and other tissue damage leftovers. “We still don’t know the function of this receptor in the context of covid-19. However, since it has several functions related to homeostasis [equilíbrio] tissue and inflammation resolution, we believe it may be relevant to indicate the severity of the disease”, says Marques.
In addition to providing more evidence on how covid-19 can develop into a systemic autoimmune disease, the researchers point out ways to therapies capable of blocking the action of these autoantibodies. ACE2 and AT1R inhibitor drugs, for example, have been tested in severe cases of covid-19. However, still to no avail. The work also has among the Brazilian authors Paula Paccielli Freire, who is a postdoctoral fellow at ICB-USP with a grant from the Foundation; in addition to Desirée Rodrigues Plaça (20/11710-2), Gabriela Crispim Baiocchi (20/07972-1) and Dennyson Leandro Mathias da Fonseca (20/16246-2), all with FAPESP direct doctoral scholarships.
The article The relationship between autoantibodies targeting GPCRs and the renin-angiotensin system associates with COVID-19 severity can be read at: www.medrxiv.org/content/10.1101/2021.08.24.21262385v1.