Molecules that attack cells and tissues in the patient’s own organism were detected in blood serum from volunteers infected by SARS-CoV-2, who progressed to moderate or severe COVID-19 after the samples were collected. The discovery could lead to novel therapeutic approaches (illustration: NIH)
Published on 09/28/2021
By André Julião | Agência FAPESP – A study by an international group of researchers has found a set of molecules in the blood serum of patients infected by SARS-CoV-2 that are normally present in autoimmune diseases and can serve as predictors of COVID-19 severity. An article reporting their findings (not yet peer-reviewed) is published on the preprint platform medRxiv. The results of the study could improve diagnosis and clinical management of the disease in future.
“Several studies have shown that auto-antibodies, which cause systemic auto-immune diseases, also appear in COVID-19. We detected autoantibodies associated with healthy people and found others at higher levels in severe cases of COVID-19. For example, we detected autoantibodies against two molecules with augmented levels days before the patients required oxygen. We expect this to help us prevent the clinical condition of patients from worsening,” said Otávio Cabral Marques, a researcher at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) and first author of the article.
Marques is the principal investigator for a project funded by FAPESP and dedicated to understanding how the immune system responds to COVID-19. The other authors of the article are from Germany, Israel and the United States, as well as Brazil.
The group analyzed blood serum samples donated by 246 volunteers recruited from Jewish communities in six US states. None of the subjects had taken any anti-SARS-CoV-2 vaccine. RT-PCR testing produced positive results for 169. The other 77 tested negative and had no symptoms. The infected group was subdivided into mild, moderate and severe.
Computational tools showed an association between antibodies and molecules from the renin-angiotensin system, which among other functions produces the protein ACE2 (angiotensin-converting enzyme 2) used by the virus to bind to and invade human cells. The researchers also found antibodies that target G protein-coupled receptors (GPCRs), which perform functions relating to inflammation and coagulation, among others.
Moderate and severe cases had the highest levels of autoantibodies. Healthy subjects and mild patients had much lower levels.
Therapeutic potential
Autoantibodies against 11 molecules were found to be the most significant to predict severity of the disease. Two of these, anti-CXCR3 and anti-AT1R, for example, were detected in patients who required supplementary oxygen two days after blood samples were taken for the study.
CXCR3 is a receptor expressed by effector T lymphocytes, some of which are memory immune cells. The receptor controls migration by these T cells to an inflammation site and helps combat the infection. AT1R helps regulate the circulatory system. Its antibody increases damage to the endothelium, the membrane that lines the inside of the heart and blood vessels.
Among these autoantibodies associated with severe cases, the researchers call attention to the presence of the antibody against the receptor labeled STAB1, which acts as a scavenger that clears dead cells and other tissue damage debris. “We don’t yet know the function of this receptor in the context of COVID-19. However, given that it has several functions relating to tissue homeostasis and inflammation resolution, we believe it may be relevant as a marker of severity,” Marques said.
After presenting additional evidence of how COVID-19 can progress to a systemic autoimmune disease, the authors indicate potential avenues for the development of therapies capable of blocking the action of these auto-antibodies. Drugs that inhibit ACE2 and AT1R, for example, have been tested in cases of severe COVID-19, but so far without success.
The other Brazilian authors of the article include Paula Paccielli Freire, a postdoctoral researcher at ICB-USP with a fellowship from FAPESP; and Desirée Rodrigues Plaça (20/11710-2), Gabriela Crispim Baiocchi (20/07972-1) and Dennyson Leandro Mathias da Fonseca (20/16246-2), all three of whom have direct doctorate scholarships from FAPESP.
The article “The relationship between autoantibodies targeting GPCRs and the renin-angiotensin system associates with COVID-19 severity” is at: www.medrxiv.org/content/10.1101/2021.08.24.21262385v1.
Source: https://agencia.fapesp.br/36945
