Researchers at the University of São Paulo (USP) in Brazil have found that severe COVID-19 is associated with an imbalance in an important immune system signaling pathway. The discovery helps explain at the molecular level why some people infected by SARS-CoV-2 develop a potentially fatal systemic inflammation. It also paves the way to the development of more specific therapies.
An article on the study, which was funded by FAPESP, is published in Frontiers in Immunology.
The researchers detected dysregulation of the immune system mediated by ATP (adenosine triphosphate), one of the main sources of energy for cellular processes. Severe COVID-19 patients had higher levels of ATP in their blood and lower levels of adenosine, which should increase when ATP is metabolized for energy production.
The immune system comprises several signaling pathways that provide alerts in response to invasion by a pathogen, for example. One involves ATP, which triggers the release of inflammatory substances in defense cells to attack the invader. The immune system also has control mechanisms to avoid excessive inflammation, but when this error in ATP metabolization occurs, it results in a huge imbalance and systemic dysfunctions in the immune response." Maria Notomi Sato, professor at USP's Medical School and last author of the article
The increase in unmetabolized ATP, according to the article, produces a pro-inflammatory state and triggers a potentially fatal systemic inflammation known as a cytokine storm. "The study pointed to an imbalance in the signaling system and a dysfunction in the regulation of these components, as one more factor at the systemic level that attacks the organs of severe COVID-19 patients," Sato said.
ATP is constantly produced by cells and is broken down in the extracellular environment by enzymes…