Scientists said severe COVID-19 is associated with an imbalance in an important immune system signaling pathway. They pointed out "dysregulation", or a dysfunctional regulation, of the immune system mediated by adenosine triphosphate (ATP), one of the main sources of energy for cellular processes.
A higher level of ATP is usually noticed among severe COVID-19 patients. "The immune system comprises several signalling 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," said study author Maria Notomi Sato.
"The immune system also has control mechanisms to avoid excessive inflammation, but when this error in ATP metabolisation occurs, it results in a huge imbalance and systemic dysfunctions in the immune response," said Sato.
The increase in unmetabolised ATP, according to the study, 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 signalling 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 called ectonucleotidases.
"ATP turns into a danger signal when it exits cells in large amounts. When does that happen? When an exacerbated inflammatory response is activated, when cells are badly injured or when some other severe damage occurs," said Anna Julia Pietrobon, co-study author of the article.
"In response, ATP triggers an inflammatory process that involves other cells in a chain reaction," said Pietrobon.
(With inputs from agencies)
