Newswise — 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.
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.
When an exacerbated inflammatory response is activated, when cells are badly injured or when some other severe damage occurs.
In the study, the researchers measured ATP and adenosine levels in blood samples from 88 severe COVID-19 patients collected in 2020-21.
“We found cell-surface ectonucleotidases that cleave ATP to be less expressed in cells from both mild and severe COVID-19 patients, but particularly the latter.
Lymphocyte levels generally tend to be low in COVID-19 patients, but in our study not only the levels of B cells in blood from severe patients were low, but these cells also expressed lower amounts of both enzymes, contributing to less ATP metabolization and hence less production of adenosine, the anti-inflammatory component that would try to regulate this response,” Pietrobon said.
A study conducted at the Center for Research on Inflammatory Diseases (CRID) had already detected a link between severe COVID-19 and inflammasome activation, which in these patients is exacerbated and fails to shut down after the infection clears (read more at: agencia.FAPESP.br/39411).
When this cellular mechanism is activated, pro-inflammatory molecules known as cytokines are produced to warn the immune system that more defense cells need to be sent to the infection site.
According to the researchers who conducted the study on ATP metabolization, the build-up of ATP in conjunction with low levels of adenosine in severe patients may contribute to exacerbation of the cytokine-mediated inflammatory response.
In these cases, in which immune system regulation is dysfunctional, the excessive inflammatory response is directly linked to multiple organ failure and frequently to death.