High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease.

Automated summary

This study investigated the changes in purinergic signaling and immune response in COVID-19 patients. The results showed altered purinergic signaling in both moderate and severe cases, including increased ATP hydrolysis in platelets and PBMCs, as well as significantly elevated ADP and AMP hydrolysis. The study also observed increased expression of CD39 and CD73 in total leukocytes, along with higher extracellular ATP levels in both groups. Additionally, moderate and severe cases exhibited elevated levels of IL-2, IL-6, IL-10, and IL-17. These findings provide valuable insights into the changes in purinergic signaling and immune response in COVID-19, highlighting the therapeutic potential of the purinergic system as a target for the treatment of SARS-CoV-2 disease.