For over a year, the
coronavirus disease 2019 has been affecting the world population by causing severe tissue
injuries and death in infected people.
Adenosine triphosphate (
ATP) and the
nicotinamide adenine dinucleotide (NAD +) are two molecules that are released into the extracellular microenvironment after direct
virus infection or cell death caused by hyper
inflammation and coagulopathy. Also, these molecules are well known to participate in multiple pathways and have a pivotal role in the purinergic signaling pathway. Thus, using public datasets available on the Gene Expression Omnibus (GEO), we analyzed raw proteomics data acquired using mass spectrometry (the gold standard method) and raw genomics data from
COVID-19 patient samples obtained by microarray. The data was analyzed using bioinformatics and statistical methods according to our objectives. Here, we compared the purinergic profile of the total leukocyte population and evaluated the levels of these soluble biomolecules in the blood, and their correlation with coagulation components in
COVID-19 patients, in comparison to healthy people or non-COVID-19 patients. The blood metabolite analysis showed a stage-dependent
inosine increase in
COVID-19 patients, while the
nucleotides ATP and
ADP had positive correlations with
fibrinogen and other coagulation
proteins. Also,
ATP,
ADP,
inosine, and
hypoxanthine had positive and negative correlations with clinical features. Regarding leukocyte gene expression,
COVID-19 patients showed an upregulation of the P2RX1, P2RX4, P2RX5, P2RX7, P2RY1, P2RY12, PANX1, ADORA2B, NLPR3, and F3 genes. Yet, the ectoenzymes of the canonical and non-canonical adenosinergic pathway (ENTPD1 and CD38) are upregulated, suggesting that
adenosine is produced by both active adenosinergic pathways. Hence, approaches targeting these biomolecules or their specific purinoreceptors and ectoenzymes may attenuate the high inflammatory state and the coagulopathy seen in
COVID-19 patients. KEY MESSAGES : Adenosinergic pathways are modulated on leukocytes from
COVID-19 patients. Plasmatic
inosine levels are increased in
COVID-19 patients.
ATP,
ADP,
AMP,
hypoxanthine, and
inosine are correlated with coagulation players. The
nucleotides and
nucleosides are correlated with patients' clinical features. The P2 receptors and ectoenzymes are correlated with
Tissue factor in
COVID-19.