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Defined by the World Health Organization as a global public health pandemic, coronavirus 2019 (COVID-19) has a global impact and has caused the death of thousands of people. The "severe acute respiratory syndrome coronavirus 2" virus (SARS-CoV-2) is the etiologic agent of this disease, which uses the angiotensinconverting enzyme receptor 2 (ACE2) to infect the body, so any organ that expresses the gene ACE2 is a possible target for the new coronavirus. In addition, in severe cases of COVID-19, a cytokine storm occurs, which triggers widespread systemic inflammation due to the uncontrolled release of proinflammatory cytokines. In this perspective, the modulation of purinergic receptors is highlighted in the literature as a possible therapy, considering its application in other viral infections and systemic inflammation. Therefore, this review aims to gather information on the modulation of the P2X7 receptor in the main organs directly affected by the virus and by the cytokine storm: the heart, brain, lung, liver and kidneys. Thus, demonstrating possible therapies for reducing inflammation and the level of morbidity and mortality of COVID-19. In severe cases of COVID-19, SARS-CoV-2 infection is capable of triggering an exacerbated release of cytokines, called a cytokine storm. With this inflammation, or less the direct infection of the virus, the whole organism can be affected. In this way, major and important organs such as the heart, lung, brain, and liver are affected, triggering different pathologies. In this perspective, purinergic signaling is highlighted in the literature for its anti-inflammatory role and has been listed in the pandemic scenario as a potential therapy. Therefore, knowing the expression of the purinergic receptor P2X7 in these tissues, the modulation of its inflammatory activity may be favorable in this severe and systemic condition.

Neuroinflammation is closely related to the development of depression, since the latter is caused, among other factors, by inflammatory processes, mainly related to the activation of microglia and expression of specific genes, which occurs during the neuroinflammatory process. Thus, COVID-19 is an important risk factor for the development of depression, since in addition to generating the feeling of stress, which also increases the activity of the immune system, it is also the cause of pathological processes and physiological ones that lead to the development of neuroinflammation, microglial activation, gene expression dysfunction and decreased concentration of available serotonin. That said, drugs are being used to combat COVID-19 to reduce the oxidative stress presented in the disease. Thus, tramadol and fluoxetine are highlighted as drugs used, however, although they present some positive results, such as the reduction of pro-inflammatory cytokines, they are also associated with negative effects such as dependence, pulmonary, cardiac and brain impairment. From this, the purinergic system is highlighted in the literature as a possible therapeutic target. This is because its mechanisms are related to the regulation of microglia, astrocytes and the physiology of important neurotransmitters and hormones. Added to this, there is a modulation of inflammatory activity, especially with regard to the P2X7 receptors of this system. The latter is an important target for the treatment of depression and COVID-19, since positive results were obtained through the genetic exclusion of this receptor and the use of selective antagonists.

COVID-19 is associated with oxidative stress, peripheral hyper inflammation, and neuroinflammation, especially in individuals with a more severe form of the disease. Some studies provide evidence on the onset or exacerbation of major depressive disorder (MDD), among other psychiatric disorders due to COVID-19. Oxidative stress and neuroinflammation are associated conditions, especially in the more severe form of MDD and in refractoriness to available therapeutic strategies. Inflammatory cytokines in the COVID-19 hyper inflammation process can activate the hypothalamic-pituitary-adrenal (HPA) axis and the indoleamine-2,3-dioxygenase (IDO) enzyme. IDO activation can reduce tryptophan and increase toxic metabolites of the kynurenine pathway, which increases glial activation, neuroinflammation, toxicity, and neuronal death. This review surveyed a number of studies and analyzed the mechanisms of oxidative stress, inflammation, and neuroinflammation involved in COVID-19 and depression. Finally, the importance of more protocols that can help elucidate the interaction between these mechanisms underlying COVID-19 and MDD and the possible therapeutic strategies involved in the interaction of these mechanisms are highlighted.

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. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.

Graphical abstract The virus “acute respiratory syndrome coronavirus 2” (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19), initially responsible for an outbreak of pneumonia in Wuhan, China, which, due to the high level of contagion and dissemination, has become a pandemic. The clinical picture varies from mild to critical cases; however, all of these signs already show neurological problems, from sensory loss to neurological diseases. Thus, patients with multiple sclerosis (MS) infected with the new coronavirus are more likely to develop severe conditions; in addition to worsening the disease, this is due to the high level of pro-inflammatory cytokines, which is closely associated with increased mortality both in COVID-19 and MS. This increase is uncontrolled and exaggerated, characterizing the cytokine storm, so a possible therapy for this neuronal inflammation is the modulation of the cholinergic anti-inflammatory pathway, since acetylcholine (ACh) acts to reduce pro-inflammatory cytokines and acts directly on the brain for being released by cholinergic neurons, as well as acting on other cells such as immune and blood cells. In addition, due to tissue damage, there is an exacerbated release of adenosine triphosphate (ATP), potentiating the inflammatory process and activating purinergic receptors which act directly on neuroinflammation and positively modulate the inflammatory cycle. Associated with this, in neurological pathologies, there is greater expression of P2X7 in the cells of the microglia, which positively activates the immune inflammatory response. Thus, the administration of blockers of this receptor can act in conjunction with the action of ACh in the anticholinergic inflammatory pathway. Finally, there will be a reduction in the cytokine storm and triggered hyperinflammation, as well as the level of mortality in patients with multiple sclerosis infected with SARS-CoV-2 and the development of possible neurological damage.

In March 11, 2020, the World Health Organization (WHO) characterized the rapid and uncontrollable spread of the new Coronavirus as a pandemic, given that this disease has high severity and morbidity and mortality. The epicenter of the SARS-CoV-2 outbreak was the city of Wuhan, China. Individuals with associated comorbidities, such as patients with chronic kidney disease (CKD), are at increased risk of being affected by the severe form of the disease. In this sense, it is known that people with CKD have a more sedentary lifestyle, with reduced physical exercise. Thus, physical exercise is able to modulate the inflammatory process resulting from CKD, acting as a regulator of the immune system, as well as assisting in the control of renal autophagy. It appears that physical activity contributes to the improvement of the population's quality of life and acts as an effect of disease prevention. Hence, people who live with CKD in times of the pandemic of COVID-19, by adopting physical activity as a life practice, will have the consequence of strengthening the immune system by modulating inflammation and increasing the control of renal autophagy. Therefore, the practice of exercise is suggested when facing COVID-19.

Novel coronavirus disease 2019 (COVID-19) causes pulmonary and cardiovascular disorders and has become a worldwide emergency. Myocardial injury can be caused by direct or indirect damage, particularly mediated by a cytokine storm, a disordered immune response that can cause myocarditis, abnormal coagulation, arrhythmia, acute coronary syndrome, and myocardial infarction. The present review focuses on the mechanisms of this viral infection, cardiac biomarkers, consequences, and the possible therapeutic role of purinergic and adenosinergic signalling systems. In particular, we focus on the interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2 and of adenosine (Ado) with A2A and A3 receptors, as well as their roles in host immune responses. We suggest that receptors of purinergic signalling could be ideal candidates for pharmacological targeting to protect against myocardial injury caused by a cytokine storm in COVID-19, in order to reduce systemic inflammatory damage to cells and tissues, preventing the progression of the disease by modulating the immune response and improving patient quality of life.

Introduction Metabolic syndrome (MetS) is a disorder that is closely associated with risk factors that increase the chance of atherosclerosis and cardiovascular diseases. We demonstrate the presence of inflammation and oxidative stress in patients with MetS through levels of antioxidants and oxidative and inflammatory markers, in order to determine influential variables in therapy. Methods: In this study, lipid peroxidation, carbonylated protein content and enzymatic and non-enzymatic antioxidants were evaluated in samples obtained from 30 patients with MetS and 30 control patients. In addition, acetylcholinesterase (AChE) activity, C-reactive protein (CRP) and uric acid (UA) levels were determined to investigate the inflammatory process in patients with MetS. Results: Our results demonstrated an increase in the levels of oxidative markers, such as substances reactive to thiobarbituric acid (TBARS) and carbonyl protein. In addition, a decrease in the defense of non-enzymatic antioxidants, such as levels of vitamin C and glutathione (GSH) in patients with MetS. As for inflammatory markers, CRP and UA were increased in patients with MetS. Finally, activation of the cholinergic anti-inflammatory pathway was observed due to decreased AchE activity in patients with MetS. Conclusion The analyzes indicated oxidative stress, together with a reduction in the levels of antioxidant enzymes, corroborating the high consumption of these proteins. In addition, inflammation and activation of the cholinergic anti-inflammatory pathway was observed by the AChE analysis. Thus, the activation of this pathway can be studied as a possible route to a potential therapy. In addition, the markers AChE, CRP and UA may be used as a focus for the treatment of MetS.