Decreased circulating CD73 and adenosine deaminase are associated with disease severity in hospitalized patients with COVID-19

Abstract

Objective SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity. Methods Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA. These concentrations were compared to healthy control plasma that is commercially available and was biobanked prior to the start of the pandemic. Additionally, outcomes such as WHO ordinal scale for disease severity, ICU admission, needed for invasive ventilation, hospital length of stay, and development of thrombosis during admission were used as markers of disease severity. Results Our results show that both CD73 and ADA are decreased during SARS-CoV-2 infection. The level of circulating CD73 is directly correlated to the severity of the disease defined by the need for ICU admission, invasive ventilation, and hospital length of stay. Low level of CD73 is also associated with clinical thrombosis, a severe complication of SARS-CoV-2 infection. Conclusion Our study indicates that adenosine metabolism is down-regulated in patients with COVID-19 and associated with severe infection. Further large-scale studies are warranted to investigate the role of the adenosinergic anti-inflammatory CD73/ADA axis in protection against COVID-19.

Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation

“…From another perspective, Rud et al [51] analyzed plasma from patients hospitalized with COVID-19 for the effects of infection on CD73 activity. As a result, they also found a reduction in the expression of these ectonucleotidases.…”

“…As a result, they also found a reduction in the expression of these ectonucleotidases. However, they suggested that reduced nucleotide hydrolysis leads to reduced Ado production, preventing its expression of anti-inflammatory activity [51]. Considering the indications from scientific data of the anti-inflammatory effects of the P1 receptor family, this lack of Ado can be seen as a mediator for reducing the anti-inflammatory and neuroprotective activity presented by these receptors [52].…”

“…Therefore, COVID-19 infection appears to increase the activity of P2 receptors linked to systemic inflammation, reducing the actions of ectonucleotides, impairing ATP hydrolysis, and generating its accumulation [29,30]. Additionally, it can also be inferred that this lack of hydrolysis causes a reduction in Ado concentrations, leading to a decrease in the activity of P1 receptors, impairing their protective and anti-inflammatory conditions [29,51,52]. Thus, SARS-CoV-2 can affect purinergic signaling, preventing its neuroprotective effects and contributing to systemic inflammation, which is a dangerous condition for ALS patients.…”