Therapeutic effects of adenosine in high flow 21% oxygen aereosol in patients with Covid19-pneumonia

Background: SARS-Cov2 infection may trigger lung inflammation and acute-respiratory-distress-syndrome (ARDS) that requires active ventilation and may have fatal outcome. Considering the severity of the disease and the lack of active treatments, 14 patients with Covid-19 and severe lung inflammation received inhaled adenosine in the attempt to therapeutically compensate for the oxygen-related loss of the endogenous adenosine→A2A adenosine receptor (A2AR)-mediated mitigation of the lung-destructing inflammatory damage. This off label-treatment was based on preclinical studies in mice with LPS-induced ARDS, where inhaled adenosine/A2AR agonists protected oxygenated lungs from the deadly inflammatory damage. The treatment was allowed, considering that adenosine has several clinical applications. Patients and treatment: Fourteen consecutively enrolled patients with Covid19-related interstitial pneumonitis and PaO2/FiO2 ratio 30%) in the PaO2/FiO2-ratio was reported in 13 out of 14 patients treated with adenosine compared with that observed in 7 out of52 patients in the control within 15 days. Additionally, we recorded a mean PaO2/FiO2-ratio increase (215 ± 45 vs. 464 ± 136, P = 0.0002) in patients receiving adenosine and no change in the control group (210±75 vs. 250±85 at 120 hours, P>0.05). A radiological response was demonstrated in 7 patients who received adenosine, while SARS-CoV-2 RNA load rapidly decreased in 13 cases within 7 days while no changes were recorded in the control group within 15 days. There was one Covid-19 related death in the experimental group and 11in the control group. Conclusion: Our short-term analysis suggests the overall safety and beneficial therapeutic effect of inhaled adenosine in patients with Covid-19-inflammatory lung disease suggesting further investigation in controlled clinical trials.