Details

Autor(en) / Beteiligte

• Correale, Pierpaolo
• Caracciolo, Massimo
• Bilotta, Federico
• Conte, Marco
• Cuzzola, Maria
• Falcone, Carmela
• Mangano, Carmelo
• Falzea, Antonella Consuelo
• Iuliano, Eleonora
• Morabito, Antonella
• Foti, Giuseppe
• Armentano, Antonio
• Caraglia, Michele
• De Lorenzo, Antonino
• Sitkovsky, Michail
• Macheda, Sebastiano
• Adrish, Muhammad

Titel

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

Ist Teil von

• PloS one, 2020-10, Vol.15 (10), p.e0239692

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Fourteen consecutively enrolled patients with Covid19-related interstitial pneumonitis and PaO2/FiO2 ratio<300 received off-label-treatment with 9 mg inhaled adenosine every 12 hours in the first 24 hours and subsequently, every 24 days for the next 4 days. Fifty-two patients with analogue features and hospitalized between February and April 2020, who did not receive adenosine, were considered as a historical control group. Patients monitoring also included hemodynamic/hematochemical studies, CTscans, and SARS-CoV2-tests. The treatment was well tolerated with no hemodynamic change and one case of moderate bronchospasm. A significant increase (> 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. 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.