Novel Link Between Myeloid-Specific Adenosine Deaminase 2 and CXCL10-CXCR3 Axis in Infectious ARDS.

Acute respiratory distress syndrome (ARDS) is a severe complication of lung injury characterized by hyperinflammation and fibrosis. Here, we show a significant association between the monocyte-derived enzyme adenosine deaminase 2 (ADA2) and SARS-CoV-2 induced ARDS. We note an interesting link between ADA2 and the chemokine CXCL10 and its receptor CXCR3. By using published datasets of spatial transcriptomics and single-cell RNAseq, we show that ADA2 is highly expressed by inflammatory CD14(+)CD16(+) monocytes, along with profibrotic genes, in lungs affected by COVID-19. This study reveals important associations between key pathophysiological features of ARDS, linking hypoxia, infiltrative CXCR3 monocytes, and a monocyte-derived exoenzyme ADA2.