COVID-19 critical illness pathophysiology driven by diffuse pulmonary thrombi and pulmonary endothelial dysfunction responsive to thrombolysis

Clin Transl Med. 2020 Jun;10(2):e44. doi: 10.1002/ctm2.44. Epub 2020 Jun 5.


Patients with severe COVID-19 disease have been characterized as having the acute respiratory distress syndrome (ARDS). Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Many patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated d-dimers and higher rates of venous thromboembolism. We present four cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock, with evidence of markedly elevated dead-space ventilation who received tPA. All showed post treatment immediate improvements in gas exchange and/or hemodynamics. We suspect that severe COVID-19 pneumonia causes respiratory failure via pulmonary microthrombi and endothelial dysfunction. Treatment for COVID-19 pneumonia may warrant anticoagulation for milder cases and thrombolysis for more severe disease.

Keywords: COVID-19; tPA; thrombolysis; tissue plasminogen activator.