Plasminogen improves lung lesions and hypoxemia in patients with COVID-19

Abstract

Background Lungs from patients with coronavirus disease 2019 (COVID-19) have shown typical signs of acute respiratory distress syndrome (ARDS), formation of hyaline membrane mainly composed of fibrin and ‘ground-glass’ opacity. Previously, we showed plasminogen itself is a key regulator in fibrin degradation, wound healing and infection. Aim We aimed to investigate whether plasminogen can improve lung lesions and hypoxemia of COVID-19. Design Thirteen clinically moderate, severe or critical COVID-19 patients were treated with atomization inhalation of freeze-dried plasminogen. Methods Levels of their lung lesions, oxygen saturation and heart rates were compared before and after treatment by computed tomography scanning images and patient monitor. Results After plasminogen inhalation, conditions of lung lesions in five clinically moderate patients have quickly improved, shown as the decreased range and density of ‘ground glass’ opacity. Improvements of oxygen saturation were observed in six clinically severe patients. In the two patients with critical conditions, the oxygen levels have significantly increased from 79–82% to 91% just about 1 h after the first inhalation. In 8 of 13 patients, the heart rates had slowed down. For the five clinically moderate patients, the difference is even statistically significant. Furthermore, a general relief of chest tightness was observed. Conclusion Whereas it is reported that plasminogen is dramatically increased in adults with ARDS, this study suggests that additional plasminogen may be effective and efficient in treating lung lesions and hypoxemia during COVID-19 infections. Although further studies are needed, this study highlights a possible hope of efficiently combating this rapid epidemic emergency.

Fibrinolysis and COVID‐19: A plasmin paradox

“…The apparent beneficial effects of plasminogen supplementation further suggests that endogenous levels of plasminogen in the pulmonary compartment had been depleted, given that its restoration appears to be beneficial. 16 Therefore, we propose that local fibrinolytic failure in COVID-19 is due, at least in part, to local consumption, most likely of plasminogen itself, but this remains to be tested.…”

“…12 While plasmin effectively removes fibrin, it also cleaves numerous matrix proteins 13 but, importantly also misfolded/necrotic proteins, 14 Direct fibrinolytic approaches for patients with severe/critical COVID-19 have now been reported. 15,16 One case series evaluating the effect of intravenous t-PA in three patients with critical COVID-19 pneumonia reported beneficial effects. 15 Although a perilously small sample size, the potential of this therapeutic approach has received recent commentary.…”

Pulmonary intravascular coagulation in COVID-19: possible pathogenesis and recommendations on anticoagulant/thrombolytic therapy

“…1). Plasminogen and TPA has been used in COVID-19 patients in a few studies and have been shown to be beneficial in improving respiratory capacity [7,8]. As the immune-pathogenesis seems to resemble endothelial dysfunction of sinusoidal obstruction syndrome we think that defibrotide can also be useful or its pro-fibrinolytic, antithrombotic, thrombolytic, anti-ischemic and anti-inflammatory functions that may help to restore the endothelial function [9].…”

Pathological Role of Angiotensin II in Severe COVID-19

“…54 In addition, inhalation of plasminogen, whose conversion to plasmin is inhibited by PAI-1, improves lung lesions and hypoxemia in patients with COVID-19. 57 There is an association between activated RAS, increased Ang II, and inflammatory cytokine expression and activation. Ang II has proinflammatory properties, including the increase of interleukin (IL)-6, which was demonstrated after infusion of Ang II in healthy controls.…”