The COVID-19 pandemic has led to unprecedented stresses on modern medical systems, overwhelming the resource infrastructure in numerous countries while presenting a unique series of pathophysiologic clinical findings.

Thrombotic coagulopathy is common in critically ill patients suffering from COVID-19, with associated high rates of respiratory failure requiring prolonged periods of mechanical ventilation.

Here we report a case series of five patients suffering from profound, medically refractory COVID-19 associated respiratory failure who were treated with fibrinolytic therapy using tissue plasminogen activator (tPA, Alteplase).

All five patients appeared to have an improved respiratory status following tPA administration: one patient had an initial marked improvement that partially regressed after several hours, one patient had transient improvements that were not sustained, and three patients had sustained clinical improvements following tPA administration.

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