APC showed beneficial effects in the PROWESS study, particularly in the subgroup of patients with CAP and a high risk of death. Heterogeneity within patient populations has hampered previous studies of APC; any future trials in COVID-19 will need patients to be carefully sub-phenotyped because the benefit in COVID-19 will likely be seen in those at high risk of death with low endogenous levels of APC. Nebulised streptokinase has shown reduced mortality in one study of ARDS patients [79] and fibrinolysis is currently being targeted in COVID-19 with trials of nebulised and systemically administered tPA; these trials are welcomed and have the potential to reduce pulmonary microthrombi and lung injury.