Plasmin cascade mediates thrombolytic events in SARS-CoV-2 infection via complement and platelet-activating systems

SUMMARY Recently emerged beta-coronavirus, SARS-CoV-2 has resulted in the current pandemic designated COVID-19. COVID-19 manifests as severe illness exhibiting systemic inflammatory response syndrome, acute respiratory distress syndrome (ARDS), thrombotic events, and shock, exacerbated further by co-morbidities and age 1–3 . Recent clinical reports suggested that the pulmonary failure seen in COVID-19 may not be solely driven by acute ARDS, but also microvascular thrombotic events, likely driven by complement activation 4,5 . However, it is not fully understood how the SARS-CoV-2 infection mechanisms mediate thrombotic events, and whether such mechanisms and responses are unique to SARS-CoV-2 infection, compared to other respiratory infections. We address these questions here, in the context of normal lung epithelia, in vitro and in vivo , using publicly available data. Our results indicate that plasmin is a crucial mediator which primes interactions between complement and platelet-activating systems in lung epithelia upon SARS-CoV-2 infection, with a potential for therapeutic intervention.