Adenoviral vector-based COVID-19 vaccines-associated cerebral venous sinus thromboses: Are those adverse events related to the formation of neutrophil extracellular traps?

Abstract

In March and April 2021 several countries temporarily suspended vaccinations with adenoviral vector-based COVID-19 vaccines. Concerns of national regulators particularly regarded very rare cases of cerebral venous sinus thrombosis after immunization with this type of vaccine. Until now, these adverse events were interpreted as standard hypercoagulable events, but their clinical characteristics suggest that they may actually represent unique thrombotic disorders referred to as immunothrombosis. In this paper it is speculated that it is possible that immunothrombosis after this type of vaccine results from formation of neutrophil extracellular traps (NETs) in veins affected by stagnant blood flow. Such a stasis occurs in individuals with anatomical variants of cerebral venous outflow, which may explain why these events are primarily seen in the cerebral veins. It has already been found that SARS-CoV-2 spike protein can evoke release of NETs. There is also a question if thrombotic events after adenoviral vector-based COVID-19 vaccines could be avoided. These vaccines will still be needed to curb COVID-19 worldwide, since they do not require transportation and storage at very low temperatures. Perhaps, vaccinations with these vaccines should be performed in combination with prophylactic administration of dipyridamole, which is an inexpensive pharmaceutical agent reducing the release of NETs.