Vaccine-induced COVID-19 mimicry syndrome

To fight the COVID-19 pandemic caused by the RNA virus SARS-CoV-2, a global vaccination campaign is in progress to achieve the immunization of billions of people mainly with adenoviral vector- or mRNA-based vaccines, all of which encode the SARS-CoV-2 Spike protein. In some rare cases, cerebral venous sinus thromboses (CVST) have been reported as a severe side effect occurring 4-14 days after the first vaccination and were often accompanied by thrombocytopenia. Besides CVST, splanchnic vein thromboses (SVT) and other thromboembolic events have been observed. These events only occurred following vaccination with adenoviral vector-based vaccines but not following vaccination with mRNA-based vaccines. Meanwhile, scientists have proposed an immune-based pathomechanism and the condition has been coined vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe an unexpected mechanism that could explain thromboembolic events occurring with DNA-based but not with RNA-based vaccines. We show that DNA-encoded mRNA coding for Spike protein can be spliced in a way that the transmembrane anchor of Spike is lost, so that nearly full-length Spike is secreted from cells. Secreted Spike variants could potentially initiate severe side effects when binding to cells via the ACE2 receptor. Avoiding such splicing events should become part of a rational vaccine design to increase safety of prospective vaccines.

Automated summary

A global vaccination campaign is underway to immunize billions of people against the COVID-19 pandemic. However, rare cases of severe side effects, such as cerebral venous sinus thrombosis (CVST), have been reported after vaccination with adenoviral vector-based vaccines. These events have not been observed with mRNA-based vaccines. Scientists have proposed a mechanism called vaccine-induced immune thrombotic thrombocytopenia (VITT) and discovered that DNA-encoded Spike protein can be spliced in a way that leads to the secretion of potentially harmful Spike variants. Avoiding such splicing events is important for the safety of future vaccines.