Both Johnson & Johnson and AstraZeneca used replication-defective adenovirus vectors to make their SARS-CoV-2 vaccines. DNA corresponding to the SARS-CoV-2 spike (fusion) protein was inserted into the vectors. Once the viral vector was inside the cell, the DNA corresponding to the spike protein was converted to mRNA, which was then translated to the spike protein itself. These vaccines were clearly effective at preventing severe COVID-19 disease. However, months after these vaccines were authorized, and had been given to hundreds of thousands of people, it became clear that there was a serious adverse event. Specifically, these vaccines could cause consequential bleeding, including intracranial bleeding that could be fatal. This problem was rare, occurring in about 1 in 200,000 recipients, but it was real. In response, the J&J vaccine was removed from the U.S. market in May 2023. At the heart of this problem was the activation of platelet factor 4 (PF-4) associated with a lower platelet count (i.e., thrombocytopenia). The syndrome was called “vaccine-induced immune thrombotic thrombocytopenia” (VITT).

Researchers have now shown that natural adenovirus infection can cause the same syndrome (Warkentin TE, Baskin-Miller J, Raybould AL, et al. Adenovirus-associated thrombocytopenia, thrombosis, and VITT-like antibodies. N Engl J Med. 2023 Aug. 10;389(6):574-577.) and (Campello E, Biolo M, Simioni P. More on adenovirus-associated thrombocytopenia, thrombosis, and VITT-like antibodies. N Engl J Med. 2023 Nov. 2;389(18):1729.). At this point, it will be interesting to see the incidence of this phenomenon following natural adenovirus infection and whether there is a predilection for specific adenovirus serotypes.

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