Thread by @JLRohmann

New @PEI_Germany report provides much needed clarity to the #AstraZeneca "pause" in Germany. Not yet available in English. I will try to summarize. /thread pei.de/SharedDocs/Dow…

As of Monday (March 15th), 2021, 7 cases of specific form of severe cerebral venous thrombosis associated with platelet deficiency (thrombocytopenia) were identified. The individuals were 20-50 years old and 3 of them subsequently died. /2

6 of the cases were women who had a particular form of cerebral venous thrombosis, namely cerebral venous sinus thrombosis. (hopkinsmedicine.org/health/conditi…) The 7th case was medically very similar (cerebral hemorrhage + platelet deficiency + thrombosis)

All cases occurred 4 to 16 days after vaccination with AstraZeneca COVID-19 vaccine. This pattern "flagged" in the surveillance data. This is what we hope good surveillance does- detect potential concerning events & investigate further. /4

The PEI writes that this number of cases following #AstraZeneca vaccination was found to be statistically significantly higher than the number of cerebral venous thromboses that normally occur in the general population. /5

The PEI ran an "observed-versus-expected analysis", comparing the # of such cases expected *without* vaccination in a 14-day period with the # of cases reported in those vaccinated with #AstraZeneca (1.6 million) in Germany. About 1 case would be expected, 7 were observed. /6

The younger to middle-aged population in which these severe cerebral venous thromboses+platelet deficiency was observed is not the group at highest risk for a severe/fatal COVID-19. (Sidenote: this is why so many of us wanted information on age group yesterday) /7

The PEI states that they consulted other experts in thrombosis, hematology, and an adenovirus specialist about this issue & all unanimously agreed that a pattern could be recognized here & a connection between the reported cases and the AZ vaccination "was not implausible". /8

They go on to explain that these aforementioned points led to yesterday's decision by the @PEI_Germany to recommend suspension of the #AstraZeneca COVID-19 vaccine as a precautionary measure until further assessment can be completed. /9

The German Federal Ministry of Health (BMG) followed this recommendation. The Pharmacovigilance Risk Assessment Committee (PRAC) at the European Medicines Agency (EMA) will also review this information this week. /10

Now we await the #EMA comments & decision on whether and how these observations (together with other European surveillance data) affect the risk-benefit profile of the AstraZeneca COVID-19 vaccine and the EU approval of the vaccine. /11

At this point, it remains unclear whether there is a causal relationship between the #AstraZeneca vaccine and these cases of cerebral thrombosis. /12

The main report is followed by a series of Q&A. I will highlight the @PEI_Germany answer to Q#6: "What can I do if I have received vaccination with AstraZeneca COVID-19 vaccine?" since many are likely faced with this question today. /13

The report emphasizes how rare these cerebral venous thrombosis events were (7 out of 1.6 million vaccinations, according to current knowledge). They point out that these individuals continued to feel unwell and experienced increasing headaches 4-16 days after vaccination. /14

Thus, the @PEI_Germany advises that people who have received the AstraZeneca COVID-19 vaccine and feel *increasingly* unwell more than four days after vaccination - with severe and persistent headaches or pinpoint bleeding on the skin seek professional medical advice. /15

Q7 asks "What changed since Friday?" The report explains that on Friday, the number of incident cerebral venous thrombosis events that occurred within the vaccinated population was still within a range that would be expected in the general (unvaccinated) population. /16

They describe the process of observed vs. expected analysis in pharmacovigilance (drug safety) and go on to say that on Friday, the threshold for the "red flag" had not yet been reached. /17

If the frequency of an event (like the cerebral venous thrombosis, in this case) is near the expected frequency, this speaks for a *random* occurrence in temporal connection with the vaccination. /18

On Monday, the 2 additional cases of cerebral venous thrombosis were reported following #AstraZeneca vaccination. These additional 2 cases put the number of observed cases "well above the expected number" & ultimately led to the decision to suspend, they write. /19&end

Now, we eagerly await more info & the #EMA recommendation. Of course, serious events in close temporal relation to vaccine should be taken seriously & weighed carefully against the strong, demonstrated benefits of the vaccine.

Since #AstraZeneca was the primary vaccine strategy in Germany and much of Europe, every day we wait is a frustrating one. I do appreciate the transparency of this report. Wish these numbers had been released yesterday though!

Update: English report now available here: ➡️pei.de/SharedDocs/Dow…