Haemorrhagic stroke risk increased with mRNA vaccine, yet risk lower vs SARS-CoV-2 infection

A self-controlled case series (SCCS) study conducted by the University of Hong Kong has found an increased risk of haemorrhagic stroke in recipients of mRNA BNT162b2 vaccine 14–27 days after the first dose and 0–13 days after the second dose, which is however lower than the incidence of haemorrhagic stroke within 28 days of confirmed SARS-CoV-2 infection.

Following reports of increased cardiovascular complications after both SARS-CoV-2 infection and COVID-19 vaccination, the researchers assessed the association between thromboembolic events and haemorrhagic stroke and the two COVID-19 vaccines available in Hong Kong, namely, the BNT162b2 mRNA vaccine and the inactivated CZ02 vaccine.

A total of 5,526,547 doses of BNT162b2 and 3,146,741 doses of CZ02 were administered between 23 February and 30 September 2021, with 4,181,121 individuals receiving two doses of COVID-19 vaccine in the same period. A total of 334 and 402 thromboembolic events occurred within 28 days after BNT162b2 and CZ02 vaccination, respectively, resulting in crude incidence of 6.04 and 12.78 per 100,000 doses, and age-standardized incidence rates of 171.37 and 183.83 per 100,000 person-years, respectively. [EClinicalMedicine 2022;doi:10.1016/j.eclinm.2022.101504]

At the same time, 57 and 49 haemorrhagic stroke cases were recorded within 28 days of BNT162b2 and CZ02 vaccination, respectively, yielding crude incidences of 1.03 and 1.56 per 100,000 doses and age-standardized incidence rates of 30.73 and 21.62 per 100,000 person-years, respectively.  

Between the local pandemic onset on 21 January 2020 and 20 September 2021, there were 11,632 SARS-CoV-2–positive cases in Hong Kong. The incidence of thromboembolic events and haemorrhagic stroke was 722.15 and 8.60 per 100,000 SARS-CoV-2 test positive cases, respectively.

“In our study, the incidence of haemorrhagic stroke and thromboembolic events within 28 days of testing positive for SARS-CoV-2 was much higher than the incidence among people who have received either COVID-19 vaccine,” commented the researchers. Of note, the breakthrough SARS-CoV-2 infection rate is estimated to be 2.6–12.3 percent among fully vaccinated individuals, according to different sources. [JAMA 2021;326:1930-1939; JAMA Netw Open 2022; doi:10.1001/jamanetworkopen.2022.15934; https://coronavirus.health.ny.gov/covid-19-breakthrough-data - accessed on 11 July 2022]

The modified SCCS model detected an increased risk of haemorrhagic stroke in BNT162b2 recipients, with an adjusted incidence rate ratio (IRR) of 2.53 (95 percent confidence interval [CI], 1.48–4.34) 14–27 days after first dose, and an adjusted IRR of 2.69 (95 percent CI, 1.54–4.69) 0–13 days after the second dose. The risk of haemorrhagic stroke was not increased in CZ02 recipients within 28 days of the first or second dose, and neither vaccine was associated with an increased risk of thromboembolic events.

“The mechanism for the potential risk of haemorrhagic stroke following BNT162b2 vaccination is unclear,” wrote the researchers. “The risk could be due to the interaction between SARS-CoV-2 spike protein and platelets, which would increase the risk of thromboembolic events and subsequently contribute to major bleeding events. However, we only detected a risk of haemorrhagic stroke but not thromboembolic events in this study.” [J Hematol Oncol 2020;doi:10.1186/s13045-020-00954-7]

“Although a possible BNT162b2 vaccination safety signal was detected, which requires further investigation and monitoring, there were considerable benefits to vaccination vs SARS-CoV-2 infection in this predominantly Chinese cohort of almost 4.5 million vaccinated individuals,” concluded the researchers.