The National Advisory Committee on Immunization (NACI) has recommended that the AstraZeneca COVID-19 vaccine should not be used in adults under age 55 years due to concerns about a rare clotting complication (www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/rapid-response-recommended-use-astrazeneca-covid-19-vaccine-younger-adults.html). Individuals aged >55 years can still receive the vaccine. NACI previously recommended that the vaccine not be used in individuals aged >65 years due to a lack of evidence.
The most recent advisory follows reports of what is being called Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT). Rare cases of cerebral sinus vein thrombosis and other thrombotic complications have been reported following administration of the AstraZeneca vaccine. In an analysis of 9 cases by the Paul-Ehrlich-Institut, Greinacher et al. described antibody formation against platelet antigens 4-16 days post-vaccination that resulted in massive platelet activation, a process analogous to heparin-induced thrombocytopenia (www.researchsquare.com/article/rs-362354/v1). The reported incidence of VIPIT varies widely from 1:100,000 to 1:1,000,000 in a vaccinated population. The mortality rate is 40%. VIPIT cases have been reported in older subjects but the number of vaccinations in this age group is not sufficient to determine risk.
Symptoms suggestive of VIPIT include persistent and severe headache; focal neurological symptoms (including blurred vision); dyspnea; abdominal or chest pain; swelling and redness in a limb; or pallor and coldness in a limb. The syndrome appears to occur 4-20 days post-vaccination. A briefing document on VIPIT has been produced by the Ontario COVID-19 Science Advisory Table (https://covid19-sciencetable.ca/wp-content/uploads/2021/03/Science-Brief_AstraZeneca_General_20210326_published.pdf).
NACI advises that adults aged >55 years may still be offered the AstraZeneca vaccine provided informed consent is obtained. However, there is little scientific evidence to support this recommendation. The pivotal trial excluded subjects aged >55 years, but later admitted older individuals after a protocol amendment (Voysey et al. Lancet 2021;397:99-111). As a result, only 2.5% of the study population were aged 56-64 years and 9.7% were aged >65 years (total 12.2%). Vaccine efficacy in subjects aged >65 years is 43.2% at the approved dosing schedule of 4-12 weeks (Health Canada recommendations, 16 March 2021. www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/recommendations-use-covid-19-vaccines.html#appc). This falls below the efficacy cut-off of 50% required by the Food and Drug Administration.
In support of the use of the AstraZeneca vaccine in an older population, Health Canada cites three preprint studies but notes that NACI did not use these data due to methodological weaknesses and the implausibility of some findings (Hyams et al. Lancet 2021, 3 March preprint, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3796835. Bernal et al. www.medrxiv.org/content/10.1101/2021.03.01.21252652v1.full.pdf. Vasileiou et al. Lancet 2021, 19 February preprint, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3789264). The Canadian product monograph states that there is limited information on the efficacy of the vaccine in individuals aged ≥65 years but does not limit its use. The monograph was updated a week ago to include a warning about a risk of thrombosis and thrombocytopenia (AstraZeneca COVID-19 vaccine, 24 March 2021).