mRNA COVID-19 vaccine safety in adults from the Canadian national vaccine safety network

The Canadian National Vaccine Safety Network (CANVAS) conducted active vaccine safety surveillance during the two-dose primary COVID-19 mRNA vaccine rollout in Canadian adults and expanded on the findings of prior active safety surveillance studies by including an unvaccinated control group. In this cohort study, vaccinated and unvaccinated adults from 7 provinces and territories were recruited to complete emailed surveys one week after each vaccine dose (or at registration for unvaccinated controls). The primary outcome was a health event that resulted in missed work or school or required medical consultation. Multivariable regression models examined health events associated with the first and second doses of BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines. Surveys were completed by 567,781 and 301,717 individuals following dose one and dose two, and by 14,984 unvaccinated participants. In the multivariate analysis, health events within a week following vaccination were higher among vaccinated individuals compared to controls, with risk ratios (RR) ranging from 2.3 [95% Confidence Interval (C·I.) 2.1 to 2.6] for the first dose of BNT162b2 to 7 [95% C·I. 6.3 to 7.8] for the second consecutive dose of mRNA-1273. Common symptoms included fatigue/malaise, headache, fever and joint pain, and most were self-limited. Health events requiring an ED visit or hospitalization were significantly increased after the first dose of mRNA-1273 (RR 2.1 [95% C.I. 1.5 to 3.1]) or the second consecutive dose of mRNA-1273 (RR 2 [95% C.I. 1.3 to 2.9]). In summary, self-limited health events were more common in the week following vaccination with a first or second dose of an mRNA COVID-19 vaccine, compared with controls, with the highest frequency occurring after a second dose of mRNA-1273. Health events requiring an ED visit or hospitalization were more common in participants who received the mRNA-1273 vaccine, compared with controls. This difference was not observed for the BNT1262b2 vaccine.