Three doses of COVID-19 mRNA vaccination are safe based on adverse events reported in electronic health records

Abstract

Recent reports on waning of COVID-19 vaccine induced immunity have led to the approval and roll-out of additional dose and booster vaccinations. At risk individuals are receiving additional vaccine dose(s), in addition to the regimen that was tested in clinical trials. The risks and the adverse event profiles associated with these additional vaccine doses are currently not well understood. Here, we performed a retrospective study analyzing vaccine-associated adverse events using electronic health records (EHRs) of individuals that have received three doses of mRNA-based COVID-19 vaccines (n = 47,999). By comparing symptoms reported in 2-week time periods after each vaccine dose and in a 2-week period before the 1st vaccine dose, we assessed the risk associated with 3rd dose vaccination, for both BNT162b2 and mRNA-1273. Reporting of severe adverse events remained low after the 3rd vaccine dose, with rates of pericarditis (0.01%, 0%-0.02% 95% CI), anaphylaxis (0.00%, 0%-0.01% 95% CI), myocarditis (0.00%, 0%-0.01% 95% CI), and cerebral venous sinus thrombosis (no cases), consistent with earlier studies. Significantly more individuals (p-value < 0.05) report low-severity adverse events after their 3rd dose compared with after their 2nd dose, including fatigue (4.92% after 3rd dose vs 3.47% after 2nd dose), lymphadenopathy (2.89% vs 2.07%), nausea (2.62% vs 2.04%), headache (2.47% vs 2.07%), arthralgia (2.12% vs 1.70%), myalgia (1.99% vs 1.63%), diarrhea (1.70% vs 1.24%), fever (1.11% vs 0.81%), vomiting (1.10% vs 0.80%), and chills (0.47% vs 0.36%). Our results show that although 3rd dose vaccination against SARS-CoV-2 infection led to increased reporting of low-severity adverse events, risk of severe adverse events remained comparable to the standard 2-dose regime. This study provides support for the safety of 3rd vaccination doses of individuals that are at high-risk of severe COVID-19 and breakthrough infection.

Incidence, risk factors, natural history, and hypothesised mechanisms of myocarditis and pericarditis following covid-19 vaccination: living evidence syntheses and review

“…Findings from 12 studies from the original review 15 were carried forward (Q1=5, 25 26 27 28 29 Q2=2, 29 30 Q3 part 2=10 25 26 27 28 31 32 33 34 35 36 ). From the search update, we identified 34 new reports across all questions (Q1=9, 37 38 39 40 41 42 43 44 45 Q2=5, 37 41 45 46 47 Q3 part 1=1, 48 Q4=3, 39 49 50 Q5=21 9 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 ). We excluded five studies that only reported on combined myocarditis and pericarditis (as we located studies reporting these separately), 71 72 73 74 75 eight studies that did not report on confirmed cases, 76 77 78 79 80 81 82 83 and three studies 84 85 <...…”

“…We included 14 studies (reported in publications, presentations, online reports, accessible data; all are considered here as studies for simplicity), with eight that used active surveillance data sources (eg, medical records or registries) and six that used passive reporting systems. 25 26 27 28 29 37 38 39 40 41 42 43 44 45 Data came from the US, Canada, the UK, Israel, Denmark, Singapore, and internationally (Moderna Global Safety Database). Four studies used the US Vaccine Adverse Events Reporting System for cases, and populations overlapped in analyses for young people aged 5-11 43 44 and 12-17 25 29 years in which two reports were included for each group because they applied different risk intervals (seven days and any duration).…”

Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination

“…Current data indicate that three doses of mRNA vaccines are safe, which included immunocompromised individuals in the population cohort. 47 Consideration should be given to the risk of myocarditis and pericarditis in vaccine recipients who demonstrate low response or non-response to COVID-19 vaccination where additional vaccine doses are warranted; while immunocompromised patient subgroups have generally been shown to elicit sufficient immune response to COVID-19 vaccination, many of those who do respond poorly may be immunocompromised, including patients with cancer or transplant recipients. 48 Further studies are required to better understand the occurrence of myocarditis and pericarditis following additional mRNA COVID-19 vaccine doses in immunocompromised individuals and for those who have demonstrated limited response to vaccination.…”

Systematic review of spontaneous reports of myocarditis and pericarditis in transplant recipients and immunocompromised patients following COVID-19 mRNA vaccination

“…While COVID-19 vaccination programmes continue to progress to widespread roll-out of third and subsequent booster doses, more immunocompromised individuals will become exposed to COVID-19 mRNA vaccines and some for the first time, particularly in countries where adenovirus vector COVID-19 vaccines were preferentially given to older members of the population and those at higher clinical risk of severe COVID-19 outcomes (many of whom were immunocompromised) for their first two doses. Current data indicates that three doses of mRNA vaccines are safe, which included immunocompromised individuals in the population cohort (49). Consideration should be given to the risk of myocarditis and pericarditis in vaccine recipients who demonstrate low-or non-response to COVID-19 vaccination where additional vaccine doses are warranted; while immunocompromised patient subgroups have generally been shown to elicit sufficient immune response to COVID-19 vaccination, many of those who do respond poorly may be immunocompromised, including cancer patients or transplant recipients (50).…”