Safety of mRNA vaccines administered during the initial 6 months of the US COVID-19 vaccination programme: an observational study of reports to the Vaccine Adverse Event Reporting System and v-safe.
Level 4 - case-series / case-control
Observational passive (VAERS) and voluntary active (v-safe) surveillance without an unvaccinated comparator cohort.
PubMed 35271805 · doi:10.1016/S1473-3099(22)00054-8
What was done
Researchers analyzed US safety surveillance data for mRNA COVID-19 vaccines administered between December 14, 2020, and June 14, 2021. Data were evaluated from two surveillance platforms: VAERS (a passive reporting system, categorizing adverse events as non-serious, serious non-death, or death, with rates calculated per doses administered) and v-safe (a voluntary active smartphone-based system assessing reactogenicity, severity, and health impacts during days 0–7 post-vaccination).
What was found
During the study period, 298,792,852 mRNA vaccine doses were administered in the USA. VAERS processed 340,522 reports: 313,499 (92.1%) were non-serious, 22,527 (6.6%) were serious non-death events, and 4,496 (1.3%) were deaths. Among 7,914,583 v-safe participants, local reactogenicity was reported by 68.6% (4,644,989/6,775,515) after dose 1 and 71.7% (4,068,447/5,674,420) after dose 2; systemic reactogenicity was reported by 52.7% (3,573,429/6,775,515) after dose 1 and 70.8% (4,018,920/5,674,420) after dose 2. Commonly reported symptoms were injection-site pain (66.2% dose 1; 68.6% dose 2), fatigue (33.9% dose 1; 55.7% dose 2), and headache (27.0% dose 1; 46.2% dose 2), peaking on day 1 post-vaccination with most reactions categorized as mild. Health impacts (unable to work, perform normal activities, or seeking care) occurred in 11.9% (808,963) after dose 1 and 32.1% (1,821,421) after dose 2, while medical care was sought by 0.8% (56,647) after dose 1 and 0.9% (53,077) after dose 2.
Why it matters
This large-scale nationwide surveillance confirms the safety profile of mRNA COVID-19 vaccines across nearly 300 million doses, demonstrating that reported adverse events were overwhelmingly mild, self-limiting, and non-serious.
Limits
VAERS relies on passive, voluntary reporting and is subject to under-reporting, stimulated reporting, variable report quality, and an inability to establish causality. v-safe participation was voluntary and required smartphone access, introducing self-selection bias. Neither system included an unvaccinated comparator group to assess baseline event rates, and detailed reactogenicity follow-up in v-safe was limited to the first 7 days post-vaccination.
Cited by
- context In VAERS reporting following COVID-19 vaccination, the highest volume of reported deaths occurs within one to two days after injection, followed by a precipitous decline.