COVID-19 vaccine side effects: Fewer than expected?

A community-based study from the UK showed that the rate of systemic side effects is relatively low following vaccination with the BNT162b2 or ChAdOx1 nCoV-19 COVID-19 vaccines.

“[S]hort-term adverse effects (AEs) of both vaccines are moderate in frequency, mild in severity, and short-lived,” the authors said.

This prospective, observational study was conducted based on information garnered from the COVID Symptom Study app. The population comprised 627,383 individuals aged 16–99 years from the UK who had received one or two doses of the BNT162b2 vaccine (n=282,103 [first dose], of whom 28,207 received the second dose a median 41 days post-first dose) or one dose of the ChAdOx1 nCoV-19 vaccine* (n=345,280) between December 8, 2020 and March 10, 2021, and reported the symptoms experienced within 8 days of vaccination in the app.

The mean age of the app users was 50.6 years and 4.8 percent were healthcare workers. Systemic and local AEs were reported by 25.4 and 66.2 percent of the population, respectively.

Within 8 days of the first dose of BNT162b2, 13.5 percent reported systemic side effects, while 22.0 percent reported systemic side effects within 8 days of the second dose. Among the ChAdOx1 nCoV-19 vaccine recipients, 33.7 percent reported systemic side effects. [Lancet Infect Dis 2021;21:939-949]

Among those who received two doses of BNT162b2, systemic effects were less frequent after the first vs second dose (11.7 percent vs 22.0 percent; p<0.0001).

Reactogenicity was significantly higher after one dose of ChAdOx1 nCoV-19 than one dose of BNT162b2 (33.7 percent vs 13.5 percent; p<0.0001).

Local side effects were less common after the second vs first dose of BNT162b2 (68.5 percent vs 71.9 percent; p<0.0001) and after the first ChAdOx1 nCoV-19 dose (58.7 percent) vs the first BNT162b2 dose (p<0.0001).

Systemic effects were more frequent after the first ChAdOx1 nCoV-19 vs second BNT162b2 dose, while local effects were less frequent (p<0.0001 for both).

The most common systemic side effects were headache (7.8, 13.2, and 22.8 percent after the first and second doses of BNT162b2 and first dose of ChAdOx1 nCoV-19, respectively) and fatigue (8.4, 14.4, and 21.1 percent), and were most often reported within 24 hours of vaccination. The most common local effect was tenderness (57.2, 50.9, and 49.3 percent, respectively), and occurred most often the day after vaccination.  

Both local and systemic effects were generally short-lived, lasting approximately 1–2 days post-injection, the authors noted.

 

Factors influencing side effect risk

Compared with individuals without prior known SARS-CoV-2 infection, those with known prior infection were more likely to experience systemic side effects following a single dose of BNT162b2 (35.8 percent vs 12.3 percent; odds ratio [OR], 3.97), second dose of BNT162b2 (38.2 percent vs 20.6 percent; OR, 2.37), or first dose of ChAdOx1 nCoV-19 (53.1 percent vs 32.9 percent; OR, 2.31; p<0.0001 for all). Local side effects were also more common among those with vs without prior known SARS-CoV-2 infection (1.4 and 1.2 times higher after the first doses of ChAdOx1 nCoV-19 and BNT162b2, respectively).

“It is possible, although it remains to be tested, that this increased reactogenicity relates to increased immunogenicity,” noted the authors.

After the first BNT162b2 dose, systemic side effects were more common in recipients aged ≤55 vs >55 years (20.7 percent vs 10.6 percent; OR, 2.19; p<0.0001). A similar trend was noted in ChAdOx1 nCoV-19 recipients (46.9 percent vs 30.7 percent; OR, 1.99; p<0.0001). Side effects were also more common among women than men after the first BNT162b2 dose (16.2 percent vs 9.3 percent; OR, 1.89) and ChAdOx1 nCoV-19 dose (39.3 percent vs 26.2 percent; OR, 1.82; p<0.0001 for both). This trend with age and sex was also noted with the incidence of local side effects. 

 

Infection risk reduced post-vaccination

A subset of 67,293 and 36,329 recipients of the first BNT162b2 and ChAdOx1 nCoV-19 doses, respectively, who had either a PCR or lateral flow test post-vaccination was compared with 464,356 unvaccinated app users who had a test between January 4 and March 10, 2021. Of these, 3,106 vaccinated and 50,340 unvaccinated individuals tested positive for SARS-CoV-2.

Infection risk among vaccinated individuals was significantly lower than those of unvaccinated individuals 12–20 days post-vaccination (risk ratios [RRs], -58 and -39 percent for BNT162b2 and ChAdOx1 nCoV-19, respectively). One BNT162b2 dose was associated with a reduced infection risk compared with unvaccinated controls (RRs, -69 and -72 percent at 21–44 and 45–59 days post-vaccination, respectively), as was one ChAdOx1 nCoV-19 dose (RR, -60 percent at 21–44 days).

The reduced risk of infection was greater among vaccine recipients aged ≤55 vs >55 years (RR, -70 percent vs -61 percent) and without vs with ≥1 comorbidity (RR, -69 percent vs -54 percent). The reductions in risk were also slightly greater with BMI <30 vs ≥30 kg/m² and in females vs males.

 

Take-home message

“Our data will enable prediction of side effects based on age, sex, and past COVID-19 status to help update guidance to health professionals to reassure the population about the safety of vaccines,” the authors said.

They acknowledged that the use of self-reported data was a limitation and some of the systemic side effects reported may not necessarily have been vaccine related. Additionally, there was a possibility of selection bias in terms of who underwent testing post-vaccination. For instance, healthcare workers undergo more frequent testing compared with the overall population. The results also pertain to short-term effects. As such, further research is necessary to identify side effects that emerge in the long term, they said.