Adverse Events After COVID-19 Vaccination More Likely With Previous Infection

Individuals previously infected with COVID-19 were more likely to experience adverse events following vaccination compared with those with no history of infection.

Previous COVID-19 infection significantly increases the risk for adverse events (AEs) following COVID-19 vaccination, though the risk is attenuated over time with repeated vaccine doses, according to study findings published in Clinical Infectious Diseases.

Evidence suggests adults who develop short-term immunity to the SARS-CoV-2 virus during infection may react more intensely to COVID-19 vaccination.

Researchers in Canada conducted a prospective, multicenter, active surveillance cohort study between December 2020 and November 2021 to investigate the short-term safety of COVID-19 vaccination in adults previously infected with COVID-19. The primary outcome was the occurrence of AEs capable of preventing daily activities within 7 days of COVID-19 vaccination. Outcome data was self-reported via an online questionnaire.

A total of 684,998 individuals who were vaccinated against COVID-19 infection were included in the analysis. Of these individuals, 369,406 received the BNT162b2 vaccine, 201,314 received the mRNA1273 vaccine, and 113,127 received the ChAdox1-S vaccine. There were 18,127 (2.6%) individuals who reported previous COVID-19 infection. The median time between infection onset and receipt of the first vaccine dose was 4 months.

Within 1 week of receipt of the first vaccine dose, a higher percentage of previously infected individual experienced AEs capable of interfering with daily activities compared with those with no history of COVID-19 infection (range, 12%-16% vs 3%-12%, respectively).

The percentage of individuals who experienced severe AEs requiring emergency department admission or hospitalization following vaccination also was increased among those who were vs were not previously infected with COVID-19 (range, 0.6%-0.7% vs 0.2%-0.5%).

Previously infected individuals demonstrated attenuated reactivity to the second and third COVID-19 vaccine doses compared with the first dose. After receipt of a booster dose (dose 3), the researchers noted that COVID-19 mRNA vaccines continued to produce increased immune reactions in previously infected individuals, whereas the adenoviral vector vaccine did not.

Providers should consider additional vaccine counseling on expected adverse effects for SARS-CoV-2 previously infected individuals prior to vaccination.

The researchers performed a multivariable logistic regression analysis, controlling for age, sex, and health status. Compared with individuals with no history of infection, those who were previously infected with moderate or severe COVID-19 had an increased risk for AEs capable of interfering with daily activities following receipt of the first vaccine dose. The highest risk was observed among previously infected individuals who received the mRNA-1273 vaccine (adjusted odds ratio [aOR], 5.01; 95% CI, 4.57-5.50), followed by those who received the BNT162b2 vaccine (aOR, 3.96; 95% CI, 3.67-4.28) and those who received the ChAdox1-S vaccine (aOR, 1.84; 95% CI, 1.54-2.20).

In contrast, this association between previous COVID-19 infection and an increased risk for AEs following vaccination was reduced or absent in individuals who self-reported asymptomatic or mild infection.

Study limitations include potential recall bias and the inability to verify AE occurrence due to the use of self-reported data. These results also may not be generalizable to all patient populations.

According to the researchers, “Providers should consider additional vaccine counseling on expected adverse effects for SARS-CoV-2 previously infected individuals prior to vaccination.

This article originally appeared on Infectious Disease Advisor


Bettinger JA, Irvine MA, Shulha HP, et al. Adverse events following immunization with mRNA and viral vector vaccines in individuals with previous SARS-CoV-2 infection from the Canadian National Vaccine Safety Network. Clin Infect Dis. Published online October 31, 2022. doi:10.1093/cid/ciac852