The severity of systemic adverse effects (AEs) reported after receipt of a second COVID-19 vaccine dose was associated with prior negative vaccine-related experiences, negative expectations about the benefits of vaccination, and the tendency to catastrophize benign bodily sensations. These study results were published in JAMA Network Open.

This prospective, longitudinal cohort study was conducted in Hamburg, Germany in August 2021. Researchers examined whether the severity of systemic AEs following receipt of a second dose of an mRNA-based COVID-19 vaccine was associated with negative expectations prior negative experiences related to vaccination. The primary outcome was a composite severity index of systemic AEs across 12 symptom areas. Systemic AE severity was measured once daily for 7 consecutive days via electronic symptom diary. Data captured from the analysis were assessed via mixed-effects multivariable ordered logistic regression, with adjustments for prevaccine symptom levels and observation times. Study participants reported expected benefits and risks and personal and observed prior experiences related to COVID-19 vaccination using a self-developed scale.

Among 1638 participants included in the final analysis, the median age was 34 years, 48.2% were men, 55.1% had a tertiary level education, and 77.3% and 22.7% received the BNT162b2 and mRNA-1273 vaccines, respectively. Overall, severe AEs following receipt of the first vaccine dose were reported by 220 (13.1%) participants, and severe AEs previously observed among close contacts were reported by 410 (24.6%) participants.

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In regard to participants’ expectations following receipt of the second COVID-19 vaccine dose, 90.3% expected a high benefit, 47.9% expected to be at increased risk for COVID-19 infection, and 31.6% expected to be at increased risk for COVID-19-related hospitalization. Other expectations, including an increased risk for systemic AEs, hospitalization due to AEs, and long-term AEs were reported among 52.1%, 7.6%, and 10.1% of participants, respectively.

Participants with high Somatosensory Amplification Scale scores were found to be at increased risk for more severe systemic AEs (odds ratio [OR], 1.21; 95% CI, 1.06-1.38; P =.004). Similar findings were observed among participants who reported higher levels of anxiety and depression (OR, 1.15; 95% CI, 1.06-1.38; P =.004). Other factors significantly associated with increased risk for more severe systemic AEs included negative expectations about the benefits of vaccination, higher expectations for AEs, and prior negative experiences following receipt of the first vaccine dose (all P <.001).

Of note, previously observed AEs among close contacts were not associated with systemic AE risk following receipt of the second vaccine dose.

The researchers found that the risk for AEs after COVID-19 vaccination increased with the severity of symptoms reported at baseline, suggesting misattribution of preexisting symptoms. However, neither expectations for COVID-19 infection nor COVID-19-related hospitalization were associated with the occurrence of AEs following vaccination.

Limitations of this study include potential selection bias, the predominance of participants younger than 50 years, and a study population that was not fully representative of the general public. In addition, the researchers did not conduct a sample size calculation.

According to the researchers, “Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines.”


Schäfer I, Oltrogge JH, Nestoriuc Y, et al. Expectations and prior experiences associated with adverse effects of covid-19 vaccinationJAMA Netw Open. 2023;6(3):e234732. doi:10.1001/jamanetworkopen.2023.4732

This article originally appeared on Infectious Disease Advisor