A new study found negative expectations prior to COVID-19 vaccination were associated with more systemic adverse events in individuals receiving their second dose of a COVID-19 vaccine.
COVID-19 vaccines are proven to reduce infection, morbidity, and mortality, even against the newest emerging COVID-19 variants, but they are only effective if a high proportion of the population gets vaccinated.
Since COVID-19 vaccines first became available, their rollout was significantly hindered by fears of adverse events. Concerns about the side effects of COVID-19 vaccination remain a significant contributor to vaccine hesitancy.
There are undoubtedly some adverse events that follow COVID-19 vaccination, including myalgia, fever, and short-term fatigue. However, psychological factors, including nocebo effects, can exacerbate the symptom burden. Nocebo effects occur when individuals taking inert substances experience adverse events.
Negative expectations, anxiety, depression, and a proclivity to heighten benign bodily sensations lead to higher reported adverse events, both for active drugs and nocebo effects. However, there has not been extensive research into whether positive vaccination attitudes and a low concern of COVID-19 vaccine adverse events lower the likelihood of experiencing vaccine side effects.
A new study, published yesterday in JAMA Network Open, examined whether positive and negative expectations prior to COVID-19 vaccination were associated with systemic adverse events in individuals receiving their second dose of a COVID-19 vaccine. The investigators theorized, “severity of systemic adverse effects would be increased in participants with lower benefit expectations, with higher expectations of adverse effects, and with more of their personal and observed prior experiences regarding adverse reactions to COVID-19 vaccines, after controlling for prevaccine symptom levels.”
This longitudinal cohort study was conducted at the COVID-19 vaccination center in Hamburg, Germany. Participants were recruited locally, between August 16-28, 2021. Eligible participants were those receiving a second dose of the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA–1273) COVID-19 vaccine to complete their primary series. Additional inclusion criteria were 18 years or older, sufficient German language skills, and capacity to consent.
Included participants completed a baseline questionnaire immediately following vaccination. The first follow-up questionnaire was activated at 9 pm that day, with remaining follow-ups activated at 6 pm on days 2-7.
The primary study outcome was a composite severity index of systemic adverse effects, measured via an electronic symptom diary participants completed for 7 consecutive days. “Systemic adverse events” were defined as whole-body reactions, such as body aches or fever, that occurred in the days following vaccination. Allergic reactions that occurred minutes after vaccination or local adverse effects that occurred within a few hours of vaccination were not included in the final analyses.
Complete data sets were provided by 1096 participants, for a cohort that averaged 34 years of age and was 51.4% female. A total of 77.3% of participants received the Pfizer-BioNTech vaccine, while 22.7% received Moderna.
At 90.3%, most participants had high benefit expectations of COVID-19 vaccination. Simultaneously, 47.9% of participants expected they were at high risk for COVID-19, and 31.6% expected they were at high risk of COVID-19—related hospitalization.
After vaccination, 52.1% of participants anticipated a high risk of systemic adverse events, 7.6% expected a high risk of hospitalization due to adverse events, and 10.1% expected a high risk of long-term adverse events. Severe adverse events after receiving the first COVID-19 vaccine dose were reported by 13.1% of participants.
During the 7 days of follow-up, 63.7% of participants reported tiredness or fatigue, 52.7% reported headache, 44.8% reported aching limbs, 36.1% reported joint pain, 32.4% reported chills, and 24.3% reported fever.
More severe adverse events were reported by participants who expected a lower benefit of vaccination, expected higher adverse events after vaccination, or experienced a higher symptom burden after their first vaccine dose.
Individuals with higher scores in anxiety and depression reported more symptoms in some observed categories. Generally, women reported more severe symptoms than male or nonbinary participants. More adverse effects were also reported in persons who received the Moderna vaccine, as opposed to those who received Pfizer-BioNTech.
The investigators concluded that severity and frequency of systemic adverse events in the week after COVID-19 vaccination “was not only caused by vaccine-specific reactogenicity but also by psychosocial context factors that can be identified prior to vaccination.” The 3 major contributors to nocebo effects included personal prior reactions to the first COVID-19 vaccination, individual expectations regarding potential harms and benefits of vaccination, and symptom misattribution.
Clinician-patient visits and public vaccine campaigns stand to benefit from these results, the study authors noted. Contextualizing information about COVID-19 vaccines, and being transparent about their risk-benefit profiles, could improve overall vaccine acceptance.