As COVID-19 restrictions are being lifted in the United States and elsewhere, this does not mean the pandemic is over but rather that we are learning to live with the virus. This means that everyone must understand the challenges we are up against and the value of vaccination to strengthen our resistance to infection. However, many people are concerned about the newness of these vaccines, the speed with which they were brought to market and the risk of side effects that may occur if they get vaccinated. Apart from clinical trials, there’s little information readily accessible about how people react to the COVID-19 vaccines and even less comparative information about different vaccines. This is where community-based insights from patient registries can help fill the gap.

Even as the timely arrival of the Moderna and Pfizer mRNA vaccines were welcomed by health leaders around the globe, widespread misinformation fuelled vaccine hesitancy in almost every country. The ‘infodemic’ of unverified information contributed to long-standing distrust, often in vulnerable and underserved communities, resulting in lower vaccination rates. This scenario likely contributed to avoidable spread of the virus.

Data from the US Census Bureau’s 2022 Household Pulse Survey (HPS) shows that there are at least seven states in the US with counties where 14-18.24% of citizens remain ‘strongly hesitant’ about getting vaccinated. This reluctance to get vaccinated poses a challenge to current efforts to control the progression of the disease and could have a significant impact on the pandemic’s trajectory. Moreover, this has major implications for public health, since vaccination has shown efficacy in reducing the severity of infection with the virus and the risk of persistent COVID-19 symptoms (also known as ‘long’ COVID).

Community-based research is invaluable for expanding our knowledge of practical health benefits and risks, including those from COVID-19, its treatments and its vaccines. Being able to describe and quantify the diversity in human reactions to infection and vaccination doesn’t just help the people being studied, but also provides valuable information for clinicians, payers and researchers. Here we describe a community-based study of short-term vaccine side effects in the hope that this information can help address the fears of people who are opposed to or uncertain about vaccination, by showing how people like them tolerated the vaccine.

‘Apart from clinical trials, there’s little information readily accessible about how people react to the COVID-19 vaccines and even less comparative information about different vaccines’

The research study
Under the auspices of The CARE Project, a web-based registry of volunteers have self-reported how COVID-19 infections, treatments and vaccines have affected them. Almost 7,000 volunteers who had received a vaccination between March and July 2021 agreed to provide information about which side effects, if any, they experienced from vaccinations. For study purposes, we looked at respondents who received either two doses of the Pfizer or Moderna vaccine or the single-dose Johnson & Johnson (J&J) vaccine.

Participant characteristics
Some characteristics of these community-based volunteers are described below:

• The majority (80%) of volunteers were women, a factor that was consistent across all the vaccine manufacturers
• There were small differences in the median age of COVID-19 vaccine recipients: Pfizer recipients had a median age of 45 years, Moderna recipients, 51 years and J&J recipients, 48 years
• 90% of respondents were white, whereas black people comprise 1.3%, Asians 1.6% and 3.6% reported being a combination of races
• A substantial number of these volunteers reported that they had various medical conditions before being vaccinated including anxiety (39.3%), depression (32.4%), insomnia or trouble sleeping (30.7%), characteristics that are common among people who respond to online surveys
• There were also small differences between those who received different vaccines in terms of tobacco smoking and education. Participants vaccinated with J&J included a higher percentage of smokers (13.6%) than those who received Moderna (9.7%) or Pfizer (8.4%) vaccines. Volunteers who received Pfizer or Moderna vaccines were more highly educated, with 63.5% having completed a four-year college degree, whereas only 50.5% of J&J vaccine recipients reported a college or other higher education.

The results of the study showed that very few people experienced severe allergic reactions or required hospitalisation. The side effects experienced by volunteers did not differ by race, age or body mass index, and most side effects had rapid resolution. These are reassuring findings, especially since there have been some concerns that the black community may be more reactive to the vaccines.
Most common reactions

Injection site reactions – generally pain and soreness – and fatigue were the most frequently reported side effects, with 78.9% and 70.3% respectively reporting these reactions. Headaches were reported by 49.0% of vaccine recipients. People who received two-dose vaccines, not surprisingly, reported more side effects than those who received a single-dose vaccine, with more reactions to the second dose than the first dose and Moderna vaccine recipients reported more side effects than those who received the Pfizer vaccine. Some people experienced muscle pain, fever or joint pain, which were also more frequent among Moderna recipients. Younger people were more likely to report vaccine side effects. As these side-effect reports decreased proportionately with age, the data suggests younger individuals are more sensitive, most likely because they have been exposed to fewer infectious diseases in their lifetimes than older people have.

Minimal hospitalisations
Only 3% of our study participants sought medical care for side effects of the vaccine, but only 0.3% (17 people) report having been hospitalised to treat side effects.

Protective factors
Older people reported fewer side effects than younger people, and interestingly, we found that people who had received an influenza vaccination prior to their COVID-19 vaccine had fewer reactions to the COVID-19 vaccine than those who had not been vaccinated against influenza.

Additional findings
Other discoveries included factors such as:

• Women reported experiencing more side effects than men or those who described themselves as transgender or having non-binary gender
• Younger people and those with autoimmune disorders were more likely to have difficulty carrying out self-care after the onset of side effects
• People with insomnia or lung disease were more likely to report three or more side effects, while those with diabetes were less likely to do so
• Nearly one-third of participants reported having missed a median of one day’s work after being vaccinated, possibly due in part to many employers giving their staff paid time off to be vaccinated.

The past two years have shone a spotlight on epidemiology, drawing extensive public attention to the discipline for the first time since the HIV/AIDS epidemic. This offers us an opportunity to educate people and teach them to think critically about the information they get. For example, it is essential to examine systematic evidence available about the vaccine and its use in humans, rather than anecdotal evidence of people reporting side effects with no regard for how common such reactions are and whether those who reported the side effects had medical conditions that put them at higher risk. People should closely examine the information they receive, determine where it came from, how it was collected and if the analysis originated from a trusted source with reputable scientific credentials. Experience and track record matter.

The community-based insights from this study provide us with an opportunity to reshape the conversation. While we need to keep an eye open for delayed vaccine benefits and risks, we should be sharing information about the short-term and highly transient nature of vaccine side effects. Is having a sore arm for a day worse than risking a serious and persistent COVID-19 infection?

Total eradication of any virus is a long-game strategy. We all want to improve our chances of not getting seriously ill and returning to everyday life as soon as possible.
Leveraging patient-reported information from vaccinated and unvaccinated individuals, including those who become infected with COVID-19, will allow us to understand how well these vaccines mitigate the seriousness of any infection.

We need to give people more reasons to believe in the vaccine, instead of simply telling them what they ‘must’ do. We also need to give them more information about the trade-offs – is it worse to get COVID-19 than to be vaccinated? How likely are asymptomatic cases? The value of community-based registries, where people can contribute to scientific evidence generation and share their experience without interference or intervention by a healthcare provider, should go a long way to addressing the concerns of people who are willing to listen and consider scientific evidence.