Lack of reaction to the COVID-19 shot doesn’t mean it’s not working

You may have had a sore arm, felt tired, or had a headache. Maybe you ran a slight fever. You might have heard these things happen because your COVID-19 shot is working as it should. On the other hand, a lack of side-effects does not point to vaccine failure, according to a new study.

The relationship between a reaction to COVID-19 vaccines and the strength of antibody response to the vaccine has been somewhat uncertain. So, a research collaboration including Frederick National Laboratory (FNL) and led by the Uniformed Services University of the Health Sciences (USU) conducted a single-center observational study to find out more. Results were published recently in the journal Open Forum Infectious Diseases.

A total of 206 healthy volunteers who work at Walter Reed National Military Medical Center in Bethesda, Md., enrolled in the study that began in August 2020. At the first monthly visit following each dose of the Pfizer/BioNTech vaccine, each volunteer completed a questionnaire about their physical reactions to the shot.

The volunteers rated 12 symptoms on an intensity scale of 0 to 4. Symptoms included soreness at the vaccination site, weakness, headache, and body aches. The volunteers reported that these symptoms increased in frequency after the second shot.

After each vaccination, antibody levels were also measured using a reliable assay. Results of these tests showed no correlation between the severity of symptoms and levels of antibodies produced by the vaccine. All volunteers had similar antibody responses to the vaccine. This was true following both the first and second doses. 

“It has become commonplace for media outlets and medical professionals to state that presence of symptoms means that a vaccine is ‘working,’” the researchers reported. “Although this statement is fundamentally true because vaccines ‘work’ by inducing inflammatory responses, it also implies incorrectly that lack of symptoms post-vaccination may indicate an absence of appropriate antiviral antibody responses.”

The study showed that after each shot, local symptoms were most common, such as pain, soreness, and redness. These reactions are like those seen in clinical trials of the Pfizer/BioNTech vaccine. Systemic symptoms -- such as feeling weak or tired or having body aches -- were less common and occurred at about the same frequency as seen in the vaccine clinical trials. 

The Pfizer/BioNTech vaccine uses molecules of genetic material (messenger RNA) to stimulate an immune response and generate antibodies against the coronavirus. The current study appears to show that side effects from the vaccine and the antibody response it provokes might arise from different parts of a person’s immune system. This suggests that future vaccines might be designed to have fewer side effects but still protect against serious disease. 

John Powers III, M.D., of FNL’s Clinical Research Program collaborated on the study led by Edward Mitre of USU, along with others from the Henry M. Jackson Foundation for the Advancement of Military Medicine, General Dynamics Information Technology, and the Naval Medical Research Center.