COVID-19 Vaccines and Fever: Scientists Have Discovered a New Potential Link

mRNA COVID-19 vaccines are a type of vaccine that uses a small piece of the virus’s genetic material, called messenger RNA (mRNA), to help the body’s immune system recognize and fight the virus that causes COVID-19. mRNA vaccines have been shown to be effective at preventing COVID-19 infection and have been authorized for use by regulatory agencies around the world.

There has been some concern about the side effects of mRNA COVID-19 vaccines, such as fever and fatigue, which are generally considered normal and transient. However, the relationship between these adverse reactions and antibody production after receiving the vaccine has not been thoroughly studied.

A team of researchers from Okayama University recently conducted a study to examine this link. They recruited 49 university staff and students who had not previously had COVID-19 and found that there is a relationship between the incidence of fever and antibody counts, particularly after the third dose of the vaccine. Their findings were published in the Journal of Epidemiology.

mRNA vaccines mimic the surface structure of SARS-CoV-2 in the body. These are then recognized as invading pathogens by immune cells, which create antibodies against them. As a result, antibody counts may be used to quantify the immune system’s response to vaccination.

Immunoglobulin G (IgG) dynamics in the first week after vaccination by presence or absence of post-vaccination fever. The red and blue lines show the IgG concentration means predicted by the mixed-effects model in the febrile and nonfebrile groups, respectively. The area of each color indicates the 95% confidence interval (CI) of the regression curve. Day 0 is a negative value owing to the effect of the modeling prediction. Credit: Yorifuji Takashi, Okayama University

All subjects were surveyed for adverse reactions a week after they received the third mRNA-1273 vaccine dose. Simultaneously, antibody levels of all subjects were measured just before receiving the vaccine, 3 days after, ~1 week after, and finally 1 month after the dose. Using statistical modeling, correlations between the incidence of fever and antibody levels at various time points were stipulated. To account for factors contributing to the onset of fever post-vaccination, the team also looked at sex, age differences, a history of allergy, and the use of antipyretics (fever-reducing drugs) amongst the participants.

The subjects were then classified into a “fever” or “non-fever” group based on the survey results. It was found that the fever group was more likely to be younger (20 to 49 years old) and had a past history of allergies. Next, antibody levels at different time points in the two groups were analyzed. At 1 week post-vaccination, the fever group had substantially higher antibody counts than the non-fever group. However, at 1-month post-vaccination there seemed to be no correlation between the incidence of fever and high antibody levels.

This is the first study to highlight associations between the induction of fever and antibody levels at various time points after the third dose of the mRNA-1273 vaccine. “Antibody titers after mRNA-1273 vaccination may be faster in the group with post-vaccination fever, but the difference may not be significant 1-month post-vaccination,” concludes the team. The researchers also suggest that while these contradictory observations may not have significant clinical relevance, a study with a larger sample size might provide better insights.

Reference: “Association Between Fever and Antibody Titer Trends After a Third Dose of the mRNA-1273 Vaccine” by Naomi Matsumoto, Tomoka Kadowaki, Rumi Matsuo, Ayako Sasaki, Chikara Miyaji, Chigusa Higuchi, Masanori Nakayama, Yasue Sakurada, Hideharu Hagiya, Soshi Takao, Fumio Otsuka and Takashi Yorifuji, 5 December 2022, Journal of Epidemiology.
DOI: 10.2188/jea.JE20220210


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