Relation of fever intensity and antipyretic use with specific antibody response after two doses of the BNT162b2 mRNA vaccine

Vaccine. 2022 Mar 18;40(13):2062-2067. doi: 10.1016/j.vaccine.2022.02.025. Epub 2022 Feb 14.


Background: The reactogenicity of BNT162b2 COVID-19 vaccine has been commonly reported and antipyretic medications are often used for mitigating adverse reactions. Possible associations between the reactogenicity events and specific antibody responses have not been fully investigated, nor has the influence of using antipyretics.

Methods: Serum samples were collected from hospital healthcare workers with no COVID-19 history and the SARS-CoV-2 spike-specific IgG titer after two doses was measured. Degree of solicited adverse reactions in a day, including the highest body temperature, were reported using a self-reporting diary for five days after each dose. The highest body temperature during the five days was divided into three grades (<37.0 °C, 37.0-37.9 °C, or ≥ 38.0 °C). Self-medicated antipyretics were reported using a questionnaire.

Results: The data of 335 participants were available for analysis. Multivariate analysis extracted the fever grade after the second dose (standardized coefficient beta = 0.301, p < 0.0001), female sex (beta = 0.196, p = 0.0014), and age (beta = -0.119, p = 0.0495) as being significantly correlated with the IgG titers. The positive correlation of the fever grade after the second dose with the IgG titers was also observed when analyzed by sex and age. The use of antipyretics did not interfere with the IgG titers irrespective of the fever grade.

Conclusions: The fever intensity after the second dose was associated with the IgG titer and antipyretic medications may be beneficial to mitigate the suffering from adverse reactions, without interfering with the acquisition of sufficient antibody responses.

Keywords: Antibody; Antipyretic; Reactogenicity; SARS-CoV-2; Vaccine.

MeSH terms

  • Antibodies, Viral
  • Antibody Formation
  • Antipyretics*
  • BNT162 Vaccine
  • COVID-19 Vaccines / adverse effects
  • COVID-19* / prevention & control
  • Female
  • Humans
  • SARS-CoV-2
  • Vaccines, Synthetic
  • mRNA Vaccines


  • Antibodies, Viral
  • Antipyretics
  • COVID-19 Vaccines
  • Vaccines, Synthetic
  • mRNA Vaccine
  • mRNA Vaccines
  • BNT162 Vaccine