Systemic Adverse Effects Induced by the BNT162b2 Vaccine Are Associated with Higher Antibody Titers from 3 to 6 Months after Vaccination

Ryousuke Koike; Michiru Sawahata; Yosikazu Nakamura; Yushi Nomura; Otohiro Katsube; Koichi Hagiwara; Seiji Niho; Norihiro Masuda; Takaaki Tanaka; Kumiya Sugiyama

doi:10.3390/vaccines10030451

Systemic Adverse Effects Induced by the BNT162b2 Vaccine Are Associated with Higher Antibody Titers from 3 to 6 Months after Vaccination

Vaccines (Basel). 2022 Mar 15;10(3):451. doi: 10.3390/vaccines10030451.

Authors

Ryousuke Koike^{1

2}, Michiru Sawahata^{1

3}, Yosikazu Nakamura⁴, Yushi Nomura^{1

2}, Otohiro Katsube¹, Koichi Hagiwara³, Seiji Niho², Norihiro Masuda⁵, Takaaki Tanaka⁶, Kumiya Sugiyama^{1

7}

Affiliations

¹ Department of Respiratory Medicine and Clinical Immunology, National Hospital Organization Utsunomiya National Hospital, Utsunomiya 329-1193, Japan.
² Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University, Shimotsuga 321-0293, Japan.
³ Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, Shimotsuke 329-0498, Japan.
⁴ Department of Public Health, Jichi Medical University, Shimotsuke 329-0498, Japan.
⁵ Department of Surgery, National Hospital Organization Utsunomiya National Hospital, Utsunomiya 329-1193, Japan.
⁶ Department of Orthopaedic Surgery, National Hospital Organization Utsunomiya National Hospital, Utsunomiya 329-1193, Japan.
⁷ Department of Respiratory Medicine and Clinical Immunology, Saitama Medical Center, Dokkyo Medical University, Shimotsuga 321-0293, Japan.

Abstract

Objective: We aimed to determine the relationship between vaccine-related adverse effects and antibody (Ab) titers from 3 to 6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) in Japan.

Methods: We enrolled 378 healthcare workers (255 women and 123 men) whose Ab titers were analyzed 3 and 6 months after the second dose in our previous study and whose characteristics and adverse effects were collected previously by using a structured self-report questionnaire.

Results: The workers' median age was 44 years. Although injection-site symptoms occurred with almost equal frequency between the first and second doses, systemic adverse effects, such as general fatigue and fever, were significantly more frequent after the second dose than after the first dose. Multivariate analysis showed that fever was significantly correlated with female participants for the second dose (odds ratio (OR), 2.139; 95% confidence interval (95% CI), 1.185-3.859), older age for the first dose (OR, 0.962; 95% CI, 0.931-0.994) and second dose (OR, 0.957; 95% CI, 0.936-0.979), and dyslipidemia for the first dose (OR, 8.750; 95% CI, 1.814-42.20). Age-adjusted Ab titers at 3 months after vaccination were 23.7% and 23.4% higher in patients with a fever than in those without a fever after the first and second dose, respectively. In addition, age-adjusted Ab titers at 3 and 6 months after the second dose were, respectively, 21.7% and 19.3% higher in the group in which an anti-inflammatory agent was used than in the group without the use of an anti-inflammatory agent.

Conclusion: Participants with systemic adverse effects tend to have higher Ab titers from 3 to 6 months after the second dose of the BNT162b2 vaccine. Our results may encourage vaccination, even among people with vaccine hesitancy related to relatively common systemic adverse effects.

Keywords: SARS-CoV-2; adverse effect; clinical epidemiology; viral infection.