A Longitudinal Study of BNT162b2 Vaccine-Induced Humoral Response and Reactogenicity in Health Care Workers with Prior COVID-19 Disease

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Abstract

Background

Current recommendations in the United States are that subjects with a previous history of COVID-19 disease receive the full 2 dose mRNA vaccine regimen. We tested the hypothesis that humoral immune responses and reactogenicity to a SARS-CoV-2 mRNA vaccine (BNT-162b2) differ qualitatively and quantitatively in subjects with prior SARS-CoV-2 infection versus infection-naïve subjects.

Methods

Health care workers (n=61) from a single academic institution with and without prior COVID-19 received two 30 µg doses of BNT162b2 vaccine 3 weeks apart. The COVID group (n=30) received vaccine approximately 7 months post infection. IgG antibody against the Spike receptor-binding domain (RBD), serum neutralizing activity and vaccine adverse reactions were assessed every 2 weeks for 56 days after the 1 st injection. A longitudinal design and long study duration allowed the onset, maximum response and initial decay rate of Spike IgG antibody to be assessed in each subject. In addition, Spike IgG antibody levels are expressed as µg / mL to provide normal values for clinical decision making.

Findings

Spike IgG responses were highly variable in both groups. However, the COVID group manifested rapid increases in Spike IgG antibody and serum neutralizing activity post 1 st vaccine dose but little or no increase in Spike IgG or serum neutralizing activity after the 2 nd dose. In fact, Spike IgG was maximum prior to the 2 nd dose in 36% of the COVID group and 0% of controls. Peak IgG antibody was lower but appeared to fall more slowly in the COVID than in the control group. Finally, adverse systemic reactions e.g., fever, headache and malaise, after both the 1 st and 2 nd injection were more frequent and lasted longer in the COVID group than in the control group.

Conclusions

Health care workers with prior COVID-19 demonstrate a robust, accelerated humoral immune response to the 1 st dose of the COVID-19 mRNA vaccine but attenuated response to the 2 nd dose. They also experience greater reactogenicity than controls. Accordingly, subjects with prior COVID-19 may require only a single dose of vaccine.

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