Fever after Vaccination against SARS-CoV-2 with mRNA-Based Vaccine Associated with Higher Antibody Levels during 6 Months Follow-Up

Abstract

Background: The effect of post-vaccination adverse events on immunogenicity is unknown. We aimed to explore relationship between post-vaccination adverse reactions and antibody levels during 6-month follow-up.

Methods: Blood was serially drawn from healthcare workers after the second dose of BNT162b2 mRNA vaccine (Day 12, 30, 60, 90, 120, 150, and 180) and anti-SARS-CoV-2 spike IgG (S-IgG) levels were measured. Following each vaccine dose, volunteers completed a questionnaire regarding adverse reactions (symptomatic vs. asymptomatic groups).

Results: A total of 395 subjects received the second dose of the vaccine. The main results were as follows: (i) fever after the 2nd dose was independently associated with the median S-IgG level at all follow-up time points; (ii) significantly higher S-IgG levels were observed in the symptomatic group of patients without prior COVID-19 infection throughout the entire follow-up period; (iii) prior COVID-19 positivity resulted in higher S-IgG levels only in the asymptomatic group from Day 90 of the follow-up period; (iv) both prior COVID-19 disease with asymptomatic status and symptomatic status without prior COVID-19 infection resulted in similar S-IgG antibody levels; (v) significantly lower serum S-IgG levels were observed in smokers.

Conclusion: Fever may play an important role in the post-vaccination immune response in the long term.

Keywords: COVID-19; adverse reaction; anti-SARS-CoV-2; fever; mRNA vaccine; spike IgG.

Figure 2

Comparison of serum level of anti-SARS-CoV-2 IgG at (A) 12, 30, 60 and (B) 90, 120, 150, 180 days after the 2nd dose of vaccination (BNT162b2 mRNA) in patients without or with at least one adverse reaction after each vaccine dose. The data are provided as median and interquartile range. The between-group differences were calculated by the Kruskal–Wallis test.

Figure 3

Comparison of serum levels of anti-SARS-CoV-2 IgG at (A) 12, 30, 60 and (B) 90, 120, 150, 180 days after the 2nd dose of vaccination (BNT162b2 mRNA). Healthcare workers were divided into four study groups: Group 1 = individuals without prior SARS-CoV-2 infection and with no adverse reaction after vaccination; Group 2 = individuals without prior SARS-CoV-2 infection and with at least one adverse reaction after vaccination; Group 3 = individuals with prior SARS-CoV-2 infection and with no adverse reaction after vaccination; Group 4 = those who had prior SARS-CoV-2 infection and at least one adverse reaction after vaccination. Sample size at each follow-up time point is shown in table below.

Figure 1

Correlation of serum level of S-IgG and age at Day 12, Day 90, and Day 180 follow-up visit after the 2nd dose of BNT162b2 mRNA (Pfizer/BioNTech, Comirnaty) vaccine. Values are Spearman correlation coefficients (rho). S-IgG; anti-spike immunoglobulin G, mRNA; messenger ribonucleic acid.