Correlation of post-vaccination fever with specific antibody response to SARS-CoV-2 BNT162b2 booster and no significant influence of antipyretic medication

Abstract

Background: A SARS-CoV-2 mRNA vaccine booster elicits sufficient antibody responses that protect against COVID-19, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 two-dose primary series. Spike-specific IgG titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for seven days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (beta=0.305, p<0.001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk: 3.97 [95% confidence interval: 2.48-6.35]); however, the IgG titers after the booster dose were not affected by fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions would not interfere with the elevation of specific IgG titers.

No evidence that analgesic use after COVID-19 vaccination negatively impacts antibody responses

“…Unlike animal models of SARS-CoV-2 infections ( 17), several prior studies observed no detriment to post-vaccination antibody responses by analgesic use, but differed on whether their use was in fact associated with elevated titers (18)(19)(20). A causal positive relationship between analgesic use and antibody levels would be unexpected, but in theory might be explained by the suppression of inflammation that is detrimental to B cell responses (24)(25)(26)(27)(28)(29)(30).…”

“…It remains unclear whether these same inhibitory effects are seen in humans after mRNA vaccination and how different classes of painkillers impact the antibody response. Several prior studies have suggested minimal or even positive impacts of antipyretic use on antibody responses (18)(19)(20). Further analysis of their impact, independent of symptoms and inflammation, as well as subgroup analyses on variables such as age, vaccine type, and the class of analgesics, would be valuable to help interpret these findings.…”