Abstract

Background
Bronchospasm has been reported as an early reaction after BNT162b2 vaccination in asthmatic patients.
Aim
To assess the impact of BNT162b2 on the sensitivity to histamine in in human hyperresponsive airways.
Methods
Human isolated airways were passively sensitized overnight and then challenged 45 min with the platelet-activating factor (100 nM) to reproduce ex vivo the condition of airways of subjects suffering from severe eosinophilic asthma. Airways were mounted in an isolated organ bath system. The effect of different concentrations of BNT162b2 was tested on the basal resting tone and airways partially pre-contracted by histamine at EC20. BNT162b2 was also tested on the concentration-response curve to histamine. Some experiments were performed by using BNT162b2 after mRNA denaturation.
Results
BNT162b2 100-1000 ng/ml weakly modified in the basal resting tone (+10.6±3.2 vs. control, P<0.05) whereas at 1-1000 ng/ml increased the contractility histamine EC20 (+56.1±10.34 vs. control, P<0.05). BNT162b2 1 ng/ml enhanced the potency of histamine (pEC50: BNT162b2 -5.4±0.1, control -4.4±0.2; P<0.01). The increased sensitivity to histamine was not significantly reduced by mRNA denaturation.
Conclusions
Low concentrations of BNT162b2 enhanced the sensitivity to histamine, an effect related to the excipients of vaccine, since mRNA denaturation did not prevent the hyperresponsiveness. This study supports the risk of exacerbation in asthmatic patients after COVID-19 vaccination. This research was granted by University of Parma through the action Bando di Ateneo 2021 per la ricerca co-funded by MUR-Italian Ministry of Universities and Research - D.M. 737/2021 - PNR - PNRR ? NextGenerationEU.