The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma

Abstract

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Significant association between asthma and a lower risk of mortality among COVID-19 patients in Spain: A meta-analysis

“… 2 , 3 The available evidence suggests that COVID-19 vaccination is the dominant strategy against severe outcomes and mortality of COVID-19, 4 while asthmatic patients were considered a higher risk group for severe bronchospasm after COVID-19 vaccine injection. 5 Then asthma was also identified as an independent variable that was significantly associated with low vaccination rates. 6 Additionally, the Barcelona study showed that asthmatic patients were not susceptible to the SARS-CoV-2 virus, on the contrary, patients with T2 asthma were even immune to the virus to a high degree.…”

Use of human airway smooth muscle in vitro and ex vivo to investigate drugs for the treatment of chronic obstructive respiratory disorders

“…Indeed, this worrying percentage fully justifies the search for new and improved therapies to treat these conditions. Unfortunately, the costs and time necessary for the development and approval of new effective drugs for the treatment of chronic obstructive respiratory disorders are increasing (Calzetta, Chetta, et al, 2023a) and apart from the introduction of some monoclonal antibodies (mAbs) for the treatment of severe asthma and COPD with type 2 inflammation, the cornerstone treatments used in the majority of patients with asthma or COPD still remains focused on pharmacological classes of drugs that have been around for decades, such as bronchodilators and corticosteroids (Bhatt et al, 2023; GINA, 2023a; GOLD, 2023). Certainly, mAbs have significantly changed the management of severe asthma, however their use is restricted to a small proportion of patients (GINA, 2023b).…”

“…approval of new effective drugs for the treatment of chronic obstructive respiratory disorders are increasing(Calzetta, Chetta, et al, 2023a) and apart from the introduction of some monoclonal antibodies (mAbs) for the treatment of severe asthma and COPD with type 2 inflammation, the cornerstone treatments used in the majority of patients with asthma or COPD still remains focused on pharmacological classes of drugs that have been around for decades, such as bronchodilators and corticosteroids(Bhatt et al, 2023; GINA, 2023a; …”