Does Trypsin Oral Spray (Viruprotect®/ ColdZyme®) Protect against COVID-19 and Common Colds or Induce Mutation? Caveats in Medical Device Regulations in the European Union

Background: nasal or oral sprays are often marketed as medical devices (MDs) in the European Union to prevent common cold (CC), with ColdZyme®/Viruprotect® (trypsin/glycerol) mouth spray claiming to prevent colds and the COVID-19 virus from infecting host cells and to shorten/reduce CC symptoms as an example We analyzed the published (pre)-clinical evidence Methods: preclinical: comparison of in vitro tests with validated host cell models to determine viral infectivity Clinical: efficacy, proportion of users protected against virus (compared with non-users) and safety associated with trypsin/glycerol Results: preclinical data showed that exogenous trypsin enhances SARSCoV2 infectivity and syncytia formation in host models, while culture passages in trypsin presence induce spike protein mutants The manufacturer claims >98% SARSCoV2 deactivation, although clinically irrelevant as based on a tryptic viral digest, inserting trypsin inactivation before host cells exposure Efficacy and safety were not adequately addressed in clinical studies or leaflets (no COVID-19 data) Protection was obtained among 9–39% of users, comparable to or lower than placebo-treated or non-users Several potential safety risks (tissue digestion, bronchoconstriction) were identified Conclusions: the current European MD regulations may result in insufficient exploration of (pre)clinical proof of action Exogenous trypsin exposure even raises concerns (higher SARS-CoV-2 infectivity, mutations), whereas its clinical protective performance against respiratory viruses as published remains poor and substandard