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.

Suzy Huijghebaert,Myriam Van Winckel,Karel Allegaert,Guido Vanham

doi:10.3390/ijerph18105066

Abstract

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 SARS-CoV-2 infectivity and syncytia formation in host models, while culture passages in trypsin presence induce spike protein mutants. The manufacturer claims >98% SARS-CoV-2 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.

Highlights

During the COVID-19 pandemic, numerous oral and nasal sprays have been investigated and promoted, each claiming to protect against viral infection and COVID-19 in particular
CZ-medical devices (MDs) claims to kill or inactivate the “human coronavirus” and SARS-CoV-2, as well as rhinovirus, adenovirus, influenza and respiratory syncytial virus (RSV), based on in vitro trypsin digests performed in laboratory tubes, and is stopped by adding a
While small mutation in virus appear to be common upon passages of coronaviruses in Vero cells, the findings suggest that trypsin may facilitate their formation and lead to mutant variants with distinct clinically relevant properties, facilitating infectivity: while for instance a spike gene mutants were common in in serum-free cultures of SARS-CoV-2 in presence of trypsin, these were not detected during the propagation in TMPRSS2 expressing

Summary

Introduction

During the COVID-19 pandemic, numerous oral and nasal sprays have been investigated and promoted, each claiming to protect against viral infection and COVID-19 in particular. A recent review identified 14 such sprays in development, all with ongoing studies, reflecting the appropriateness to generate data on efficacy and safety—both preclinical and clinical—before marketing such products [1]. A scoping internet search by us identified a wealth of promising treatments for the nose and throat against COVID-19, while a number of these sprays are already marketed as medical devices (MDs) in Europe. Such oral or nasal sprays may enter the European Economic Area (EEA) as MDs, as MDs are not conditioned the same way as medicines [2,3].

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