Low energy nebulization preserves integrity of SARS-CoV-2 mRNA vaccines for respiratory delivery.

Nebulization of mRNA therapeutics can be used to directly target the respiratory tract. A promising prospect is that mucosal administration of lipid nanoparticle (LNP)-based mRNA vaccines may lead to a more efficient protection against respiratory viruses. However, the nebulization process can rupture the LNP vehicles and degrade the mRNA molecules inside. Here we present a novel nebulization method able to preserve substantially the integrity of vaccines, as tested with two SARS-CoV-2 mRNA vaccines. We compare the new method with well-known nebulization methods used for medical respiratory applications. We find that a lower energy level in generating LNP droplets using the new nebulization method helps safeguard the integrity of the LNP and vaccine. By comparing nebulization techniques with different energy dissipation levels we find that LNPs and mRNAs can be kept largely intact if the energy dissipation remains below a threshold value, for LNP integrity 5-10 J/g and for mRNA integrity 10-20 J/g for both vaccines.

Risk of Aerosol Formation During High-Flow Nasal Cannula Treatment in Critically Ill Subjects.

BACKGROUND: There is a persistent concern over the risk of respiratory pathogen transmission, including SARS-CoV-2, via the formation of aerosols (ie, a suspension of microdroplets and residual microparticles after evaporation) generated during high-flow nasal cannula (HFNC) oxygen therapy in critically ill patients. This concern is fueled by limited available studies on this subject. In this study, we tested our hypothesis that HFNC treatment is not associated with increased aerosol formation as compared to conventional oxygen therapy. METHODS: We used laser light scattering and a handheld particle counter to detect and quantify aerosols in healthy subjects and in adults with acute respiratory disease, including COVID-19, during HFNC or conventional oxygen therapy. RESULTS: The use of HFNC was not associated with increased formation of aerosols as compared to conventional oxygen therapy in both healthy subjects (n = 3) and subjects with acute respiratory disease, including COVID-19 (n = 17). CONCLUSIONS: In line with scarce previous clinical and experimental findings, our results indicate that HFNC itself does not result in overall increased aerosol formation as compared to conventional oxygen therapy. This suggests there is no increased risk of respiratory pathogen transmission to health care workers during HFNC.

Measurement of small droplet aerosol concentrations in public spaces using handheld particle counters.

We measure aerosol persistence to assess the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in public spaces. Direct measurement of aerosol concentrations, however, has proven to be technically difficult; we propose the use of handheld particle counters as a novel and easily applicable method to measure aerosol concentrations. This allows us to perform measurements in typical public spaces, each differing in volume, the number of people, and the ventilation rate. These data are used to estimate the relation between the aerosol persistence time and the risk of infection with SARS-CoV-2.

Aerosol persistence in relation to possible transmission of SARS-CoV-2.

Transmission of SARS-CoV-2 leading to COVID-19 occurs through exhaled respiratory droplets from infected humans. Currently, however, there is much controversy over whether respiratory aerosol microdroplets play an important role as a route of transmission. By measuring and modeling the dynamics of exhaled respiratory droplets, we can assess the relative contribution of aerosols to the spreading of SARS-CoV-2. We measure size distribution, total numbers, and volumes of respiratory droplets, including aerosols, by speaking and coughing from healthy subjects. Dynamic modeling of exhaled respiratory droplets allows us to account for aerosol persistence times in confined public spaces. The probability of infection by inhalation of aerosols when breathing in the same space can then be estimated using current estimates of viral load and infectivity of SARS-CoV-2. The current known reproduction numbers show a lower infectivity of SARS-CoV-2 compared to, for instance, measles, which is known to be efficiently transmitted through the air. In line with this, our study of transmission of SARS-CoV-2 suggests that aerosol transmission is a possible but perhaps not a very efficient route, in particular from non-symptomatic or mildly symptomatic individuals that exhibit low viral loads.