Transmission-blocking strategies that slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protect against coronavirus disease 2019 (COVID-19) are needed. We have developed an orally delivered adenovirus type 5–vectored SARS-CoV-2 vaccine candidate that expresses the spike protein. Here, we demonstrated that hamsters vaccinated by the oral or intranasal route had robust and cross-reactive antibody responses. We then induced a postvaccination infection by inoculating vaccinated hamsters with SARS-CoV-2. Orally or intranasally vaccinated hamsters had decreased viral RNA and infectious virus in the nose and lungs and experienced less lung pathology compared to mock-vaccinated hamsters after SARS-CoV-2 challenge. Naïve hamsters exposed in a unidirectional air flow chamber to mucosally vaccinated, SARS-CoV-2–infected hamsters also had lower nasal swab viral RNA and exhibited fewer clinical symptoms than control animals, suggesting that the mucosal route reduced viral transmission. The same platform encoding the SARS-CoV-2 spike and nucleocapsid proteins elicited mucosal cross-reactive SARS-CoV-2–specific IgA responses in a phase 1 clinical trial (NCT04563702). Our data demonstrate that mucosal immunization is a viable strategy to decrease SARS-CoV-2 disease and airborne transmission.

Deleterious consequences of exposure to traffic emissions may derive from interactions between carbonaceous particulate matter (PM) and gaseous components in a manner that is dependent on the surface area or complexity of the particles. To determine the validity of this hypothesis, we examined pulmonary and neurological inflammatory outcomes in C57BL/6 and apolipoprotein E knockout (ApoE−/−) male mice after acute and chronic exposure to vehicle engine-derived particulate matter, generated as ultrafine (UFP) and fine (FP) sizes, with additional exposures using UFP or FP combined with gaseous copollutants derived from fresh gasoline and diesel emissions, labeled as UFP + G and FP + G. The UFP and UFP + G exposure groups resulted in the most profound pulmonary and neuroinflammatory effects. Phagocytosis of UFP + G particles via resident alveolar macrophages was substantial in both mouse strains, particularly after chronic exposure, with concurrent increased proinflammatory cytokine expression of CXCL1 and TNFα in the bronchial lavage fluid. In the acute exposure paradigm, only UFP and UFP + G induced significant changes in pulmonary inflammation and only in the ApoE−/− animals. Similarly, acute exposure to UFP and UFP + G increased the expression of several cytokines in the hippocampus of ApoE−/− mice including Il-1β, IL-6, Tgf-β and Tnf-α and in the hippocampus of C57BL/6 mice including Ccl5, Cxcl1, Il-1β, and Tnf-α. Interestingly, Il-6 and Tgf-β expression were decreased in the C57BL/6 hippocampus after acute exposure. Chronic exposure to UFP + G increased expression of Ccl5, Cxcl1, Il-6, and Tgf-β in the ApoE−/− hippocampus, but this effect was minimal in the C57BL/6 mice, suggesting compensatory mechanisms to manage neuroinflammation in this strain. Inflammatory responses the lung and brain were most substantial in ApoE−/− animals exposed to UFP + G, suggesting that the surface area-dependent interaction of gases and particles is an important determinant of toxic responses. As such, freshly generated UFP, in the presence of combustion-derived gas phase pollutants, may be a greater health hazard than would be predicted from PM concentration, alone, lending support for epidemiological findings of adverse neurological outcomes associated with roadway proximity.

Remdesivir (RDV) is a nucleotide analog prodrug with demonstrated clinical benefit in patients with coronavirus disease 2019 (COVID-19). In October 2020, the U.S. FDA approved intravenous RDV as the first treatment for hospitalized COVID-19 patients. Furthermore, RDV has been approved or authorized for emergency use in more than 50 countries. To make RDV more convenient for nonhospitalized patients earlier in disease, alternative routes of administration are being evaluated. Here, we investigated the pharmacokinetics and efficacy of RDV administered by head dome inhalation in African green monkeys (AGM). Relative to an intravenous administration of RDV at 10 mg/kg, an about 20-fold lower dose administered by inhalation produced comparable concentrations of the pharmacologically active triphosphate in lower respiratory tract tissues. Distribution of the active triphosphate into the upper respiratory tract was also observed after inhaled RDV exposure. Inhalation RDV dosing resulted in lower systemic exposures to RDV and its metabolites as compared with intravenous RDV dosing. An efficacy study with repeated dosing of inhaled RDV in an AGM model of SARS-CoV-2 infection demonstrated reductions in viral replication in bronchoalveolar lavage fluid and respiratory tract tissues compared with placebo. Efficacy was observed with inhaled RDV administered once daily at a pulmonary deposited dose of 0.35 mg/kg beginning about 8 hours after infection. Moreover, the efficacy of inhaled RDV was similar to that of intravenous RDV administered once at 10 mg/kg followed by 5 mg/kg daily in the same study. Together, these findings support further clinical development of inhalation RDV.

Objective: The purpose of the present study is to investigate the inactivation of bioaerosols containing Bovine Coronavirus, BCov, under repetitively pulsed radio frequency (RF) electromagnetic exposure. Methods: These experiments were performed in a waveguide containing a flowing aerosol stream and were limited to a single RF waveform: ∼2 μs square envelope, 5.6 GHz, 4.8 kHz repetition rate. Aerosol streams were exposed to RF electric field amplitudes in the range of 41.9 +/- 6.2 kV/m. Under laminar flow conditions, 75% of the total collected aerosol stream spends 0.85 seconds or less in the RF exposure region. Results: Application of the RF waveform changes mean survival rate of the aerosolized BCov by -0.58 decades (roughly a 74% reduction) and impacted the variance and standard deviation of the experimental results, with the RF exposure data showing an 800% increase in variance and 196% increase in standard deviation over the control results. Experimental results were compared to those from an analytic electromagnetic-heating inactivation model. Conclusion: The comparison indicated the feasibility that the observed reduction in BCov survival rate might be due to a combination of thermal effects and non-thermal electric field effects. Significance: Developing better insight into the mechanisms of inactivation is important for understanding the potential limits of efficacy for this method. Additionally, these results contribute an important baseline for the impact of electromagnetic fields on aerosolized pathogens.

Sampling of air for radioactive particles is one of the most important techniques used to determine the nuclear debris from a nuclear weapon test in the Earth’s atmosphere or those particles vented from underground or underwater tests. Massive-flow air samplers are used to sample air for any indication of radionuclides that are a signature of nuclear tests. The International Monitoring System of the Comprehensive Nuclear Test Ban Treaty Organization includes seismic, hydroacoustic, infrasound, and gaseous xenon isotopes sampling technologies, in addition to radionuclide sampling, to monitor for any violation of the treaty. Lovelace Respiratory Research Institute has developed a large wind tunnel to test the outdoor radionuclide samplers for the International Monitoring System. The inlets for these samplers are tested for their collection efficiencies for different particle sizes at various wind speeds. This paper describes the results from the testing of two radionuclide sampling units used in the International Monitoring System. The possible areas of depositional wall losses are identified and the losses in these areas are determined. Sampling inlet type 1 was tested at 2.2 m s⁻¹ wind speed for 5, 10, and 20-μm aerodynamic diameter particles. The global collection efficiency was about 87.6% for 10-μm particles for sampling inlet type 1. Sampling inlet type 2 was tested for three wind speeds at 0.56, 2.2, and 6.6 m s⁻¹ for 5, 10, and 20-μm aerodynamic diameter particles in two different configurations (sampling head lowered and raised). The global collection efficiencies for these configurations for 10-μm particles at 2.2 m s⁻¹ wind speed were 77.4% and 82.5%, respectively. The sampling flow rate was 600 m³ h⁻¹ for both sampling inlets.

A system capable of exposing a flowing aerosol stream to short duration (2–4 ns), high-power RF waveforms is described. The system utilizes a C-band gyromagnetic nonlinear transmission line source having peak power outputs ranging as high as 80 kW at a center frequency of 4.2 GHz. RF electric field magnitudes of up to 280 kV/m ± 17% are achieved within the aerosol flow region of the RF exposure apparatus.