Treatment with dry hydrogen peroxide accelerates the decay of severe acute syndrome coronavirus-2 on non-porous hard surfaces.

BACKGROUND: Disinfection of contaminated or potentially contaminated surfaces has become an integral part of the mitigation strategies for controlling coronavirus disease 2019. Whilst a broad range of disinfectants are effective in inactivating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), application of disinfectants has a low throughput in areas that receive treatments. Disinfection of large surface areas often involves the use of reactive microbiocidal materials, including ultraviolet germicidal irradiation, chlorine dioxide, and hydrogen peroxide vapor. Albeit these methods are highly effective in inactivating SARS-CoV-2, the deployment of these approaches creates unacceptable health hazards and precludes the treatment of occupied indoor spaces using existing disinfection technologies. In this study, the feasibility of using dry hydrogen peroxide (DHP) in inactivating SARS-CoV-2 on contaminated surfaces in large indoor spaces was evaluated. METHODS: Glass slides were inoculated with SARS-CoV-2 and treated with DHP between 5 and 25 ppb for up to 24 hours. Residual infectious virus samples were eluted from three replicates at each time point and titrated in African green monkey VeroE6 cells. RESULTS: In comparison with the observed relatively high stability of SARS-CoV-2 on contaminated glass slides (control group), residual infectious titers of glass slides inoculated with SARS-CoV-2 were significantly reduced after receiving 120 minutes of DHP treatment. CONCLUSIONS: The accelerated decay of SARS-CoV-2 on contaminated glass slides suggests that treatment with DHP can be an effective surface disinfection method for occupied indoor spaces.

Activation of Heme Oxygenase Expression by Cobalt Protoporphyrin Treatment Prevents Pneumonic Plague Caused by Inhalation of Yersinia pestis.

Pneumonic plague, caused by the Gram-negative bacteria Yersinia pestis, is an invasive, rapidly progressing disease with poor survival rates. Following inhalation of Y. pestis, bacterial invasion of the lungs and a tissue-damaging inflammatory response allows vascular spread of the infection. Consequently, primary pneumonic plague is a multiorgan disease involving sepsis and necrosis of immune tissues and the liver, as well as bronchopneumonia and rampant bacterial growth. Given the likely role of the hyperinflammatory response in accelerating the destruction of tissue, in this work we evaluated the therapeutic potential of the inducible cytoprotective enzyme heme oxygenase 1 (HO-1) against primary pneumonic plague. On its own, the HO-1 inducer cobalt protoporphyrin IX (CoPP) provided mice protection from lethal challenge with Y. pestis CO92 with improved pulmonary bacterial clearance and a dampened inflammatory response compared to vehicle-treated mice. Furthermore, CoPP treatment combined with doxycycline strongly enhanced protection in a rat aerosol challenge model. Compared to doxycycline alone, CoPP treatment increased survival, with a 3-log decrease in median bacterial titer recovered from the lungs and the general absence of a systemic hyperinflammatory response. In contrast, treatment with the HO-1 inhibitor SnPP had no detectable impact on doxycycline efficacy. The combined data indicate that countering inflammatory toxicity by therapeutically inducing HO-1 is effective in reducing the rampant growth of Y. pestis and preventing pneumonic plague.

Standardized Method for Aerosol Challenge of Rodents with Yersinia pestis for Modeling Primary Pneumonic Plague.

Primary pneumonic plague occurs when Yersinia pestis is inhaled into the lower respiratory tract where it invades the alveoli and grows. Rapid bacterial growth eventually elicits a neutrophilic inflammatory response that is ineffective and damaging, leading to accelerated progression of disease. In the laboratory, modeling of primary pneumonic plague can be accomplished by instillation of bacterial culture in the nares of anesthetized mice and rats. Although primary pneumonic plague can develop from this method, variability in dosing and side effects of anesthesia can complicate data interpretation. In contrast, aerosol challenge models allow for well-controlled studies of pneumonic plague with minimal experimental bias and unwanted side effects. For these reasons, antibiotic testing and the licensing of new treatments depend on efficacy data generated from aerosol delivery of Y. pestis in order to more accurately model transmission and the early stages of human pneumonic plague. In order to meet this need, we have extensively characterized pneumonic plague in mice and rats challenged by nose-only exposure to Yersinia pestis. With this approach, simultaneous challenge of large cohorts of animals, gently restrained and not anesthetized, assures safe, well-controlled, unbiased, and uniform infection. In this chapter, we present a standardized method for reproducible aerosol delivery of wild-type Y. pestis to rodents for experimental models of primary pneumonic plague.