Outbreak investigation in a COVID-19 designated hospital: The combination of phylogenetic analysis and field epidemiology study suggesting airborne transmission
“…We observed antiviral activity of a novel peptoid TM9 for all three MHV strains, suggesting that TM9 will be effective against all coronaviruses, including SARS-CoV-2. We utilize an aerosol route of infection for MHV in mice via a Madison chamber that produces a dry aerosol, making this model closely mimic the natural route of SARS-CoV-2 transmission (32) (33) and confirming that MHV represents an inexpensive, rapid, and straightforward model for COVID-19 therapeutic screening.…”
New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.
“…We observed antiviral activity of a novel peptoid TM9 for all three MHV strains, suggesting that TM9 will be effective against all coronaviruses, including SARS-CoV-2. We utilize an aerosol route of infection for MHV in mice via a Madison chamber that produces a dry aerosol, making this model closely mimic the natural route of SARS-CoV-2 transmission (32) (33) and confirming that MHV represents an inexpensive, rapid, and straightforward model for COVID-19 therapeutic screening.…”
New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.
“…105 The unique aerosols were found widely dispersed throughout the floor, potentially facilitated by ventilation air movement or recirculated air without adequate filtering, demonstrating the possibility of airborne infections amongst the cluster. Huang et al 106 also used tracer gas to investigate the spatial relations and potential airborne transmission within nosocomial COVID-19 groups.…”
Section: Resultsmentioning
confidence: 99%
“…Sung et al 104 and Huang et al). 106 This technique was also used in mock-ups to investigate respiratory contaminants’ dispersion influenced by various factors, including building ventilation. The experimental set-up constructed by Qian et al 112 for identifying the exhaled bio-contaminant dispersion under different exhalation modes, face orientations and ventilation strategies using N 2 O released from a manikin is shown in Figure 5 to demonstrate the tracer gas technique.Figure 5.(a) and (b) Photos of the manikin employed to simulate the exhalation of biological contaminants using tracer gas N 2 O under different exhalation modes and face orientations; (c) the direction of the exhalation jet during mouth-breathing; and (d) the direction of the exhalation jet during nose-breathing.…”
Section: Resultsmentioning
confidence: 99%
“…Sung et al 104 and Huang et al). 106 This technique was also used in mock-ups to investigate respiratory contaminants' dispersion influenced by various factors, including building ventilation. The experimental set-up constructed by Qian et al 112 for identifying the exhaled bio-contaminant dispersion under different exhalation modes, face orientations and ventilation strategies using N 2 O released from a manikin is shown in Figure 5 to demonstrate the tracer gas technique.…”
Experimental studies can provide understanding, knowledge and real-case empirical evidence on the effects of building ventilation and environmental factors on airborne transmission in hospitals. Information obtained from existing studies gives insight into formulating engineering solutions and management practices to combat nosocomial airborne infections. A systemic review was conducted to summarize the experimental methods, research interests, useful results and limitations. With a steady but slow trend of increasing interest, experimental studies have been focusing mainly on the effects of ventilation systems, strategies and configurations on airborne transmission. The dispersion of bioaerosols under the combined effects of environmental factors, emission scenarios and human movement was investigated. Localized ventilation, air purifiers and disinfection technologies were also examined. The experimental techniques and some useful insights on optimal ventilation strategies and management practices were summarized and highlighted. Limitations of the empirical studies included sampling difficulties, limited scale and a number of testing scenarios, uncontrolled/unconsidered influencing factors and the media for experimentations. Using IoT-based sampling devices for experiments and real-time monitoring of bioaerosols or their surrogates, field surveys on a case-by-case basis in hospitals and interdisciplinary studies and collaborations could help overcome the research challenges and provide practical and effective solutions to minimize airborne transmission in hospitals.
“…We observed antiviral activity of a novel peptoid TM9 for all three MHV strains, suggesting that TM9 will be effective against all coronaviruses, including SARS-CoV-2. We utilize an aerosol route of infection for MHV in mice via a Madison chamber that produces a dry aerosol, making this model closely mimic the natural route of SARS-CoV-2 transmission [ 38 , 39 ] and confirming that MHV represents an inexpensive, rapid, and straightforward model for COVID-19 therapeutic screening.…”
New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study, TM9 was effective against three murine coronavirus strains, demonstrating that the therapeutic window is large enough to allow the use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber, and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from the liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
