Recent nosocomial transmission events of emerging and re-emerging viruses, including Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Crimean–Congo hemorrhagic fever ...orthonairovirus, have highlighted the risk of nosocomial transmission of emerging viruses in health-care settings. In particular, concerns and precautions have increased regarding the use of aerosol-generating medical procedures when treating patients with such viral infections. In spite of increasing associations between aerosol-generating medical procedures and the nosocomial transmission of viruses, we still have a poor understanding of the risks of specific procedures and viruses. In order to identify which aerosol-generating medical procedures and emerging viruses pose a high risk to health-care workers, we explore the mechanisms of aerosol-generating medical procedures, as well as the transmission pathways and characteristics of highly pathogenic viruses associated with nosocomial transmission. We then propose how research, both in clinical and experimental settings, could advance current infection control guidelines.
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first ...century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.
SARS-CoV-2 emerged in late 2019 and resulted in the ongoing COVID-19 pandemic. Several animal models have been rapidly developed that recapitulate the asymptomatic to moderate disease spectrum. Now, ...there is a direct need for additional small animal models to study the pathogenesis of severe COVID-19 and for fast-tracked medical countermeasure development. Here, we show that transgenic mice expressing the human SARS-CoV-2 receptor (angiotensin-converting enzyme 2 hACE2) under a cytokeratin 18 promoter (K18) are susceptible to SARS-CoV-2 and that infection resulted in a dose-dependent lethal disease course. After inoculation with either 104 TCID50 or 105 TCID50, the SARS-CoV-2 infection resulted in rapid weight loss in both groups and uniform lethality in the 105 TCID50 group. High levels of viral RNA shedding were observed from the upper and lower respiratory tract and intermittent shedding was observed from the intestinal tract. Inoculation with SARS-CoV-2 resulted in upper and lower respiratory tract infection with high infectious virus titers in nasal turbinates, trachea and lungs. The observed interstitial pneumonia and pulmonary pathology, with SARS-CoV-2 replication evident in pneumocytes, were similar to that reported in severe cases of COVID-19. SARS-CoV-2 infection resulted in macrophage and lymphocyte infiltration in the lungs and upregulation of Th1 and proinflammatory cytokines/chemokines. Extrapulmonary replication of SARS-CoV-2 was observed in the cerebral cortex and hippocampus of several animals at 7 DPI but not at 3 DPI. The rapid inflammatory response and observed pathology bears resemblance to COVID-19. Additionally, we demonstrate that a mild disease course can be simulated by low dose infection with 102 TCID50 SARS-CoV-2, resulting in minimal clinical manifestation and near uniform survival. Taken together, these data support future application of this model to studies of pathogenesis and medical countermeasure development.
A novel coronavirus, designated as 2019-nCoV, emerged in Wuhan, China, at the end of 2019. Although many details of the emergence of this virus remain unknown, it has put global public health ...institutions on high alert.
We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity ...conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.
Ebola virus disease afflicts both human and animal populations and is caused by four ebolaviruses. These different ebolaviruses may have distinct reservoir hosts and ecological contexts that ...determine how, where, and when different ebolavirus spillover events occur. Understanding these virus-specific relationships is important for preventing transmission of ebolaviruses from wildlife to humans. We examine the ecological contexts surrounding 34 human index case infections of ebolaviruses from 1976-2014. Determining possible sources of spillover from wildlife, characterizing the environment of each event, and creating ecological niche models to estimate habitats suitable for spillover, we find that index case infections of two ebolaviruses, Ebola virus and Sudan virus, have occurred under different ecological contexts. The index cases of Ebola virus infection are more associated with tropical evergreen broadleaf forests and consuming bushmeat than the cases of Sudan virus. Given these differences, we emphasize caution when generalizing across different ebolaviruses and that location and virus-specific ecological knowledge will be essential to unravelling how human and animal behavior lead to the emergence of Ebola virus disease.
Most viral pathogens in humans have animal origins and arose through cross-species transmission. Over the past 50 years, several viruses, including Ebola virus, Marburg virus, Nipah virus, Hendra ...virus, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory coronavirus (MERS-CoV) and SARS-CoV-2, have been linked back to various bat species. Despite decades of research into bats and the pathogens they carry, the fields of bat virus ecology and molecular biology are still nascent, with many questions largely unexplored, thus hindering our ability to anticipate and prepare for the next viral outbreak. In this Review, we discuss the latest advancements and understanding of bat-borne viruses, reflecting on current knowledge gaps and outlining the potential routes for future research as well as for outbreak response and prevention efforts.
The coronavirus pandemic has created worldwide shortages of N95 respirators. We analyzed 4 decontamination methods for effectiveness in deactivating severe acute respiratory syndrome coronavirus 2 ...virus and effect on respirator function. Our results indicate that N95 respirators can be decontaminated and reused, but the integrity of respirator fit and seal must be maintained.
In this research letter, investigators report on the stability of SARS-CoV-2 and SARS-CoV-1 under experimental conditions. The viability of the two viruses was assessed in aerosols and on plastic, ...stainless steel, copper, and cardboard.
Ambient temperature and humidity strongly affect inactivation rates of enveloped viruses, but a mechanistic, quantitative theory of these effects has been elusive. We measure the stability of ...SARS-CoV-2 on an inert surface at nine temperature and humidity conditions and develop a mechanistic model to explain and predict how temperature and humidity alter virus inactivation. We find SARS-CoV-2 survives longest at low temperatures and extreme relative humidities (RH); median estimated virus half-life is >24 hours at 10C and 40% RH, but ~1.5 hours at 27C and 65% RH. Our mechanistic model uses fundamental chemistry to explain why inactivation rate increases with increased temperature and shows a U-shaped dependence on RH. The model accurately predicts existing measurements of five different human coronaviruses, suggesting that shared mechanisms may affect stability for many viruses. The results indicate scenarios of high transmission risk, point to mitigation strategies, and advance the mechanistic study of virus transmission.
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