By providing consultation to the United States Government (USG) on matters of biosecurity, the National Science Advisory Board for Biosecurity (NSABB) plays a critical role in ensuring the safety of biomedical research in the United States. In February 2022, the NSABB was tasked with evaluating and providing recommendations on 2 current frameworks for USG oversight of research on pathogens of high consequence: Dual Use Research of Concern (DURC) (1) and Potential Pandemic Pathogen Care and Oversight (P3CO) (2). In response to this USG request, on January 27, 2023, the Board voted to approve 13 recommendations with minor modifications (3). If adopted, these recommendations will vastly change federal oversight of USG funded research on pathogens. Here, we restate the recommendations of the Board and give our response to each, with the goals of promoting modification of some aspects and of providing a resource to USG entities charged with implementing new policies that follow from the recommendations. We provide these responses out of concern for the potential consequences of excessive oversight: policy that unduly restricts microbiology regardless of associated risk will limit our preparedness for and ability to respond to public health threats, constrain efforts to control infectious diseases of all kinds, diminish our international engagement in these critical global issues and damage US economic competitiveness.

Secondary infection with Streptococcus pneumoniae has contributed significantly to morbidity and mortality during multiple influenza virus pandemics and remains a common threat today. During a concurrent infection, both pathogens can influence the transmission of each other, but the mechanisms behind this are unclear. In this study, condensation air sampling and cyclone bioaerosol sampling were performed using ferrets first infected with the 2009 H1N1 pandemic influenza virus (H1N1pdm09) and secondarily infected with S. pneumoniae strain D39 (Spn). We detected viable pathogens and microbial nucleic acid in expelled aerosols from co-infected ferrets, suggesting that these microbes could be present in the same respiratory expulsions. To assess whether microbial communities impact pathogen stability within an expelled droplet, we performed experiments measuring viral and bacterial persistence in 1 µL droplets. We observed that H1N1pdm09 stability was unchanged in the presence of Spn. Further, Spn stability was moderately increased in the presence of H1N1pdm09, although the degree of stabilization differed between airway surface liquid collected from individual patient cultures. These findings are the first to collect both pathogens from the air and in doing so, they provide insight into the interplay between these pathogens and their hosts. IMPORTANCE The impact of microbial communities on transmission fitness and environmental persistence is under-studied. Environmental stability of microbes is crucial to identifying transmission risks and mitigation strategies, such as removal of contaminated aerosols and decontamination of surfaces. Co-infection with S. pneumoniae is very common during influenza virus infection, but little work has been done to understand whether S. pneumoniae alters stability of influenza virus, or vice versa, in a relevant system. Here, we demonstrate that influenza virus and S. pneumoniae are expelled by co-infected hosts. Our stability assays did not reveal any impact of S. pneumoniae on influenza virus stability, but did show a trend towards increased stability of S. pneumoniae in the presence of influenza viruses. Future work characterizing environmental persistence of viruses and bacteria should include microbially complex solutions to better mimic physiologically relevant conditions.

By providing consultation to the United States Government (USG) on matters of biosecurity, the National Science Advisory Board for Biosecurity (NSABB) plays a critical role in ensuring the safety of biomedical research in the United States. In February 2022, the NSABB was tasked with evaluating and providing recommendations on 2 current frameworks for USG oversight of research on pathogens of high consequence: Dual Use Research of Concern (DURC) (1) and Potential Pandemic Pathogen Care and Oversight (P3CO) (2). In response to this USG request, on January 27, 2023, the Board voted to approve 13 recommendations with minor modifications (3). If adopted, these recommendations will vastly change federal oversight of USG funded research on pathogens.

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 601 years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Respiratory viruses can be transmitted by multiple modes, including contaminated surfaces, commonly referred to as fomites. Efficient fomite transmission requires that a virus remain infectious on a given surface material over a wide range of environmental conditions, including different relative humidities. Prior work examining the stability of influenza viruses on surfaces has relied upon virus grown in media or eggs, which does not mimic the composition of virus-containing droplets expelled from the human respiratory tract. In this study, we examined the stability of the 2009 pandemic H1N1 (H1N1pdm09) virus on a variety of nonporous surface materials at four different humidities. Importantly, we used virus grown in primary human bronchial epithelial cell (HBE) cultures from different donors to recapitulate the physiological microenvironment of expelled viruses. We observed rapid inactivation of H1N1pdm09 on copper under all experimental conditions. In contrast to copper, viruses were stable on polystyrene plastic, stainless steel, aluminum, and glass, at multiple relative humidities, but greater decay on acrylonitrile butadiene styrene (ABS) plastic was observed at short time points. However, the half-lives of viruses at 23% relative humidity were similar among noncopper surfaces and ranged from 4.5 to 5.9 h. Assessment of H1N1pdm09 longevity on nonporous surfaces revealed that virus persistence was governed more by differences among HBE culture donors than by surface material. Our findings highlight the potential role of an individual's respiratory fluid on viral persistence and could help explain heterogeneity in transmission dynamics. IMPORTANCE Seasonal epidemics and sporadic pandemics of influenza cause a large public health burden. Although influenza viruses disseminate through the environment in respiratory secretions expelled from infected individuals, they can also be transmitted by contaminated surfaces where virus-laden expulsions can be deposited. Understanding virus stability on surfaces within the indoor environment is critical to assessing influenza transmission risk. We found that influenza virus stability is affected by the host respiratory secretion in which the virus is expelled, the surface material on which the droplet lands, and the ambient relative humidity of the environment. Influenza viruses can remain infectious on many common surfaces for prolonged periods, with half-lives of 4.5 to 5.9 h. These data imply that influenza viruses are persistent in indoor environments in biologically relevant matrices. Decontamination and engineering controls should be used to mitigate influenza virus transmission.

The interface between humans and wildlife is changing and, with it, the potential for pathogen introduction into humans has increased. Avian influenza is a prominent example, with an ongoing outbreak showing the unprecedented expansion of both geographic and host ranges. Research in the field is essential to understand this and other zoonotic threats. Only by monitoring dynamic viral populations and defining their biology in situ can we gather the information needed to ensure effective pandemic preparation.

Efficient spread of respiratory viruses requires the virus to maintain infectivity in the environment. Environmental stability of viruses can be influenced by many factors, including temperature and humidity. Our study measured the impact of initial droplet volume (50, 5, and 1 mL) and relative humidity (RH; 40%, 65%, and 85%) on the stability of influenza A virus, bacteriophage Phi6 (a common surrogate for enveloped viruses), and severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) under a limited set of conditions. Our data suggest that the drying time required for the droplets to reach quasi-equilibrium (i.e., a plateau in mass) varied with RH and initial droplet volume. The macroscale physical characteristics of the droplets at quasi-equilibrium varied with RH but not with the initial droplet volume. Virus decay rates differed between the wet phase, while the droplets were still evaporating, and the dry phase. For Phi6, decay was faster in the wet phase than in the dry phase under most conditions. For H1N1pdm09, decay rates between the two phases were distinct and initial droplet volume had an effect on virus viability within 2 h. Importantly, we observed differences in virus decay characteristics by droplet size and virus. In general, influenza virus and SARS-CoV-2 decayed similarly, whereas Phi6 decayed more rapidly under certain conditions. Overall, this study suggests that virus decay in media is related to the extent of droplet evaporation, which is controlled by RH. Importantly, accurate assessment of transmission risk requires the use of physiologically relevant droplet volumes and careful consideration of the use of surrogates. IMPORTANCE During the COVID-19 pandemic, policy decisions were being driven by virus stability experiments with SARS-CoV-2 in different droplet volumes under various humidity conditions. Our study, the first of its kind, provides a model for the decay of multiple enveloped RNA viruses in cell culture medium deposited in 50-, 5-, and 1-mL droplets at 40%, 65%, and 85% RH over time. The results of our study indicate that determination of half-lives for emerging pathogens in large droplets may overestimate transmission risk for contaminated surfaces, as observed during the COVID-19 pandemic. Our study implicates the need for the use of physiologically relevant droplet sizes with use of relevant surrogates in addition to what is already known about the importance of physiologically relevant media for risk assessment of future emerging pathogens.

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

By providing consultation to the United States Government (USG) on matters of biosecurity, the National Science Advisory Board for Biosecurity (NSABB) plays a critical role in ensuring the safety of biomedical research in the United States. In February 2022, the NSABB was tasked with evaluating and providing recommendations on two current frameworks for USG oversight of research on pathogens of high consequence: Dual Use Research of Concern (DURC) (1) and Potential Pandemic Pathogen Care and Oversight (P3CO) (2). In response to this USG request, on 27 January 2023, the Board voted to approve 13 recommendations with minor modifications (3). If adopted, these recommendations will vastly change federal oversight of USG-funded research on pathogens.

UNLABELLED: Secondary infection with Streptococcus pneumoniae has contributed significantly to morbidity and mortality during multiple influenza virus pandemics and remains a common threat today. During a concurrent infection, both pathogens can influence the transmission of each other, but the mechanisms behind this are unclear. In this study, condensation air sampling and cyclone bioaerosol sampling were performed using ferrets first infected with the 2009 H1N1 pandemic influenza virus (H1N1pdm09) and secondarily infected with S. pneumoniae strain D39 (Spn). We detected viable pathogens and microbial nucleic acid in expelled aerosols from co-infected ferrets, suggesting that these microbes could be present in the same respiratory expulsions. To assess whether microbial communities impact pathogen stability within an expelled droplet, we performed experiments measuring viral and bacterial persistence in 1 μL droplets. We observed that H1N1pdm09 stability was unchanged in the presence of Spn. Further, Spn stability was moderately increased in the presence of H1N1pdm09, although the degree of stabilization differed between airways surface liquid collected from individual patient cultures. These findings are the first to collect both pathogens from the air and in doing so, they provide insight into the interplay between these pathogens and their hosts. IMPORTANCE: The impact of microbial communities on transmission fitness and environmental persistence is under-studied. Environmental stability of microbes is crucial to identifying transmission risks and mitigation strategies, such as removal of contaminated aerosols and decontamination of surfaces. Co-infection with S. pneumoniae is very common during influenza virus infection, but little work has been done to understand whether S. pneumoniae alters stability of influenza virus, or vice versa, in a relevant system. Here, we demonstrate that influenza virus and S. pneumoniae are expelled by co-infected hosts. Our stability assays did not reveal any impact of S. pneumoniae on influenza virus stability, and a trend towards increased stability of S. pneumoniae in the presence of influenza viruses. Future work characterizing environmental persistence of viruses and bacteria should include microbially-complex solutions to better mimic physiologically relevant conditions.