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In the past two decades, three coronaviruses with ancestral origins in bats have emerged and caused widespread outbreaks in humans, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS epidemic in 2002–2003, the appreciation of bats as key hosts of zoonotic coronaviruses has advanced rapidly. More than 4,000 coronavirus sequences from 14 bat families have been identified, yet the true diversity of bat coronaviruses is probably much greater. Given that bats are the likely evolutionary source for several human coronaviruses, including strains that cause mild upper respiratory tract disease, their role in historic and future pandemics requires ongoing investigation. We review and integrate information on bat–coronavirus interactions at the molecular, tissue, host and population levels. We identify critical gaps in knowledge of bat coronaviruses, which relate to spillover and pandemic risk, including the pathways to zoonotic spillover, the infection dynamics within bat reservoir hosts, the role of prior adaptation in intermediate hosts for zoonotic transmission and the viral genotypes or traits that predict zoonotic capacity and pandemic potential. Filling these knowledge gaps may help prevent the next pandemic.Bats harbour a multitude of coronaviruses and owing to their diversity and wide distribution are prime reservoir hosts of emerging viruses. Ruiz-Aravena, McKee and colleagues analyse the currently available information on bat coronaviruses and discuss their role in recent and potential future spillovers.

Substantial global attention is focused on how to reduce the risk of future pandemics. Reducing this risk requires investment in prevention, preparedness, and response. Although preparedness and response have received significant focus, prevention, especially the prevention of zoonotic spillover, remains largely absent from global conversations. This oversight is due in part to the lack of a clear definition of prevention and lack of guidance on how to achieve it. To address this gap, we elucidate the mechanisms linking environmental change and zoonotic spillover using spillover of viruses from bats as a case study. We identify ecological interventions that can disrupt these spillover mechanisms and propose policy frameworks for their implementation. Recognizing that pandemics originate in ecological systems, we advocate for integrating ecological approaches alongside biomedical approaches in a comprehensive and balanced pandemic prevention strategy. In this Perspective, the authors discuss the importance of preventing zoonotic spillover to prevent pandemics. They highlight mechanisms by which environmental changes can enable spillover, identify ecological interventions for spillover prevention and suggest policy frameworks through which interventions can be implemented.

Co-infection is an underappreciated phenomenon in contemporary disease ecology despite its ubiquity and importance in nature. Viruses, and other co-infecting agents, can interact in ways that shape host and agent communities, influence infection dynamics, and drive evolutionary selective pressures. Bats are host to many viruses of zoonotic potential and have drawn increasing attention in their role as wildlife reservoirs for human spillover. However, the role of co-infection in driving viral transmission dynamics within bats is unknown. Here, we systematically review peer-reviewed literature reporting viral co-infections in bats. We show that viral co-infection is common in bats but is often only reported as an incidental finding. Biases identified in our study database related to virus and host species were pre-existing in virus studies of bats generally. Studies largely speculated on the role co-infection plays in viral recombination and few investigated potential drivers or impacts of co-infection. Our results demonstrate that current knowledge of co-infection in bats is an ad hoc by-product of viral discovery efforts, and that future targeted co-infection studies will improve our understanding of the role it plays. Adding to the broader context of co-infection studies in other wildlife species, we anticipate our review will inform future co-infection study design and reporting in bats. Consideration of detection strategy, including potential viral targets, and appropriate analysis methodology will provide more robust results and facilitate further investigation of the role of viral co-infection in bat reservoirs.

We identifi ed and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be eff ective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed fl ying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral- host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by fl ying foxes.

Bats host a high diversity of coronaviruses, including betacoronaviruses that have caused outbreaks and pandemics in humans and other species. Here, we study the spatiotemporal dynamics of co-circulating coronaviruses in Pteropus spp bats (flying foxes) in eastern Australia over a three-year period across five roost sites ( n  = 2537 fecal samples). In total, we identify six betacoronavirus clades, all within the nobecovirus subgenus. Genome sequencing supports overall clade assignments, however, also demonstrates the important role recombination has played in both the long-term and contemporary evolution of these viruses. Using a statistical framework that integrates individual and population level data, we assess the variability in prevalence of viral clades over space and time. Coronavirus infections and co-infections are highest among juveniles and subadults, particularly around the time of weaning. The overlapping shedding dynamics across multiple clades suggest opportunities for recombination, especially in younger bats. Understanding the ecological and host-viral drivers of these seasonally dynamic infections, co-infections, and recombination events will inform future predictive frameworks for coronavirus emergence in humans and other animals. Bats harbor diverse coronaviruses but temporal dynamics are less well studied. Here, the authors analyzed coronaviruses in Australian flying foxes over 3 years showing peak shedding and co-infections in juveniles and subadults and providing evidence of historical and contemporary recombination between viral clades.

Dose is the nexus between exposure and all upstream processes that determine pathogen pressure, and is thereby an important element underlying disease dynamics. Understanding the relationship between dose and disease is particularly important in the context of spillover, where nonlinearities in the dose–response could determine the likelihood of transmission. There is a need to explore dose–response models for directly transmitted and zoonotic pathogens, and how these interactions integrate within-host factors to consider, for example, heterogeneity in host susceptibility and dose-dependent antagonism. Here, we review the dose–response literature and discuss the unique role dose–response models have to play in understanding and predicting spillover events. We present a re-analysis of dose–response experiments for two important zoonotic pathogens (Middle East respiratory syndrome coronavirus and Nipah virus), to exemplify potential difficulties in differentiating between appropriate models with small exposure experiment datasets. We also discuss the data requirements needed for robust selection between dose–response models. We then suggest how these processes could be modelled to gain more realistic predictions of zoonotic transmission outcomes and highlight the exciting opportunities that could arise with increased collaboration between the virology and epidemiology disciplines. This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

Understanding the non-human reservoirs of zoonotic pathogens is critical for effective disease control, but identifying the relative contributions of the various reservoirs of multi-host pathogens is challenging. For Ross River virus (RRV), knowledge of the transmission dynamics, in particular the role of non-human species, is important. In Australia, RRV accounts for the highest number of human mosquito-borne virus infections. The long held dogma that marsupials are better reservoirs than placental mammals, which are better reservoirs than birds, deserves critical review. We present a review of 50 years of evidence on non-human reservoirs of RRV, which includes experimental infection studies, virus isolation studies and serosurveys. We find that whilst marsupials are competent reservoirs of RRV, there is potential for placental mammals and birds to contribute to transmission dynamics. However, the role of these animals as reservoirs of RRV remains unclear due to fragmented evidence and sampling bias. Future investigations of RRV reservoirs should focus on quantifying complex transmission dynamics across environments.

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.

We explored the role of black flying foxes (Pteropus alecto) in Australia as reservoirs of Borrelia bacteria. We found bats infected with 2 Borrelia haplotypes phylogenetically distinct from Lyme or relapsing fever clades. Efforts to sample black flying foxes and their ectoparasites are needed to evaluate zoonotic potential of those Borrelia lineages.

Many serious emerging zoonotic infections have recently arisen from bats, including Ebola, Marburg, SARS-coronavirus, Hendra, Nipah, and a number of rabies and rabies-related viruses, consistent with the overall observation that wildlife are an important source of emerging zoonoses for the human population. Mechanisms underlying the recognized association between ecosystem health and human health remain poorly understood and responding appropriately to the ecological, social and economic conditions that facilitate disease emergence and transmission represents a substantial societal challenge. In the context of disease emergence from wildlife, wildlife and habitat should be conserved, which in turn will preserve vital ecosystem structure and function, which has broader implications for human wellbeing and environmental sustainability, while simultaneously minimizing the spillover of pathogens from wild animals into human beings. In this review, we propose a novel framework for the holistic and interdisciplinary investigation of zoonotic disease emergence and its drivers, using the spillover of bat pathogens as a case study. This study has been developed to gain a detailed interdisciplinary understanding, and it combines cutting-edge perspectives from both natural and social sciences, linked to policy impacts on public health, land use and conservation.