Predictors of severity of influenza-related hospitalizations: Results from the Global Influenza Hospital Surveillance Network (GIHSN).

BACKGROUND: The Global Influenza Hospital Surveillance Network (GIHSN) has since 2012 provided patient-level data on severe influenza-like illnesses from over 100 participating clinical sites worldwide based on a core protocol and consistent case definitions. To our knowledge, this is the first study to analyze multiple years of global, patient-level data generated by prospective, hospital-based surveillance across a large number of countries to investigate geographic differences in influenza severity. METHODS: We used multivariable logistic regression to assess the risk of intensive care unit admission, mechanical ventilation, and in-hospital death among hospitalized patients with influenza and explored the role of patient-level covariates and country income. RESULTS: The dataset included 73,121 patients hospitalized with respiratory illness in 22 countries, with 15,660 laboratory-confirmed for influenza. After adjusting for patient-level covariates we found a 7-fold increase in the risk of influenza-related intensive care unit admission in lower middle-income countries, compared to high-income countries (p = 0.01). The risk of mechanical ventilation and in-hospital death also increases by four-fold in lower middle-income countries, though these values were not statistically significant. We also find that influenza severity increased with older age and number of comorbidities. Across all severity outcomes studied and after controlling for patient characteristics, infection with influenza A/H1N1pdm09 was more severe than with A/H3N2. CONCLUSIONS: Our study provides new information on influenza severity in under-resourced populations, particularly those in lower middle-income countries. Understanding the mechanisms responsible for these disparities will be important to improve management of influenza, optimize vaccine allocation, and mitigate global disease burden.

Coronavirus sampling and surveillance in bats from 1996-2019: a systematic review and meta-analysis.

The emergence of SARS-CoV-2 highlights a need for evidence-based strategies to monitor bat viruses. We performed a systematic review of coronavirus sampling (testing for RNA positivity) in bats globally. We identified 110 studies published between 2005 and 2020 that collectively reported positivity from 89,752 bat samples. We compiled 2,274 records of infection prevalence at the finest methodological, spatiotemporal and phylogenetic level of detail possible from public records into an open, static database named datacov, together with metadata on sampling and diagnostic methods. We found substantial heterogeneity in viral prevalence across studies, reflecting spatiotemporal variation in viral dynamics and methodological differences. Meta-analysis identified sample type and sampling design as the best predictors of prevalence, with virus detection maximized in rectal and faecal samples and by repeat sampling of the same site. Fewer than one in five studies collected and reported longitudinal data, and euthanasia did not improve virus detection. We show that bat sampling before the SARS-CoV-2 pandemic was concentrated in China, with research gaps in South Asia, the Americas and sub-Saharan Africa, and in subfamilies of phyllostomid bats. We propose that surveillance strategies should address these gaps to improve global health security and enable the origins of zoonotic coronaviruses to be identified.

Projecting the SARS-CoV-2 transition from pandemicity to endemicity: Epidemiological and immunological considerations.

In this review, we discuss the epidemiological dynamics of different viral infections to project how the transition from a pandemic to endemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) might take shape. Drawing from theories of disease invasion and transmission dynamics, waning immunity in the face of viral evolution and antigenic drift, and empirical data from influenza, dengue, and seasonal coronaviruses, we discuss the putative periodicity, severity, and age dynamics of SARS-CoV-2 as it becomes endemic. We review recent studies on SARS-CoV-2 epidemiology, immunology, and evolution that are particularly useful in projecting the transition to endemicity and highlight gaps that warrant further research.

Urban-adapted mammal species have more known pathogens.

The world is rapidly urbanizing, inviting mounting concern that urban environments will experience increased zoonotic disease risk. Urban animals could have more frequent contact with humans, therefore transmitting more zoonotic parasites; however, this relationship is complicated by sampling bias and phenotypic confounders. Here we test whether urban mammal species host more zoonotic parasites, investigating the underlying drivers alongside a suite of phenotypic, taxonomic and geographic predictors. We found that urban-adapted mammals have more documented parasites and more zoonotic parasites: despite comprising only 6% of investigated species, urban mammals provided 39% of known host-parasite combinations. However, contrary to predictions, much of the observed effect was attributable to parasite discovery and research effort rather than to urban adaptation status, and urban-adapted species in fact hosted fewer zoonotic parasites than expected on the basis of their total parasite richness. We conclude that extended historical contact with humans has had a limited impact on zoonotic parasite richness in urban-adapted mammals; instead, their greater observed zoonotic richness probably reflects sampling bias arising from proximity to humans, supporting a near-universal conflation between zoonotic risk, research effort and synanthropy. These findings underscore the need to resolve the mechanisms linking anthropogenic change, sampling bias and observed wildlife disease dynamics.

Assessing the risk of human-to-wildlife pathogen transmission for conservation and public health.

The SARS-CoV-2 pandemic has led to increased concern over transmission of pathogens from humans to animals, and its potential to threaten conservation and public health. To assess this threat, we reviewed published evidence of human-to-wildlife transmission events, with a focus on how such events could threaten animal and human health. We identified 97 verified examples, involving a wide range of pathogens; however, reported hosts were mostly non-human primates or large, long-lived captive animals. Relatively few documented examples resulted in morbidity and mortality, and very few led to maintenance of a human pathogen in a new reservoir or subsequent "secondary spillover" back into humans. We discuss limitations in the literature surrounding these phenomena, including strong evidence of sampling bias towards non-human primates and human-proximate mammals and the possibility of systematic bias against reporting human parasites in wildlife, both of which limit our ability to assess the risk of human-to-wildlife pathogen transmission. We outline how researchers can collect experimental and observational evidence that will expand our capacity for risk assessment for human-to-wildlife pathogen transmission.

Optimising predictive models to prioritise viral discovery in zoonotic reservoirs.

Despite the global investment in One Health disease surveillance, it remains difficult and costly to identify and monitor the wildlife reservoirs of novel zoonotic viruses. Statistical models can guide sampling target prioritisation, but the predictions from any given model might be highly uncertain; moreover, systematic model validation is rare, and the drivers of model performance are consequently under-documented. Here, we use the bat hosts of betacoronaviruses as a case study for the data-driven process of comparing and validating predictive models of probable reservoir hosts. In early 2020, we generated an ensemble of eight statistical models that predicted host-virus associations and developed priority sampling recommendations for potential bat reservoirs of betacoronaviruses and bridge hosts for SARS-CoV-2. During a time frame of more than a year, we tracked the discovery of 47 new bat hosts of betacoronaviruses, validated the initial predictions, and dynamically updated our analytical pipeline. We found that ecological trait-based models performed well at predicting these novel hosts, whereas network methods consistently performed approximately as well or worse than expected at random. These findings illustrate the importance of ensemble modelling as a buffer against mixed-model quality and highlight the value of including host ecology in predictive models. Our revised models showed an improved performance compared with the initial ensemble, and predicted more than 400 bat species globally that could be undetected betacoronavirus hosts. We show, through systematic validation, that machine learning models can help to optimise wildlife sampling for undiscovered viruses and illustrates how such approaches are best implemented through a dynamic process of prediction, data collection, validation, and updating.

The science of the host-virus network.

Better methods to predict and prevent the emergence of zoonotic viruses could support future efforts to reduce the risk of epidemics. We propose a network science framework for understanding and predicting human and animal susceptibility to viral infections. Related approaches have so far helped to identify basic biological rules that govern cross-species transmission and structure the global virome. We highlight ways to make modelling both accurate and actionable, and discuss the barriers that prevent researchers from translating viral ecology into public health policies that could prevent future pandemics.

The future of zoonotic risk prediction.

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue 'Infectious disease macroecology: parasite diversity and dynamics across the globe'.