Predicting the animal hosts of coronaviruses from compositional biases of spike protein and whole genome sequences through machine learning

The COVID-19 pandemic has demonstrated the serious potential for novel zoonotic coronaviruses to emerge and cause major outbreaks. The immediate animal origin of the causative virus, SARS-CoV-2, remains unknown, a notoriously challenging task for emerging disease investigations. Coevolution with hosts leads to specific evolutionary signatures within viral genomes that can inform likely animal origins. We obtained a set of 650 spike protein and 511 whole genome nucleotide sequences from 225 and 187 viruses belonging to the family Coronaviridae, respectively. We then trained random forest models independently on genome composition biases of spike protein and whole genome sequences, including dinucleotide and codon usage biases in order to predict animal host (of nine possible categories, including human). In hold-one-out cross-validation, predictive accuracy on unseen coronaviruses consistently reached [~]73%, indicating evolutionary signal in spike proteins to be just as informative as whole genome sequences. However, different composition biases were informative in each case. Applying optimised random forest models to classify human sequences of MERS-CoV and SARS-CoV revealed evolutionary signatures consistent with their recognised intermediate hosts (camelids, carnivores), while human sequences of SARS-CoV-2 were predicted as having bat hosts (suborder Yinpterochiroptera), supporting bats as the suspected origins of the current pandemic. In addition to phylogeny, variation in genome composition can act as an informative approach to predict emerging virus traits as soon as sequences are available. More widely, this work demonstrates the potential in combining genetic resources with machine learning algorithms to address long-standing challenges in emerging infectious diseases.

Impact of climatic, demographic and disease control factors on the transmission dynamics of COVID-19 in large cities worldwide

We are now over seven months into a pandemic of COVID-19 caused by the SARS-CoV-2 virus and global incidence continues to rise. In some regions such as the temperate northern hemisphere there are fears of "second waves" of infections over the coming months, while in other, vulnerable regions such as Africa and South America, concerns remain that cases may still rise, further impacting local economies and livelihoods. Despite substantial research efforts to date, it remains unresolved as to whether COVID-19 transmission has the same sensitivity to climate and seasonality observed for other common respiratory viruses such as seasonal influenza. Here we investigate any empirical evidence of seasonality using a robust estimation framework. For 304 large cities across the world, we estimated the basic reproduction number (R0) using logistic growth curves fitted to cumulative case data. We then assessed evidence for association with climatic variables through mixed-effects and ordinary least squares (OLS) regression while adjusting for city-level variation in demographic and disease control factors. We find evidence of association between temperature and R0 during the early phase of the epidemic in China only. During subsequent pandemic spread outside China, we instead find evidence of seasonal change in R0, with greater R0 within cities experiencing shorter daylight hours (direct effect coefficient = -0.247, p = 0.006), after separating out effects of calendar day. The effect of daylight hours may be driven by levels of UV radiation, which is known to have detrimental effects on coronaviruses, including SARS-CoV-2. In the global analysis excluding China, climatic variables had weaker explanatory power compared to demographic or disease control factors. Overall, we find a weak but detectable signal of climate variables on the transmission of COVID-19. As seasonal changes occur later in 2020, it is feasible that the transmission dynamics of COVID-19 may shift in a detectable manner. However, rates of transmission and health burden of the pandemic in the coming months will be ultimately determined by population factors and disease control policies.

Preprinting a pandemic: the role of preprints in the COVID-19 pandemic

The world continues to face a life-threatening viral pandemic. The virus underlying the COVID-19 disease, SARS-CoV-2, has caused over 98 million confirmed cases and 2.2 million deaths since January 2020. Although the most recent respiratory viral pandemic swept the globe only a decade ago, the way science operates and responds to current events has experienced a paradigm shift in the interim. The scientific community has responded rapidly to the COVID-19 pandemic, releasing over 125,000 COVID-19 related scientific articles within 10 months of the first confirmed case, of which more than 30,000 were hosted by preprint servers. We focused our analysis on bioRxiv and medRxiv, two growing preprint servers for biomedical research, investigating the attributes of COVID-19 preprints, their access and usage rates, as well as characteristics of their propagation on online platforms. Our data provides evidence for increased scientific and public engagement with preprints related to COVID-19 (COVID-19 preprints are accessed more, cited more, and shared more on various online platforms than non-COVID-19 preprints), as well as changes in the use of preprints by journalists and policymakers. We also find evidence for changes in preprinting and publishing behaviour: COVID-19 preprints are shorter and reviewed faster. Our results highlight the unprecedented role of preprints and preprint servers in the dissemination of COVID-19 science, and the impact of the pandemic on the scientific communication landscape.