Assessing the risk of vaccine-driven virulence evolution in SARS-CoV-2

The evolution of SARS-CoV-2 virulence, or lethality, threatens to exacerbate the burden of COVID-19 on society. How might COVID-19 vaccines alter selection for increased SARS-CoV-2 virulence? Framing current evidence surrounding SARS-CoV-2 biology and COVID-19 vaccines in the context of evolutionary theory indicates that prospects for virulence evolution remain uncertain. However, differential effects of vaccinal immunity on transmission and disease severity between respiratory compartments could select for increased virulence. To bound expectations for this outcome, we analyse an evo-epidemiological model. Synthesizing model predictions with vaccine efficacy data, we conclude that while vaccine-driven virulence remains a theoretical possibility, the risk is low if vaccines provide sustained robust protection against infection. Furthermore, we found that any increases in transmission concomitant with increases in virulence would be unlikely to threaten prospects for herd immunity in a highly immunized population. Given that virulence evolution would nevertheless impact unvaccinated individuals and populations with low vaccination rates, it is important to achieve high vaccination rates worldwide and ensure that vaccinal immunity provides robust protection against both infection and disease, potentially through the use of booster doses.

Genetic and environmental influences on the evolution of virulence in the HIV-associated opportunistic human fungal pathogen Cryptococcus neoformans

The fungus Cryptococcus neoformans is considered the leading cause of death in immunocompromised patients. Despite numerous investigations concerning its molecular epidemiology, there are only a few studies addressing the impacts of varying factors on genotype-phenotype correlations. It remains largely unknown whether genetic and environmental variabilities among isolates from different sources may have dramatic consequences on virulence. In this study, we analyzed 105 Chinese C. neoformans isolates, including 54 from HIV-infected patients, 44 from HIV-uninfected individuals and 7 from a natural environment, to investigate factors influencing the outcome of C. neoformans infection. MLST analysis clearly identified sequence type (ST) 5 as the prevalent sequence type in all clinical isolates and interestingly, genotypic diversities were observed in isolates from both HIV-uninfected individual and natural environment but not those from HIV-infected patients. Moreover, we found that compared to those from HIV-infected patients, the isolates from HIV-uninfected individuals exhibited enhanced virulence-associated traits including significantly elevated capsule production and melanin formation, increases in survival in human cerebrospinal fluid (CSF), less effective uptake by host phagocytes, and higher mortality in a mouse model of cryptococcosis. Consistently, pathogenic phenotypes were associated with CD4 counts of patients, implying environmental impact on within-host C. neoformans virulence. Importantly, a large-scale whole-genome sequencing analysis revealed that genomic variations within genes related to specific functions may act as a vital driving force of host intrinsic virulence evolution. Taken together, our results support a strong genotype-phenotype correlation suggesting that the pathogenic evolution of C. neoformans could be heavily affected by both genetic and environmental factors.

Reservoir host immunology and life history shape virulence evolution in zoonotic viruses

Future pandemic risk management requires better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, suggesting that reservoir host immunological and life history traits may be important drivers of cross-species virulence. Using a nested population-level and within-host modelling approach, we generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, successfully recapturing corresponding virus-induced human mortality rates from the literature. Our work offers a mechanistic explanation for the virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, tolerance, and population density impact the evolution of viral traits that generate severe disease following spillover to humans. We provide a theoretical framework that offers a series of testable questions and hypotheses designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts.

The ghost of hosts past: impacts of host extinction on parasite specificity

A growing body of research is focused on the extinction of parasite species in response to host endangerment and declines. Beyond the loss of parasite species richness, host extinction can impact apparent parasite host specificity, as measured by host richness or the phylogenetic distances among hosts. Such impacts on the distribution of parasites across the host phylogeny can have knock-on effects that may reshape the adaptation of both hosts and parasites, ultimately shifting the evolutionary landscape underlying the potential for emergence and the evolution of virulence across hosts. Here, we examine how the reshaping of host phylogenies through extinction may impact the host specificity of parasites, and offer examples from historical extinctions, present-day endangerment, and future projections of biodiversity loss. We suggest that an improved understanding of the impact of host extinction on contemporary host–parasite interactions may shed light on core aspects of disease ecology, including comparative studies of host specificity, virulence evolution in multi-host parasite systems, and future trajectories for host and parasite biodiversity. This article is part of the theme issue ‘Infectious disease macroecology: parasite diversity and dynamics across the globe’.

Social hosts evade predation but have deadlier parasites

Parasites exploit hosts to replicate and transmit, but overexploitation kills both host and parasite1: parasite virulence evolves to balance these costs and benefits. Predators can in theory shift this balance by consuming hosts2–4. However, the non-consumptive effects of predators may be as important as their consumptive effects5. Here, we use an eco-coevolutionary model to show that predators select for host grouping, a common anti-predator, defensive social behaviour6. Host grouping simultaneously increases parasite transmission, thus within-host parasite competition, and therefore favours more exploitative, virulent, parasites7. When parametrized with data from the guppy-Gyrodactylus spp. system, including our experimentally demonstrated trade-off between virulence and transmission, our model accurately predicted the common garden-assayed virulence of 18 parasite lines collected from four Trinidadian guppy populations under different predation regimes. The quantitative match between theory and data lends credence to the model’s insight that the non-consumptive, social behaviour pathway is entirely responsible for the observed increase in virulence with predation pressure. Our results indicate that parasites play an important, underappreciated role in guppy evolutionary ecology. Moreover, group living is a common anti-predator defence6 and our general model accommodates host-parasite interactions across taxa: its insight into the interactions among predation, sociality, and virulence evolution may apply broadly. Our results additionally suggest that social distancing, by reducing host-host contact, can select for less virulent parasites and pathogens.