Antigenic evolution of SARS-CoV-2 in immunocompromised hosts.

OBJECTIVES/AIMS: Prolonged infections of immunocompromised individuals have been proposed as a crucial source of new variants of SARS-CoV-2 during the COVID-19 pandemic. In principle, sustained within-host antigenic evolution in immunocompromised hosts could allow novel immune escape variants to emerge more rapidly, but little is known about how and when immunocompromised hosts play a critical role in pathogen evolution. MATERIALS AND METHODS: Here, we use a simple mathematical model to understand the effects of immunocompromised hosts on the emergence of immune escape variants in the presence and absence of epistasis. CONCLUSIONS: We show that when the pathogen does not have to cross a fitness valley for immune escape to occur (no epistasis), immunocompromised individuals have no qualitative effect on antigenic evolution (although they may accelerate immune escape if within-host evolutionary dynamics are faster in immunocompromised individuals). But if a fitness valley exists between immune escape variants at the between-host level (epistasis), then persistent infections of immunocompromised individuals allow mutations to accumulate, therefore, facilitating rather than simply speeding up antigenic evolution. Our results suggest that better genomic surveillance of infected immunocompromised individuals and better global health equality, including improving access to vaccines and treatments for individuals who are immunocompromised (especially in lower- and middle-income countries), may be crucial to preventing the emergence of future immune escape variants of SARS-CoV-2.

Health care's response to climate change: a carbon footprint assessment of the NHS in England.

BACKGROUND: Climate change threatens to undermine the past 50 years of gains in public health. In response, the National Health Service (NHS) in England has been working since 2008 to quantify and reduce its carbon footprint. This Article presents the latest update to its greenhouse gas accounting, identifying interventions for mitigation efforts and describing an approach applicable to other health systems across the world. METHODS: A hybrid model was used to quantify emissions within Scopes 1, 2, and 3 of the Greenhouse Gas Protocol, as well as patient and visitor travel emissions, from 1990 to 2019. This approach complements the broad coverage of top-down economic modelling with the high accuracy of bottom-up data wherever available. Available data were backcasted or forecasted to cover all years. To enable the identification of measures to reduce carbon emissions, results were disaggregated by organisation type. FINDINGS: In 2019, the health service's emissions totalled 25 megatonnes of carbon dioxide equivalent, a reduction of 26% since 1990, and a decrease of 64% in the emissions per inpatient finished admission episode. Of the 2019 footprint, 62% came from the supply chain, 24% from the direct delivery of care, 10% from staff commute and patient and visitor travel, and 4% from private health and care services commissioned by the NHS. INTERPRETATION: This work represents the longest and most comprehensive accounting of national health-care emissions globally, and underscores the importance of incorporating bottom-up data to improve the accuracy of top-down modelling and enabling detailed monitoring of progress as health systems act to reduce emissions. FUNDING: Wellcome Trust.

Parasitic castration promotes coevolutionary cycling but also imposes a cost on sex.

Antagonistic coevolution between hosts and parasites is thought to drive a range of biological phenomena including the maintenance of sexual reproduction. Of particular interest are conditions that produce persistent fluctuations in the frequencies of genes governing host-parasite specificity (coevolutionary cycling), as sex may be more beneficial than asexual reproduction in a constantly changing environment. Although many studies have shown that coevolutionary cycling can lead to the maintenance of sex, the effects of ecological feedbacks on the persistence of these fluctuations in gene frequencies are not well understood. Here, we use a simple deterministic model that incorporates ecological feedbacks to explore how parasitic reductions in host fecundity affect the maintenance of coevolutionary cycling. We demonstrate that parasitic castration is inherently destabilizing and may be necessary for coevolutionary cycling to persist indefinitely, but also reduces the likelihood that sexually reproducing individuals will find a fertile partner, which may select against sex. These findings suggest that castrators can play an important role in shaping host evolution and are likely to be good targets for observing fluctuations in gene frequencies that govern specificity in host-parasite interactions.

Spatial structure mitigates fitness costs in host-parasite coevolution.

The extent of population mixing is known to influence the coevolutionary outcomes of many host and parasite traits, including the evolution of generalism (the ability to resist or infect a broad range of genotypes). While the segregation of populations into interconnected demes has been shown to influence the evolution of generalism, the role of local interactions between individuals is unclear. Here, we combine an individual-based model of microbial communities with a well-established framework of genetic specificity that matches empirical observations of bacterium-phage interactions. We find the evolution of generalism in well-mixed populations to be highly sensitive to the severity of associated fitness costs, but the constraining effect of costs on the evolution of generalism is lessened in spatially structured populations. The contrasting outcomes between the two environments can be explained by different scales of competition (i.e., global vs. local). These findings suggest that local interactions may have important effects on the evolution of generalism in host-parasite interactions, particularly in the presence of high fitness costs.