SARS-CoV-2 Evolution and Spike-Specific CD4+ T-Cell Response in Persistent COVID-19 with Severe HIV Immune Suppression

Intra-host evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in cases with persistent coronavirus disease 2019 (COVID-19). In this study, we describe a severely immunosuppressed individual with HIV-1/SARS-CoV-2 coinfection with a long-term course of SARS-CoV-2 infection. A 28-year-old man was diagnosed with HIV-1 infection (CD4+ count: 3 cells/µL nd 563000 HIV-1 RNA copies/mL) and simultaneous Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection and SARS-CoV-2 infection. SARS-CoV-2 real-time reverse transcription polymerase chain reaction positivity from nasopharyngeal samples was prolonged for 15 weeks. SARS-CoV-2 was identified as variant Alpha (PANGO lineage B.1.1.7) with mutation S:E484K. Spike-specific T-cell response was similar to HIV-negative controls although enriched in IL-2, and showed disproportionately increased immunological exhaustion marker levels. Despite persistent SARS-CoV-2 infection, adaptive intra-host SARS-CoV-2 evolution, was not identified. Spike-specific T-cell response protected against a severe COVID-19 outcome and the increased immunological exhaustion marker levels might have favoured SARS-CoV-2 persistence.

Unconstrained coevolution of bacterial size and the latent period of plastic phage

Viruses play critical roles in the dynamics of microbial communities. Lytic viruses, for example, kill significant proportions of autotrophic and heterotrophic microbes. The dynamic interplay between viruses and microbes results from an overlap of physiological, ecological, and evolutionary responses: environmental changes trigger host physiological changes, affecting the ecological interactions of host and virus and, ultimately, the evolutionary pressures influencing the two populations. Recent theoretical work studied how the dependence of viral traits on host physiology (viral plasticity) affects the evolutionarily stable host cell size and viral infection time emerging from coevolution. Here, we broaden the scope of the framework to consider any coevolutionary outcome, including potential evolutionary collapses of the system. We used the case study of Escherichia coli and T-like viruses under chemostat conditions, but the framework can be adapted to any microbe-virus system. Oligotrophic conditions led to smaller, lower-quality but more abundant hosts, and infections that were longer but produced a reduced viral offspring. Conversely, eutrophic conditions resulted in fewer but larger higher-quality hosts, and shorter but more productive infections. The virus influenced host evolution decreasing host radius more noticeably for low than for high dilution rates, and for high than for low nutrient input concentration. For low dilution rates, the emergent infection time minimized host need/use, but higher dilution led to an opportunistic strategy that shortened the duration of infections. System collapses driven by evolution resulted from host failure to adapt quickly enough to the evolving virus. Our results contribute to understanding the eco-evolutionary dynamics of microbes and virus, and to improving the predictability of current models for host-virus interactions. The large quantitative and qualitative differences observed with respect to a classic description (in which viral traits are assumed to be constant) highlights the importance of including viral plasticity in theories describing short- and long-term host-virus dynamics.

Stepwise Evolution of a Klebsiella pneumoniae Clone within a Host Leading to Increased Multidrug Resistance

Within-host evolution is a survival strategy that can occur in many pathogens and is often associated with the emergence of novel antimicrobial-resistant (AMR) bacteria. To analyze this process, suitable sets of clinical isolates are required.

Identification of diverse viruses associated with grasshoppers unveils phylogenetic congruence between hosts and viruses

Locusts and grasshoppers are one of the most dangerous agricultural pests. Environmentally benign microbial pesticides are increasingly desirable for controlling locust outbreaks in fragile ecosystems. Here we use metagenomic sequencing to profile the rich viral communities in 34 grasshopper species and report 322 viruses, including 202 novel species. Most of the identified viruses are related to other insect viruses and some are targeted by antiviral RNAi pathway, indicating they infect grasshoppers. Some plant/fungi/vertebrate associated viruses are also abundant in our samples. Our analysis of relationships between host and virus phylogenies suggests that the composition of viromes is closely allied with host evolution, and there is significant phylogenetic relatedness between grasshoppers and viruses from Lispiviridae, Partitiviridae, Orthomyxoviridae, Virgaviridae and Flaviviridae. Overall, this study is a thorough exploration of viruses in grasshoppers and provide an essential evolutionary and ecological context for host-virus interaction in Acridoidea.

Organ-specific genome diversity of replication-competent SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not always confined to the respiratory system, as it impacts people on a broad clinical spectrum from asymptomatic to severe systemic manifestations resulting in death. Further, accumulation of intra-host single nucleotide variants during prolonged SARS-CoV-2 infection may lead to emergence of variants of concern (VOCs). Still, information on virus infectivity and intra-host evolution across organs is sparse. We report a detailed virological analysis of thirteen postmortem coronavirus disease 2019 (COVID-19) cases that provides proof of viremia and presence of replication-competent SARS-CoV-2 in extrapulmonary organs of immunocompromised patients, including heart, kidney, liver, and spleen (NCT04366882). In parallel, we identify organ-specific SARS-CoV-2 genome diversity and mutations of concern N501Y, T1027I, and Y453F, while the patient had died long before reported emergence of VOCs. These mutations appear in multiple organs and replicate in Vero E6 cells, highlighting their infectivity. Finally, we show two stages of fatal disease evolution based on disease duration and viral loads in lungs and plasma. Our results provide insights about the pathogenesis and intra-host evolution of SARS-CoV-2 and show that COVID-19 treatment and hygiene measures need to be tailored to specific needs of immunocompromised patients, even when respiratory symptoms cease.

Competition and coevolution drive the evolution and the diversification of CRISPR immunity

The diversity of resistance fuels host adaptation to infectious diseases and challenges the ability of pathogens to exploit host populations. Yet, how this host diversity evolves over time remains unclear because it depends on the interplay between intraspecific competition and coevolution with pathogens. Here we study the effect of a coevolving phage population on the diversification of bacterial CRISPR immunity across space and time. We demonstrate that the negative-frequency-dependent selection generated by coevolution is a powerful force that maintains host resistance diversity and selects for new resistance mutations in the host. We also find that host evolution is driven by asymmetries in competitive abilities among different host genotypes. Even if the fittest host genotypes are targeted preferentially by the evolving phages they often escape extinctions through the acquisition of new CRISPR immunity. Together, these fluctuating selective pressures maintain diversity, but not by preserving the pre-existing host composition. Instead, we repeatedly observe the introduction of new resistance genotypes stemming from the fittest hosts in each population. These results highlight the importance of competition on the transient dynamics of host-pathogen coevolution.

Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient as a source of immune escape variants

The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient’s escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.

Diet and Domestication Drive Evolution of the Gut Holobiome

The host microbiome encompasses all microorganisms of a host. Host and microbiome coevolution in the gut result in differing microbial compositions, functionality, and host diet [1]. Host diet modulates what macromolecules are used for gut microbial metabolism, which can determine digestion, health, and behavior [2, 3]. Microbial composition across animals provides data on how microbiomes segregate between species and diets [4]. Here we show that microbiome data from GenBank can model host evolution, providing a holobiome insight to the important roles of diet and domestication. The main findings of this study in respect to microbial composition among species were: (1) herbivores are more similar than hosts with other diets; (2) domesticated species are more similar than wild relatives; and (3) humans are distinct from primates. Microbial composition between diets indicates a difference in functionality, where protein and fiber degradation are seen more in carnivores and herbivores respectively. Additionally, herbivores show the most microbial diversity among the diets. Finally, this analysis informs us of gaps in current microbiome data collection, which is biased toward pathogens. Thus, the host-microbiome relationship depicts a complex web of microbial functionality, composition, and diet that impact coevolution.

SynTracker: a synteny based tool for tracking microbial strains

In the human gut microbiome, specific strains emerge due to within-host evolution and can occasionally be transferred to or from other hosts. Phenotypic variance among such strains can have implications for strain transmission and interaction with the host. Surveilling strains of the same species, within and between individuals, can further our knowledge about the way in which microbial diversity is generated and maintained in host populations. Existing methods to estimate the biological relatedness of similar strains usually rely on either detection of single nucleotide polymorphisms (SNP), which may include sequencing errors, or on the analysis of pangenomes, which can be limited by the requirement for extensive gene databases. To complement existing methods, we developed SynTracker. This strain-comparison tool is based on synteny comparisons between strains, or the comparison of the arrangement of sequence blocks in two homologous genomic regions in pairs of metagenomic assemblies or genomes. Our method is executed in a species-specific manner, has a low sensitivity to SNPs, does not require a pre-existing database, and can correctly resolve strains using complete or draft genomes and metagenomic samples using <5% of the genome length. When applied to metagenomic datasets, we detected person-specific strains with an average sensitivity of 97% and specificity of 99%, and strain-sharing events in mother-infant pairs. SynTracker can be used to study the population structure of specific microbial species between and within environments, to identify evolutionary trajectories in longitudinal datasets, and to further understanding of strain sharing networks.