TRIM7 ubiquitinates SARS-CoV-2 membrane protein to limit apoptosis and viral replication.

SARS-CoV-2 is a highly transmissible virus that causes COVID-19 disease. Mechanisms of viral pathogenesis include excessive inflammation and viral-induced cell death, resulting in tissue damage. We identified the host E3-ubiquitin ligase TRIM7 as an inhibitor of apoptosis and SARS-CoV-2 replication via ubiquitination of the viral membrane (M) protein. Trim7 -/- mice exhibited increased pathology and virus titers associated with epithelial apoptosis and dysregulated immune responses. Mechanistically, TRIM7 ubiquitinates M on K14, which protects cells from cell death. Longitudinal SARS-CoV-2 sequence analysis from infected patients revealed that mutations on M-K14 appeared in circulating variants during the pandemic. The relevance of these mutations was tested in a mouse model. A recombinant M-K14/K15R virus showed reduced viral replication, consistent with the role of K15 in virus assembly, and increased levels of apoptosis associated with the loss of ubiquitination on K14. TRIM7 antiviral activity requires caspase-6 inhibition, linking apoptosis with viral replication and pathology.

OMEinfo: global geographic metadata for -omics experiments.

Summary: Microbiome studies increasingly associate geographical features like rurality and climate with microbiomes. It is essential to correctly integrate rich geographical metadata; and inconsistent definitions of rurality, can hinder cross-study comparisons. We address this with OMEinfo, a tool for automated retrieval of consistent geographical metadata from user-provided location data. OMEinfo leverages open data sources such as the Global Human Settlement Layer, and Open-Data Inventory for Anthropogenic Carbon dioxide. OMEinfo's web-app enables users to visualize and investigate the spatial distribution of metadata features. OMEinfo promotes reproducibility and consistency in microbiome metadata through a standardized metadata retrieval approach. To demonstrate utility, OMEinfo is used to replicate the results of a previous study linking population density to bacterial diversity. As the field explores relationships between microbiomes and geographical features, tools like OMEinfo will prove vital in developing a robust, accurate, and interconnected understanding of these interactions, whilst having applicability beyond this field to any studies utilizing location-based metadata. Finally, we release the OMEinfo annotation dataset of 5.3 million OMEinfo annotated samples from the ENA, for use in retrospective analyses of sequencing samples, and suggest several ways researchers and sequencing read repositories can improve the quality of underlying metadata submitted to these public stores. Availability and implementation: OMEinfo is freely available and released under an MIT licence. OMEinfo source code is available at https://github.com/m-crown/OMEinfo/ and https://doi.org/10.5281/zenodo.10518763.

Prevalence of persistent SARS-CoV-2 in a large community surveillance study.

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

Environmental microbiome in the home and daycare settings during the COVID-19 pandemic, and potential risk of non-communicable disease in children.

An exposure to diverse microbial population early in life is important for the development of immunity against various non-communicable diseases including asthma, childhood leukaemia and other cancers. Social mixing in daycare settings helps with exposure to a variety of microbes. However, social isolation and a high emphasis on workplace hygiene during the COVID pandemic may have affected children's exposure to diverse microbiota. The structure of microbial communities and their role in developing immunity to various diseases are not well understood. In this study, we investigated the structure of microbial communities in daycare and home settings during the pandemic. Interestingly, microbial diversity was relatively higher in dust samples collected from homes, with human-associated taxa being more prevalent compared to those from daycare settings. Environmental microbes were more abundant in dust samples from daycare providers. These results potentially suggest that cleaning practices during the pandemic may have influenced the diversity and microbial abundance of the daycare samples. Several bacterial taxa detected in both the environments are known to induce anti-inflammatory and immunomodulatory responses, conferring protection from various diseases. Therefore, exposure to diverse microbial population in early childhood may play an important role in developing immunity against various non-communicable and infectious diseases.

Correction: Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

[This corrects the article DOI: 10.1371/journal.ppat.1011461.].

Lineage replacement and evolution captured by 3 years of the United Kingdom Coronavirus (COVID-19) Infection Survey.

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens.

Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant.

SPEAR: Systematic ProtEin AnnotatoR.

SUMMARY: We present Systematic ProtEin AnnotatoR (SPEAR), a lightweight and rapid SARS-CoV-2 variant annotation and scoring tool, for identifying mutations contributing to potential immune escape and transmissibility (ACE2 binding) at point of sequencing. SPEAR can be used in the field to evaluate genomic surveillance results in real time and features a powerful interactive data visualization report. AVAILABILITY AND IMPLEMENTATION: SPEAR and documentation are freely available on GitHub: https://github.com/m-crown/SPEAR and are implemented in Python and installable via Conda environment. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.