Metagenomic analysis reveals differences in the co-occurrence and abundance of viral species in SARS-CoV-2 patients with different severity of disease.

BACKGROUND: SARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized. METHODS: In this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing. RESULTS: Genetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals. CONCLUSIONS: Results show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis.

Single-stranded circular DNA theranostics.

The past decade has witnessed the blossom of nucleic acid therapeutics and diagnostics (theranostics). Unlike conventional small molecule medicines or protein biologics, nucleic acid theranostics have characteristic features such as the intrinsic ability as "information drugs" to code and execute genetic and theranostic information, ready programmability for nucleic acid engineering, intrinsic stimulatory or regulatory immunomodulation, versatile functionalities, and easy conformational recovery upon thermal or chemical denaturation. Single-stranded circular DNA (circDNA) are a class of single-stranded DNAs (ssDNA) featured with their covalently-closed topology. In addition to the basic advantages of nucleic acids-based materials, such as low cost, biocompatibility, and simplicity of chemical modification, the lack of terminals in circDNA prevents exonuclease degradation, resulting in enhanced biostability relative to the corresponding linear ssDNA. circDNA has been explored for versatile theranostic applications. For instance, circDNA has been extensively studied as templates for bioanalytical signal amplification and the synthesis of nano-/micro-/macro- biomaterials via rolling circle amplification (RCA) and rolling circle transcription (RCT) technologies. circDNA has also been commonly used as the scaffolds for the self-assembly of versatile DNA origami. Finally, circDNA has been implemented as theranostic aptamers, miRNA inhibitors, as well as clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) gene editing donors. In this review article, we will discuss the chemistry, characteristic properties, and the theranostic applications of circDNA (excluding double-stranded circular DNA such as plasmids); we will also envision the challenges and opportunities in this research field.