Deep untargeted #wastewater #metagenomic #sequencing from #sewersheds across the #USA

Abstract

Wastewater monitoring enables non-invasive, population-scale tracking of community infections independent of healthcare-seeking behavior and clinical diagnosis. Metagenomic sequencing extends this capability by enabling broad, pathogen-agnostic detection, genomic characterization, and identification of novel or unexpected threats. Here, we present data from CASPER (the Coalition for Agnostic Sequencing of Pathogens from Environmental Reservoirs), a U.S.-based wastewater metagenomic sequencing network designed for deep, untargeted pathogen monitoring at national scale. This release includes 1,206 samples collected between December 2023 and December 2025 from 27 sites across nine states, covering 13 million people. Deep sequencing (~1 billion read pairs per sample) generated 1.2 trillion read pairs (347 terabases), enabling detection of even rare taxa, with CASPER representing 66% of all untargeted wastewater sequencing data currently available on the NCBI Sequence Read Archive. Virus abundance trends correlate with nationwide wastewater PCR and clinical data for SARS-CoV-2, influenza A, and respiratory syncytial virus, while the pathogen-agnostic approach captures emerging threats, including avian influenza H5N1 during initial dairy cattle outbreaks, West Nile virus, and measles, among hundreds of viral taxa. As the largest publicly available untargeted wastewater sequencing dataset to date, CASPER provides a shared and growing resource for pathogen surveillance and microbial ecology.

Competing Interest Statement

D.H.O. received support for this project from Inkfish and Heart of Racing. D.H.O. is a managing partner of Pathogenuity LLC, a consultancy that advises on topics including environmental monitoring for pathogens. P.C.S. hold several patents related to diagnostic and surveillance technologies and is a co-founder and equity holder in Delve Biosciences and Lyra Labs, a board member and equity holder in Polaris Genomics, and an equity holder of NextGenJane. P.C.S was formerly a co-founder of Sherlock Biosciences and board member of Danaher Corporation, until December 2024. All potential conflicts are managed in accordance with institutional policy.

Funding Statement

L.J.J. was supported by the Draper Scholar program at The Charles Stark Draper Laboratory. J.K., O.S.H., R.F-O., S.L.G., W.J.B., H.B., D.P.R., K.S., J.D.F., and M.R.M. received support for this work from Coefficient Giving via a gift to SecureBio. C.R., A.T-M., E.E.C., M.C.J., and D.H.O. were supported by Inkfish and Heart of Racing. L.J.J., J.P., and P.C.S. were supported by the CDC Pathogen Genomics Centers of Excellence (contract INTF5104H78W22195346) and a CDC Broad Agency Announcement (contract 75D30123C17983). J.E.L. and G.A. were supported by a subcontract under CDC Broad Agency Announcement contract 75D30123C17983. H.M.S-G. and A.A. were supported in part by the National Institute on Drug Abuse of the National Institutes of Health under Award Number U01DA053941, and by the University of Miami Initiative on Virology and Infectious Disease and SecureBio. R.P. was supported by the Illinois Department of Public Health and the Chicago Department of Public Health. This work used Expanse at the San Diego Supercomputer Center through allocation BIO240238 to J.A.R. from the Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) program, which is supported by U.S. National Science Foundation grants #2138259, #2138286, #2138307, #2137603, and #2138296.

Source:

Link: https://www.medrxiv.org/content/10.64898/2026.03.05.26345726v1

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#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...

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