Detecting SARS-CoV-2 Cryptic Lineages using Publicly Available Whole Genome Wastewater Sequencing Data

Publication date: Dec 26, 2024

Beginning in early 2021, unique and highly divergent lineages of SARS-CoV-2 were sporadically found in wastewater sewersheds using a sequencing strategy focused on the most mutagenic region of SARS-CoV-2, the receptor binding domain (RBD). Because these RBD sequences did not match known circulating strains and their source was not known, we termed them “cryptic lineages”. To date, more than 20 cryptic lineages have been identified using the RBD-focused sequencing strategy. Here, we identified and characterized additional cryptic lineages from SARS-CoV-2 wastewater sequences submitted to NCBIs Sequence Read Archives (SRA). Wastewater sequence datasets were screened for individual sequence reads that contained combinations of mutations frequently found in cryptic lineages but not contemporary circulating lineages. Using this method, we identified 18 cryptic lineages that appeared in multiple samples from the same sewershed, including 12 that were not previously reported. Partial consensus sequences were generated for each cryptic lineage by extracting and mapping sequences containing cryptic-specific mutations. Surprisingly, seven of the mutations that appeared convergently in cryptic lineages were reversions to sequences that were highly conserved in SARS-CoV-2-related bat Sarbecoviruses. The apparent reversion to bat Sarbecovirus sequences suggests that SARS-CoV-2 adaptation to replicate efficiently in respiratory tissues preceded the COVID-19 pandemic.

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Concepts Keywords
50ml Cov
Astroviruses Cryptic
Baker Https
Biotechnology International
Gtgactggagttcagacgtgtgctcttccgatctactactactctgtatggttggtaac Lineage
Lineages
Medrxiv
Mutations
Org
Preprint
Sars
Sequence
Sequences
Specific
Wastewater

Semantics

Type Source Name
disease MESH COVID-19 pandemic
disease MESH infections
drug DRUGBANK Ademetionine
disease IDO process
disease IDO replication
drug DRUGBANK Antithymocyte immunoglobulin (rabbit)
disease IDO pathogen
drug DRUGBANK Papain
drug DRUGBANK Coenzyme M
disease IDO site
drug DRUGBANK Polyethylene glycol
disease IDO assay
drug DRUGBANK Water
disease IDO host
disease IDO history
disease MESH severe acute respiratory syndrome
disease IDO protein
drug DRUGBANK (S)-Des-Me-Ampa

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