Highlights
• This study evaluated differences in SARS-CoV-2 variant severity from 2020-2023
• SARS-CoV-2 whole-genome sequencing from 6,916 respiratory swabs was performed
• Four conserved kmer sequences associated with severity were identified
• Infections from the Delta variant had highest likelihood of severe infection
• Omicron BA.4/5 variant was more severe than BA.1 in children, vice-versa in adults
Abstract
We performed virus whole-genome sequencing of 6,916 upper respiratory swabs from adults and children from March 2020 through May 2023 and collected clinical metadata to assess differences in SARS-CoV-2 variant severity and symptomatology. Multivariable logistic regression showed a severity peak with Delta, which had the highest likelihood of severe infection. In children, another peak was observed with BA.4/BA.5, which was associated with more severe infection than both prior (BA.1) and later (BQ.1, BF.7, and XBB) Omicron variants. In contrast, BA.4/BA.5 in adults was associated with less severe infection than BA.1. Genome-wide association studies revealed that nonstructural protein 5 (nsp5, also called 3C-chymotrypsin-like protease), the Paxlovid target, and the spike N-terminal domain were strongly associated with severity. Kmers (contiguous nucleotide sequences of a fixed length k) from these regions matched the prototype Wuhan sequence exactly, corroborating decreases in severity over time. One kmer in the spike gene region was conserved in Delta genomes, with the kmer retained in higher proportions in patients with more severe infection. Our results show, with the exception of Delta, decreased severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity.
Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000757?dgcid=rss_sd_all
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