tetano
Editor, Senior Moderator
J Clin Virol
. 2025 Jul 7:180:105833.
doi: 10.1016/j.jcv.2025.105833. Online ahead of print. Differential severity of SARS-CoV-2 variant infections in children and adults with COVID-19
Noah Brazer[SUP] 1 [/SUP], Venice Servellita[SUP] 1 [/SUP], Chengshi Jin[SUP] 2 [/SUP], Abiodun Foresythe[SUP] 1 [/SUP], Miriam Oseguera[SUP] 1 [/SUP], Jenny Nguyen[SUP] 1 [/SUP], Nanami Sumimoto[SUP] 1 [/SUP], Hee Jae Huh[SUP] 3 [/SUP], Andries Feder[SUP] 4 [/SUP], Sanchita Bhattacharya[SUP] 5 [/SUP], Surabhi Bhaskar[SUP] 1 [/SUP], Alicia Sotomayor-Gonzalez[SUP] 1 [/SUP], Prachi Saldhi[SUP] 1 [/SUP], Chris Choi[SUP] 6 [/SUP], Grace X Li[SUP] 6 [/SUP], Komal Gopchandani[SUP] 6 [/SUP], Ashley Tippett[SUP] 6 [/SUP], Hui-Mien Hsiao[SUP] 6 [/SUP], Mark D Gonzalez[SUP] 7 [/SUP], Dalia Gulick[SUP] 6 [/SUP], Colleen Kraft[SUP] 6 [/SUP], Vyjayanti Kasinathan[SUP] 6 [/SUP], Yun F Wayne Wang[SUP] 8 [/SUP], Pei Ying Chen[SUP] 9 [/SUP], Jessica Flores-Vazquez[SUP] 9 [/SUP], Krisha Patel[SUP] 4 [/SUP], Audrey R Odom John[SUP] 10 [/SUP], Jennifer K Spinler[SUP] 11 [/SUP], Sridevi Devaraj[SUP] 12 [/SUP], Ananth V Annapragada[SUP] 13 [/SUP], Ruth Ann Luna[SUP] 11 [/SUP], Xiaowu Gai[SUP] 14 [/SUP], Jennifer Dien Bard[SUP] 14 [/SUP], Christina A Rostad[SUP] 15 [/SUP], Paul J Planet[SUP] 10 [/SUP], Ann A Lazar[SUP] 16 [/SUP], Charles Y Chiu[SUP] 17 [/SUP]
Affiliations
We performed virus whole-genome sequencing of 6916 upper respiratory swabs from adults and children from March 2020 to 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, decreases in severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity.
Keywords: COVID-19; Coronavirus; Delta; Epsilon; Omicron; Pediatric; Respiratory disease; Severe Acute Respiratory Syndrome; Severity; Symptoms; Variant of concern (VOC); Variant of interest (VOI); Virus whole-genome sequencing.
. 2025 Jul 7:180:105833.
doi: 10.1016/j.jcv.2025.105833. Online ahead of print. Differential severity of SARS-CoV-2 variant infections in children and adults with COVID-19
Noah Brazer[SUP] 1 [/SUP], Venice Servellita[SUP] 1 [/SUP], Chengshi Jin[SUP] 2 [/SUP], Abiodun Foresythe[SUP] 1 [/SUP], Miriam Oseguera[SUP] 1 [/SUP], Jenny Nguyen[SUP] 1 [/SUP], Nanami Sumimoto[SUP] 1 [/SUP], Hee Jae Huh[SUP] 3 [/SUP], Andries Feder[SUP] 4 [/SUP], Sanchita Bhattacharya[SUP] 5 [/SUP], Surabhi Bhaskar[SUP] 1 [/SUP], Alicia Sotomayor-Gonzalez[SUP] 1 [/SUP], Prachi Saldhi[SUP] 1 [/SUP], Chris Choi[SUP] 6 [/SUP], Grace X Li[SUP] 6 [/SUP], Komal Gopchandani[SUP] 6 [/SUP], Ashley Tippett[SUP] 6 [/SUP], Hui-Mien Hsiao[SUP] 6 [/SUP], Mark D Gonzalez[SUP] 7 [/SUP], Dalia Gulick[SUP] 6 [/SUP], Colleen Kraft[SUP] 6 [/SUP], Vyjayanti Kasinathan[SUP] 6 [/SUP], Yun F Wayne Wang[SUP] 8 [/SUP], Pei Ying Chen[SUP] 9 [/SUP], Jessica Flores-Vazquez[SUP] 9 [/SUP], Krisha Patel[SUP] 4 [/SUP], Audrey R Odom John[SUP] 10 [/SUP], Jennifer K Spinler[SUP] 11 [/SUP], Sridevi Devaraj[SUP] 12 [/SUP], Ananth V Annapragada[SUP] 13 [/SUP], Ruth Ann Luna[SUP] 11 [/SUP], Xiaowu Gai[SUP] 14 [/SUP], Jennifer Dien Bard[SUP] 14 [/SUP], Christina A Rostad[SUP] 15 [/SUP], Paul J Planet[SUP] 10 [/SUP], Ann A Lazar[SUP] 16 [/SUP], Charles Y Chiu[SUP] 17 [/SUP]
Affiliations
- PMID: 40674918
- DOI: 10.1016/j.jcv.2025.105833
We performed virus whole-genome sequencing of 6916 upper respiratory swabs from adults and children from March 2020 to 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, decreases in severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity.
Keywords: COVID-19; Coronavirus; Delta; Epsilon; Omicron; Pediatric; Respiratory disease; Severe Acute Respiratory Syndrome; Severity; Symptoms; Variant of concern (VOC); Variant of interest (VOI); Virus whole-genome sequencing.