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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22281012

ABSTRACT

We conducted weekly surveillance for SARS-CoV-2 infection among a sample of households with [≥]1 child aged 0-17 years from selected Utah counties. A Cox proportional hazards model approach was used to calculate infection hazard rate and vaccine effectiveness. Findings show that the recommended primary series of COVID-19 vaccine was effective against circulating variants during a Delta-predominant wave in Utah.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22278452

ABSTRACT

BackgroundThe reliability of sequence-based inference of SARS-CoV-2 transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. MethodsSARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with an RT-PCR cycle threshold [≤]30 underwent whole genome sequencing. Intrahost single nucleotide variants (iSNV) were identified at [≥]5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. ResultsThere were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had [≥]1 consensus that differed by 1-2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and 6 of 11 with distinct ones. ConclusionsIn multiple infection households, whole genome consensus sequences differed by 0-1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. SummaryHigh depth of coverage whole genome sequencing can identify SARS-CoV-2 transmission chains in settings where there is strong epidemiologic linkage but is not reliable as a stand-alone method for transmission inference.

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-477987

ABSTRACT

During the SARS-CoV-2 pandemic, multiple variants with differing amounts of escape from pre-existing immunity have emerged, causing concerns about continued protection. Here, we use antigenic cartography to quantify and visualize the antigenic relationships among 16 SARS-CoV-2 variants titrated against serum samples taken post-vaccination and post-infection with seven different variants. We find major antigenic differences caused by substitutions at spike positions 417, 452, 484, and possibly 501. B.1.1.529 (Omicron BA.1) showed the highest escape from all sera tested. Visualization of serological responses as antibody landscapes shows how reactivity clusters in different regions of antigenic space. We find changes in immunodominance of different spike regions depending on the variant an individual was exposed to, with implications for variant risk assessment and vaccine strain selection. One sentence summaryAntigenic Cartography of SARS-CoV-2 variants reveals amino acid substitutions governing immune escape and immunodominance patterns.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-21268034

ABSTRACT

SARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children. We compared Receptor Binding Domain binding antibody (RBDAb) and SARS-CoV-2 neutralizing antibody (neutAb) in children aged 0-4 years, 5-17 years, and in adults aged 18-62 years in a SARS-CoV-2 household study. Among 55 participants seropositive at enrollment, children aged 0-4 years had >10-fold higher RBDAb titers than adults (373 vs.35, P<0.0001), and the highest RBDAb titers in 11/12 households with seropositive children and adults. Children aged 0-4 years had 2-fold higher neutAb than adults, resulting in higher binding to neutralizing (B/N)Ab ratios compared to adults (1.9 vs. 0.4 for ID50, P=0.0002). Findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutAb to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years.

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