Shared within-host SARS-CoV-2 variation in households
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Abstract
Background
The limited variation observed among SARS-CoV-2 consensus sequences makes it difficult to reconstruct transmission linkages in outbreak settings. Previous studies have recovered variation within individual SARS-CoV-2 infections but have not yet measured the informativeness of within-host variation for transmission inference.
Methods
We performed tiled amplicon sequencing on 307 SARS-CoV-2 samples from four prospective studies and combined sequence data with household membership data, a proxy for transmission linkage.
Results
Consensus sequences from households had limited diversity (mean pairwise distance, 3.06 SNPs; range, 0-40). Most (83.1%, 255/307) samples harbored at least one intrahost single nucleotide variant (iSNV; median: 117; IQR: 17-208), when applying a liberal minor allele frequency of 0.5% and prior to filtering. A mean of 15.4% of within-host iSNVs were recovered one day later. Pairs in the same household shared significantly more iSNVs (mean: 1.20 iSNVs; 95% CI: 1.02-1.39) than did pairs in different households infected with the same viral clade (mean: 0.31 iSNVs; 95% CI: 0.28-0.34), a signal that increases with increasingly liberal thresholds.
Conclusions
Although only a subset of within-host variation is consistently shared across likely transmission pairs, shared iSNVs may augment the information in consensus sequences for predicting transmission linkages.
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SciScore for 10.1101/2022.05.26.22275279: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All study participants provided written consent and all studies were approved by the Institutional Review Board of Stanford University (Numbers: 55479, 57686, 56032, and 55619).
IRB: All study participants provided written consent and all studies were approved by the Institutional Review Board of Stanford University (Numbers: 55479, 57686, 56032, and 55619).Sex as a biological variable not detected. Randomization (b) A randomized, single-blind, placebo-controlled trial of Peginterferon Lambda-1a (Lambda) for reducing the duration of viral shedding or symptoms[17] in which oropharyngeal swabs were collected for 28 days following enrollment. Blinding not detected. Power Analysis not detected. SciScore for 10.1101/2022.05.26.22275279: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All study participants provided written consent and all studies were approved by the Institutional Review Board of Stanford University (Numbers: 55479, 57686, 56032, and 55619).
IRB: All study participants provided written consent and all studies were approved by the Institutional Review Board of Stanford University (Numbers: 55479, 57686, 56032, and 55619).Sex as a biological variable not detected. Randomization (b) A randomized, single-blind, placebo-controlled trial of Peginterferon Lambda-1a (Lambda) for reducing the duration of viral shedding or symptoms[17] in which oropharyngeal swabs were collected for 28 days following enrollment. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Sequence data is available at SRA (BioProject ID: PRJNA842503). BioProjectsuggested: (NCBI BioProject, RRID:SCR_004801)We also used this pipeline to remove reads mapping to the host genome with Kraken2[24], map reads with Bowtie 2[22], generate consensus sequences with bcftools[25], and assign Nextclade lineages[26]. Kraken2suggested: NoneResults from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. First, we focused on a convenience sample of residual samples with accompanying household information collected in California from March 2020 through May 2021. Replicating these findings in other settings and with more recently emerged SARS-CoV-2 lineages is critical to understand the generalizability of our findings. Second, our study focused on the potential epidemiological value of within-host viral variation. Our focus was on transmission linkage rather than in viral evolutionary dynamics or transmission bottlenecks, which might have different optimal variant identification approaches. Third, many groups have hypothesized that evolution within immune-compromised or immune-suppressed populations may be an important driver of the emergence of new variants of concern or interest[37–41]. Our sample collection did not enable us to test these hypotheses. Forth, the epidemiological utility of within-host variation depends on SARS-CoV-2 sampling and sequencing. Routine sequencing may always not generate sufficient depth to accurately recover within-host variation. In conclusion, we find that SARS-CoV-2 variation within individual hosts may be shared across transmission pairs and may contribute information on transmission linkage on a backdrop of limited diversity among consensus sequences. More broadly, pathogen diversity within individual infections holds largely untapped information that may enhance the resolution of transmission inferences.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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Results from scite Reference Check: We found no unreliable references.
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