Epidemiological data and genome sequencing reveals that nosocomial transmission of SARS-CoV-2 is underestimated and mostly mediated by a small number of highly infectious individuals

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1. Version published to 10.1016/j.jinf.2021.07.034

   Oct 1, 2021
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   ScreenIT

   Jul 5, 2021

   SciScore for 10.1101/2021.06.28.21259028: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	IRB: Ethics statement: Deidentified data were obtained from the Infections in Oxfordshire Research Database which has generic Research Ethics Committee, Health Research Authority and Confidentiality Advisory Group approvals (19/SC/0403, 19/CAG/0144).
   Sex as a biological variable	not detected.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.

   Table 2: Resources

   Software and Algorithms
   Sentences	Resources
   PCR-positive samples were stored at -80℃ for WGS.	WGS suggested: None
   Combined epidemiological and genomic analysis was performed using R version 4.0.2 [21], with visualisation using ggplot2[22] and igraph[23] packages.	ggplot2 suggested: (ggplot2, RRID:SCR_014601)
   Multiple …

   SciScore for 10.1101/2021.06.28.21259028: (What is this?)

   Please note, not all rigor criteria are appropriate for all manuscripts.

   Table 1: Rigor

   Ethics	IRB: Ethics statement: Deidentified data were obtained from the Infections in Oxfordshire Research Database which has generic Research Ethics Committee, Health Research Authority and Confidentiality Advisory Group approvals (19/SC/0403, 19/CAG/0144).
   Sex as a biological variable	not detected.
   Randomization	not detected.
   Blinding	not detected.
   Power Analysis	not detected.

   Table 2: Resources

   Software and Algorithms
   Sentences	Resources
   PCR-positive samples were stored at -80℃ for WGS.	WGS suggested: None
   Combined epidemiological and genomic analysis was performed using R version 4.0.2 [21], with visualisation using ggplot2[22] and igraph[23] packages.	ggplot2 suggested: (ggplot2, RRID:SCR_014601)
   Multiple sequence alignment and phylogenetic analysis were performed with MAFFT)[24]and IQTree[25] respectively; phylogenies were prepared and visualised using Treeswift[26] and Toytree[27].	MAFFT suggested: (MAFFT, RRID:SCR_011811)

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   Results from OddPub: Thank you for sharing your data.

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   Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

   The main limitations of genomic data were two-fold. Firstly, although epidemiological data is available for all patients, genomic data is limited by sample availability and difficulty of generating sequences at low viral loads. Here 67% of the cohort were successfully sequenced, in line with other similar hospital cohorts (20-70%)[7,11,34]. As such, genomic data does not enable nosocomial acquisition to be ruled out. Incomplete hospital sequencing datasets suffer from an ‘absence of evidence’ when attempting to exclude nosocomial acquisition, which should not be mistaken for ‘evidence of absence’ of nosocomial acquisition. This may be mitigated in the future by integrated community epidemiological and genomic datasets, and could be addressed through probabilistic inference methods that can account for missing data, or by further optimising sequencing yields. Future approaches to evaluating transmission could also consider proxy markers of infectiousness such as Ct values (reflecting viral loads). Secondly, the rapid transmission of SARS-CoV-2 in relation to viral evolution and the short time spans of outbreaks are insufficient for substantial genetic variation to accumulate, and therefore genomic data alone is insufficient to confer linkage or resolve the ordering of transmission; a combination of epidemiological and genomic data is required. A 1 SNP cut-off for defining linkage captures the majority of cases genuinely linked to the cluster, with the compromise of including a...

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   Results from TrialIdentifier: No clinical trial numbers were referenced.

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   Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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   Results from JetFighter: We did not find any issues relating to colormaps.

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   Results from rtransparent:

   • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
   • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
   • No protocol registration statement was detected.

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   Results from scite Reference Check: We found no unreliable references.

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3. 

   Version published to 10.1101/2021.06.28.21259028 on medRxiv

   Jul 2, 2021