SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations

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Abstract

College reopening decisions during the SARS-CoV-2 pandemic represent a trade-off between competing risks to students, faculty and staff, and college finances. Additionally, risks taken in reopening colleges can impose significant burdens on individuals living in surrounding communities. Many colleges that reopened for in-person instruction have reported frequent SARS-CoV-2 outbreaks. La Crosse County, Wisconsin experienced a substantial SARS-CoV-2 outbreak (2,002 cases in September 2020) that coincided with the return to in-person instruction at three local academic institutions. Genomic sequencing of SARS-CoV-2 cases in La Crosse during that period found rapid expansion of two viral substrains. Although the majority of cases were among college-age individuals, from a total of 111 genomes sequenced we identified rapid transmission of the virus into more vulnerable populations. Eight sampled genomes represented two independent transmission events into two skilled nursing facilities, resulting in two fatalities. Our study highlights the very significant risks imposed by college administrator reopening decisions, not just on college-associated populations, but on vulnerable individuals in surrounding communities.

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  1. SciScore for 10.1101/2020.10.12.20210294: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical approval was obtained from the Gundersen Health System Institutional Review Board (#2-20-03-008; PI: Kenny) to perform additional next-generation sequencing on remnant specimens after completion of diagnostic testing.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Samples for this study include only those testing positive in Gundersen Healthcare System’s diagnostic laboratories and, as such, do not include other cases from the region which may have been tested in other healthcare systems and/or public health laboratories
    Gundersen Healthcare
    suggested: None
    To overcome difficulties caused by read soft-clipping by this non-splice aware aligner, individual sequence reads were extracted using samtools (4) and re-aligned to the SARS-CoV-2 genome using a splice-aware aligner, hisat2 (5).
    samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.
    • 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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Our take

    Using genomic sequencing of SARS-CoV-2 positive individuals from communities surrounding three academic institutions in La Cross County, Wisconsin, preceding and during college re-opening, this study, available as a preprint and thus not yet peer reviewed, demonstrated how endemic SARS-CoV-2 strains can rapidly spread within a large intermixing susceptible group of newly introduced individuals and spill-over into neighboring vulnerable populations. Supporting previous findings that outbreaks among younger individuals precede outbreaks among older populations, these data suggest that alternate strategies such as frequent and widespread testing of all university students regardless of on-campus housing status, rather than pre-/re-entry screening alone, may be important for outbreak prevention.

    Study design

    retrospective-cohort

    Study population and setting

    Using surveillance and sequencing data from Gundersen Healthcare System’s diagnostic laboratories serving Wisconsin, Iowa and Minnesota, this study assessed the role of college reopening on community transmission in La Cross County, Wisconsin. The database included sequencing of all SARS-CoV-2 positive cases diagnosed between March 18 and September 9, 2020, noting a rapid rise in September 2020 in La Cross County coinciding with three local college campus re-openings. A total of 514 genome-length sequences of the SARS-CoV-2 virus were obtained from the March to September period via next generation sequencing. Through phylogenetic analyses and the use of college/university curated online “COVID19 Dashboards”, the genetic similarities between each viral sequence were used to infer college-associated viral clusters and identify likely transmission events within La Crosse County, Wisconsin.

    Summary of main findings

    Rapid increase in cases among younger people occurred in early September, which largely concentrated around two viral clusters circulating at that time, designated College A and College B, and occurring around increases in cases as ascertained through local college Dashboards. Through the genomic sequencing and assessments of time lags, college-associated viral clusters of endemic SARS-CoV-2 strains within younger individuals were identified to be the source of multiple transmission events into the broader community, including skilled nursing facilities (resulting in two fatalities).

    Study strengths

    This study utilized a well described viral whole-genome isolation, amplification, sequencing, and analysis workflow and made effective use of varying data types from multiple sources to support their conclusions.

    Limitations

    Only those samples processed by Gundersen Healthcare System's diagnostic labs were available for sequencing. As such, students in dormitories who were tested by university labs were not represented though it is expected their viral genomes would be similar. The community experienced an increased prevalence of the college-associated viral clusters around the time of college re-openings, which cannot be ruled out as responsible for the observed outbreak in the skilled nursing facility. It is also unclear what quality control steps were conducted for each sample prior to the generation of a sample-specific consensus sequence, as no details are provided.

    Value added

    Through genomic sequencing, this study linked an outbreak among college-aged individuals to transmission events within vulnerable/older individuals living in the surrounding community, supporting previous research noting increased SARS-CoV-2 infections among younger individuals often precedes an increase of cases among older individuals. Based on their observations, the authors suggest pre-/re-entry testing of students would fail to prevent such outbreaks within areas of active community transmission and instead recommend the use of frequent widespread testing of the entire student population, regardless of housing status, to prevent such outbreaks.