Are presymptomatic SARS-CoV-2 infections in nursing home residents unrecognised symptomatic infections? Sequence and metadata from weekly testing in an extensive nursing home outbreak

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Abstract

Background

Sars-CoV-2 outbreaks resulted in a high case fatality rate in nursing homes (NH) worldwide. It is unknown to which extent presymptomatic residents and staff contribute to the spread of the virus.

Aims

To assess the contribution of asymptomatic and presymptomatic residents and staff in SARS-CoV-2 transmission during a large outbreak in a Dutch NH.

Methods

Observational study in a 185-bed NH with two consecutive testing strategies: testing of symptomatic cases only, followed by weekly facility-wide testing of staff and residents regardless of symptoms. Nasopharyngeal and oropharyngeal testing with RT-PCR for SARs-CoV-2, including sequencing of positive samples, was conducted with a standardised symptom assessment.

Results

185 residents and 244 staff participated. Sequencing identified one cluster. In the symptom-based test strategy period, 3/39 residents were presymptomatic versus 38/74 residents in the period of weekly facility-wide testing (P-value < 0.001). In total, 51/59 (91.1%) of SARS-CoV-2 positive staff was symptomatic, with no difference between both testing strategies (P-value 0.763). Loss of smell and taste, sore throat, headache or myalga was hardly reported in residents compared to staff (P-value <0.001). Median Ct-value of presymptomatic residents was 21.3, which did not differ from symptomatic (20.8) or asymptomatic (20.5) residents (P-value 0.624).

Conclusions

Symptoms in residents and staff are insufficiently recognised, reported or attributed to a possible SARS-CoV-2 infection. However, residents without (recognised) symptoms showed the same potential for viral shedding as residents with symptoms. Weekly testing was an effective strategy for early identification of SARS-Cov-2 cases, resulting in fast mitigation of the outbreak.

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  1. SciScore for 10.1101/2020.09.15.20195396: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Health care professionals were asked informed consent for participating in the study prior to digital questionnaire completion.
    IRB: The Medical Ethics Committee of the VU University Medical Centre in Amsterdam reviewed the study protocol and confirmed that the study does not fall under the scope of the Medical Research Involving Human Subjects Act.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The phylogenetic trees were visualized in Figtree.
    Figtree
    suggested: (FigTree, RRID:SCR_008515)
    All analyses were done using SPSS, version 26 (IBM, Armonk, NY) and Excel. Ethics: Written information about the study was sent out to residents and their legal representatives at May 18th, with the possibility to opt-out.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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: We detected the following sentences addressing limitations in the study:
    Limitations: Not all staff members who tested positive participated in the study. In addition, some staff members had to answer the questionnaire retrospectively, which gives the risk of recall bias. Also, the questionnaire did not inquire if staff worked with symptoms. Further, the difference between symptomatic staff and residents could perhaps be explained by the fact that staff was tested less frequent than residents: residents were tested weekly, but staff was tested biweekly. This may have contributed partly to the higher proportion of symptomatic staff. Last, not all SARS-CoV-2 positive samples were sequenced. However, a lot of time points could be analyzed and they show all the same cluster which makes it unlikely that multiple clusters were circulating in the NH. Conclusion: This study suggests that part of the presymptomatic cases in NHs are unrecognized symptomatic cases. Our study supports the guideline of the CDC and ECDC that facility-wide testing of residents and staff needs to be undertaken after the first confirmed SARS-CoV-2 case in the facility. If there is limited viral testing capacity, initial testing of (asymptomatic) close contacts is advised (CDC). This allows identification of possible asymptomatic, presymptomatic cases and unrecognized symptomatic cases and prevent further spread of the virusSequencing should be performed to discriminate ongoing intramural transmission and multiple introductions. Box 1 summarizes the lessons learned during this stud...

    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.