Transmission of SARS-CoV-2 within households: a remote prospective cohort study in European countries

  1. Janneke D. M. Verberk
  2. Marieke L. A. de Hoog
  3. Ilse Westerhof
  4. Sam van Goethem
  5. Christine Lammens
  6. Greet Ieven
  7. Erwin de Bruin
  8. Dirk Eggink
  9. Julia A. Bielicki
  10. Samuel Coenen
  11. Janko van Beek
  12. Marc J. M. Bonten
  13. Herman Goossens
  14. Patricia C. J. L. Bruijning-Verhagen

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Abstract

Household transmission studies are useful to quantify SARS-CoV-2 transmission dynamics. We conducted a remote prospective household study to quantify transmission, and the effects of subject characteristics, household characteristics, and implemented infection control measures on transmission. Households with a laboratory-confirmed SARS-CoV-2 index case were enrolled < 48 h following test result. Follow-up included digitally daily symptom recording, regular nose-throat self-sampling and paired dried blood spots from all household members. Samples were tested for virus detection and SARS-CoV-2 antibodies. Secondary attack rates (SARs) and associated factors were estimated using logistic regression. In 276 households with 920 participants (276 index cases and 644 household members) daily symptom diaries and questionnaires were completed by 95%, and > 85% completed sample collection. 200 secondary SARS-CoV-2 infections were detected, yielding a household SAR of 45.7% (95% CI 39.7–51.7%) and per-person SAR of 32.6% (95%CI: 28.1-37.4%). 126 (63%) secondary cases were detected at enrollment. Mild (aRR = 0.57) and asymptomatic index cases (aRR = 0.29) were less likely to transmit SARS-CoV-2, compared to index cases with an acute respiratory illness ( p  = 0.03 for trend), and child index cases (< 12 years aRR = 0.60 and 12-18 years aRR = 0.85) compared to adults ( p  = 0.03 for trend). Infection control interventions in households had no significant effect on transmission. We found high SARs with the majority of transmissions occuring early after SARS-CoV-2 introduction into the household. This may explain the futile effect of implemented household measures. Age and symptom status of the index case influence secondary transmission. Remote, digitally-supported study designs with self-sampling are feasible for studying transmission under pandemic restrictions.

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  1. Version published to 10.1007/s10654-022-00870-9
  2. ScreenIT

    SciScore for 10.1101/2021.04.23.21255846: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Written informed consent was obtained from all participating household members or their legal guardians.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    DBS specimens were tested in a final dilution of 1:40 by multiplex protein microarray for IgG antibodies targeting recombinant SARS-CoV-2 spike (S) ectodomain and S1 domain subunit antigens expressed in HEK293 cells as described elsewhere.[7-9] The S1 antigen signal exceeding 13,000 relative fluorescence units (RFU) and a S ectodomain exceeding 2,000 RFU were considered positive.
    IgG
    suggested: None
    S1 domain subunit
    suggested: (Active Motif Cat# 91345, RRID:AB_2847847)
    Experimental Models: Cell Lines
    SentencesResources
    DBS specimens were tested in a final dilution of 1:40 by multiplex protein microarray for IgG antibodies targeting recombinant SARS-CoV-2 spike (S) ectodomain and S1 domain subunit antigens expressed in HEK293 cells as described elsewhere.[7-9] The S1 antigen signal exceeding 13,000 relative fluorescence units (RFU) and a S ectodomain exceeding 2,000 RFU were considered positive.
    HEK293
    suggested: RRID:CVCL_UG79)

    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:
    Our study has some limitations that merit discussion. First, the first detected household case was considered the index case, but it is possible that other household members were infected concurrently by an external source (co-primary case), or that transmission occurred in the opposite direction. This could influence analysis of SAR by index or household contacts characteristics and for co-primary cases, may overestimate the within household transmission. Alternative enrollment criteria, for instance based on household exposure rather than confirmed infection, would be needed to improve differentiation between index and secondary cases and reconstruction of transmission chains. Second, we assumed that household transmission was responsible for all infections among household contacts. The household SAR could therefore be overestimated. However, the quarantine and isolation orders should have limited community exposure. Third, we might have underestimated the SAR to some extent for study-specific reasons as 1) asymptomatic or subjects with mild symptoms were less likely to show a detectable humoral response compared to subjects with ARI.[29] This suggests that some of the asymptomatic infections during follow-up were possibly missed since only subjects with ARI were tested with RT-PCR and; 2) swabs and DBS samples were self-collected which may have reduced the sensitivity. In addition, the percentage failed tests due to insufficient sampling is probably higher compared to samp...

    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.

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

    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.

  3. Version published to 10.1101/2021.04.23.21255846 on medRxiv