Household Transmission of SARS-CoV-2: Insights from a Population-based Serological Survey

  1. Qifang Bi
  2. Justin Lessler
  3. Isabella Eckerle
  4. Stephen A Lauer
  5. Laurent Kaiser
  6. Nicolas Vuilleumier
  7. Derek AT Cummings
  8. Antoine Flahault
  9. Dusan Petrovic
  10. Idris Guessous
  11. Silvia Stringhini
  12. Andrew S. Azman
  13. for the SEROCoV-POP Study Group

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Abstract

Background

Knowing the transmissibility of asymptomatic infections and risk of infection from household- and community-exposures is critical to SARS-CoV-2 control. Limited previous evidence is based primarily on virologic testing, which disproportionately misses mild and asymptomatic infections. Serologic measures are more likely to capture all previously infected individuals.

Objective

Estimate the risk of SARS-CoV-2 infection from household and community exposures, and identify key risk factors for transmission and infection.

Design

Cross-sectional household serosurvey and transmission model.

Setting

Geneva, Switzerland

Participants

4,524 household members ≥5 years from 2,267 households enrolled April-June 2020.

Measurements

Past SARS-CoV-2 infection confirmed through IgG ELISA. Chain-binomial models based on the number of infections within households used to estimate the cumulative extra-household infection risk and infection risk from exposure to an infected household member by demographics and infector’s symptoms.

Results

The chance of being infected by a SARS-CoV-2 infected household member was 17.3% (95%CrI,13.7-21.7%) compared to a cumulative extra-household infection risk of 5.1% (95%CrI,4.5-5.8%). Infection risk from an infected household member increased with age, with 5-9 year olds having 0.4 times (95%CrI, 0.07-1.4) the odds of infection, and ≥65 years olds having 2.7 (95%CrI,0.88-7.4) times the odds of infection of 20-49 year olds. Working-age adults had the highest extra-household infection risk. Seropositive asymptomatic household members had 69.6% lower odds (95%CrI,33.7-88.1%) of infecting another household member compared to those reporting symptoms, accounting for 14.7% (95%CrI,6.3-23.2%) of all household infections.

Limitations

Self-reported symptoms, small number of seropositive kids and imperfect serologic tests.

Conclusion

The risk of infection from exposure to a single infected household member was more than three-times that of extra-household exposures over the first pandemic wave. Young children had a lower risk of infection from household members. Asymptomatic infections are far less likely to transmit than symptomatic ones but do cause infections.

Funding Source

Swiss Federal Office of Public Health, Swiss School of Public Health (Corona Immunitas research program), Fondation de Bienfaisance du Groupe Pictet, Fondation Ancrage, Fondation Privée des Hôpitaux Universitaires de Genève, and Center for Emerging Viral Diseases.

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  3. ScreenIT

    SciScore for 10.1101/2020.11.04.20225573: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory analysis: We assessed anti-SARS-CoV-2 IgG antibodies in each participant using an ELISA (Euroimmun; Lübeck, Germany #EI 2606-9601 G) targeting the S1 domain of the spike protein of SARS-CoV-2; sera diluted 1:101 were processed on a EuroLabWorkstation ELISA (Euroimmun).
    anti-SARS-CoV-2 IgG
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our study has a number of important limitations. Symptoms were self-reported and, given that the times of infection are unknown, they may not necessarily have been a result of the SARS-CoV-2 infection. We cannot exclude recall bias in symptom reports and other self-reported exposures. Further, we looked at only a narrow range of symptoms to increase specificity, which left out more general potentially SARS-CoV-2-related symptoms (e.g., nausea, diarrhea). We detected only eight seropositive children under the age of 10, leading to large uncertainty in age-specific risk estimates for this group. While validation data of the Euroimmun ELISA from across the world have confirmed its high specificity and sensitivity for detecting recent infections,13,24,25 most data are from adults, and it is possible that performance in young children may be different. Although most of the participants in the study were recruited after the epidemic peak, it is possible that we did not fully capture all infections in each household due to insufficient time to mount a detectable response or due to waning of responses. However, when conducting stratified analyses including households recruited early and late, we found few qualitative differences in the primary results (Figure S5). While we included only households where all household members provided blood samples in the main analysis, sensitivity analyses of all enrolled individuals led to similar primary results (Table S6). This study captures infe...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

  4. Version published to 10.1101/2020.11.04.20225573v2 on medRxiv
  5. NCRC

    Our take

    This study, available as a preprint and thus not yet peer reviewed, leveraged seropositivity data from a large family-based cohort study in Geneva, Switzerland during the early phase of the SARS-CoV-2 pandemic and supports previous findings that working age, male sex, and symptomatic infection play important roles in increased transmission and infection risk. Individuals were estimated to have a 20% risk of being infected from a single SARS-CoV-2 positive household member compared to a 5% risk of being infected due to community transmission, the authors note these risks may not be widely generalizable. The authors also estimated asymptomatically infected individuals account for roughly 20% of all household infections, and thus play a non-insignificant role in household transmission risk.

    Study design

    other

    Study population and setting

    This retrospective population-based serological analysis leveraged serological data from 4,534 individuals older than five from 2,267 households in Geneva, Switzerland between April and June 2020. Serology-based analyses were conducted to confirm previous SARS-CoV-2 infections of household members, which were combined with demographic data, reported contacts, reported symptoms, and behavior to estimate the risk of SARS-CoV-2 infection from household members and the risk of infection from extra-household exposures.

    Summary of main findings

    Overall, 6.6% of individuals included within the study has evidence of prior SARS-CoV-2 infection, of whom 70.6% were symptomatic. While 9.8% of households had at least one seropositive household member, this proportion increased with household size (4.8% of single-person households to 17% of three-person households). Overall, the probability of being infected from a single infected household member was 17.2 % (95% Credible Interval [CrI]: 13.3%-21.5%), with the risk of infection increasing with age (Aged 5-9 years: 7.5% (95% CrI: 1.3%-20.3%), Aged >65 years: 30.2% (95% CrI: 14.3%-48.2%)). Those without any defined symptoms (cough, fever, shortness of breath, loss of smell/taste) had 0.25 times the odds (95% CrI: 0.10-0.56) of infecting other household members, reflecting an estimated 19.6% (95% CrI: 12.9%-24.5%) of all within-household infections, compared to symptomatic individuals. The cumulative risk of infection from extra-household sources was 5.1% (95% CrI: 4.5%-5.8%), with men being more likely to be infected outside the household (Odds Ratio 1.4, 95% CrI: 1.1-1.8). While those 20-49 years old had the highest risk (7.4%, 95% CrI: 5.9%-9.0%) of extra-household infection, those who reduced extra-household contacts in this age-group had a reduced risk of extra-household infection (OR 0.66 , 95% CrI: 0.39-1.2). The authors estimate that 18.8% (95% CrI: 16.7%-20.4%) of all infections were due to household transmission, with the attributable proportion of intra-household infection increasing with household size (16.1% of two-person households (95% CrI: 13.7%-20.4%) to 41.2% (95% CrI: 35.3%-46.5%) of five-person households).

    Study strengths

    This study builds off a well-described population-based survey study, SEROCoV-POP, which is well suited to explore household-associated transmission risks. In addition to using appropriate transmission models , all code and related notes are provided.

    Limitations

    As noted by the authors, while symptomatic infection was defined using multiple COVID-19-assocated symptoms, additional known symptoms such as muscle aches or pain, chills, tiredness, and gastro-intestinal symptoms were not used to identify symptomatic infections and thus individuals with symptomatic disease could have been misclassified as asymptomatic. It is unclear how the final analytical sample was selected (2,627 households had available data and 2,267 households were included), which potentially introduces selection biases if the included households had more (or less) household transmission compared to excluded households. It is also unclear how extra-household transmission results from younger individuals were obtained (extra-household contact data was not collected for those <14, yet extra-household transmission results for these children are provided). The authors point out Geneva is an urban high-income area with a small average household size (37.9% of households with available data were single-person households), which affects the ability to generalize these results outside high-income urban settings. Additionally, as the initial surge of the SARS-CoV-2 pandemic in Geneva may not reflect the burden of disease elsewhere, extrapolating any estimated extra-household infection risks to other regions should be made with caution.

    Value added

    This study provides important findings related to the risks of household and extra-household SARS-CoV-2 infection, and confirms the important role asymptomatic infection plays in transmission. In addition to reaffirming the importance of age and sex in the risk of infection, this study quantified the risk attributable to asymptomatic infections within the household. Additional study in non-wealthy or urban areas with small household sizes, and in cohorts with a greater number of young children, is needed.

  6. ScreenIT

    SciScore for 10.1101/2020.11.04.20225573: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Antibodies
    SentencesResources
    Laboratory analysis We assessed anti-SARS-CoV-2 IgG antibodies in each participant using an ELISA (Euroimmun; Lübeck, Germany #EI 2606-9601 G) targeting the S1 domain of the spike protein of SARS-CoV-2; sera diluted 1:101 were processed on a EuroLabWorkstation ELISA (Euroimmun).
    anti-SARS-CoV-2 IgG
    suggested: None

    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 a number of important limitations. Symptoms were self-reported and, given that the times of infection are unknown, they may not necessarily have been a result of the SARS-CoV-2 infection. Further, we looked at only a narrow range of symptoms to increase specificity, which left out more general symptoms (e.g., nausea, diarrhea) which may have been SARS-CoV-2 related. We detected only eight seropositive children under the age of 10, leading to large uncertainty in age-specific risk estimates for this group. While validation data of the Euroimmun ELISA from across the world have confirmed its high specificity and sensitivity for detecting recent infections,8,15,16 most data are from adults, and it is possible that performance in young children may be different. Although most of the participants in the study were recruited after the epidemic peak, it is possible that we did not fully capture all infections in each household due to insufficient time to mount a detectable response or due to waning of responses. However, when conducting stratified analyses including households recruited early and late, we found few qualitative differences in the primary results (Figure S4). Furthermore, this study captures infections that occurred during the first wave of the pandemic in Geneva, a unique period of time when workplaces and schools were largely closed and peoples’ social contacts were greatly reduced. In future phases of this pandemic, we may expect differences in our es...

    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.

    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.

  7. Version published to 10.1101/2020.11.04.20225573v1 on medRxiv