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High infection attack rates of SARS-CoV-2 in Dutch households revealed by dense sampling

Daphne F.M. Reukers, Michiel van Boven, Adam Meijer, Nynke Y. Rots, Chantal Reusken, Inge Roof, Arianne B van Gageldonk-Lafeber, Wim van der Hoek, Susan van den Hof 
26 Jan 2021-medRxiv (Cold Spring Harbor Laboratory Press)-
TL;DR: In this article, the authors analyzed data from a SARS-CoV-2 household study and found higher secondary attack rates than reported earlier, presumably owing to a dense sampling protocol.
Abstract: Background Indoor environments are considered a main setting for transmission of SARS-CoV-2. Households in particular present a close-contact environment with high probability of transmission between persons of different ages and with different roles in society. Methods Complete households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands (March-May 2020) were included. At least three home visits were performed during 4-6 week of follow-up, collecting naso- and oropharyngeal swabs, oral fluid, faeces and blood samples for molecular and serological analyses of all household members. Symptoms were recorded from two weeks before the first visit up to the last visit. Secondary attack rates (SAR) were estimated with logistic regression. A transmission model was used to assess transmission routes in the household. Results A total of 55 households with 187 household contacts were included. In 17 households no transmission took place, and in 11 households all persons were infected. Estimated SARs were high, ranging from 35% (95%CI: 24%-46%) in children to 51% (95%CI: 39%-63%) in adults. Estimated transmission rates in the household were high, with reduced susceptibility of children compared to adolescents and adults (0.67; 95%CI: 0.40-1.1). Conclusion Estimated SARs were higher than reported in earlier household studies, presumably owing to a dense sampling protocol. Children were shown to be less susceptible than adults, but the estimated SAR in children was still high. Our results reinforce the role of households as main multiplier of SARS-CoV-2 infection in the population. Key points We analyze data from a SARS-CoV-2 household study and find higher secondary attack rates than reported earlier. We argue that this is due to a dense sampling strategy that includes sampling at multiple time points and of multiple anatomical sites.

Summary (3 min read)

Jump to: [Introduction] – [Methods] – [Population] – [Data collection] – [Symptoms and severity of COVID-19] – [Primary case] – [Secondary attack rate] – [Transmission model] – [Ethics] – [Descriptive analysis] – [Secondary attack rates] – [Household transmission] and [Discussion]

Introduction

  • The first case of the coronavirus disease (COVID-19) emerged in Wuhan in December 2019 [1].
  • In combination with evidence that a sizeable fraction of transmission events occur pre-symptomatically, the household constitutes a high risk setting for SARS-CoV-2 transmission [7].
  • Main aims of this study were to estimate secondary attack rates and to determine factors that impact susceptibility and infectiousness, with a specific focus on age of household contacts.

Methods

  • The generic protocol was tailored to the current COVID-19 pandemic with input from the WHO First Few Hundred protocol [15].
  • The generic and adapted study protocols were approved by the Medical-Ethical Review Committee of the University Medical Center Utrecht (NL13529.041.06).
  • A prospective cohort study was performed following households where one household member was tested positive for SARS-CoV-2 in the period March 24-April 6 2020 (one household was included later on May 24).

Population

  • Any person 18 years and older testing positive for SARS-CoV-2 who had at least one child in their household below the age of 18 and consented to be contacted for scientific research were reported by the Public Health Service of the region Utrecht.
  • The authors contacted this person (i.e. the index case) to request enrolment of the entire household in this study.
  • Every household contact (persons living in the same house as the index patient) was to be enrolled in the study, except for contacts below the age of one year.
  • Households were excluded if one or more of the household contacts did not want to participate in the study upfront, as in that case it would not be possible to fully determine household transmission patterns.

Data collection

  • Two research nurses performed the first home visit within 24 hours after inclusion to collect the informed consent forms and the first samples from all participants (see Table 1 for schedule of sample collection).
  • Participants reported whether they had symptoms in the 2 weeks prior to the first visit.
  • The copyright holder for thisthis version posted January 26, 2021.
  • Molecular diagnostics and serological analysis Total nucleic acid was extracted from the nasopharyngeal swab (NP), oropharyngeal swab (OP), oral fluid and faeces specimens using MagNApure 96 with total nucleic acid kit small volume and elution in 50 µl.
  • As no other Sarbeco viruses are currently detected in humans, a positive Sarbeco E-gene RT-qPCR is validly taken as positive for SARS-CoV-2.

Symptoms and severity of COVID-19

  • The day of symptom onset as reported by the participant was set as the first day of illness.
  • Participants were considered symptomatic if at least one of the following symptoms occurred at any timepoint: respiratory symptoms (including sore throat, cough, dyspnoea or other respiratory difficulties, rhinorrhoea), fever, chills, headache, anosmia or ageusia, muscle pain, joint ache, diarrhoea, nausea, vomiting, loss of appetite or fatigue.
  • Is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint.
  • The copyright holder for thisthis version posted January 26, 2021.

Primary case

  • In every household, a primary case (the most likely first case of the household) was determined based on laboratory confirmation, symptom onset and travel history.
  • A household contact was considered the primary case if they had a laboratory-confirmed SARS-CoV-2 infection with a symptom onset at least 2-14 days before the index case.

Secondary attack rate

  • Household secondary attack rates (SARs) were estimated excluding the index case (i.e. the labconfirmed person that led to inclusion of the household in the study), but including the primary case.
  • This corresponds to common practice as reliable information on the primary case in the household often is lacking [19, 20].
  • To take clustered nature of the data into account, SARs were estimated with a logistic regression using generalized estimating equations (GEEs), with household as the unit of clustering and assuming an exchangeable correlation structure.
  • Model selection was based on the Quasi Information Criterion for small sample sizes (QICc).

Transmission model

  • Next to the estimates of the SAR the authors analysed the data using the final size distribution of a stochastic SEIR transmission model.
  • The copyright holder for thisthis version posted January 26, 2021.
  • ; https://doi.org/10.1101/2021.01.26.21250512doi: medRxiv preprint to the contact process, the authors assumed frequency-dependent transmission as this mode of transmission is preferred over density-dependent transmission by information criteria (not shown) [23].
  • Here, because households were included only if an infected person was present, the final-size distributions needed to be conditioned on the presence of an infected index case if the index case was not also the primary case [22].
  • Model selection was performed using LOOIC, a measure for predictive performance [23, 24].

Ethics

  • The Medical Ethical Review Board of the University Medical Centre Utrecht reviewed and approved the study protocol (NL13529.041.06).
  • All participants above the age of 12 gave written informed consent.
  • Parents or guardians of participating children below the age of 16 gave written informed consent for participation, for children 12-16 both parents and children had to give consent.

Descriptive analysis

  • Fifty-five households were included, with in total 242 participants of which 55 index cases and 187 household contacts (Table 2).
  • Seven index cases were admitted to the hospital before or during participation in the study, and none of the other cases in the household required hospitalization.
  • In children, fewer SARS-CoV-2 infections were found compared to adolescent and adult household contacts.
  • Is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint.
  • The copyright holder for thisthis version posted January 26, 2021.

Secondary attack rates

  • In a multivariable analysis that included sex and age group (child, adolescent, adults), being a child was strongly associated with decreased probability of infection (p=0.006), while there was marginal evidence that female sex was associated with increased probability of infection (p=0.053).
  • The univariable model with age was the preferred model based on QICc.

Household transmission

  • Building on the results of the SAR estimates, the authors analyzed transmission models that differed with respect to assumptions on the susceptibility and transmissibility of age groups (children, adolescents, adults).
  • In the unstructured model the transmission rate was estimated at 1.2 (unit: per infectious period).
  • Given their assumption on frequency-dependent transmission this implies that the probability of direct transmission from an infected to an uninfected person (i.e. without taking indirect transmission via intermediate persons into account) in a household of four persons would be 1-exp[-1.2/4]=0.26.
  • Overall, differences between models were modest, and the data did not allow estimation of more than 2-3 parameters.
  • Judged by the LOOIC information criterion, the unstructured model and the model with a parameter for the susceptibility of children performed best, while the model with full age dependence was overparameterized.

Discussion

  • Estimated household secondary attack rates in their study were high (43%) and substantially higher than reported in earlier studies (reviewed in [8]).
  • CC-BY-NC-ND 4.0 International licenseIt is made available under a perpetuity.
  • Is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint.
  • The authors study differs from earlier household studies for SAR-CoV-2 in that the authors observed substantially higher SARs [11, 27].
  • For inclusion of households their study depended on the prevailing testing policies and infected population in difference age groups.

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Figures (4)

Content maybe subject to copyright    Report

1
High infection attack rates of SARS-CoV-2 in Dutch households revealed by
dense sampling
Daphne F.M. Reukers
1
Michiel van Boven
1
Adam Meijer
1
Nynke Rots
1
Chantal Reusken
1
Inge Roof
1
Arianne B. van Gageldonk-Lafeber
1
Wim van der Hoek
1*
Susan van den Hof
1*
1
Centre for Infectious Disease Control, National Institute for Public Health and the Environment,
Bilthoven, the Netherlands
*
These authors contributed equally
Corresponding author
Daphne F.M. Reukers
Centre for Epidemiology and Surveillance of Infectious Diseases, Centre for Infectious Disease
Control (CIb), National Institute for Public Health and the Environment (RIVM)
PO Box 1, 3720 BA Bilthoven, the Netherlands
Tel.: +31 302743419
E-mail: Daphne.Reukers@rivm.nl
WORD COUNT ABSTRACT: 236; WORD COUNT MAIN TEXT: 2,913
Key points: We analyze data from a SARS-CoV-2 household study and find higher secondary attack
rates than reported earlier. We argue that this is due to a dense sampling strategy that includes
sampling at multiple time points and of multiple anatomical sites.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted January 26, 2021. ; https://doi.org/10.1101/2021.01.26.21250512doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
2
Abstract
Background
Indoor environments are considered a main setting for transmission of SARS-CoV-2. Households in
particular present a close-contact environment with high probability of transmission between
persons of different ages and with different roles in society.
Methods
Complete households with a laboratory-confirmed SARS-CoV-2 positive case in the Netherlands
(March-May 2020) were included. At least three home visits were performed during 4-6 week of
follow-up, collecting naso- and oropharyngeal swabs, oral fluid, faeces and blood samples for
molecular and serological analyses of all household members. Symptoms were recorded from two
weeks before the first visit up to the last visit. Secondary attack rates (SAR) were estimated with
logistic regression. A transmission model was used to assess transmission routes in the household.
Results
A total of 55 households with 187 household contacts were included. In 17 households no
transmission took place, and in 11 households all persons were infected. Estimated SARs were high,
ranging from 35% (95%CI: 24%-46%) in children to 51% (95%CI: 39%-63%) in adults. Estimated
transmission rates in the household were high, with reduced susceptibility of children compared to
adolescents and adults (0.67; 95%CI: 0.40-1.1).
Conclusion
Estimated SARs were higher than reported in earlier household studies, presumably owing to a
dense sampling protocol. Children were shown to be less susceptible than adults, but the estimated
SAR in children was still high. Our results reinforce the role of households as main multiplier of SARS-
CoV-2 infection in the population.
Key words: SARS-CoV-2, COVID-19, Secondary Attack Rate, Household study, Transmission model
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted January 26, 2021. ; https://doi.org/10.1101/2021.01.26.21250512doi: medRxiv preprint
3
Introduction
The first case of the coronavirus disease (COVID-19) emerged in Wuhan in December 2019 [1].
Starting with an outbreak of pneumonia of unknown etiology, the causative agent severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified early January 2020 [2]. Since then,
the virus has spread rapidly across the world [3].
Evidence from case and cluster reports shows that SARS-CoV-2 is largely spread through respiratory
droplets from infected persons, with proper distance and indoor air ventilation being significant
factors reducing the risk of transmission [4]. Therefore, social distancing measures are important to
reduce transmission, and most countries have instated strategies based on this premise. In the
Netherlands, the first COVID-19 case was detected on February 27 [5]. In March, the Dutch
government mandated a partial lockdown, characterized by social distancing, self-quarantine and
self-isolation orders, closing of schools, bars, and restaurants, and urging people to work from home
[6]. These measures generally increased the time spent at home. As household members live in close
contact it is difficult to attain a proper physical distance after a COVID-19 diagnosis of a household
contact. In combination with evidence that a sizeable fraction of transmission events occur
pre-symptomatically, the household constitutes a high risk setting for SARS-CoV-2 transmission [7].
The secondary attack rate (SAR) of SARS-CoV-2 infection among household contacts is a useful
measure to gauge the risk of transmission in this close-contact setting. It provides insight in the
susceptibility of contacts and infectiousness of cases given certain characteristics, such as age,
gender, household size, and severity of infection. Household studies performed in the first six
months of the pandemic, mostly in China, found a relatively high household SAR of 15-22% [8]. In
most countries, paediatric patients are underrepresented in the statistics of the COVID-19 outbreak
and children usually exhibit mild symptoms [9, 10]. If children have lower susceptibility or
infectiousness, this can have important implications for strategies to curb the spread of SARS-CoV-2.
Previously household studies observed that the SAR was significantly higher for adult contacts
compared to child contacts [11]. However, most studies only tested household contacts with COVID-
19 related symptoms, relied on RT-PCR in nasopharyngeal swabs only, and did not perform any
follow-up sampling. These studies may have missed mild, pre- or asymptomatic cases, especially in
children [12, 13]. In the present study all household contacts were tested as soon as possible after a
laboratory-confirmed infection in the household was established, and subsequently followed-up for
4 to 6 weeks. A dense sampling strategy was employed that included sampling from various
anatomical sites while using multiple molecular and serological diagnostic methods to establish
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted January 26, 2021. ; https://doi.org/10.1101/2021.01.26.21250512doi: medRxiv preprint
4
infection. This increases the chance of detecting every SARS-CoV-2 infected household contact and
of determining transmission routes, including asymptomatic transmission, as accurately as possible
[8]. Main aims of this study were to estimate secondary attack rates and to determine factors that
impact susceptibility and infectiousness, with a specific focus on age of household contacts.
Methods
This study is an update of a generic stand-by protocol drafted in 2006 to quickly initiate scientific
research in the case of an outbreak of an emerging pathogen [14]. The generic protocol was tailored
to the current COVID-19 pandemic with input from the WHO First Few Hundred protocol [15]. The
generic and adapted study protocols were approved by the Medical-Ethical Review Committee of
the University Medical Center Utrecht (NL13529.041.06). A prospective cohort study was performed
following households where one household member was tested positive for SARS-CoV-2 in the
period March 24-April 6 2020 (one household was included later on May 24).
Population
Any person 18 years and older testing positive for SARS-CoV-2 who had at least one child in their
household below the age of 18 and consented to be contacted for scientific research were reported
by the Public Health Service of the region Utrecht. We contacted this person (i.e. the index case) to
request enrolment of the entire household in this study. Every household contact (persons living in
the same house as the index patient) was to be enrolled in the study, except for contacts below the
age of one year. Households were excluded if one or more of the household contacts did not want
to participate in the study upfront, as in that case it would not be possible to fully determine
household transmission patterns.
Data collection
Two research nurses performed the first home visit within 24 hours after inclusion to collect the
informed consent forms and the first samples from all participants (see Table 1 for schedule of
sample collection). Household contacts completed a questionnaire to collect demographic
characteristics, medical history, travel history, anti-viral drug use, symptoms, symptom onset and
hospital admission. Participants reported whether they had symptoms in the 2 weeks prior to the
first visit. After the first visit, they filled in a symptoms diary for 2 weeks. A second visit was included
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted January 26, 2021. ; https://doi.org/10.1101/2021.01.26.21250512doi: medRxiv preprint
5
at 2-3 weeks post-inclusion, and at the last home visit at 4-6 weeks post-inclusion, participants
reported whether they had developed symptoms in the weeks between the second and third home
visit. We defined three age strata: adults 18 years of age or older, adolescents 12 to 17 years of age
(corresponding to secondary school age) and children 1 to 11 years of age (corresponding to day
care and primary school age).
Molecular diagnostics and serological analysis
Total nucleic acid was extracted from the nasopharyngeal swab (NP), oropharyngeal swab (OP), oral
fluid and faeces specimens using MagNApure 96 with total nucleic acid kit small volume and elution
in 50 µl. RT-qPCR was performed on 5 µl extract using TaqMan® Fast Virus 1-Step Master Mix
(Thermo Fisher) on Roche LC480II thermal cycler with SARS-like beta coronavirus (Sarbeco) specific
E-gene primers and probe as described previously [16]. As no other Sarbeco viruses are currently
detected in humans, a positive Sarbeco E-gene RT-qPCR is validly taken as positive for SARS-CoV-2.
The results of the NP and OP swabs were combined to one result: upper respiratory tract (URT)
negative (NP and OP negative) or positive (NP and/or OP positive). For detection of antibodies
against SARS-CoV-2 we used the Wantai total Ig ELISA as described previously [17].
Classification of index and primary case
Laboratory-confirmed SARS-CoV-2 infection was defined as, either at least one positive PCR on any
of the clinical samples taken during follow-up and/or detection of antibodies at any sampling
timepoint. Every index case was by definition infected, as they had at least one positive PCR on an
URT swab.
Symptoms and severity of COVID-19
The day of symptom onset as reported by the participant was set as the first day of illness.
Participants were considered symptomatic if at least one of the following symptoms occurred at any
timepoint: respiratory symptoms (including sore throat, cough, dyspnoea or other respiratory
difficulties, rhinorrhoea), fever, chills, headache, anosmia or ageusia, muscle pain, joint ache,
diarrhoea, nausea, vomiting, loss of appetite or fatigue. For household contacts, symptom onset
occurring more than 2 weeks prior to the first day of illness or first positive test result of the index
case were considered not related to SARS-CoV-2 transmission within the household.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
perpetuity.
is the author/funder, who has granted medRxiv a license to display the preprint in(which was not certified by peer review)preprint
The copyright holder for thisthis version posted January 26, 2021. ; https://doi.org/10.1101/2021.01.26.21250512doi: medRxiv preprint
Citations
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Journal Article•DOI•
Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support: REACT-SCOT case-control study.

[...]

Paul M. McKeigue1, David A. McAllister2, David H Caldwell, Ciara Gribben, J. L. Bishop, Stuart J. McGurnaghan3, Matthew J. Armstrong, Joke Delvaux, Sam Colville, Sharon J. Hutchinson4, Chris Robertson5, Nazir I Lone1, Jim McMenamin, David M. Goldberg, Helen M. Colhoun3 •
University of Edinburgh1, University of Glasgow2, Western General Hospital3, Glasgow Caledonian University4, University of Strathclyde5
23 Jun 2021-BMC Medicine
TL;DR: In this paper, the authors investigated the rate ratio of severe COVID-19 associated with eligibility for the shielding program in Scotland across the first and second waves of the epidemic and the relation of severe CoVid-19 to transmission-related factors in those in shielding and the general population.
Abstract: Clinically vulnerable individuals have been advised to shield themselves during the COVID-19 epidemic. The objectives of this study were to investigate (1) the rate ratio of severe COVID-19 associated with eligibility for the shielding programme in Scotland across the first and second waves of the epidemic and (2) the relation of severe COVID-19 to transmission-related factors in those in shielding and the general population. In a matched case-control design, all 178,578 diagnosed cases of COVID-19 in Scotland from 1 March 2020 to 18 February 2021 were matched for age, sex and primary care practice to 1,744,283 controls from the general population. This dataset (REACT-SCOT) was linked to the list of 212,702 individuals identified as eligible for shielding. Severe COVID-19 was defined as cases that entered critical care or were fatal. Rate ratios were estimated by conditional logistic regression. With those without risk conditions as reference category, the univariate rate ratio for severe COVID-19 was 3.21 (95% CI 3.01 to 3.41) in those with moderate risk conditions and 6.3 (95% CI 5.8 to 6.8) in those eligible for shielding. The highest rate was in solid organ transplant recipients: rate ratio 13.4 (95% CI 9.6 to 18.8). Risk of severe COVID-19 increased with the number of adults but decreased with the number of school-age children in the household. Severe COVID-19 was strongly associated with recent exposure to hospital (defined as 5 to 14 days before presentation date): rate ratio 12.3 (95% CI 11.5 to 13.2) overall. The population attributable risk fraction for recent exposure to hospital peaked at 50% in May 2020 and again at 65% in December 2020. The effectiveness of shielding vulnerable individuals was limited by the inability to control transmission in hospital and from other adults in the household. Mitigating the impact of the epidemic requires control of nosocomial transmission.

22 citations

Journal Article•DOI•
Children and Adults With Mild COVID-19: Dynamics of the Memory T Cell Response up to 10 Months

[...]

Patricia Kaaijk, Veronica Olivo Pimentel, Maarten E. Emmelot, Martien C. M. Poelen, Alper Cevirgel, Rutger M. Schepp, Gerco den Hartog, Daphne F.M. Reukers, Lisa Beckers, Josine van Beek, Cécile A. C. M. van Els, Adam Meijer, Nynke Y. Rots, J. J. de Wit 
07 Feb 2022-Frontiers in Immunology
TL;DR: The authors' data indicate that an antigen-specific T cell and antibody response is developed after mild SARS-CoV-2 infection in children and adults, and it remains to be elucidated to what extent this Sars-Cov-2-specific response can contribute to an effective recall response after reinfection.
Abstract: Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory. Methods To determine whether a memory T cell response is being developed, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker analyses of peripheral blood samples from unvaccinated children and adults with mild-to-moderate COVID-19. Results Upon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-γ T cell responses in infected children (83%) and adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially in those with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-γ T cell response correlated with S1-SARS-CoV-2-specific serum antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens. Frequencies of SARS-CoV-2-specific T cells were significantly reduced at 10 months after symptom onset, while S1-SARS-CoV-2-specific IgG concentrations were still detectable in 90% of all children and adults. Conclusions Our data indicate that an antigen-specific T cell and antibody response is developed after mild SARS-CoV-2 infection in children and adults. It remains to be elucidated to what extent this SARS-CoV-2-specific response can contribute to an effective recall response after reinfection.

15 citations

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

[...]

Janneke D M Verberk, Marieke L. A. de Hoog, Ilse Westerhof, Sam Van Goethem, Christine Lammens, Greet Ieven, Erwin de Bruin, Dirk Eggink, Julia Bielicki, Samuel Coenen, Janko van Beek, Marc J. M. Bonten, Herman Goossens, Patricia Bruijning-Verhagen 
01 May 2022-European Journal of Epidemiology
TL;DR: In this paper , the authors conducted a remote prospective household study to quantify transmission, and the effects of subject characteristics, household characteristics, and implemented infection control measures on transmission of SARS-CoV-2.
Abstract: 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.

11 citations

Journal Article•DOI•
Inferring risks of coronavirus transmission from community household data

[...]

01 Sep 2022-Statistical Methods in Medical Research
TL;DR: In this article , the authors performed exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England.
Abstract: The response of many governments to the COVID-19 pandemic has involved measures to control within- and between-household transmission, providing motivation to improve understanding of the absolute and relative risks in these contexts. Here, we perform exploratory, residual-based, and transmission-dynamic household analysis of the Office for National Statistics COVID-19 Infection Survey data from 26 April 2020 to 15 July 2021 in England. This provides evidence for: (i) temporally varying rates of introduction of infection into households broadly following the trajectory of the overall epidemic and vaccination programme; (ii) susceptible-Infectious transmission probabilities of within-household transmission in the 15–35% range; (iii) the emergence of the Alpha and Delta variants, with the former being around 50% more infectious than wildtype and 35% less infectious than Delta within households; (iv) significantly (in the range of 25–300%) more risk of bringing infection into the household for workers in patient-facing roles pre-vaccine; (v) increased risk for secondary school-age children of bringing the infection into the household when schools are open; (vi) increased risk for primary school-age children of bringing the infection into the household when schools were open since the emergence of new variants.

9 citations

Posted Content•DOI•
Transmission of SARS-CoV-2 within households: a prospective cohort study in the Netherlands and Belgium - Interim results

[...]

Marieke L. A. de Hoog1, Janneke Dm Verberk1, Ilse Westerhof1, Sam van Goethem2, Christine Lammens2, Greet Ieven2, Erwin de Bruin3, Julia Bielicki4, Samuel Coenen2, Janko van Beek3, Marc J. M. Bonten1, Herman Goossens2, Patricia Cjl Bruijning-Verhagen1 •
University Medical Center Utrecht1, University of Antwerp2, Erasmus University Medical Center3, Boston Children's Hospital4
26 Apr 2021-medRxiv
TL;DR: In this article, the authors investigated secondary attack rates (SAR) by household and subject characteristics in the Netherlands and Belgium and found a high household SAR, with the large majority of transmissions detected early after identification of the index case.
Abstract: Background Household transmission studies are useful to obtain granular data on SARS-CoV-2 transmission dynamics and to gain insight into the main determinants. In this interim report we investigated secondary attack rates (SAR) by household and subject characteristics in the Netherlands and Belgium. Methods Households with a real-time reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 index case were enrolled Results This analysis includes 117 households that completed follow-up between April-December 2020. Among 382 subjects, 74 secondary infections were detected, of which 13 (17.6%) were asymptomatic and 20 (27.0%) infections were detected by seroconversion only. Of cases detected by RT-PCR, 50 (67.6%) were found at enrollment. The household SAR was 44.4% (95%-CI: 35.4-53.9%) and was higher for index cases meeting the ARI case definition (52.3%; 95%-CI 41.4-62.9%) compared to mildly symptomatic (22.2%; 95%-CI: 9.4-42.7%) and asymptomatic index cases (0.0%; 95%-CI: 0.0-80.2%). The per-person SAR was 27.9% (95%-CI: 22.7-33.8%). Transmission was lowest from child to parent (9.1%; 95%-CI: 2.4-25.5%) and highest from parent to child (28.1%; 95%-CI: 19.7-38.4%) and in children 6-12 years (34.2%; 95%-CI: 20.1-51.4%). Among 141 subjects with RT-PCR confirmed SARS-CoV-2 infections, seroconversion was detected in 111 (78.7%). Conclusion We found a high household SAR, with the large majority of transmissions detected early after identification of the index case. Our findings confirm differential SAR by symptom status of the index. In almost a quarter of RT-PCR positive cases, no antibodies were detected. Other factors influencing transmission will be further explored as more data accumulate.

5 citations

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Stan : A Probabilistic Programming Language

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Bob Carpenter, Andrew Gelman, Matthew D. Hoffman, Daniel D. Lee, Ben Goodrich, Michael Betancourt, Marcus A. Brubaker, Jiqiang Guo, Peter Li, Allen Riddell 
11 Jan 2017-Journal of Statistical Software
TL;DR: Stan as discussed by the authors is a probabilistic programming language for specifying statistical models, where a program imperatively defines a log probability function over parameters conditioned on specified data and constants, which can be used in alternative algorithms such as variational Bayes, expectation propagation, and marginal inference using approximate integration.
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Yuanyuan Dong1, Xi Mo1, Yabin Hu1, Xin Qi, Fang Jiang1, Zhongyi Jiang1, Shilu Tong2, Shilu Tong1, Shilu Tong3 •
Shanghai Jiao Tong University1, Anhui Medical University2, Nanjing Medical University3
01 Mar 2020-Pediatrics
TL;DR: The distribution of children’s COVID-19 cases varied with time and space, and most of the cases were concentrated in Hubei province and surrounding areas, providing strong evidence of human-to-human transmission.
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Jonas F. Ludvigsson
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1,756 citations

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Frequently Asked Questions (2)
Q1. What contributions have the authors mentioned in the paper "High infection attack rates of sars-cov-2 in dutch households revealed by dense sampling" ?

The authors analyze data from a SARS-CoV-2 household study and find higher secondary attack rates than reported earlier. Is the author/funder, who has granted medRxiv a license to display the preprint in ( which was not certified by peer review ) preprint 

Estimated transmission rates in the household were high, with reduced susceptibility of children compared to adolescents and adults (0.67; 95%CI: 0.40-1.1).