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      Factors Associated With Household Transmission of SARS-CoV-2 : An Updated Systematic Review and Meta-analysis

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      , PhD 1 , , , PhD 1 , , PhD 1 , , MD, DSc 2 , 3 , , PhD 1
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          Are early estimates of household transmission of SARS-CoV-2 indicative of current household transmission?

          Findings

          In this updated systematic review and meta-analysis of 87 studies representing 1 249 163 household contacts from 30 countries, the estimated household secondary attack rate was 19%. An increase in household transmission was observed over time, perhaps owing to improved diagnostic procedures and tools, longer follow-up, more contagious variants, and different study locations.

          Meaning

          These findings suggest that the household remains an important site of SARS-CoV-2 transmission, and recent studies have generated higher household secondary attack rate estimates compared with the earliest reports; more transmissible variants and vaccines may be associated with additional changes in the future.

          Abstract

          Importance

          A previous systematic review and meta-analysis of household transmission of SARS-CoV-2 that summarized 54 published studies through October 19, 2020, found an overall secondary attack rate (SAR) of 16.6% (95% CI, 14.0%-19.3%). However, the understanding of household secondary attack rates for SARS-CoV-2 is still evolving, and updated analysis is needed.

          Objective

          To use newly published data to further the understanding of SARS-CoV-2 transmission in the household.

          Data Sources

          PubMed and reference lists of eligible articles were used to search for records published between October 20, 2020, and June 17, 2021. No restrictions on language, study design, time, or place of publication were applied. Studies published as preprints were included.

          Study Selection

          Articles with original data that reported at least 2 of the following factors were included: number of household contacts with infection, total number of household contacts, and secondary attack rates among household contacts. Studies that reported household infection prevalence (which includes index cases), that tested contacts using antibody tests only, and that included populations overlapping with another included study were excluded. Search terms were SARS-CoV-2 or COVID-19 with secondary attack rate, household, close contacts, contact transmission, contact attack rate, or family transmission.

          Data Extraction and Synthesis

          Meta-analyses were performed using generalized linear mixed models to obtain SAR estimates and 95% CIs. The Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA) reporting guideline was followed.

          Main Outcomes and Measures

          Overall household SAR for SARS-CoV-2, SAR by covariates (contact age, sex, ethnicity, comorbidities, and relationship; index case age, sex, symptom status, presence of fever, and presence of cough; number of contacts; study location; and variant), and SAR by index case identification period.

          Results

          A total of 2722 records (2710 records from database searches and 12 records from the reference lists of eligible articles) published between October 20, 2020, and June 17, 2021, were identified. Of those, 93 full-text articles reporting household transmission of SARS-CoV-2 were assessed for eligibility, and 37 studies were included. These 37 new studies were combined with 50 of the 54 studies (published through October 19, 2020) from our previous review (4 studies from Wuhan, China, were excluded because their study populations overlapped with another recent study), resulting in a total of 87 studies representing 1 249 163 household contacts from 30 countries. The estimated household SAR for all 87 studies was 18.9% (95% CI, 16.2%-22.0%). Compared with studies from January to February 2020, the SAR for studies from July 2020 to March 2021 was higher (13.4% [95% CI, 10.7%-16.7%] vs 31.1% [95% CI, 22.6%-41.1%], respectively). Results from subgroup analyses were similar to those reported in a previous systematic review and meta-analysis; however, the SAR was higher to contacts with comorbidities (3 studies; 50.0% [95% CI, 41.4%-58.6%]) compared with previous findings, and the estimated household SAR for the B.1.1.7 (α) variant was 24.5% (3 studies; 95% CI, 10.9%-46.2%).

          Conclusions and Relevance

          The findings of this study suggest that the household remains an important site of SARS-CoV-2 transmission, and recent studies have higher household SAR estimates compared with the earliest reports. More transmissible variants and vaccines may be associated with further changes.

          Abstract

          This systematic review and meta-analysis combines data from a previous meta-analysis of SARS-CoV-2 household transmission through October 19, 2020, with new data from studies published between October 20, 2020, and June 17, 2021, to provide updated estimates of household secondary attack rates.

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          Most cited references109

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          Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England

          Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the capacity to generate variants with major genomic changes. The UK variant B.1.1.7 (also known as VOC 202012/01) has many mutations that alter virus attachment and entry into human cells. Using a variety of statistical and dynamic modeling approaches, Davies et al. characterized the spread of the B.1.1.7 variant in the United Kingdom. The authors found that the variant is 43 to 90% more transmissible than the predecessor lineage but saw no clear evidence for a change in disease severity, although enhanced transmission will lead to higher incidence and more hospital admissions. Large resurgences of the virus are likely to occur after the easing of control measures, and it may be necessary to greatly accelerate vaccine roll-out to control the epidemic. Science , this issue p. eabg3055 The major coronavirus variant that emerged at the end of 2020 in the UK is more transmissible than its predecessors and could spark resurgences. INTRODUCTION Several novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, emerged in late 2020. One of these, Variant of Concern (VOC) 202012/01 (lineage B.1.1.7), was first detected in southeast England in September 2020 and spread to become the dominant lineage in the United Kingdom in just a few months. B.1.1.7 has since spread to at least 114 countries worldwide. RATIONALE The rapid spread of VOC 202012/01 suggests that it transmits more efficiently from person to person than preexisting variants of SARS-CoV-2. This could lead to global surges in COVID-19 hospitalizations and deaths, so there is an urgent need to estimate how much more quickly VOC 202012/01 spreads, whether it is associated with greater or lesser severity of disease, and what control measures might be effective in mitigating its impact. We used social contact and mobility data, as well as demographic indicators linked to SARS-CoV-2 community testing data in England, to assess whether the spread of the new variant may be an artifact of higher baseline transmission rates in certain geographical areas or among specific demographic subpopulations. We then used a series of complementary statistical analyses and mathematical models to estimate the transmissibility of VOC 202012/01 across multiple datasets from the UK, Denmark, Switzerland, and the United States. Finally, we extended a mathematical model that has been extensively used to forecast COVID-19 dynamics in the UK to consider two competing SARS-CoV-2 lineages: VOC 202012/01 and preexisting variants. By fitting this model to a variety of data sources on infections, hospitalizations, and deaths across seven regions of England, we assessed different hypotheses for why the new variant appears to be spreading more quickly, estimated the severity of disease associated with the new variant, and evaluated control measures including vaccination and nonpharmaceutical interventions. Combining multiple lines of evidence allowed us to draw robust inferences. RESULTS The rapid spread of VOC 202012/01 is not an artifact of geographical differences in contact behavior and does not substantially differ by age, sex, or socioeconomic stratum. We estimate that the new variant has a 43 to 90% higher reproduction number (range of 95% credible intervals, 38 to 130%) than preexisting variants. Similar increases are observed in Denmark, Switzerland, and the United States. The most parsimonious explanation for this increase in the reproduction number is that people infected with VOC 202012/01 are more infectious than people infected with a preexisting variant, although there is also reasonable support for a longer infectious period and multiple mechanisms may be operating. Our estimates of severity are uncertain and are consistent with anything from a moderate decrease to a moderate increase in severity (e.g., 32% lower to 20% higher odds of death given infection). Nonetheless, our mathematical model, fitted to data up to 24 December 2020, predicted a large surge in COVID-19 cases and deaths in 2021, which has been borne out so far by the observed burden in England up to the end of March 2021. In the absence of stringent nonpharmaceutical interventions and an accelerated vaccine rollout, COVID-19 deaths in the first 6 months of 2021 were projected to exceed those in 2020 in England. CONCLUSION More than 98% of positive SARS-CoV-2 infections in England are now due to VOC 202012/01, and the spread of this new variant has led to a surge in COVID-19 cases and deaths. Other countries should prepare for potentially similar outcomes. Impact of SARS-CoV-2 Variant of Concern 202012/01. ( A ) Spread of VOC 202012/01 (lineage B.1.1.7) in England. ( B ) The estimated relative transmissibility of VOC 202012/01 (mean and 95% confidence interval) is similar across the United Kingdom as a whole, England, Denmark, Switzerland, and the United States. ( C ) Projected COVID-19 deaths (median and 95% confidence interval) in England, 15 December 2020 to 30 June 2021. Vaccine rollout and control measures help to mitigate the burden of VOC 202012/01. A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.
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            Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study

            Summary Background Rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, prompted heightened surveillance in Shenzhen, China. The resulting data provide a rare opportunity to measure key metrics of disease course, transmission, and the impact of control measures. Methods From Jan 14 to Feb 12, 2020, the Shenzhen Center for Disease Control and Prevention identified 391 SARS-CoV-2 cases and 1286 close contacts. We compared cases identified through symptomatic surveillance and contact tracing, and estimated the time from symptom onset to confirmation, isolation, and admission to hospital. We estimated metrics of disease transmission and analysed factors influencing transmission risk. Findings Cases were older than the general population (mean age 45 years) and balanced between males (n=187) and females (n=204). 356 (91%) of 391 cases had mild or moderate clinical severity at initial assessment. As of Feb 22, 2020, three cases had died and 225 had recovered (median time to recovery 21 days; 95% CI 20–22). Cases were isolated on average 4·6 days (95% CI 4·1–5·0) after developing symptoms; contact tracing reduced this by 1·9 days (95% CI 1·1–2·7). Household contacts and those travelling with a case were at higher risk of infection (odds ratio 6·27 [95% CI 1·49–26·33] for household contacts and 7·06 [1·43–34·91] for those travelling with a case) than other close contacts. The household secondary attack rate was 11·2% (95% CI 9·1–13·8), and children were as likely to be infected as adults (infection rate 7·4% in children <10 years vs population average of 6·6%). The observed reproductive number (R) was 0·4 (95% CI 0·3–0·5), with a mean serial interval of 6·3 days (95% CI 5·2–7·6). Interpretation Our data on cases as well as their infected and uninfected close contacts provide key insights into the epidemiology of SARS-CoV-2. This analysis shows that isolation and contact tracing reduce the time during which cases are infectious in the community, thereby reducing the R. The overall impact of isolation and contact tracing, however, is uncertain and highly dependent on the number of asymptomatic cases. Moreover, children are at a similar risk of infection to the general population, although less likely to have severe symptoms; hence they should be considered in analyses of transmission and control. Funding Emergency Response Program of Harbin Institute of Technology, Emergency Response Program of Peng Cheng Laboratory, US Centers for Disease Control and Prevention.
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              Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset

              Key Points Question What is the transmissibility of coronavirus disease 2019 (COVID-19) to close contacts? Findings In this case-ascertained study of 100 cases of confirmed COVID-19 and 2761 close contacts, the overall secondary clinical attack rate was 0.7%. The attack rate was higher among contacts whose exposure to the index case started within 5 days of symptom onset than those who were exposed later. Meaning High transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to interrupt transmission, and that more generalized measures might be required, such as social distancing.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                27 August 2021
                August 2021
                27 August 2021
                : 4
                : 8
                : e2122240
                Affiliations
                [1 ]Department of Biostatistics, University of Florida, Gainesville
                [2 ]Fred Hutchinson Cancer Research Center, Seattle, Washington
                [3 ]Department of Biostatistics, University of Washington, Seattle
                Author notes
                Article Information
                Accepted for Publication: June 19, 2021.
                Published: August 27, 2021. doi:10.1001/jamanetworkopen.2021.22240
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Madewell ZJ et al. JAMA Network Open.
                Corresponding Author: Zachary J. Madewell, PhD, Department of Biostatistics, University of Florida, PO Box 117450, Gainesville, FL 32611 ( zmadewell@ 123456ufl.edu ).
                Author Contributions: Dr Madewell had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Madewell, Longini, Halloran, Dean.
                Acquisition, analysis, or interpretation of data: Madewell, Yang, Longini, Halloran.
                Drafting of the manuscript: Madewell, Longini, Dean.
                Critical revision of the manuscript for important intellectual content: Madewell, Yang, Longini, Halloran.
                Statistical analysis: Madewell, Longini, Halloran.
                Obtained funding: Longini, Dean.
                Supervision: Yang, Halloran, Dean.
                Conflict of Interest Disclosures: Dr Halloran reported receiving grants from the National Institute of Allergy and Infectious Diseases during the conduct of the study. No other disclosures were reported.
                Funding/Support: This work was supported by grant R01-AI139761 from the National Institutes of Health (all authors).
                Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Article
                zoi210658
                10.1001/jamanetworkopen.2021.22240
                8397928
                34448865
                0011f25c-902c-48c7-af89-1f79c6209672
                Copyright 2021 Madewell ZJ et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 6 May 2021
                : 19 June 2021
                Categories
                Research
                Original Investigation
                Online Only
                Global Health

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