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The role of children in household transmission of COVID-19: a systematic review and meta-analysis

  • Feifan Chen
    Affiliations
    Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
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  • Author Footnotes
    # Yan Tian and Lixin Zhang have contributed equally to this work (listed as co-second authors).
    Yan Tian
    Footnotes
    # Yan Tian and Lixin Zhang have contributed equally to this work (listed as co-second authors).
    Affiliations
    Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
    Search for articles by this author
  • Author Footnotes
    # Yan Tian and Lixin Zhang have contributed equally to this work (listed as co-second authors).
    Lixin Zhang
    Footnotes
    # Yan Tian and Lixin Zhang have contributed equally to this work (listed as co-second authors).
    Affiliations
    Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
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  • Yuan Shi
    Correspondence
    Corresponding author: Yuan Shi, Children's Hospital of Chongqing Medical University, Chongqing 400014, China, Mob: 00862363635678.
    Affiliations
    Department of Neonatology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China
    Search for articles by this author
  • Author Footnotes
    # Yan Tian and Lixin Zhang have contributed equally to this work (listed as co-second authors).
Open AccessPublished:May 10, 2022DOI:https://doi.org/10.1016/j.ijid.2022.05.016

      Highlights

      • Pediatric COVID-19 only accounted for a minority of household transmission.
      • Lower household COVID-19 transmissibility was shown in children than adults.
      • Younger children were as susceptible to COVID-19 as the older children in the households.
      • Increased household transmissibility was observed in children with new variants.
      • Children seemed as susceptible as adults in households with new variants.

      ABSTRACT

      Objectives

      To explore household transmissibility of SARS-CoV-2 in children in new-variants dominating periods.

      Methods

      Through retrieval in PubMed and Embase, studies were included in two parts: meta-analysis of the household secondary attack rate (SAR) and case analysis of household pediatric infections.

      Results

      A total of 95 articles were included: 48 for meta-analysis and 47 for case analysis. Pediatric COVID-19 only comprised a minority of the household transmission. The total pooled household SAR of child index cases and contacts were 0.20 (95% confidence interval [CI]: 0.15–0.26) and 0.24 (95% CI: 0.18–0.30). Lower household transmissibility was reported in both child index cases and contacts than in adults (relative risk [RR] = 0.64, 95% CI: 0.50–0.81; RR = 0.74, 95% CI: 0.64–0.85). Younger children were as susceptible as the older children (RR = 0.89, 95% CI: 0.72–1.10). Through subgroup analyses of different variants and periods, increased household SAR was observed in children (Wild: 0.20; Alpha: 0.42; Delta: 0.35; Omicron: 0.56), and no significant difference was found in household SAR between children and adults when new variants dominated.

      Conclusion

      Although children were found not to be dominant in the household transmission, their transmissibility of SARS-CoV-2 appeared to be on the rise as new variants emerged.

      Keywords

      Introduction

      As of April 29, 2022, there have been 510.2 million confirmed COVID-19 cases and 6.2 million confirmed deaths worldwide, and individuals around the world are still experiencing the aftermath of the fourth wave of the pandemic, which was caused by the Omicron variant of SARS-CoV-2 (

      World Health Organization, WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/, 2022 (accessed 29 April 2022).

      ).
      For outbreak control, breaking the chain of virus transmission is generally considered to be one of the most effective strategies besides vaccination. Previous studies have suggested that the household is potentially the highest-risk exposure setting of SARS-CoV-2 transmission, which may have led to a steep escalation of COVID-19 cases even after the policy of national lockdowns and extreme social distancing norms in many countries (
      • Chakrabarti SS
      • Kaur U
      • Banerjee A
      • et al.
      COVID-19 in India: are biological and environmental factors helping to stem the incidence and severity?.
      ;
      • Coccia M.
      Factors determining the diffusion of COVID-19 and suggested strategy to prevent future accelerated viral infectivity similar to COVID.
      ;
      • Lewis NM
      • Chu VT
      • Ye D
      • et al.
      Household transmission of severe acute respiratory syndrome coronavirus-2 in the United States.
      ). Children often play an important role in the transmission of some respiratory infectious diseases, such as influenza and measles (
      • García-Salido A.
      SARS-COV-2 children transmission: the evidence is that today we do not have enough evidence.
      ;
      • Viner RM
      • Russell SJ
      • Croker H
      • et al.
      School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review.
      ;
      • Yang W.
      Transmission dynamics of and insights from the 2018-2019 measles outbreak in New York City: a modeling study.
      ). However, for SARS-CoV-2, it remains controversial (
      • García-Salido A.
      SARS-COV-2 children transmission: the evidence is that today we do not have enough evidence.
      ;
      • Goldstein E
      • Lipsitch M
      • Cevik M.
      On the effect of age on the transmission of SARS-CoV-2 in households, schools, and the community.
      ;
      • Lau MSY
      • Grenfell B
      • Thomas M
      • Bryan M
      • Nelson K
      • Lopman B.
      Characterizing superspreading events and age-specific infectiousness of SARS-CoV-2 transmission in Georgia, USA.
      ;
      • Lee B
      • Raszka Jr., WV
      COVID-19 transmission and children: the child is not to blame.
      ). Pediatric infections only comprise a small proportion of the total reported cases and children are usually reported with a lower infection rate and a milder clinical course compared with adult cases (
      • Dong Y
      • Mo X
      • Hu Y
      • et al.
      Epidemiology of COVID-19 among children in China.
      ;
      • Hoang A
      • Chorath K
      • Moreira A
      • et al.
      COVID-19 in 7780 pediatric patients: a systematic review.
      ;
      • Irfan O
      • Li J
      • Tang K
      • Wang Z
      • Bhutta ZA.
      Risk of infection and transmission of SARS-CoV-2 among children and adolescents in households, communities and educational settings: a systematic review and meta-analysis.
      ;
      • Ye F
      • Xu S
      • Rong Z
      • et al.
      Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster.
      ). However, children may represent an essential chain of viral transmission and be responsible for the continuous spread of the virus on account of children frequently being asymptomatic carriers (
      • de Souza TH
      • Nadal JA
      • Nogueira RJN
      • Pereira RM
      • Brandão MB.
      Clinical manifestations of children with COVID-19: a systematic review.
      ;
      • Irfan O
      • Muttalib F
      • Tang K
      • Jiang L
      • Lassi ZS
      • Bhutta Z.
      Clinical characteristics, treatment and outcomes of paediatric COVID-19: a systematic review and meta-analysis.
      ). With the emergence of some new virus variants, such as Delta and Omicron, increased transmissibility of SARS-CoV-2 in children has been reported by many studies (
      • Chun JY
      • Jeong H
      • Kim Y.
      Age-varying susceptibility to the delta variant (B.1.617.2) of SARS-CoV-2.
      ;
      • Cloete J
      • Kruger A
      • Masha M
      • et al.
      Paediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 omicron (B.1.1.529) variant wave in South Africa: a multicentre observational study.
      ;
      • Elliott P
      • Bodinier B
      • Eales O
      • et al.
      Rapid increase in Omicron infections in England during December 2021: REACT-1 study.
      ;
      • Marks KJ
      • Whitaker M
      • Agathis NT
      • et al.
      Hospitalization of infants and children aged 0–4 years with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 2020-February 2022.
      ;
      • Thelwall S
      • Aiano F
      • Harman K
      • Dabrera G
      • Ladhani SN.
      Risk of hospitalisation and death in children with SARS-CoV-2 delta (B.1.612.2) infection.
      ). What is worse is that although vaccinations for adults are ongoing, there is still a vacuum in children, especially for those younger than 12 years (
      • Walter EB
      • Talaat KR
      • Sabharwal C
      • et al.
      Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age.
      ), which also may be an important reason for the viral transmission (
      • Li H
      • Lin H
      • Chen X
      • et al.
      Unvaccinated children are an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2): comparative clinical evidence from a recent community surge.
      ).
      Because an understanding of the role of children in the household transmission of SARS-CoV-2 is still evolving, further analysis is necessary. This study aimed to (1) assess the prevalence of pediatric COVID-19 in family clusters, (2) estimate the household secondary attack rate (SAR) of children in different periods and variants, and (3) compare the transmissibility of SARS-CoV-2 in different age groups and explore its potential determinants.

      Methods

      This systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the protocol was registered on PROSPERO (CRD42022313960).

      Definition

      A household transmission cluster was defined as a group of ≥2 confirmed COVID-19 cases in cohabiting individuals where the diagnosis of cases occurred within 2 weeks of each other. The index case, the primary case, was defined as the first person in the household to be infected with SARS-CoV-2. Household contacts were defined as family members or close relatives who had unprotected contact with the index case but did not necessarily live together. The transmissibility of SARS-CoV-2 was empirically estimated by the SAR. The household SAR was defined as the number of household secondary cases divided by the total household contacts. Children were individuals aged <18 years. Notably, for studies dividing the age groups by 10 years, individuals aged 10–19 years were included in the child group.

      Search strategy and eligibility criteria

      A systematic retrieval was performed on two databases (PubMed and Embase) from inception to April 20, 2022, using the key search terms: COVID-19, SARS-CoV-2, family characteristics, household transmission, and so on (details in Table S1), with no restriction on the language, date, study type, or place of publication. Nonprimary documents and modeling studies were excluded.
      Depending on the study type and provided data, studies were included in two parts: case analyses of household pediatric infections and meta-analysis on the household SAR. Case analyses mainly included case reports focusing on individual household transmission of SARS-CoV-2. The personal information of index cases, household contacts, family relationships, and the disease progression of COVID-19 cases must be provided. Although the SAR meta-analysis mainly included descriptive studies that had reported the household SARS-CoV-2 SAR in different age groups, at least two of the following were required: household contacts, household secondary cases, and SAR. Studies with insufficient data or possible duplicate cases were excluded.

      Data extraction and quality assessment

      Two authors (Tian and Zhang) independently extracted the following information from each of the included study: author, country, study type, study period, case definitions, testing protocol, contact tracing methods, demographic characteristic, COVID-19 data (exposures, index cases, household contacts, secondary infection cases, SAR), potential factors, and so on. Disagreements were resolved through consultation with the third author (Chen). To critically appraise the methodologic quality of included studies, the JBI critical appraisal checklist was applied (

      JBI, Critical appraisal tools – checklist for systematic reviews. https://jbi.global/critical-appraisal-tools, 2020 (accessed 14 February 2022).

      ). Each included study was scored independently by two authors (Tian and Zhang) and was given an average point. Studies were ranked as high quality if they were scored ≥10, medium if they were scored 7–9, and low if they were scored <7.

      Data analysis

      All analyses were performed using R 4.1.2 software. The SAR and its relative risk (RR) were calculated for each study. SARs were pooled with a random intercept logistic regression model after a Freeman-Tukey double arcsine transformation, and RRs were pooled using a random-effects model with Der Simonian and Laird weights. The within-study variation was estimated with the 95% confidence interval (CI), and the Higgin and Thompsons I2 was used to assess heterogeneity between studies. Subgroup analyses were conducted to explore the source of heterogeneity. Publication bias was detected using the funnel plot and Egger test. P < 0.05 was considered statistically significant in all tests.

      Results

      As shown in the flow diagram in Figure S1, a total of 1632 records were identified through the data search and 236 articles were retrieved for full-text assessment. Finally, 95 articles were included in our analysis: 48 articles for household SAR meta-analysis and 47 articles for case analysis. Studies included in the SAR meta-analysis are listed in Table 1, of 48 studies, 26 were of high quality and 22 were of medium quality according to the quality assessment in Table S2, and the full details of family clusters included in case analyses are shown in Table S3. All included studies reported household COVID-19 from 18 countries and regions with a total of 1,153,693 participants (834,613 adults and 319,080 children).
      Table 1Studies included in meta-analysis of household SAR.
      Author (year)CountryStudy typeCluster sizePublic lockdownDiagnostic methodFollow-up (days)Quality
      • Afonso ET
      • Marques SM
      • Costa LDC
      • et al.
      Secondary household transmission of SARS-CoV-2 among children and adolescents: clinical and epidemiological aspects.
      BrazilCross-sectional and analytical studyNAYesRT-PCR14Medium
      • Baker JM
      • Nakayama JY
      • O'Hegarty M
      • et al.
      SARS-CoV-2 B.1.1.529 (Omicron) variant transmission within households - four U.S. jurisdictions, November 2021-February 2022.
      United StatesRetrospective study183NART-PCRNAHigh
      • Bhatt M
      • Plint AC
      • Tang K
      • et al.
      Household transmission of SARS-CoV-2 from unvaccinated asymptomatic and symptomatic household members with confirmed SARS-CoV-2 infection: an antibody-surveillance study.
      CanadaProspective study180NART-PCR14High
      • Bi Q
      • Lessler J
      • Eckerle I
      • et al.
      Insights into household transmission of SARS-CoV-2 from a population-based serological survey.
      SwitzerlandCross-sectional population serosurvey2267YesSerological testNAHigh
      • Bi Q
      • Wu Y
      • Mei S
      • et al.
      Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study.
      ChinaRetrospective cohort studyNAYesRT-PCR14High
      • Calvani M
      • Cantiello G
      • Cavani M
      • et al.
      Reasons for SARS-CoV-2 infection in children and their role in the transmission of infection according to age: a case-control study.
      ItalyCase-control studyNANART-PCRNAMedium
      • Cerami C
      • Popkin-Hall ZR
      • Rapp T
      • et al.
      Household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color.
      United StatesProspective study100NART-PCR28High
      • Chaw L
      • Koh WC
      • Jamaludin SA
      • Naing L
      • Alikhan MF
      • Wong J.
      Analysis of SARS-CoV-2 transmission in different settings.
      MalaysiaRetrospective study28NART-PCR14Medium
      • de Gier B
      • Andeweg S
      • Backer JA
      • et al.
      Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), the Netherlands, August to September 2021.
      The NetherlandsRetrospective studyNANART-PCR10Medium
      • Donnelly MAP
      • Chuey MR
      • Soto R
      • et al.
      Household transmission of SARS-CoV-2 Alpha variant - United States, 2021.
      United StatesProspective study127NART-PCR14High
      • Dupraz J
      • Butty A
      • Duperrex O
      • et al.
      Prevalence of SARS-CoV-2 in household members and other close contacts of COVID-19 cases: a serologic study in canton of Vaud, Switzerland.
      SwitzerlandCross-sectional epidemiological studyNAYesSerological test14Medium
      • Galow L
      • Haag L
      • Kahre E
      • et al.
      Lower household transmission rates of SARS-CoV-2 from children compared to adults.
      GermanySeroprevalence study106NASerological testNAMedium
      • Harris RJ
      • Hall JA
      • Zaidi A
      • Andrews NJ
      • Dunbar JK
      • Dabrera G.
      Effect of vaccination on household transmission of SARS-CoV-2 in England.
      EnglandRetrospective studyNANART-PCR14High
      • Hu P
      • Ma M
      • Jing Q
      • et al.
      Retrospective study identifies infection related risk factors in close contacts during COVID-19 epidemic.
      ChinaRetrospective cohort studyNAYesRT-PCR14High
      • Hua CZ
      • Miao ZP
      • Zheng JS
      • et al.
      Epidemiological features and viral shedding in children with SARS-CoV-2 infection.
      ChinaRetrospective cohort, multicenter study314YesRT-PCRNAMedium

      Jalali N, Brustad HK, Frigessi A, et al. Increased household transmission and immune escape of the SARS-CoV-2 Omicron variant compared to the Delta variant: evidence from Norwegian contact tracing and vaccination data. Research Square. 18 February 2022. https://www.researchsquare.com/article/rs-1370541/v1 (accessed 25 Apr 2022).

      NorwayCohort studyNANART-PCR10High
      • Jing QL
      • Liu MJ
      • Zhang ZB
      • et al.
      Household secondary attack rate of COVID-19 and associated determinants in Guangzhou, China: a retrospective cohort study.
      ChinaRetrospective cohort study195YesRT-PCR14High
      • Kim J
      • Choe YJ
      • Lee J
      • et al.
      Role of children in household transmission of COVID-19.
      South KoreaRetrospective observational studyNANART-PCRNAMedium
      • Koureas M
      • Speletas M
      • Bogogiannidou Z
      • et al.
      Transmission dynamics of SARS-CoV-2 during an outbreak in a Roma community in Thessaly, Greece-control measures and lessons learned.
      GreeceRetrospective cohort study40YesRT-PCRNAMedium
      • Kuba Y
      • Shingaki A
      • Nidaira M
      • et al.
      Characteristics of household transmission of COVID-19 during its outbreak in Okinawa, Japan from February to May 2020.
      JapanCohort studyNAYesRT-PCR14Medium
      • Lewis NM
      • Chu VT
      • Ye D
      • et al.
      Household transmission of severe acute respiratory syndrome coronavirus-2 in the United States.
      United States58YesRT-PCR14High
      • Li F
      • Li YY
      • Liu MJ
      • et al.
      Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study.
      ChinaRetrospective cohort study24985YesRT-PCR≥22High
      • Li W
      • Zhang B
      • Lu J
      • et al.
      Characteristics of household transmission of COVID-19.
      ChinaRetrospective study105NART-PCR14Medium
      • Liu PY
      • Gragnani CM
      • Timmerman J
      • et al.
      Pediatric household transmission of severe acute respiratory coronavirus-2 infection - Los Angeles County, December 2020 to February 2021.
      United StatesProspective study15NART-PCR14High
      • Lopez Bernal J
      • Panagiotopoulos N
      • Byers C
      • et al.
      Transmission dynamics of COVID-19 in household and community settings in the United Kingdom, January to March 2020.
      EnglandProspective case-ascertained study329NART-PCR14High

      Lyngse FP, Mølbak K, Denwood M, et al. Effect of vaccination on household transmission of SARS-CoV-2 Delta VOC. medRxiv. 6 January 2022. https://www.medrxiv.org/content/10.1101/2022.01.06.22268841v1.full.pdf. (accessed 25 Apr 2022).

      DenmarkRetrospective study24693NART-PCR14High
      • McLean HQ
      • Grijalva CG
      • Hanson KE
      • et al.
      Household transmission and clinical features of SARS-CoV-2 infections.
      United StatesProspective case-ascertained study302NART-PCR14High
      • Metlay JP
      • Haas JS
      • Soltoff AE
      • Armstrong KA.
      Household transmission of SARS-CoV-2.
      United StatesRetrospective cohort studyNANART-PCRNAMedium
      • Miller E
      • Waight PA
      • Andrews NJ
      • et al.
      Transmission of SARS-CoV-2 in the household setting: a prospective cohort study in children and adults in England.
      EnglandProspective cohort studyNANART-PCRNAMedium
      • Miyahara R
      • Tsuchiya N
      • Yasuda I
      • et al.
      Familial clusters of coronavirus disease in 10 prefectures, Japan, February-May 2020.
      JapanCohort study87YesRT-PCR14Medium
      • Musa S
      • Kissling E
      • Valenciano M
      • et al.
      Household transmission of SARS-CoV-2: a prospective observational study in Bosnia and Herzegovina, August–December 2020.
      Bosnia and HerzegovinaProspective observational study360NART-PCR28High
      • Ng DC
      • Tan KK
      • Chin L
      • et al.
      Risk factors associated with household transmission of SARS-CoV-2 in Negeri Sembilan.
      MalaysiaRetrospective observational study185YesRT-PCR14Medium
      • Ng OT
      • Koh V
      • Chiew CJ
      • et al.
      Impact of SARS-CoV-2 vaccination and paediatric age on Delta variant household transmission.
      SingaporeRetrospective cohort studyNAYesRT-PCR14High
      • Ogata T
      • Irie F
      • Ogawa E
      • et al.
      Secondary attack rate among non-spousal household contacts of coronavirus disease 2019 in Tsuchiura, Japan, August 2020-February 2021.
      JapanCross-sectional study183YesRT-PCRNAMedium
      • Ogata T
      • Tanaka H
      • Nozawa Y
      • et al.
      Increased secondary attack rate among unvaccinated household contacts of coronavirus disease 2019 patients with Delta variant in Japan.
      JapanObservational study580NART-PCRNAHigh
      • Park SY
      • Kim YM
      • Yi S
      • et al.
      Coronavirus disease outbreak in call center.
      South KoreaCohort studyNANART-PCR14Medium
      • Reukers DFM
      • van Boven M
      • Meijer A
      • et al.
      High infection secondary attack rates of severe acute respiratory syndrome coronavirus 2 in Dutch households revealed by dense sampling.
      The NetherlandsProspective cohort study55NART-PCRNAHigh
      • Rosenberg ES
      • Dufort EM
      • Blog DS
      • et al.
      COVID-19 testing, epidemic features, hospital outcomes, and household prevalence, New York State-March 2020.
      United StatesRetrospective study155YesRT-PCRNAHigh
      • Song JS
      • Lee J
      • Kim M
      • et al.
      Serial intervals and household transmission of SARS-CoV-2 Omicron variant, South Korea, 2021.
      South KoreaProspective study25NANANAHigh
      • Soriano-Arandes A
      • Gatell A
      • Serrano P
      • et al.
      Household severe acute respiratory syndrome coronavirus 2 transmission and children: a network prospective study.
      SpainProspective, observational study1108YesRT-PCRNAMedium
      • Stich M
      • Elling R
      • Renk H
      • et al.
      Transmission of severe acute respiratory syndrome coronavirus 2 in households with children, Southwest Germany, May-August 2020.
      GermanyMulticenter, cross-sectional study405NASerological testNAHigh
      • Tanaka H
      • Hirayama A
      • Nagai H
      • et al.
      Increased transmissibility of the SARS-CoV-2 alpha variant in a Japanese population.
      JapanCross-sectional studyNANART-PCR14Medium
      • Waltenburg MA
      • Whaley MJ
      • Chancey RJ
      • et al.
      Household transmission and symptomology of SARS-CoV-2 Alpha variant among children-California and Colorado, 2021.
      United StatesProspective study127NART-PCR14High
      • Wang Y
      • Tian H
      • Zhang L
      • et al.
      Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China.
      ChinaRetrospective cohort study124NART-PCR14High
      • Wang Z
      • Ma W
      • Zheng X
      • Wu G
      • Zhang R.
      Household transmission of SARS-CoV-2.
      ChinaRetrospective case series85YesRT-PCR14High
      • Wu J
      • Huang Y
      • Tu C
      • et al.
      Household transmission of SARS-CoV-2, Zhuhai, China, 2020.
      ChinaProspective observational study35NART-PCRNAMedium
      • Yousaf AR
      • Duca LM
      • Chu V
      • et al.
      A prospective cohort study in nonhospitalized household contacts with severe acute respiratory syndrome coronavirus 2 infection: symptom profiles and symptom change over time.
      United StatesProspective cohort studyNANART-PCR14High
      • Yung CF
      • Kam KQ
      • Chong CY
      • et al.
      Household transmission of severe acute respiratory syndrome coronavirus 2 from adults to children.
      SingaporeProspective study137NART-PCR14Medium
      NA, not applicable; RT-PCR, reverse transcription polymerase chain reaction; SAR, secondary attack rate.

      Case analyses of household pediatric COVID-19

      In the case analysis of pediatric COVID-19, 47 articles were included, identifying 78 household transmission clusters. As shown in Table 2, only 10.3% (8/78) familial clusters were identified with a pediatric index case. These pediatric index cases only led to 7.7% (16/207) of all secondary cases compared with the 92.3% of secondary cases caused by the adult index cases. Child contacts were identified as 29.8% (84/282) of all household contacts and reported in 60.3% (47/78) familial clusters. The child secondary infections only accounted for 30% (62/207) of all secondary infections compared with the 70% as adults.
      Table 2Case analyses of household pediatric COVID-19 infections.
      CharacteristicsCluster (n = 78), %Secondary cases (n = 207), %
      Child as the index case8 (10.3)16 (7.7)
      Adult as the index case70 (89.7)191 (92.3)
      Child as the contacts47 (60.3)62 (30.0)
      Adult as the contacts77 (98.7)145 (70.0)
      COVID-19, coronavirus disease.

      Meta-analyses on household SAR of SARS-COV-2

      Household SAR of child contacts

      Secondary infections of the pediatric household contacts were identified in 41 studies, and the pooled SAR was 0.24 (95% CI: 0.18–0.30, I2 = 100%) (Figure 1). Publication bias was reported upon examination of a funnel plot (Egger test, P = 0.021) (Figure S2).
      Figure 1
      Figure 1Pooled household SAR of child contacts. CI, confidence interval; SAR, secondary attack rate.
      Subgroup analyses on household SAR of child contacts were performed on research periods and SARS-CoV-2 variants, as provided in Table 3. In different research periods, 31 studies were carried out between 2019 and February 2021, and the SAR was estimated at 0.18 (95% CI: 0.13–0.25, I2 = 99%). A total of 9 studies were conducted between February and November 2021, and the SAR was 0.39 (95% CI: 0.30–0.48, I2 = 97%). The SAR of two studies between November 2021 and 2022 was 0.51 (95% CI: 0.47–0.54, I2 = 0%). Significant difference in SAR was reported in different groups of research period (P < 0.01). For different SARS-CoV-2 variants, the SAR of Wild type in 33 included studies was 0.20 (95% CI: 0.14–0.26, I2 = 99%). The SAR of the Alpha variant in the three included studies was 0.42 (95% CI: 0.23–0.62, I2 = 94%). The Delta variant was investigated in five studies, and the SAR was 0.35 (95% CI: 0.25–0.45, I2 = 98%). The SAR of the Omicron variant in two studies was 0.56 (95% CI: 0.51–0.61, I2 = 20%). A significant difference in SAR was also reported among different variants (P < 0.01).
      Table 3Subgroup analyses on household SAR of child contacts.
      SubgroupsNo. of studiesSAR (95% CI)I2P-value
      Research period<0.01
       2019-Feb, 2021310.18 (0.13–0.25)99%
       Feb-Nov, 202190.39 (0.30–0.48)97%
       Nov, 2021-202220.51 (0.47–0.54)0%
      SARS-CoV-2 variant<0.01
       Wild type330.20 (0.14–0.26)99%
       Alpha30.42 (0.23–0.62)94%
       Delta50.35 (0.25–0.45)98%
       Omicron20.56 (0.51–0.61)20%
      CI, confidence interval; SAR, secondary attack rate; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
      In the analyses on household SAR of child contacts in different age groups, children younger than 10 years were found to be less susceptible than children older than 10 years (RR = 0.74, 95% CI: 0.56–0.97, I2 = 0%). However, no significant difference was shown between children younger and older than 12 years (RR = 1.12, 95% CI: 0.90–1.39, I2 = 77%). In the combined analysis on the previous two cases, the younger child contacts were not significantly associated with a lower SAR than the older ones (RR = 1.01, 95% CI: 0.84–1.21, I2 = 66%) (Figure 2).
      Figure 2
      Figure 2Subgroup analyses on household SAR of child contacts in different age groups. CI, confidence interval; RR, risk ratio; SAR, secondary attack rate.

      Household SAR of adult contacts

      The SAR of adult household contacts was estimated at 0.32 (95% CI: 0.27–0.37, I2 = 99%) on the basis of 41 included studies (Figure S3). Publication bias was also reported in the funnel plot of Figure S4 (Egger test, P < 0.01). In the analysis on adult household contacts of different age groups, the old adults were significantly associated with a higher SAR than young adults (>60 vs <60 years: RR = 1.45, 95% CI: 1.24–1.70, I2 = 52%; >65 vs <65 years: RR = 1.24, 95% CI: 1.02–1.50, I2 = 55%). The same trend was also found in the combined analysis (the old adults vs the young adults: RR = 1.35, 95% CI: 1.19–1.54, I2 = 77%) (Figure S5).

      Household SAR comparison between child and adult contacts

      In the household SAR comparison between child and adult contacts in 37 studies, children were demonstrated to be less likely to be infected with SARS-COV-2 than adults when exposed to household index cases (RR = 0.74, 95% CI: 0.64–0.85, I2 = 97%) (Figure 3). No obvious publication bias was found in the funnel plot of Figure S6 (Egger test, P = 0.31).
      Figure 3
      Figure 3Household SAR comparison between child and adult contacts. CI, confidence interval; RR, risk ratio; SAR, secondary attack rate.
      Subgroup analyses of the comparison were performed on research periods and SARS-CoV-2 variants, as detailed in Table 4. In different research periods, 27 studies were carried out between 2019 and February 2021, in which lower transmissibility was reported in child contacts than adult contacts (RR = 0.62, 95% CI: 0.52–0.75, I2 = 95%). For nine studies between February and November 2021 and two studies between November 2021 and 2022, no significant difference in SAR was found between child and adult contacts (RR = 0.98, 95% CI: 0.86–1.12, I2 = 80%; RR = 1.09, 95% CI: 0.89–1.34, I2 = 73%). A significant difference in RR was reported in different groups of research period (P < 0.01). For different SARS-CoV-2 variants, children were significantly associated with a lower SAR than adult contacts in 29 studies of the Wild type variant (RR = 0.65, 95% CI: 0.55–0.77, I2 = 95%). However, no significant difference in SAR was observed between child and adult contacts in studies of other variants (Alpha: RR = 1.04, 95% CI: 0.76–1.42, I2 = 76%; Delta: RR = 0.99, 95% CI: 0.82–1.19, I2 = 88%; Omicron: RR = 1.09, 95% CI: 0.88–1.35, I2 = 74%). Significant difference in RR was also reported in different variants (P < 0.01).
      Table 4Subgroup analyses of household SAR comparison between child and adult contacts.
      SubgroupsNo. of studiesRR (95% CI)I2P-value
      Research period<0.01
       2019–June, 2020270.62 (0.52–0.75)95%<0.01
       February–November, 202190.98 (0.86–1.12)80%>0.05
       November, 2021–202221.09 (0.89–1.34)73%>0.05
      SARS-CoV-2 variant<0.01
       Wild type290.65 (0.55–0.77)95%<0.01
       Alpha31.04 (0.76–1.42)76%>0.05
       Delta50.99 (0.82–1.19)88%>0.05
       Omicron21.09 (0.88–1.35)74%>0.05
      CI, confidence interval; RR, relative risk; SAR, secondary attack rate; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

      Household SAR of child and adult index cases

      A total of 18 studies reported the respective SAR of child and adult index cases in familial clusters. The estimated SAR of the child index case was 0.20 (95% CI: 0.15–0.26, I2 = 100%). For the adult index cases, it was 0.36 (95% CI: 0.27–0.46, I2 = 100%). Compared with the adult index cases, the child index cases were significantly associated with a lower possibility to transmit SARS-CoV-2 to their family members (RR = 0.64, 95% CI: 0.50–0.81, I2 = 96%) (Figure 4).
      Figure 4
      Figure 4Comparison on household SAR between child and adult index cases. CI, confidence interval; RR, risk ratio; SAR, secondary attack rate.

      Potential determinants of the household SAR

      Potential determinants of the household transmission of SARS-COV-2 were identified on the basis of prespecified characteristics and studies with sufficient data (Table S4). Symptomatic index cases were associated with a higher SAR than asymptomatic index cases (RR = 2.68, 95% CI: 1.39–3.58, I2 = 94%). In different family relationships, the spouse relationship-to-index case was reported to have a significantly higher SAR than other relationships (RR = 1.78, 95% CI: 1.25–2.53, I2 = 91%), whereas the same trend was not shown in the parent-child relationship (RR = 0.84, 95% CI: 0.59–1.19, I2 = 87%). Household contacts with comorbidities were at a higher risk for secondary infections than those without comorbidities (RR = 1.98, 95% CI: 1.52–2.59, I2 = 63%). In terms of sex, the female contacts were observed to be slightly more susceptible than the male contacts (RR = 1.08, 95% CI: 1.01–1.16, I2 = 42%). Another important factor was the household size: a larger household size might be associated with a lower SAR (>4 was <4 members: RR = 0.69, 95% CI: 0.55–0.85, I2 = 94%; >6 vs <6 members: RR = 0.69, 95% CI: 0.50–0.95, I2 = 90%).

      Discussion

      Analyses of the household transmission of SARS-COV-2 will certainly facilitate a better understanding of the transmission chain and contribute to the epidemic control. Many studies have been conducted on household SAR of SARS-COV-2 (
      • Fung HF
      • Martinez L
      • Alarid-Escudero F
      • et al.
      The household secondary attack rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a rapid review.
      ;
      • Koh WC
      • Naing L
      • Chaw L
      • et al.
      What do we know about SARS-CoV-2 transmission? A systematic review and meta-analysis of the secondary attack rate and associated risk factors.
      ;
      • Li F
      • Li YY
      • Liu MJ
      • et al.
      Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study.
      ;
      • Madewell ZJ
      • Yang Y
      • Longini Jr, IM
      • Halloran ME
      • Dean NE.
      Household transmission of SARS-CoV-2: a systematic review and meta-analysis.
      ;
      • Shah K
      • Saxena D
      • Mavalankar D.
      Secondary attack rate of COVID-19 in household contacts: a systematic review.
      ;
      • Thompson HA
      • Mousa A
      • Dighe A
      • et al.
      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) setting-specific transmission rates: a systematic review and meta-analysis.
      ), but only a minority focused on the child group. Irfan et al. (2021) and
      • Zhu Y
      • Bloxham CJ
      • Hulme KD
      • et al.
      A meta-analysis on the role of children in severe acute respiratory syndrome coronavirus 2 in household transmission clusters.
      performed meta-analyses on the role of children in household transmission in the early periods of the epidemic, but the results were still unclear because of the limited number of included studies and pediatric index cases. On the basis of previous research, more articles were included in our study. With more timely articles, more comprehensive analyses were conducted. Other than the total pooled household SAR of child contacts and index cases, subgroup analyses were also performed in different SARS-CoV-2 variants and different periods, as well as the transmissibility comparison between child and adult contacts. To the best of our knowledge, almost no previous meta-analyses have been conducted on the pediatric household transmission of different SARS-CoV-2 variants.
      Our results show that both the child index cases and secondary cases only comprised a small proportion of the household transmission in case analyses, which suggested that children were unlikely to be the main source of SARS-COV-2 in familial clusters. In the total unclassified results of SAR meta-analyses, lower household transmissibility was demonstrated in both pediatric index cases and contacts than in adults. This was consistent with these previous meta-analyses (
      • Grijalva CG
      • Rolfes MA
      • Zhu Y
      • et al.
      Transmission of SARS-COV-2 infections in households - Tennessee and Wisconsin, April–September 2020.
      ;
      • Madewell ZJ
      • Yang Y
      • Longini Jr, IM
      • Halloran ME
      • Dean NE.
      Factors associated with household transmission of SARS-CoV-2: an updated systematic review and meta-analysis.
      ,
      • Madewell ZJ
      • Yang Y
      • Longini Jr, IM
      • Halloran ME
      • Dean NE.
      Household transmission of SARS-CoV-2: a systematic review and meta-analysis.
      ;
      • Zhu Y
      • Bloxham CJ
      • Hulme KD
      • et al.
      A meta-analysis on the role of children in severe acute respiratory syndrome coronavirus 2 in household transmission clusters.
      ). These findings imply that children are less vulnerable to SARS-COV-2 than adults. Similar to what previous data have shown, the older adults also had a higher SAR than the young adults. Contrary to the analysis by
      • Zhu Y
      • Bloxham CJ
      • Hulme KD
      • et al.
      A meta-analysis on the role of children in severe acute respiratory syndrome coronavirus 2 in household transmission clusters.
      , a significant difference was found between children younger than and older than 10 years in our analyses, and a recent population-based cohort study also suggested a higher transmissibility of SARS-COV-2 in younger children than older children (
      • Paul LA
      • Daneman N
      • Schwartz KL
      • et al.
      Association of age and pediatric household transmission of SARS-CoV-2 infection.
      ). However, this difference still lacked statistical power because of the limited included studies and relatively little advantage, and negative results were also noted in our comprehensive analyses. Therefore, future studies are still required.
      Notably, some new findings were found in the subgroup analyses on household SAR of different periods and SARS-COV-2 variants. In the early period of the pandemic (the Wild type mainly dominated during 2019–2020), a relatively low household SAR was observed in children (10–30%), and child contacts usually had lower transmissibility than adults. However, with the emergence of some new variants (Alpha and Delta) in the beginning of 2021, household SAR in children seemed to increase (30–40%). Consistent with our results, many epidemiologic studies have pointed out that children and adolescents had become more susceptible to these new variants (
      • Allen H
      • Vusirikala A
      • Flannagan J
      • et al.
      Household transmission of COVID-19 cases associated with SARS-CoV-2 delta variant (B.1.617.2): national case-control study.
      ;
      • Chun JY
      • Jeong H
      • Kim Y.
      Age-varying susceptibility to the delta variant (B.1.617.2) of SARS-CoV-2.
      ;
      • Li H
      • Lin H
      • Chen X
      • et al.
      Unvaccinated children are an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2): comparative clinical evidence from a recent community surge.
      ;
      • Ng OT
      • Koh V
      • Chiew CJ
      • et al.
      Impact of Delta variant and vaccination on SARS-CoV-2 secondary attack rate among household close contacts.
      ;
      • Paul LA
      • Daneman N
      • Schwartz KL
      • et al.
      Association of age and pediatric household transmission of SARS-CoV-2 infection.
      ). At the end of 2021, the Omicron variant emerged with the highest transmissibility so far: household SAR in both children and adults seemed to be more than 50%. Plenty of recent research also reported that the rapid increase in infections and hospitalizations was caused by the Omicron variant (
      • Baker JM
      • Nakayama JY
      • O'Hegarty M
      • et al.
      SARS-CoV-2 B.1.1.529 (Omicron) variant transmission within households - four U.S. jurisdictions, November 2021-February 2022.
      ;
      • Cloete J
      • Kruger A
      • Masha M
      • et al.
      Paediatric hospitalisations due to COVID-19 during the first SARS-CoV-2 omicron (B.1.1.529) variant wave in South Africa: a multicentre observational study.
      ;
      • Elliott P
      • Bodinier B
      • Eales O
      • et al.
      Rapid increase in Omicron infections in England during December 2021: REACT-1 study.
      ;
      • Marks KJ
      • Whitaker M
      • Agathis NT
      • et al.
      Hospitalization of infants and children aged 0–4 years with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 2020-February 2022.
      ). Additionally, no significant difference was found in household SAR comparison between children and adults with new variants in our analyses, which also supported the increased vulnerability in children. This was in line with the result of a newly published meta-analysis conducted by
      • Viner R
      • Waddington C
      • Mytton O
      • et al.
      Transmission of SARS-CoV-2 by children and young people in households and schools: a meta-analysis of population-based and contact-tracing studies.
      . Some research attributed the increased transmissibility to immune escape and reduced effectiveness of vaccination (
      • Meng B
      • Abdullahi A
      • Ferreira IATM
      • et al.
      Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity.
      ;
      • Mlcochova P
      • Kemp SA
      • Dhar MS
      • et al.
      SARS-CoV-2 B.1.617. 2 Delta variant replication and immune evasion.
      ;
      • Planas D
      • Veyer D
      • Baidaliuk A
      • et al.
      Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization.
      ). However, data have proven the protective effect of vaccination even in new variant periods (
      • Fowlkes AL
      • Yoon SK
      • Lutrick K
      • et al.
      Effectiveness of 2-dose BNT162b2 (Pfizer BioNTech) mRNA vaccine in preventing SARS-CoV-2 infection among children aged 5–11 years and adolescents aged 12–15 years—PROTECT cohort, July 2021–February 2022.
      ;
      • Harris RJ
      • Hall JA
      • Zaidi A
      • Andrews NJ
      • Dunbar JK
      • Dabrera G.
      Effect of vaccination on household transmission of SARS-CoV-2 in England.
      ;
      • Prunas O
      • Warren JL
      • Crawford FW
      • et al.
      Vaccination with BNT162b2 reduces transmission of SARS-CoV-2 to household contacts in Israel.
      ). Limited by insufficient data, the subgroup analysis on vaccination status was not conducted and the number of articles included in variants analyses was also few. Therefore, original studies that include more virologic data and information on the vaccination status of the participants are still necessary for more convincing results.
      Interpretation of the results in the determinant assessment should be more conservative in consideration of the high heterogeneity. A higher SAR was observed in the symptomatic index cases than in asymptomatic. Extensive evidence has proved that mild or asymptomatic patients are less contagious than those with typical clinical symptoms (
      • Cevik M
      • Tate M
      • Lloyd O
      • Maraolo AE
      • Schafers J
      • Ho A.
      SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
      ;
      • Heald-Sargent T
      • Muller WJ
      • Zheng X
      • Rippe J
      • Patel AB
      • Kociolek LK.
      Age-related differences in nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in patients with mild to moderate coronavirus disease 2019 (COVID-19).
      ;
      • Luo L
      • Liu D
      • Liao X
      • et al.
      Contact settings and risk for transmission in 3410 close contacts of patients with COVID-19 in Guangzhou, China: a prospective cohort study.
      ). A larger household size might be associated with a lower SAR. One possible reason may be that large families usually have a low average age and young people tend to be less susceptible. The spouse relationship emerged as a susceptible group in our result.
      • Chaw L
      • Koh WC
      • Jamaludin SA
      • Naing L
      • Alikhan MF
      • Wong J.
      Analysis of SARS-CoV-2 transmission in different settings.
      suggested that intimate relationships with frequent interaction and prolonged proximity in a closed environment were risk factors. However, negative outcome occurred in the parent-child relationship, which might result from the children's low vulnerability. Household contacts with comorbidities or female contacts were found to be more susceptible, which was also reported in many large population studies (

      Lyngse FP, Mølbak K, Denwood M, et al. Effect of vaccination on household transmission of SARS-CoV-2 Delta VOC. medRxiv. 6 January 2022. https://www.medrxiv.org/content/10.1101/2022.01.06.22268841v1.full.pdf. (accessed 25 Apr 2022).

      ;
      • Prunas O
      • Warren JL
      • Crawford FW
      • et al.
      Vaccination with BNT162b2 reduces transmission of SARS-CoV-2 to household contacts in Israel.
      ).
      There are several limitations of our systematic review and meta-analysis. First, because the articles included in case analyses were limited and relatively insufficient, larger data sets or more scientific methods are necessary for a more accurate prevalence assessment. In meta-analyses, some included studies were of the retrospective or cross-sectional type, and the information of index cases and contacts was mainly obtained from contact-tracing data sets. Therefore, the determination of the case status might be uncertain, especially the asymptomatic child index cases, which were often mistakenly identified as secondary cases, distorting transmission pathways. The epidemiologic information was self‐reported and subject to recall bias and response bias. In addition, the SAR would be overestimated for not excluding infection resource outside the household and was also underestimated in studies in which only the symptomatic contacts were tested. Because of data insufficiency, many other potential determinants associated with the SAR were not investigated in detail, such as the incubation and infectious periods and public lockdown policy; subgroup analyses of child index cases were also not conducted. Last and most importantly, high unexplained heterogeneity in our analyses constituted an important obstacle when interpreting the results. This might be attributed to the great variation in the design of studies: different definitions of index cases and contacts, inconsistent testing protocols and follow-up time, sociodemographic factors, and so on. Many previous meta-analyses on SAR also ran into the same dilemma (Irfan et al., 2021;
      • Madewell ZJ
      • Yang Y
      • Longini Jr, IM
      • Halloran ME
      • Dean NE.
      Household transmission of SARS-CoV-2: a systematic review and meta-analysis.
      ;
      • Shah K
      • Saxena D
      • Mavalankar D.
      Secondary attack rate of COVID-19 in household contacts: a systematic review.
      ;
      • Zhu Y
      • Bloxham CJ
      • Hulme KD
      • et al.
      A meta-analysis on the role of children in severe acute respiratory syndrome coronavirus 2 in household transmission clusters.
      ). All of these implied a multitude of related factors and substantial differences among populations. Therefore, the generalizability of our results is limited; compared with the quantitative results, the qualitative conclusions might be more reliable.

      Conclusion

      Although children were demonstrated to be not dominant in the household transmission, their transmissibility of SARS-CoV-2 appeared to increase as new variants emerged. Given the potentially serious complications of pediatric COVID-19, vaccination research and implementation in children remain a must.

      Potential competing interest

      None.

      Financial support

      None.

      Ethics approval

      No ethics approval was required for this work.

      Acknowledgment

      The authors especially express their appreciation to Miss Mou for her kind help with data analysis (Jialing Mou, Ph.D., Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences).

      Author contributions

      Concept and design: Yuan Shi and Feifan Chen. Retrieval, selection, and extraction: Feifan Chen, Yan Tian, and Lixin Zhang. Statistical analysis and interpretation: all authors. Drafting of the manuscript: Feifan Chen, Yan Tian, and Lixin Zhang. Critical revision: Yuan Shi and Feifan Chen. Supervision: Yuan Shi.

      Appendix. Supplementary materials

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