Susceptibility and infectiousness of SARS-CoV-2 in children versus adults, by variant (wild-type, Alpha, Delta): a systematic review and meta-analysis of household contact studies

Importance Understanding the susceptibility and infectiousness of children and adolescents in comparison to adults is important to appreciate their role in the COVID-19 pandemic. Objective To determine SARS-CoV-2 susceptibility and infectiousness of children and adolescents with adults as comparator for three variants (wild-type, Alpha, Delta) in the household setting. We aimed to identify the effects independent of vaccination. Data Sources We searched EMBASE, PubMed and medRxiv up to January 2022. Additional studies were identified through contacting subject experts. Study Selection Two reviewers independently identified studies providing secondary attack rates (SAR) for SARS-CoV-2 infection in children (0-9 years), adolescents (10-19 years) or both compared with adults (20 years and older) derived from household data. Data Extraction and Synthesis Two reviewers independently performed data extraction. We assessed risk of bias of included studies using a critical appraisal checklist and a random-effects meta-analysis model to pool association estimates. Main Outcomes and Measures Odds ratio (OR) for SARS-CoV-2 infection comparing children and adolescents with adults stratified by wild-type, Alpha, and Delta variant, respectively. Susceptibility was defined as the secondary attack rate (SAR) among susceptible household contacts irrespective of the age of the index case. Infectiousness was defined as the SAR irrespective of the age of household contacts when children/adolescents/adults were the index case. Results Twenty-eight studies (308,857 contacts) were included in the susceptibility analysis, for Delta only one (large) study was available. Compared to adults children and adolescents were less susceptible to the wild-type and Delta variant, but equally susceptible to the Alpha variant. In the infectiousness analysis, 21 studies (201,199 index cases) were included. Compared to adults, children and adolescents were less infectious when infected with the wild-type and Delta variant. Alpha variant-related infectiousness remained unclear, 0-9 year old children were at least as infectious as adults. SAR among household contacts was highest during circulation of the Alpha variant, lowest during wild-type circulation and intermediate during Delta circulation. Conclusions and Relevance When considering the potential role of children and adolescents, for each variant susceptibility, infectiousness, age group and overall transmissibility need to be assessed to guide public health policy. Question What is the evidence on the susceptibility and infectiousness of wild-type, Alpha and Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and adolescents compared with adults in the household setting? Findings In this systematic review and meta-analysis of 28 studies that included 308,857 household contacts, children and adolescents were less susceptible to the wild-type and Delta variant and likely equally susceptible to the Alpha variant of SARS-Cov-2. Children aged 0-9 years old infected with the Alpha variant may be more infectious than adults, but for adolescents, Alpha infectiousness is unclear. The overall secondary attack rate (SAR) rose substantially from wild-type to Alpha and dropped somewhat from Alpha to Delta. Meaning The epidemiological role of children and adolescents towards SARS-CoV-2 may be influenced by susceptibility, infectiousness, variant, age group and overall (relative) contagiousness. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Robert Koch Institute, Germany. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript