The role of SARS-CoV-2 variants of concern in children and adolescents with COVID-19: a systematic review

BackgroundInfections by SARS-CoV-2 variants of concern (VOCs) might affect children and adolescents differently than earlier viral lineages. We aimed to address five questions about SARS-CoV-2 VOC infections in children and adolescents: i) symptoms and severity, ii) risk factors for severe disease, iii) the risk of becoming infected, iv) the risk of transmission and v) long-term consequences following a VOC infection. MethodsWe carried out a systematic review. We searched the COVID-19 Open Access Project database up to 1 March 2022 and PubMed up to 9 May 2022 for observational epidemiological studies about alpha, beta, gamma, delta and omicron VOCs among 0 to 18 year olds. We synthesised data for each question descriptively and assessed the risks of bias at the outcome level. ResultsWe included 53 articles, of which 47% were from high-income countries and none were from low-income countries, according to World Bank categories. Most children with any VOC infection presented with mild disease, with more severe disease being described with the delta or the gamma VOC. Diabetes and obesity were reported as risk factors for severe disease during the whole pandemic period. The risk of becoming infected with a SARS-CoV-2 VOC seemed to increase with age, while in daycare settings the risk of onward transmission of VOCs was higher for younger than older children or at least partially vaccinated adults. Long-term symptoms or signs following an infection with a VOC were described in <5% of children and adolescents. ConclusionOverall patterns of SARS-CoV-2 VOC infections in children and adolescents are similar to those of earlier lineages. Comparisons between different pandemic periods, countries and age groups should be improved with complete reporting of relevant contextual factors, including VOCs, vaccination status of study participants and the risk of exposure of the population to SARS-CoV-2. PROSPERO registration numberCRD42022295207 Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSSARS-CoV-2 variants of concern (VOCs) might affect children and adolescents differently from earlier viral lineages. What this study addsChildren and adolescents are susceptible to SARS-CoV-2 VOC infection, though they mostly experience mild disease, and can transmit the VOCs. More severe disease was described with the delta or the gamma VOC but comparison within paediatric age groups as well as to adults is hindered by the lack of reporting of contextual factors such as the vaccination status of these groups. How this study might affect research practice or policyThe applicability of our findings about clinical presentations, susceptibility and transmissibility of SARS-CoV-2 VOCs is limited by an absence of research from low-and middle-income settings. As new VOCs continue to emerge, new studies are needed globally, with methods and results reported in ways that allow comparison between different VOCs and age groups.