In this Personal View, we discuss current knowledge on SARS-CoV-2 RNA or antigen persistence in children infected with SARS-CoV-2. Based on the evidence that the virus can persist in adults, we have done a literature review and analysed studies that looked for SARS-CoV-2 RNA or antigens in children undergoing autopsy, biopsy, or surgery for either death from COVID-19 or multisystem inflammatory syndrome, or assessments for long COVID-19 or other conditions. Our analysis suggests that in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months. We discuss what is known about the biological effects of viral persistence for other viral infections and highlight new scenarios for clinical, pharmacological, and basic research exploration. Such an approach will improve the understanding and management of post-viral syndromes.