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Many theories have been formulated through decades regarding the causes of the mysterious syndrome known as Kawasaki disease (KD).1 This pediatric self-limited vasculitis has been escaping full characterization since Tomizaku Kawasaki, PhD, identified the disease that was then named after him.2 In many of the clinical histories, the role of external factors seems already clear, because the appearance of respiratory symptoms is reported to occur a few days before KD symptoms emerge (eg, an abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase).3 However, the many attempts to characterize a unique agent have been unsuccessful so far. Whether this is an indication of a multiplicity of agents (ie, multiple-agent disease) or a complex interplay of factors interacting with the immune system of children who are genetically predisposed still remains an open question. However, in this race against time, a study by Hara and colleagues4 takes advantage of the unique epidemiological situation caused by the COVID-19 pandemic in Japan to perform a natural experiment that sheds new light on the hidden etiological processes of KD. Indeed, the pandemic itself already has provided KD research with other interesting hints, such as multisystem inflammatory syndrome in children (MIS-C), which was originally named Kawasaki-like multisystem inflammatory syndrome, with symptoms including shock, cardiac, respiratory, kidney, gastrointestinal, or neurological disorders. MIS-C was temporally associated with SARS-CoV-2 infection.5 Despite MIS-C later having been found to have characteristics different from those of classic Kawasaki disease, the nature of MIS-C gives further credibility to the idea that an infection or exposure to an infectious agent (eg, a virus, bacteria, or fungus) can cause symptoms similar to those observed in children with KD. During the COVID-19 pandemic, old theories on KD’s viral origin come to life again, bringing back to the spotlight past studies6 that found associations even between human coronaviruses and KD.
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Published: April 6, 2021. doi:10.1001/jamanetworkopen.2021.4624
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Rodó X et al. JAMA Network Open.
Corresponding Author: Xavier Rodó, PhD, Climate and Health Program, ISGlobal, Doctor Aiguader 88, Barcelona, Catalonia 08003, Spain (email@example.com).
Conflict of Interest Disclosures: None reported.
Funding/Support: Dr Rodó acknowledges support from the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa 2019 2023 Program (grant No. CEX2018 000806S), and support from the Generalitat de Catalunya through the Catalong Research Centers Program. Mr Fontal acknowledges the financial support of Health Data Linkage for Clinical Benefit as part of the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 81354.
Role of the Funder/Sponsor: The funders had no role in the preparation, review, or approval of the manuscript and decision to submit the manuscript for publication.
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