Background: Kawasaki disease is characterized by high fever, rash, cervical lymphadenopathy, conjunctival injection, oral mucous membrane changes and swelling of the extremities followed by skin sloughing. Despite >50 years of study, no bacterial, viral or other infectious agent has been consistently associated with the illness. The lockdown and social distancing for COVID-19 in March 2020 led to a marked decrease in respiratory virus circulation. This provided an "experiment of nature" to determine whether Kawasaki disease would decline in parallel. Methods: Discharge ICD-10 diagnosis codes were obtained from the Vizient Clinical Data Base for Kawasaki disease and respiratory viruses, and analyzed for the age group < 5 years. Weekly respiratory virus positivity data were also obtained from BioFire Diagnostics. Results: Common enveloped respiratory viruses declined precipitously from April 2020 through March 2021 to levels at or below historical seasonal minimum levels. Kawasaki Disease declined about 40% compared with 2018-2019, which is distinctly different from the pattern seen for the enveloped respiratory viruses. Strong seasonality was seen for Kawasaki disease as far back as 2010, and correlated most closely with respiratory syncytial virus, human metapneumovirus and less so with influenza virus suggesting there is a baseline level of Kawasaki disease activity that is heightened during yearly respiratory virus activity but that remains at a certain level even in the near total absence of respiratory viruses. Conclusions: The striking decrease in enveloped respiratory viruses after lockdown and social distancing was not paralleled by a comparable decrease in Kawasaki disease incidence, suggesting a different epidemiology.

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To the Editor, Chimeric antigen receptor (CAR) T cell therapy has made an impact on the treatment of hematological malignancies. In the United States of America, since August 2017, six commercial CAR-T cell products were developed and approved by the Food and Drug Administration (FDA).The indications include acute lymphoblastic leukemia, several types of non-Hodgkin lymphomas and multiple myeloma. They come with a unique set of toxicities, of which, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are best known. 1 A lesser known but very serious side effect that is increasingly recognized is severe toxicity resembling hemophagocytic lymphohistiocytosis (HLH), termed as CAR-HLH. It is debated whether CAR-HLH is a separate entity or an extended or delayed inflammatory phase of CRS. 2,3 Limited data indicate that CAR-HLH may be refractory to cytokine neutralization with tocilizumab. 4 Early studies reported an incidence of 1% for CAR-HLH 5 while a survey from EBMT centers in 2020 indicated an incidence of 3.5%. 3 Except for two case reports of patients developing HLH after the infusion of CAR-T cells, no additional data on this potentially lethal toxicity were published. 6,7 As far as experimental, non-FDA approved CAR T cells are concerned, a significantly higher incidence was recently observed with a CD22 product. 8 Therefore, we decided to access the FDA and Vizient databases to get further insight into trends, incidence, risk factors, and potential outcomes of CAR-HLH.The FDA Adverse Events Reporting System (FAERS) was last accessed on March 3, 2022, to collect data on the reported cases of CAR-HLH. The search terms included all currently approved CAR-T cell products including axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel). Familial HLH cases were excluded. Four cases were eliminated because of likely duplicate reporting.We identified and manually reviewed 121 cases of CAR-HLH. The data were analyzed with regards to the associated CAR-T cell product, country, year, and mortality. To further understand the incidence of CAR-HLH cases, we further searched for secondary HLH (listed as "Overall Adverse Events" in FAERS over the last 10 years). Since the diagnostic criteria for CAR-HLH depended on each submitting institution, no further review was possible. The trend of secondary HLH cases

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