key: cord-0912994-5o883sqv
authors: Shulman, Stanford T.; Rowley, Anne H.
title: An Unintended Consequence of Pandemic Control Measures: Fewer Cases of Kawasaki Disease
date: 2021-08-26
journal: J Pediatr
DOI: 10.1016/j.jpeds.2021.08.069
sha: 19c83363f8f051fda8385ad618db306e331c6f38
doc_id: 912994
cord_uid: 5o883sqv

nan

Shortly after the contours of the COVID-19 pandemic became apparent in early 2020, specific measures to reduce the risk of person-to-person transmission of SARS-CoV-2 were implemented. By mid-to late-March, 2020, recommendations for masking, social distancing and school closures were in place in many areas, with other regions adopting these precautions later . By June 2020, it had been recognized that these measures appeared to be impacting the transmission of other infectious agents of childhood, especially those spread by the respiratory route. Hatoun Shortly after Hatoun's report, we noted that fewer children were being diagnosed with Kawasaki disease at our institution compared with previous years 4 . We subsequently reported a 67% decline in KD diagnoses from April-December 2020 at our large children's hospital and a closely affiliated institution compared with cases diagnosed in the same months of the eight pre-pandemic years 2012-2019 (13 cases in 2020 J o u r n a l P r e -p r o o f compared with the pre-pandemic mean of 46.6 cases, p<.01). Our updated data encompassing 12 full months from April 2020 through March 2021 indicate that this phenomenon has continued. This is of interest because a leading theory of the etiology of KD is that it is triggered by an as yet unidentified ubiquitous respiratory agent, which would also likely be impacted by pandemic mitigation measures 5 were seen, corresponding to school closures and persisting through 2020. The number of cases of Kawasaki disease remained as much as 60% lower from week 12 through 32 compared with previous years. Rates of exanthem subitum changed little, presumably because this disease frequently is transmitted within the home by previously infected individuals 6 . Additionally, there was no evidence that parents of children with KD were J o u r n a l P r e -p r o o f avoiding hospital visits in 2020, because the illness day of KD presentation did not change in 2020 compared with earlier years. It is highly unlikely that misdiagnosis of KD cases as multisystem inflammatory syndrome of childhood (MIS-C), a late complication of SARS-CoV-2 infection that has some overlapping clinical features with KD, could account for the reduced number of KD cases during the pandemic. This is especially true in Asian countries where MIS-C has not appeared 7 . However, to address this issue, the authors found that cases of incomplete KD had not increased in 2020, as might occur if MIS-C was misdiagnosed as KD. Because the number of cases of KD did not decrease as much as the number of cases of RSV, and because the prevalence of KD in unmasked children less than age two years did not decrease as much as it did for masked older children, the authors proposed that KD can be acquired both outside and within the home (from a previously infected sibling or parent). This theory is consistent with several other lines of evidence supporting a persistent infectious etiologic agent for KD. [8] [9] [10] Kang et al studied all cases of KD diagnosed in children 0-19 years old in Korea from January 2010 to September 2020 using the Korean National Health Insurance Service database 11 . February through September 2020 was defined as the period when nonpharmaceutical interventions (e.g., masking, distancing) were utilized to mitigate coronavirus transmission. The incidence of Kawasaki disease during this period (18.8/100,000) was compared with the annual mean incidence during the same months in the previous 10 years (31.5/100,000). This represents a 40% decline in of Kawasaki disease during the pandemic mitigation period. In children under age 4 years, the incidence declined from 123/100,000 in the pre-pandemic period to 80/100,000 during the pandemic mitigation period, a 35% decline. In 5-9 year-old children the prepandemic rate was 23.8/100,000, and during the pandemic mitigation period was J o u r n a l P r e -p r o o f 10.6/100,000 (55% decline). There was no significant change in KD incidence in the 10- We demonstrated that plasmablasts, the precursors to antibody-producing plasma cells, are clonally expanded in the peripheral blood of children with KD at 1-2 weeks after fever onset, indicating an antigen-driven immunologic response to a recent infection. (5) We further demonstrated that these plasmablasts encode antibodies that recognize antigen in intracytoplasmic inclusion bodies in ciliated bronchial epithelial cells of children who died of KD 5 . These results support clinical, epidemiologic, ultrastructural, and RNA evidence that suggests a novel ubiquitous respiratory virus as the cause of KD 18 . It seems logical that transmission of this agent also would be reduced by school closures, masking, and social distancing. Other potential explanations for the decline in KD cases J o u r n a l P r e -p r o o f appear to have been ruled out. In particular, there has been a lack of decrease in diagnoses of other serious medical conditions such as urinary tract infections/pyelonephritis 4, 13 , a lack of delayed diagnosis of KD 3, 4 , and lack of potential confusion with MIS-C 3, 4 (which is rare in Asia) during the period of pandemic mitigation.

It is ironic that several of the studies of KD in the COVID era initially aimed to investigate the possibility that SARS-CoV-2 could be a trigger for KD. Aggregate data do not support this premise, and in fact convincing support declining KD cases during the 

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