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An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

Our take —

This study documented a significantly elevated incidence of Kawasaki-like disease among children in a northern Italian hospital during the COVID-19 epidemic, and detected SARS-CoV-2 antibodies in 80% of these cases. Compared to the prior 5-year period, children presenting with Kawasaki-like disease during the COVID-19 epidemic were older and had more severe clinical presentations, including cardiac involvement and macrophage activation syndrome. While additional evidence is needed to establish a causal association, these findings suggest that COVID-19 may subsequently trigger a severe form of Kawasaki disease among a small percentage of children, and are consistent with early reports from other settings.

Study design

Case Series; Other

Study population and setting

The study population included all pediatric patients diagnosed with a Kawasaki-like disease (n=29, 48% male, mean age 4.9 years) at a single tertiary pediatric hospital in Bergamo, Italy from January 1, 2015 to April 20, 2020. Patients diagnosed during the COVID-19 epidemic (February 18, 2020 to April 20, 2020) were compared to those diagnosed during the preceding 5 years (January 1, 2015 to February 17, 2020). Patients presenting during the COVID-19 epidemic were tested for SARS-CoV-2 by PCR assay on nasopharyngeal and oropharyngeal swab samples; antibody response was assessed by serologic testing (IgG and IgM).

Summary of Main Findings

The incidence of Kawasaki-like disease was significantly higher during the COVID-19 epidemic. There were ten children (70% boys, mean age 7.5 years) diagnosed during the two months after the COVID-19 epidemic began, compared to 19 children (37% boys, mean age 3.5 years) diagnosed during the prior 5-year period. Among the 10 children diagnosed during the COVID-19 period, 8/10 tested positive for SARS-CoV-2 antibodies, of whom 2 also tested positive for SARS-CoV-2 via PCR; two tested negative for both. Severe disease was more prevalent during the COVID-19 period than the earlier period, including abnormal echocardiogram results (60% vs 10%), Kawasaki disease shock syndrome (50% vs. 0%), and macrophage activation syndrome (50% vs 0%); the mean age of children during the COVID-19 period was significantly higher. Children in both periods were successfully treated with intravenous immunoglobulin and aspirin, though during the COVID-19 period more children required steroid treatment (80% vs 16%); all were discharged without further complications.

Study Strengths

The cases were tested multiple times for SARS-CoV-2 infection and antibodies, demonstrating that most of the COVID-19 exposure would have been missed by PCR test alone at the time of admission for Kawasaki-like symptoms. Cases diagnosed prior to the COVID-19 epidemic were used as a comparison group.

Limitations

This study consists of a small number of cases from a single referral hospital. The incidence for the COVID-19 period appears to have been calculated using a smaller denominator of time (one month) than the seven-week period defined throughout the methods, inflating the incidence and incidence rate ratio reported, though the inference of a significant increase in cases during the COVID-19 epidemic stands nevertheless.

Value added

This was among the first published case series of Kawasaki-like disease in children during the COVID-19 epidemic.