Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet published online May 6, 2020 https://doi.org/10.1016/S0140-6736(20)31094-1

Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2epidemic: an observational cohort study. Lancet published online May 13, 2020 https://doi.org/10.1016/S0140-6736(20)31103-X

Sandra Arnold, MD, MSc University of Tennessee Health Science Center, Le Bonheur Children’s Hospital

Reviewers: Josh Wolf, PhD, MBBS St Jude Children’s Research Hospital
David Bernstein: David Bernstein, University of Cincinnati, Cincinnati Children’s Hospital

Background

The burden of COVID-19 in children has been small compared with adults; children under 18 years of age comprising <2% of all cases. Recently, a syndrome resembling Kawasaki Disease (KD) has been described in children with current or recent infection with SARS-CoV-2. Since then, additional cases have been identified, including 15 patients reported to the New York City Department of Health. As a result, the CDC recently distributed a health advisory through the Health Alert Network for Healthcare providers to report similar cases to their local, state, or territorial health department. These two articles, published online in the past two weeks, describe clusters of cases of a hyperinflammatory syndrome (Kawasaki-like) in South East England and the Lombardy region of Italy.

Methods and results

The British and Italian case series comprise 8 and 10 children, respectively, presenting with fever and a Kawasaki Disease (KD)-like syndrome. In the British series, they present descriptions of each patient including demographics, clinical presentation, imaging and lab results, treatment, and outcomes. In the Italian series, they present similar clinical details; however, they present these within a KD framework, reporting IVIG failure (by Kobayashi score), and the presence of macrophage activation syndrome (MAS) or Kawasaki Disease Shock Syndrome (KDSS). They also present data on the preceding 5 years of cases of KD for comparison of case characteristics and incidence of disease.

Most patients had evidence of either current (RT-PCR positive – 4/18 children overall) or past (antibody positive 8/10 in Italian series) SARS-CoV-2 infection or close exposure to a confirmed case (8/18 overall.) The presenting findings were similar among the two cohorts including persistent fever, and varying combinations of rash, non-purulent conjunctivitis, peripheral edema, oropharyngeal erythema, and cervical lymphadenopathy (one patient). Additional findings included diarrhea, abdominal pain, and meningism. All children in the British series required vasopressors for shock with myocardial dysfunction; 2 children had dilated or echo-bright coronaries. In the Italian series, 5/10 were diagnosed as having Kawasaki Disease Shock Syndrome with 6/10 having cardiac abnormalities of myocardial dysfunction, dilated coronaries, or mitral valve regurgitation; 5/9 patients met criteria for MAS. All patients received IVIG, but 14 failed to respond; all 14 received steroids and one also received infliximab. In the Italian series, the diagnosis of KD was much more common (OR 184) during the COVID period than the preceding 5 years. Patients diagnosed with KD during the COVID period were older, and more likely to have KDSS and MAS (with associated thrombocytopenia and hyperferritinemia) compared to previous cases. All but one patient, in the British series (required ECMO) survived.

Comment

Although the authors of these articles have given different names to this syndrome, these reports appear to be describing the same disease, what we are now calling Multisystem Inflammatory Syndrome in children (MIS-C; in the US), or Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS; in Europe). MIS-C may be the pediatric version of the cytokine storm occurring in adults during the second week of infection without the severe respiratory illness from which adults are suffering. Other Coronaviruses have been suspected of triggering KD in the past1,2 and might represent one trigger of hyperinflammation among many. In these studies, most patients responded to IVIG and steroids, but some required additional therapies. Beyond steroids, many have used infliximab for KD, as in the British series; however, toculizumab and anakinra have been use for COVID inflammatory syndrome in adults. Better understanding of the pathogenesis of this syndrome should lead to improved therapeutic choices. Awareness of this serious though rare complication has raised our concern for pediatric Covid-19 infections and shows that our children are not immune from the ill-effects of this pandemic.

  1. Esper F, Shapiro ED, Weibel C, Ferguson D, Landry ML, Kahn JS. Association between a novel human coronavirus and Kawasaki disease. J Infect Dis 2005; 191: 499–502.
  2. Shirato K, Imada Y, Kawase M, Nakagaki K, Matsuyama S, Taguchi F. Possible involvement of infection with human coronavirus 229E, but not NL63, in Kawasaki disease. J Med Virol 2014; 86: 2146–53.