COVID-19 and Hyperinflammatory Syndrome in Children: Kawasaki Disease with Macrophage Activation Syndrome in Disguise?

Abstract

A hyperinflammatory syndrome has been described in times of COVID-19 in children. In the setting of uncertainty due to a new virus, the so-called hyperinflammatory syndrome has been coined as a novel entity by some and is being referred to as pediatric inflammatory multisystem syndrome (PIMS). However, the characteristics of the syndrome resemble those of Kawasaki disease (KD), an inflammatory syndrome in children that can lead to coronary artery abnormalities due to a subsequent vasculitis. Furthermore, Kawasaki disease may occasionally trigger macrophage activation syndrome (MAS), a condition in which there is uncontrolled activation and proliferation of macrophages and other cell types, and could lead to multiorgan system dysfunction. This study provides a review of the data regarding COVID-19, Kawasaki disease, and macrophage activation syndrome to demonstrate the similarities and differences between the inflammatory syndrome seen with COVID-19 and KD. In addition, a framework for diagnosis and evaluation is provided that focuses on the pathway previously established for KD and MAS. The authors believe that based on current knowledge, KD treatment delays may carry deleterious effects in the near future for children with COVID-19-related Kawasaki disease.

Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of COVID-19 death

“…Our data showing a great accumulation of CD163 positive myeloid cells in the lung consolidations and hilar lymph nodes in parallel with CD8 T, NK and B cell depletions in these tissues are in line with previous suggestions of M2 polarized macrophage induced effector T cell depletion 30 , 31 . The elevated level of CD163 with the subsequent shedding is an emerging marker of virus infection associated macrophage activation syndrome with dismal outcome 32 , 33 .…”

Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: clinical presentations, diagnosis, and treatment

“…However, MAS is more frequently seen in children with MIS-C, with an incidence of 3-50%. MAS can lead to multi-organ system dysfunction and is associated with high morbidity and mortality [2,13,14]. Respiratory distress is rarely seen in KD patients, whereas, in MIS-C, 12-46% of the patients receive oxygen or mechanical ventilation [2][3][4][5][6][7][8][9][10].…”

“…No reports of MIS-C have been observed in China and Singapore. This syndrome has clinical manifestations similar to Kawasaki disease (KD) and Kawasaki disease shock syndrome (KDSS) [ 12 ], or KD with macrophage activation syndrome (MAS) [ 13 ]. Patients may present with high fever, lymphadenopathy, pleomorphic rash, conjunctivitis, mucosal pathology changes, and coronary artery dilation.…”

“…The release of excessive pro-inflammatory cytokines occurs in both MIS-C and KD cases, and the “cytokine storm” is found in adults with SARS-CoV-2, too. Frequently, about 7–80% of biological drugs are added as a supplemental therapy for MIS-C patients, especially for those with clinical features consistent with those of the MAS [ 2 – 10 , 13 , 14 , 23 , 35 ] (Table 1 ).…”

Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of Covid-19 death

“…Our data showing a great accumulation of CD163 positive myeloid cells in the lung consolidations and hilar lymph nodes in parallel with CD8 T, NK and B cell depletions in these tissues are in line with previous suggestions of M2 polarized macrophage induced effector T cell depletion (Liu et al, 2020)(Schulte-Schrepping et al, 2020). The elevated level of CD163 with the subsequent shedding is an emerging marker of virus infection associated macrophage activation syndrome with dismal outcome (McElroy et al, 2019) (Loomba et al, 2020).…”