Case Report: Case Series of Children With Multisystem Inflammatory Syndrome Following SARS-CoV-2 Infection in Switzerland

Abstract

Since the beginning of the severe SARS-CoV-2 pandemic, an increasing number of countries reported cases of a systemic hyperinflammatory condition defined as multi-system inflammatory syndrome in children (MIS-C). The clinical features of MIS-C can be an overlap of Kawasaki Disease (KD), Toxic Shock Syndrome (TSS), Macrophage Activation Syndrome (MAS), or have often an acute abdominal presentation. Intravenous immunoglobulin (IVIG) is recommended as first line therapy in KD. Recent evidence suggests intravenous immunoglobulins (IVIG) resistance in some cases of SARS-CoV-2 related MIS-C, thereby questioning the benefit of immunomodulators such as IL-1 or IL-6 blocking agents. We report on a cohort of 6 Swiss children with SARS-CoV2 related MIS-C presenting with clinical features compatible with Incomplete KD and Toxic Shock Syndrome associated to a cytokine storm. Serum cytokine profile investigations showed increased IL1RA levels (8 to 22-fold) in 5 of the 6 patients (one patient had not been tested), whereas, IL-6 serum levels were increased only in the 3 patients of the 6 who were tested. With exception of one patient who had only benefited by Anakinra, all patients received at least one dose of IVIG. One patient has only received Anakinra with favorable evolution, and three patients had also a steroid treatment. In addition to all this anti-inflammatory medication two patients have also received one dose of anti-IL6. In conclusion, our case series reports on clinical and laboratory findings of most of Swiss cases with MIS-C and suggests the use of Anakinra as an alternative to steroids in these children, most of whom presented with high IL-1RA levels.

Case Series of Multisystem Inflammatory Syndrome (MIS-C) in Children during the SARS-CoV-2 Pandemic in Latvia

“…In our study MIS-C cases occurred two to six weeks after acute illness or contact with a COVID-19 positive person after the COVID-19 infection peaked in Latvia. This was similar to previous studies reported in Europe [ 10 , 11 , 12 , 13 ]. We observed a tendency for children to be hospitalized at a relatively late stage in their illness, as observed in Santiago [ 14 ].…”

Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland

“…A number of limitations need to be considered. First, while the expert group includes specialists from the relevant disciplines, numbers of children with PIMS-TS during the first wave of COVID-19 in Switzerland were low, limiting experience in managing the disease ( 14 , 45 ). However, the group assessed institutional pathways from other health care systems and consulted world leading experts in the field during the process.…”

“…Despite its limited licensed indication, anakinra is increasingly chosen for off-label use in PIMS-TS patients (4,(45)(46)(47). Anakinra has been approved for subcutaneous administration, however continuous intravenous administration has been reported (48).…”

Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids

“…To our knowledge, this is the first report describing the use of a blocker of IL-1 receptor, anakinra, in MIS-A, with a very good outcome. Anakinra has been largely used and studied in the treatment of COVID-19 and is part of several clinical trials for this disease [ 13 , 14 , 15 ]; furthermore, its use has been described in a series of MIS-C cases, with good results [ 16 ]. Interestingly, successful use of anakinra in two cases of MIS-C refractive to IVIG and systemic glucocorticoids has also recently been described [ 17 ].…”