Multisystem inflammatory syndrome in children related to COVID-19: a systematic review

Abstract

An association between a novel pediatric hyperinflammatory condition and SARS-CoV-2 was recently published and termed pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome (in children) (MIS(-C)). We performed a systematic review and describe the epidemiological, clinical, and prognostic characteristics of 953 PIMS-TS/MIS(-C) cases in 68 records. Additionally, we studied the sensitivity of different case definitions that are currently applied. PIMS-TS/MIS(-C) presents at a median age of 8 years. Epidemiological enrichment for males (58.9%) and ethnic minorities (37.0% Black) is present. Apart from obesity (25.3%), comorbidities are rare. PIMS-TS/MIS(-C) is characterized by fever (99.4%), gastrointestinal (85.6%) and cardiocirculatory manifestations (79.3%), and increased inflammatory biomarkers. Nevertheless, 50.3% present respiratory symptoms as well. Over half of patients (56.3%) present with shock. The majority of the patients (73.3%) need intensive care treatment, including extracorporal membrane oxygenation (ECMO) in 3.8%. Despite severe disease, mortality is rather low (1.9%). Of the currently used case definitions, the WHO definition is preferred, as it is more precise, while encompassing most cases. Conclusion : PIMS-TS/MIS(-C) is a severe, heterogeneous disease with epidemiological enrichment for males, adolescents, and racial and ethnic minorities. However, mortality rate is low and short-term outcome favorable. Long-term follow-up of chronic complications and additional clinical research to elucidate the underlying pathogenesis is crucial. What is Known: • A novel pediatric inflammatory syndrome with multisystem involvement has been described in association with SARS-CoV-2. • To date, the scattered reporting of cases and use of different case definitions provides insufficient insight in the full clinical spectrum, epidemiological and immunological features, and prognosis. What is New: • This systematic review illustrates the heterogeneous spectrum of PIMS-TS/MIS(-C) and its epidemiological enrichment for males, adolescents, and racial and ethnic minorities. • Despite its severe presentation, overall short-term outcome is good. • The WHO MIS definition is preferred, as it is more precise, while encompassing most cases. Supplementary Information The online version contains supplementary material available at 10.1007/s00431-021-03993-5.

The innate and adaptive immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery

“…In accordance with previous reports 2,3,7,18 , both KD patients and almost all MIS-C patients had abnormally low lymphocyte and abnormally high neutrophils counts ( Figure 1E ). The absolute number of monocytes was normal for the KD patients but at the lower limit of normal for almost all MIS-C patients.…”

“…The first is an acute infection of the respiratory tract that in most cases is asymptomatic or associated with mild respiratory symptoms 1 . The second is a rare, severe hyperinflammatory syndrome called Multisystem Inflammatory Syndrome in Children (MIS-C) by the World Health Organisation or paediatric inflammatory multisystem inflammatory syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) in the UK 2–5 . Children with MIS-C present with fever, inflammation and evidence of single or multi-organ failure that manifests with cardiac dysfunction, hypotension and life-threatening shock, several weeks after the primary infection.…”

“…While MIS-C shares features with KD there are also notable differences 10,11 . For example, MIS-C patients often present with shock, cardiac dysfunction and hyperferritaemia, all of which are rarely seen in KD 2,3,7 . These differences suggest probable differences in the underpinning pathology.…”

“…The optimal treatment strategy for MIS-C is not known and a range of anti-inflammatory agents have been deployed based on KD and adult COVID protocols 2,3,7,12 . IVIG is widely used, often in combination with steroids, but a range of biological agents targeting the interleukin (IL) IL-6, IL1-β or Tumour Necrosis Factor alpha (TNF-α) pathways have also been used 2,3,10,11,13–16 . Identifying the immunological changes occurring in MIS-C patients, and how these relate to other paediatric inflammatory conditions, is important both to understand the pathogenesis of this new disease and inform rational treatment selection.…”

SARS-CoV-2 Acquisition and Immune Pathogenesis Among School-Aged Learners in Four Diverse Schools

“…Factors relating to obesity and physical activity are known to affect COVID-19 disease's severity in adults and children. [17][18][19] Overweight and obesity are associated with these lipid abnormalities, all of which tend to occur with greater incidence in low-income school aged children. 20,21 Levels of HDL seem to be particularly sensitive to physical activity.…”