Clinicolaboratory Profile, Treatment, Intensive Care Needs, and Outcome of Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2: A Systematic Review and Meta-analysis

Abstract

This study was aimed to summarize the current data on clinicolaboratory features, treatment, intensive care needs, and outcome of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2; PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C). Articles published in PubMed, Web of Science, Scopus, Google Scholar, and novel coronavirus disease 2019 (COVID-19) research database of World Health Organization (WHO), Centers for Disease Control and Prevention (CDC) database, and Cochrane COVID-19 study register between December 1, 2019 and July 10, 2020. Observational studies involving patients <21 years with PIMS-TS or MIS-C were reported the clinicolaboratory features, treatment, intensive care needs, and outcome. The search identified 422 citations and finally 18 studies with 833 participants that were included in this study, and pooled estimate was calculated for parameters of interest utilizing random effect model. The median age was 9 (range: 8–11) years. Fever, gastrointestinal symptoms, rash, conjunctival injection, and respiratory symptoms were common clinical features. Majority (84%) had positive SARS-CoV-2 antibody test and only one-third had positive reverse transcript polymerase chain reaction (RT-PCR). The most common laboratory abnormalities noted were elevated C-reactive protein (CRP), D-dimer, procalcitonin, brain natriuretic peptide (BNP), fibrinogen, ferritin, troponin, interleukin 6 (IL-6), lymphopenia, hypoalbuminemia, and thrombocytopenia. Cardiovascular complications included shock (65%), myocardial dysfunction (61%), myocarditis (65%), and coronary artery abnormalities (39%). Three-fourths of children required admission to pediatric intensive care unit (PICU) where they received vasoactive medications (61%) and mechanical ventilation (25%). Treatment strategies used included intravenous immunoglobulin (IVIg; 82%), steroids (54%), antiplatelet drugs (64%), and anticoagulation (51%). Mortality for patients with PIMS-TS or MIS-C was low (n = 13). In this systematic review, we highlight key clinical features, laboratory findings, therapeutic strategies, intensive care needs, and observed outcomes for patients with PIMS-TS or MIS-C. Commonly observed clinical manifestations include fever, gastrointestinal symptoms, mucocutaneous findings, cardiac dysfunction, shock, and evidence of hyperinflammation. The majority of children required PICU admission, received immunomodulatory treatment, and had good outcome with low mortality.

Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2

“…However, in the present cohort, only 9 children reported history of COVID-19 infection or contact with COVID infection in the recent past. The median age group was similar to other published reports [ 5 , 8 , 9 ] and as described in other reports, a male preponderance was found in this study as well [ 10 ]. Data from the present study add to the evidence that a large proportion of children with PIMS-TS present with gastrointestinal manifestations [ 8 , 11 – 15 ], thus highlighting that PIMS-TS should be considered in children presenting with fever and GI symptoms.…”

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

“…Using available literature and guidelines from international institutions, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to facilitate and standardize treatment of children with suspected PIMS-TS in Switzerland. The available literature is limited to retrospective and prospective studies from different part of the world ( 66 , 67 ). There are no trials comparing different treatment modalities.…”

Multisystem Inflammatory Syndrome in Children: Follow-Up of a Cohort from North India

“…1,2 It is characterized by fever, mucocutaneous features (conjunctivitis, strawberry tongue, cervical lymphadenopathy, rash, and peripheral limb edema), gastrointestinal (GI) involvement (pain abdomen, vomiting, and diarrhea), cardiovascular manifestations (myocardial dysfunction, coronary artery changes, and shock), raised inflammatory markers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], procalcitonin, ferritin, interleukin-6 [IL-6]), and evidence of an epidemiological link to SARS-CoV-2 infection in recent past (positive SARS-CoV-2 reverse transcriptase polymerase chain reaction [RT-PCR] or serology, contact with a case of SARS-CoV-2 infection, or symptoms suggestive of SARS-CoV-2 infection in the last 2-6 weeks). 1,[3][4][5] A significant proportion of children with MIS-C have cardiovascular manifestations in the form of myocardial dysfunction, shock, coronary artery dilatation and aneurysms, pericardial effusion, and rhythm disturbances. [3][4][5][6][7] With supportive treatment and immunomodulation (intravenous immunoglobulin [IVIG] and steroids), the short-term outcome is good and mortality is 0-2%.…”

“…1,[3][4][5] A significant proportion of children with MIS-C have cardiovascular manifestations in the form of myocardial dysfunction, shock, coronary artery dilatation and aneurysms, pericardial effusion, and rhythm disturbances. [3][4][5][6][7] With supportive treatment and immunomodulation (intravenous immunoglobulin [IVIG] and steroids), the short-term outcome is good and mortality is 0-2%. [3][4][5][6][7][8] Long-term treatment with glucocorticoids, aspirin, or anticoagulants in MIS-C is based on experience with other inflammatory conditions like Kawasaki disease (KD) and the exact duration of treatment is not known.…”