Clinical Features Which Distinguish Multisystem Inflammatory Syndrome from Severe Paediatric Febrile Disease in Cape Town, South Africa

Background: Multi-system inflammatory syndrome in children (MIS-C) presents with fever, shock, rash, abdominal pain and raised inflammatory markers- features common to many serious childhood illnesses. Data comparing MIS-C to mimicking diseases at presentation are needed, especially from settings where infectious diseases are common and access to specialised tests may be limited.Methods: Prospective data were collected from a cross-sectional group of children admitted with suspected MIS-C to the Red Cross Children’s Hospital in Cape Town, South Africa from May 2020 to end November 2021. Clinical features on the day of admission were compared between confirmed MIS-C (MIS-C+) and those with alternate diagnoses (MIS-C-).Findings: 60 children were MIS-C+ and 34 were MIS-C-. The presence of conjunctivitis (OR=8.12), rash (OR=8.67), tachycardia (OR=2.8) and oral mucosal changes (OR=3.75) associated with MIS-C+ while abdominal pain and hypotension did not. MIS-C+ had higher median C-reactive protein (CRP), pro-brain natriuretic protein and ferritin, and lower median lymphocyte count, platelet count and sodium tests than MIS-C-. Ferritin discriminated MISC+ well (AUC=0.86) with a 94% sensitivity and 60% specificity at a cut off >195ng/L. Sodium had an AUC of 0.72, with a 70% sensitivity and 71% specificity at a cut off of <132.5mmol/L. CRP did not distinguish MIS-C well (AUC=0.52) and although they had good AUC, platelet count and pro-BNP had cut off values in the normal range decreasing clinical utility.Interpretation: We provide evidence for the use of accessible clinical and laboratory variables for the diagnosis of MIS-C.Funding Information: This work was supported by the Crick African Network (CAN), through a fellowship to Dr Kate Webb. This fellowship funded Dr Webb's salary and study consumables. The CAN receives its funding from the UK’s Global Challenges Research Fund (MR/P028071/1), and by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC1001647), the UK Medical Research Council (FC1001647), and the Wellcome Trust 2 (FC1001647). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was also funded by a grant from the Wellcome Centre for Infectious disease research in Africa (CIDRI) through a rapid COVID grant to Prof Liesl Zühlke and Dr Kate Webb which allowed for the funding of members of the team salaries (HFT, DA, CB, TS) and study consumables, software and hardware. This research was supported by South African Medical Research Council with funds received from National Treasury.Declaration of Interests: There are no relevant conflicts of interest.Ethics Approval Statement: Children were included with parental/legal guardian consent and this study was approved by the Human Research Ethics Committee of the University of Cape Town (UCT HREC 112/2012, 599/2020).