Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome

Maria Fernanda Badue Pereira, Nadia Litvinov, Sylvia Costa Lima Farhat, Adriana Pasmanik Eisencraft, Maria Augusta Bento Cicaroni Gibelli, Werther Brunow de Carvalho, Vinicius Rodrigues Fernandes, Thais de Toledo Fink, Juliana Valéria de Souza Framil, Karine Vusberg Galleti, Alice Lima Fante, Maria Fernanda Mota Fonseca, Andreia Watanabe, Camila Sanson Yoshino de Paula, Giovanna Gavros Palandri, Gabriela Nunes Leal, Maria de Fatima Rodrigues Diniz, João Renato Rebello Pinho, Clovis Artur Silva, Heloisa Helena de Sousa Marques, Pediatric COVID HC-FMUSP Study Group, Alfio Rossi, Artur Figueiredo Delgado, Anarella Penha Meirelles de Andrade, Claudio Schvartsman, Ester Cerdeira Sabino, Mussya Cisotto Rocha, Kelly Aparecida Kanunfre, Thelma Suely Okay, Magda Maria Sales Carneiro-Sampaio, Patricia Palmeira Daenekas Jorge

To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C). This cross-sectional study included 471 samples collected from 371 patients (age<18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control. MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034); pediatric SARS (67% vs. 13%, p=0.008); hypoxemia (83% vs. 23%, p=0.006); and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels >50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels >1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p<0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p<0.001), vasoactive agent use (83% vs. 3%, p<0.001), shock (83% vs. 5%, p<0.001), cardiac abnormalities (100% vs. 2%, p<0.001), and death (67% vs. 3%, p<0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p<0.001), aspirin therapy (50% vs. 0%, p<0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98; 95%CI (95% confidence interval)=1.20-100.86; p=0.034] and hypoxemia [OR=16.85; 95%CI=1.34-211.80; p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00; 95%CI=6.39-526.79; p<0.0001]. Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia.