We present a series of 6 critically ill children with multisystem inflammatory syndrome in children. Key findings of this syndrome include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes.

BACKGROUND. Initial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology. METHODS. We prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data. RESULTS. Twenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C. CONCLUSION. Pediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.

Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.

The coronavirus disease 2019 (COVID-19) pandemic has unleashed major and substantial changes in the provision of health care, including public health policy and the practice of medicine, and in the ways most individuals live their lives. 1 Significant changes also have occurred in vaccine development, with shortening the usual 15-to 20-year timeline to one that might be as short as 1 to 1.5 years. 2 COVID-19, the acute illness due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, Hubei province, China, in December 2019, and rapidly progressed to a global pandemic. By June 27, 2020, a total of 9.76 million people had been infected with this virus and 492 000 had died. Although widespread quarantine, isolation, and social distancing measures have, to some extent, countered the spread of SARS-CoV-2 and "flattened the curve," countries now face a multitude of challenges to the "re-opening" of society. Yet, it is clear the only way to provide effective herd immunity is with a safe and effective vaccine. With this background, the US Department of Health and Human Services (HHS) launched Operation Warp Speed-a partnership between government and industry-with the goal of delivering 300 million doses of a safe and effective vaccine by January 2021. 3 This ambitious plan initially focused on 125 potential vaccine candidates, but was rapidly narrowed to 14 candidates

There are no proven safe and effective therapies for children who develop lifethreatening complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2, but has theoretical risks.We present the first report of CP in children with life-threatening coronavirus disease 2019 (COVID-19), providing data on Abbreviations: ADE, antibody-dependent enhancement; CHOP, Children's Hospital of Philadelphia; COVID-19, coronavirus disease 2019; CP, convalescent plasma; ELISA, enzyme-linked immunosorbent assay; FDA, Food and Drug Administration; MIS-C, multisystem inflammatory syndrome in children; N protein, nucleocapsid protein; RBD, receptor-binding domain; S protein, spike protein; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.