Background: Recently, severe manifestations associated with coronavirus disease 2019 (COVID-19) called multisystem inflammatory syndrome in children (MIS-C) have been recognized. Analysis of studies for this novel syndrome is needed for a better understanding of effective management among affected children. Methods: An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020. Observational cross-sectional, cohort, case series, and case reports were included. Results: A total of 328 articles were identified. Sixteen studies with 655 participants (3 months–20 years of age) were included in the final analysis. Most of the children in reported studies presented with fever, gastrointestinal symptoms, and Kawasaki Disease-like symptoms. Sixty-eight percent of the patients required critical care; 40% needed inotropes; 34% received anticoagulation; and 15% required mechanical ventilation. More than two-thirds of the patients received intravenous immunoglobulin and 49% received corticosteroids. Remdesivir and convalescent plasma were the least commonly utilized therapies. Left ventricular dysfunction was reported in 32% of patients. Among patients presenting with KD-like symptoms, 23% developed coronary abnormalities and 26% had circulatory shock. The majority recovered; 11 (1.7%) children died. Conclusions: This systematic review delineates and summarizes clinical features, management, and outcomes of MIS-C associated with SARS-CoV-2 infection. Although most children required intensive care and immunomodulatory therapies, favorable outcomes were reported in the majority with low-mortality rates.

Background Emerging studies indicate that some COVID-19 patients suffer from persistent symptoms including breathlessness and chronic fatigue; however the long-term immune response in these patients presently remains ill-defined. Methods Here we describe the phenotypic and functional characteristics of B and T cells in hospitalised COVID-19 patients during acute disease and at 3-6 months of convalescence. Findings We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic programme evident in CD8 + T cells as well as elevated production of type-1 cytokines and IL-17. Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to toll-like receptor activation, skewed towards a pro-inflammatory phenotype. Whereas the frequency of IL-6 + B cells was restored in convalescent patients irrespective of clinical outcome, recovery of IL-10 + B cells was associated with resolution of lung pathology. Conclusions Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with one subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalisation with COVID-19 could impact longer term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients. Funding Provided by UKRI, Lister Institute of Preventative Medicine, The Wellcome Trust, The Kennedy Trust for Rheumatology Research and 3M Global Giving.

This study examines the relative efficiency of the R&D process across a group of 22 developed and developing countries using Data Envelopment Analysis (DEA). The R&D technical efficiency is examined using a model with patents granted to residents as an output and gross domestic expenditure on R&D and the number of researchers as inputs. Under CRS (Constant Returns to Scale), Japan, the Republic of Korea and China are found to be efficient, whereas under the VRS (Variable Returns to Scale) framework, Japan, the Republic of Korea, China, India, Slovenia and Hungary are found to be efficient. The emergence of some of the developing nations on the efficiency frontier indicates that these nations can also serve as benchmarks for their efficient use of R&D resources. The inefficiency in the R&D resource usage highlighted by this study indicates the underlying potential that can be tapped for the development and growth of nations.

With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished preprints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries (p < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C. Keywords COVID-19. Hemophagocytic lympho-histiocytosis. Kawasaki disease. SARS-CoV-2. Macrophage activation syndrome. Multisystem inflammatory syndrome in children (MIS-C). Toxic shock syndrome This article is part of the Topical Collection on Covid-19