An association between a novel pediatric hyperinflammatory condition and SARS-CoV-2 was recently published and termed pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome (in children) (MIS(-C)). We performed a systematic review and describe the epidemiological, clinical, and prognostic characteristics of 953 PIMS-TS/MIS(-C) cases in 68 records. Additionally, we studied the sensitivity of different case definitions that are currently applied. PIMS-TS/MIS(-C) presents at a median age of 8 years. Epidemiological enrichment for males (58.9%) and ethnic minorities (37.0% Black) is present. Apart from obesity (25.3%), comorbidities are rare. PIMS-TS/MIS(-C) is characterized by fever (99.4%), gastrointestinal (85.6%) and cardiocirculatory manifestations (79.3%), and increased inflammatory biomarkers. Nevertheless, 50.3% present respiratory symptoms as well. Over half of patients (56.3%) present with shock. The majority of the patients (73.3%) need intensive care treatment, including extracorporal membrane oxygenation (ECMO) in 3.8%. Despite severe disease, mortality is rather low (1.9%). Of the currently used case definitions, the WHO definition is preferred, as it is more precise, while encompassing most cases.Conclusion: PIMS-TS/MIS(-C) is a severe, heterogeneous disease with epidemiological enrichment for males, adolescents, and racial and ethnic minorities. However, mortality rate is low and short-term outcome favorable. Long-term follow-up of chronic complications and additional clinical research to elucidate the underlying pathogenesis is crucial. What is Known: • A novel pediatric inflammatory syndrome with multisystem involvement has been described in association with SARS-CoV-2. • To date, the scattered reporting of cases and use of different case definitions provides insufficient insight in the full clinical spectrum, epidemiological and immunological features, and prognosis. What is New: • This systematic review illustrates the heterogeneous spectrum of PIMS-TS/MIS(-C) and its epidemiological enrichment for males, adolescents, and racial and ethnic minorities. • Despite its severe presentation, overall short-term outcome is good. • The WHO MIS definition is preferred, as it is more precise, while encompassing most cases.
BACKGROUND: Kawasaki-like disease (KLD) and multisystem inflammatory syndrome in children (MIS-C) are considered as challenges for pediatric patients under the age of 18 infected with coronavirus disease 2019 (COVID-19).
METHODS: A systematic search was performed on July 2, 2020, and updated on December 1, 2020, to identify studies on KLD/MIS-C associated with COVID-19. The databases of Scopus, PubMed, Web of Science, Embase, and Scholar were searched. The hospitalized children with a presentation of Kawasaki disease (KD), KLD, MIS-C, or inflammatory shock syndromes were included.
RESULTS: A total number of 133 children in 45 studies were reviewed. Seventy-four (55.6%) cases had been admitted to pediatric intensive care units (PICUs). As well, 49 (36.8%) patients had required respiratory supports, of whom 31 (23.3%) cases had been required mechanical ventilation/intubation, 18 (13.5%) cases had required other oxygen therapies. In total, 79 (59.4 %) cases had been discharged from hospitals, 3 (2.2%) had been readmitted, 9 (6.7%) had been hospitalized at the time of the study, and 9 (6.7%) patients had expired due to the severe heart failure, shock, brain infarction. The outcomes had not been reported in other patients.
CONCLUSION: Approximately two-thirds of the children with KLD associated with COVID-19 had been admitted to PICUs, around one-fourth of them had required mechanical ventilation/intubation, and even some of them had been required readmissions. Therefore, physicians are strongly recommended to monitor children presented with the characteristics of KD during the pandemic as they can be the dominant manifestations in children with COVID-19. This article is protected by copyright. All rights reserved.
OBJECTIVES: The aim of this narrative review was to collect all findings from literature about oral signs and symptoms of COVID-19, in order to draw a picture of oral involvement of this challenging viral infection, to help oral professionals in a better triage and early diagnosis.
MATERIAL AND METHODS: The search for international literature was made including articles written in English and reporting about oral manifestations in patients with a diagnosis of COVID-19. The publication time was limited to 2019 and 2020, up to May 20, 2020. A narrative review was performed.
RESULTS: Twenty-three articles were included in this review. Three different oral manifestations were found: taste alteration, oral blister and ulcers, and oral lesions associated with Kawasaki-like diseases (erythema, bleeding of lips, "strawberry tongue"). The higher expression of Angiotensin-converting enzyme 2 in the oral cavity and in endothelial cells might be responsible for oral manifestation and the major report of signs and symptoms in the occidental countries.
CONCLUSIONS: Detecting oral signs and symptoms of COVID-19 could be useful to perform a better preliminary triage in dental setting, and in recognizing possible early manifestations of the disease. However, considering the outbreak of COVID-19 and the consequent difficulty of undergoing oral examinations, the oral manifestations might be misdiagnosed; then, we would encourage oral professionals to perform other studies about this topic.
Multisystem Inflammatory Syndrome in Children (MIS-C) is a new phenomenon reported worldwide with temporal association with Covid-19. The objective of this paper is to evaluate reported cases in children and adolescents. From 1726 papers, 35 documented papers related to MIS-C cases identified 783 individual cases of MIS-C between March-June 2020; with 55% being male (n = 435) and a median age of 8.6 years (IQR, 7-10 years; range 3 months-20 years). Patients with MIS-C were noted to have a high frequency of gastrointestinal symptoms (71%) including abdominal pain (34%) and diarrhea (27%). Cough and respiratory distress were reported in 4.5% and 9.6% cases respectively. Blood parameters showed neutrophilia in 345/418 (83%) of cases and a high CRP in 587/626 (94%). 362/619 (59%) cases were SARS-CoV-2 infection positive (serology or PCR) however only 41% demonstrated pulmonary changes on chest imaging. Severity of illness was high with 68% cases requiring intensive care admission; 63% requiring inotropic support; 244/783 (28%) cases needing some form of respiratory support (138 mechanically ventilated), and 31 required extra-corporeal membrane oxygenation. Treatment strategies included intravenous immunoglobulin (63%) and intravenous steroids (44%). 29 cases received Infliximab, 47 received IL1 (interleukin) receptor antagonist, and 47 received IL6-receptor antagonist. 12/783 (1.5%) children died. In summary, a higher incidence of gastrointestinal symptoms were noted in MIS-C. In contrast to acute Covid-19 infection in children, MIS-C appears to be a condition of higher severity with 68% of cases having required critical care support.
ABSTRACT Objective: To analyze the current scientific literature to document, in an integrative review, the main findings that correlate Kawasaki disease (KD) to COVID-19. Data sources: The search was carried out in June 2020 in the following databases: Biblioteca Virtual em Saúde (BVS), periódico da CAPES and U.S National Library of Medicine (PubMed). The combination of descriptors used was [(COVID-19 OR SARS-CoV-2) AND (Kawasaki disease)], and the inclusion criteria stipulated were studies published from January 2019 to June 2020, without restriction of language or location, and available online in full. News, editorials, comments, and letters, as well as duplicates and articles that did not answer the guiding question were excluded. Data synthesis: A total of 97 articles were identified, of which seven comprised this review. The association of KD to the new coronavirus appears to trigger a severe clinical condition of vasculitis. Different from the usual, in this inflammatory syndrome, patients are older, and prevalence is higher in children from African or Caribbean ancestry; clinical and laboratory manifestations are also atypical, with a predominance of abdominal complaints and exaggerated elevation of inflammatory markers. In addition, there was a greater report of rare complications and greater resistance to the recommended treatment for KD. Conclusions: Pediatric COVID-19 and its potential association to severe KD, still unfamiliar to health professionals, reinforces the importance of testing patients with vasculitis for the new coronavirus and the need to wage high surveillance and preparation of the health system during the current pandemic.
Children with Coronavirus disease 2019 (COVID-19) are being reported to have manifestations of hyperinflammatory states and/or Kawasaki-like disease. In this study, we investigated children with typical and atypical Kawasaki disease (KD) likely to be associated with COVID-19. We have reported four children with Kawasaki-like disease probably associated with COVID-19. The clinical features were consistent with incomplete KD in three patients. SARS-CoV-2 RT-PCR was positive in one and the serology was positive in one patient with negative RT-PCR. Corticosteroids, anakinra, intravenous immunoglobulin (IVIG), and acetylsalicylic acid were used in the treatment. Three patients recovered after the treatment while one patient died. The literature review revealed 36 articles describing 320 children with Kawasaki-like disease associated with COVID-19. SARS-CoV-2 RT-PCR was negative in 120 (65.5%) of 183 patients while the serology was positive in 130 (83.8%) of 155 patients. The therapeutic options have included IVIG, acetylsalicylic acid, tocilizumab, anakinra, enoxaparin, and methylprednisolone. Pediatric COVID-19 cases may present with atypical/incomplete Kawasaki-like disease. Thus, pediatricians need to be aware of such atypical presentations resembling KD for early diagnosis of COVID-19.
BACKGROUND: Different proportions of musculoskeletal or autoimmune manifestations associated with COVID-19 have been reported in literature. We performed a systematic review and meta-analysis with the aim of assessing the prevalence of rheumatic manifestations in patients affected by COVID-19, as initial symptom or during disease course.
METHODS: A database search was run on May 18th, 2020, using two distinct strategies. We were interested in the percentage of symptoms of potential rheumatologic interest observed in large population studies of COVID-19 cases, and in identifying uncommon autoimmune disorders described in patients with COVID-19. For manifestations individually reported, a meta-analysis was performed taking into consideration the proportion of COVID-19 patients presenting the symptom.
RESULTS: Eighty eight original articles were included in the systematic review and 51 in the meta-analysis. We found pooled estimates of 19% for muscle pain and 32% for fatigue as initial symptom of COVID-19 presentation and, respectively, of 16 and 36% during the disease course. Only one article discussed arthralgia as unique symptom. Additionally, we found that vasculitis, chilblains, presence of autoantibodies commonly found in patients with rheumatic diseases, or autoimmune haematological and neurological disorders have all been reported in patients with COVID-19.
CONCLUSIONS: In conclusion, our review and meta-analysis emphasises that symptoms potentially leading to rheumatologic referral are common in patients with COVID-19. Therefore, COVID-19 is a new differential diagnosis to bear in mind when evaluating patients with musculoskeletal symptoms and rheumatologists might play a crucial role in identifying COVID-19 cases in early phases of the illness.
ImportanceIn April 2020, multiple reports of an association between a hyperinflammatory, Kawasaki-like condition and SARS-CoV-2 were published and termed as pediatric inflammatory multisystem syndrome (PIMS) or multisystem inflammatory syndrome (MIS). A thorough characterization of this syndrome (demographics, presentation, diagnosis, and outcome) is currently lacking.
ObjectiveWe aimed to perform a systematic review of published cases of this novel multisystem inflammatory syndrome in children associated with COVID-19.
Evidence reviewA literature search of Pubmed, Embase, BioRxiv, MedRxiv and COVID-19 specific research repositories (Cochrane COVID-19 Study Register and the World Health Organization (WHO) COVID-19 Global Research Database) was conducted from December 30th, 2019 to June 30th, 2020. Publications describing inflammatory syndromes associated with COVID-19 were included. Of 333 unique publications, 229 records were excluded based on title and abstract. After screening the full text, 40 observational studies and case reports were included, comprising 687 cases (published between May 9th, 2020 and June 30th, 2020).
FindingsIn contrast to classic Kawasaki disease, epidemiological enrichment for adolescents (median age 9 [6.0-12.3]) and ethnic minorities (35.8% black and 24.5% Hispanic/Latino) was observed. There was a male predominance (59.1%). Apart from obesity (24.4%), pre-existing conditions were infrequent. The majority suffered from gastrointestinal (87.2%) and cardiocirculatory (79.2%) manifestations. Respiratory symptoms (51.2%) were less frequent. Over half of patients (56.3%) presented with hemodynamic shock, and critical care interventions were often necessary (inotropics (56.5%), mechanical ventilation (22.9%), non-invasive ventilation (30.6%), extracorporal membrane oxygenation (ECMO;4.5%)). Anti-SARS-CoV-2 IgG and RT-PCR were positive in respectively 69.4% and 36.7%. Eleven deaths were reported (1.6%). The RCPCH case definition proved to be most comprehensive comprising all single cases. In contrast, WHO and CDC MIS definitions are more stringent, with the CDC case definition often missing severe cases requiring intensive care (n = 33 out of 95 cases).
Conclusions and RelevanceThis novel pediatric multisystem hyperinflammatory condition, associated with COVID-19, is characterized by a severe and heterogeneous disease spectrum. Despite frequent intensive care interventions, mortality rate was low and short-term outcome favorable. Long-term follow-up of possible chronic complications and additional clinical research, to elucidate the underlying immunological pathogenesis and possible genetic predisposition is crucial.
Key pointsO_ST_ABSQuestionC_ST_ABSHow is the novel pediatric multisystem inflammatory condition associated with coronavirus disease 2019 (COVID-19) characterized?
FindingsThis systematic review of 40 studies, comprising 687 cases, represents the heterogeneous spectrum of this novel pediatric disease related to COVID-19, including contrasting features with previously-described hyperinflammatory conditions. Adolescents and particular racial/ethnic minorities are affected more. Gastrointestinal and cardiocirculatory manifestations are often found, along with critical care interventions. Nevertheless, only 11 deaths are reported.
MeaningThis novel condition has variable severity but good short-term outcome. Uniform case definitions are required to guide future (preferably controlled) research on epidemiological clustering, immunopathology, and long-term prognosis.
BACKGROUND: Limited pediatric cases with coronavirus disease 2019 (COVID-19) have been reported and the clinical profiles regarding COVID-19 in children remain obscure. Our aim was to investigate the clinical characteristics of COVID-19 in children.
METHODS: PUBMED and EMBASE were searched through June 20, 2020, for case reports and case series reporting pediatric COVID-19 cases. Epidemiological, clinical, laboratory, and radiological data were collected and analyzed to compare by age.
RESULTS: Our search identified 46 eligible case reports and case series. A total of 114 pediatric cases with COVID-19 were included. The main clinical features were mild symptoms including fever (64%), cough (35%), and rhinorrhea (16%), or no symptoms (15%). Ground-like opacities were common radiological findings (54%). The main laboratory findings were lymphopenia (33%) and elevated D-dimer (52%) and C-reactive protein (40%) levels. We identified 17 patients (15%) with multisystem inflammatory syndrome in children (MIS-C) manifesting with symptoms overlapping with, but distinct from, Kawasaki disease, including gastrointestinal symptoms, left ventricular systolic dysfunction, shock, and marked elevated inflammatory biomarkers. Twelve percent of the patients including 65% of the MIS-C cases required intensive care because of hypotension. No deaths were reported.
CONCLUSION: This systematic review found that children with COVID-19 are generally less severe or asymptomatic. However, infants might be seriously ill and older children might develop MIS-C with severe illness. Early detection of children with mild symptoms or an asymptomatic state and early diagnosis of MIS-C are mandatory for the management of COVID-19 and the prevention of transmission and a severe inflammatory state. This article is protected by copyright. All rights reserved.
An association between a novel pediatric hyperinflammatory condition and SARS-CoV-2 was recently published and termed pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome (in children) (MIS(-C)). We performed a systematic review and describe the epidemiological, clinical, and prognostic characteristics of 953 PIMS-TS/MIS(-C) cases in 68 records. Additionally, we studied the sensitivity of different case definitions that are currently applied. PIMS-TS/MIS(-C) presents at a median age of 8 years. Epidemiological enrichment for males (58.9%) and ethnic minorities (37.0% Black) is present. Apart from obesity (25.3%), comorbidities are rare. PIMS-TS/MIS(-C) is characterized by fever (99.4%), gastrointestinal (85.6%) and cardiocirculatory manifestations (79.3%), and increased inflammatory biomarkers. Nevertheless, 50.3% present respiratory symptoms as well. Over half of patients (56.3%) present with shock. The majority of the patients (73.3%) need intensive care treatment, including extracorporal membrane oxygenation (ECMO) in 3.8%. Despite severe disease, mortality is rather low (1.9%). Of the currently used case definitions, the WHO definition is preferred, as it is more precise, while encompassing most cases.Conclusion: PIMS-TS/MIS(-C) is a severe, heterogeneous disease with epidemiological enrichment for males, adolescents, and racial and ethnic minorities. However, mortality rate is low and short-term outcome favorable. Long-term follow-up of chronic complications and additional clinical research to elucidate the underlying pathogenesis is crucial. What is Known: • A novel pediatric inflammatory syndrome with multisystem involvement has been described in association with SARS-CoV-2. • To date, the scattered reporting of cases and use of different case definitions provides insufficient insight in the full clinical spectrum, epidemiological and immunological features, and prognosis. What is New: • This systematic review illustrates the heterogeneous spectrum of PIMS-TS/MIS(-C) and its epidemiological enrichment for males, adolescents, and racial and ethnic minorities. • Despite its severe presentation, overall short-term outcome is good. • The WHO MIS definition is preferred, as it is more precise, while encompassing most cases.
