Clinical-epidemiological relation between sars-cov-2 and kawasaki disease: an integrative literature / Relação clínico-epidemiológica entre sars-cov-2 e doença de kawasaki: uma revisão integrativa da literatura

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.

RESUMO Objetivo: Analisar a literatura científica atual a fim de documentar, por meio de revisão integrativa, os principais achados que associam a doença de Kawasaki (DK) à doença do coronavírus (COVID-19). Fonte de dados: A busca ocorreu em junho de 2020, nas bases de dados: Biblioteca Virtual em Saúde (BVS), periódico da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e U.S. National Library of Medicine (PubMed). Os descritores utilizados foram [(COVID-19 OR SARS-CoV-2) AND (Kawasaki Disease)], e os critérios de inclusão estipulados compreenderam estudos publicados de janeiro de 2019 a junho de 2020, sem restrição de idioma ou localização e disponíveis online integralmente. Foram excluídos notícias, editoriais, comentários e cartas de apresentação, assim como duplicatas e artigos que não respondiam à pergunta norteadora. Síntese dos dados: Identificaram-se 97 artigos, dos quais sete compuseram esta revisão. A associação da DK com o novo coronavírus parece desencadear um quadro de vasculite grave. Diferentemente do usual, nessa síndrome inflamatória, os pacientes são mais velhos e a descendência prevalente é africana ou caribenha; as manifestações clínicas e laboratoriais também são atípicas, com predomínio de queixas abdominais e elevação exagerada de marcadores inflamatórios. Além disso, houve maior relato de complicações raras e maior resistência ao tratamento preconizado para DK. Conclusões: A COVID-19 pediátrica e sua potencial associação com uma DK grave, ainda pouco conhecida pelos profissionais da saúde, reforçam a importância da testagem de pacientes com vasculite para o novo coronavírus e a necessidade de empreender alta vigilância e preparação do sistema de saúde durante a atual pandemia.

Recomendación para la sospecha, manejo y seguimiento del compromiso cardiovascular en pacientes con Síndrome Inflamatorio Multisistémico en Pediatría asociado a COVID-19 (PIMS-TC). Declaración de Posición de la Sociedad Chilena de Pediatría (SOCHIPE) y Sociedad Chilena de Cardiología y Cirugía Cardiovascular (SOCHICAR) / Recommendation for the recognition, management and follow up of cardiovascular compromise in patients with Pediatric Multisystemic Inflammatory Syndrome associated with COVID-19 (PIMS-CT). Position statement of Chilean Scientific Societies

Desde la aparición de la pandemia por SARS-CoV-2, la población pediátrica ha sido menos afectada por la enfermedad tanto en frecuencia como en severidad. Sin embargo, desde abril de este año se han reportado casos de presentación y gravedad variables, caracterizados por fenómenos inflamato rios que afectan múltiples órganos, condición denominada Síndrome Inflamatorio Multisistémico Pediátrico (PIMS). La literatura describe frecuente compromiso cardíaco, hasta en un 80%. Este se caracteriza por injuria miocárdica con significativa elevación de biomarcadores: Troponinas séricas I/T, BNP o NT-ProBNP, unido a diversos grados de disfunción ventricular, pericarditis, valvulitis y arritmias. Además, se ha evidenciado la presencia de compromiso coronario el cual puede ocurrir hasta en un 23% de los casos, en un rango que va desde dilataciones hasta aneurismas. El seguimien to cardiológico hospitalizado y ambulatorio se ha sistematizado en base a los fenotipos clínicos de presentación: injuria miocárdica (miocarditis, valvulitis, pericarditis), shock (habitualmente de tipo "vasopléjico"), manifestaciones tipo Enfermedad de Kawasaki y aquellos casos PIMS que no cumplen con la clínica de los tres precedentes. Este último grupo es el que representa el mayor desafío en el cor to, mediano y seguimiento a largo plazo. Por esta razón se requiere un equipo multidisciplinario para su manejo. Considerando la alta frecuencia del compromiso cardíaco en el PIMS y la importancia de lograr un consenso en su manejo y seguimiento, se presentan estas recomendaciones según el estado actual del conocimiento de esta patología recientemente descrita.

Since the onset of the SARS-CoV-2 pandemic, the pediatric population has been less affected by the disease both in frequency and severity. However, since April cases of variable presentation and severity characterized by inflammatory phenomena that affect multiple organs have been reported, a condition called Multisystem Inflammatory Syndrome in Children (MIS-C). The literature has reported frequent cardiac involvement, up to 80%. This is characterized by myocardial injury with a significant increase of biomarkers such as serum troponins I and T, BNP, or NT-ProBNP coupled with varying degrees of ventricular dysfunction, pericarditis, valvulitis, and arrhythmias. Coronary compromise has also been described, which can occur in up to 23% of cases, and ranges from dila tations to aneurysms. Inpatient and outpatient cardiology follow-up has been systematized based on the clinical phenotypes such as myocardial injury (myocarditis, valvulitis, pericarditis), shock (usua lly vasoplegic), Kawasaki disease-type manifestations, and those MIS-C that do not comply with the clinic of the previous three. This last group represents the main challenge in the short-, medium- and long-term follow-up, therefore, it is necessary a multidisciplinary team for managing these patients. Considering the high frequency of cardiac compromise in MIS-C, and the importance of reaching a consensus regarding its management and follow-up, we present these recommendations according to the current state of knowledge regarding this recently described pathology.

Kawasaki and COVID-19 disease in children: a systematic review

SUMMARY OBJECTIVE To present scientific evidence based on a systematic literature review (PRISMA) evaluating the association of Kawasaki Disease (DK) and COVID-19 in children. METHODS For the selection of studies, a combination based on the Medical Subject Heading Terms (MeSH) was used. The Medline (Pubmed), LILACS, SciELO, COCHRANE, and BIREME databases were used. The search period for the articles comprised the last 10 years (2010 to 2020). RESULTS 840 articles with potential for inclusion were retrieved, one of which met the inclusion criteria and the guiding question that consisted of evaluating the association of Kawasaki disease and COVID-19 in children. CONCLUSION A significant increase in the incidence of Kawasaki-type diseases after the onset of the epidemic has been reported, suggesting an association between the COVID-19 epidemic and the high incidence of a severe form of KD. However, further studies are needed to conduct an investigation of the association between these two diseases.

RESUMO OBJETIVO Apresentar evidências científicas com base em revisão sistemática da literatura (Prisma) avaliando a associação da Doença de Kawasaki (DK) e COVID-19 em crianças. MÉTODOS Para a seleção dos estudos foi utilizada a combinação baseada no Medical Subject Heading Terms (MeSH). Foram utilizadas as bases de dados Medline (PubMed), Lilacs, SciELO, Cochrane e Bireme.O período de busca dos artigos compreendeu os últimos dez anos (2010 a 2020). RESULTADOS Foram recuperados 840 artigos com potencial de inclusão, sendo que um respondeu aos critérios de inclusão e à pergunta norteadora que consistiu em avaliar a associação da Doença de Kawasaki e COVID-19 em crianças. CONCLUSÃO Um aumento significativo na incidência de doenças do tipo Kawasaki após o início da epidemia já foi relatado, sugerindo a associação entre a epidemia de COVID-19 e a elevada incidência de uma forma grave da DK. Contudo, mais estudos são necessários para conduzir a investigação da associação entre essas duas doenças.

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

OBJECTIVES: To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C). METHODS: 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. RESULTS: 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]. CONCLUSIONS: 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.

Epstein-Barr Virus Antibodies in Kawasaki Disease

The prevalent ages at onset for Kawasaki Disease (KD) and Epstein-Barr virus (EBV) infection are known to be similar in Korea and Japan. We evaluated the correlation between EBV infection and KD. The antibodies to EBV such as anti-viral capsid antigen (VCA) IgG and IgM, anti-diffuse and restricted early antigen IgG (anti-EADR IgG), and the anti-EBV determined nuclear antigen IgG (anti-EBNA IgG) were examined in 29KD patients at five separate times sequentially during a period of one year, and also in 14 other children with a past history of KD. The results of each group were compared with those of age-matched controls. The positive rates of anti-VCA IgG and IgM at presentation in the KD patients were 41.4% (12/29) and 0% (0/29), respectively. Only one patient was found to be anti-VCA IgM-positive within two months. There were no cases of anti-VCA IgG except one, anti-EADR IgG and anti-EBNA IgG positive to negative seroconversion during the year. The children with a past history of KD showed higher anti-EBNA IgG-positive rates than the controls (p=0.04). There was no difference in the seropositive rates of the antibodies to EBV, cytomegalovirus, herpes simplex virus and herpes zoster virus. In conclusion, children with KD were noted to have normal immune responses to EBV infection. Children with a past history of KD seemed to be infected with EBV at a later age than children with no history of KD.