The Spectrum of COVID-19 in Children in Spain (preprint)

Background: We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). Methods: : We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. Results: We enrolled 1 200 children. A total of 666 (55.5%) were hospitalized, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were: mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalized children, the proportions were: 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were MIS-C (odds ratio [OR]: 37.5,95% CI 22.7 to 57.8), moderate or severe liver disease (OR: 9,95% CI 1.6 to 47.6), chronic cardiac disease (OR: 4.8,95% CI 1.8 to 13) and asthma or recurrent wheezing (OR: 2.8,95% CI 1.3 to 5.8). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare. Conclusion: Hospitalized children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease.

PIMS-TS Innate Cell Signature and Immunophenotype, Description and Comparison with a Cohort of Healthy Children, Kawasaki Disease, Severe Viral and Bacterial Infections. (preprint)

A new clinical syndrome named as Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) has been described. This new disease is a main cause of hospital and pediatric intensive care unit (PICU). We made a prospective-retrospective observational study to describe the innate cell signature and immunophenotype of children admitted to PICU because of PIMS-TS (from March 2020 to September 2020). They were compared with previous cohorts of healthy controls and children admitted to PICU because bacterial infection, viral infection and Kawasaki disease (KD). Two hundred and forty seven children were studied: 183 healthy controls, 25 viral infections, 20 bacterial infections, 6 KD and 13 PIMS-TS. PIMT-TS showed the lowest percentage of lymphocytes and monocytes with higher relative numbers of CD4+ (p =0,000). Monocytes and neutrophils in PIMS-TS showed higher levels of CD64 expression (p = 0,000). Also, CD11a and CD11b were highly expressed compare to other severe viral or bacterial infections (p = 0,000). In conclusion, we describe and compare for the first time the innate cellular response of children with PIMS-TS with other severe forms of viral or bacterial infection and KD. These data should be further studied and may facilitate the diagnosis and management of these patients. 

Description and comparison of PIMS-TS innate cell signature and immunophenotype with a cohort of healthy children, severe viral and bacterial infections and Kawasaki Disease (preprint)

A new clinical syndrome associated to SARS-CoV-2 has been described in children. It has been named as Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). This new disease is a main cause of hospital and pediatric intensive care unit (PICU). In this work we describe the innate cell signature and immunophenotype of children admitted to PICU because of PIMS-TS. Also, we compare it with healthy controls and children admitted to PICU because bacterial infection, viral infection and Kawasaki disease. We made a prospective-retrospective observational study in a tertiary pediatric hospital. Children admitted to PICU because of PIMS-TS from March 2020 to September 2020 were consecutively included. They were compare with previous cohorts from our center. A total of 247 children were included: 183 healthy controls, 25 viral infections, 20 bacterial infections, 6 Kawasaki disease and 13 PIMS-TS. PIMT-TS showed the lowest percentage of lymphocytes and monocytes with higher relative numbers of CD4+ (p =0,000). At the same time, we describe a differential expression of CD64, CD11a and CD11b. Monocytes and neutrophils in PIMS-TS showed higher levels of CD64 expression compared to all groups (p = 0,000). Also, proteins involved in leukocyte tissue migration, like CD11a and CD11b were highly expressed compare to other severe viral or bacterial infections (p = 0,000). In PIMS-TS this increased CD11a expression could be a sign of the activation and trafficking of these leukocytes. These findings are congruent with an inflammatory process and the trend of these cells to leave the bloodstream. In conclusion, we compare for the first time the innate cellular response of children with PIMS-TS with other severe forms of viral or bacterial infection and Kawasaki disease. Our findings define a differential cell innate signature. These data should be further studied and may facilitate the diagnosis and management of these patients.