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Background

In April 2020 some children presented with signs of multisystem inflammation with clinical signs overlapping with Kawasaki disease (KD), most of them requiring admission to the pediatric intensive care unit (PICU).

Methods

Medical data of KD patients from 1st January 2018 until 30th May 2020 was collected from the KAWA-RACE study group. We compared the KD cases diagnosed during the COVID-19 period (1st March-30th May 2020) that were either SARS-CoV-2 confirmed (CoV+) or negative (CoV-) to those from the same period during 2018 and 2019 (PreCoV).

Results

One hundred and twenty-four cases were collected. There was a significant increase in cases and PICU admissions in 2020 (P-trend = 0.001 and 0.0004 respectively).

We found that 56% of KD patients presenting during the pandemic had confirmed SARS-COV-2 infection. Twenty-three (88.5%) of the CoV+ patients fulfilled both PIMS-TC and MIS-C criteria; from CoV- cohort, 45% of patients fulfilled the criteria for MIS-C, and 40% for PIMS-TS.

CoV+ patients were significantly older (7.5 vs 2.5yr), mainly non-Caucasian (64 vs 29%), had incomplete KD presentation (73 vs 32%), lower leucocyte (9.5 vs 15.5x109) and platelet count (174 vs 423x109/L), higher inflammatory markers (C-Reactive Protein 18.5 vs 10.9 mg/dl) and terminal segment of the natriuretic atrial peptide (4766 vs 505 pg/ml), less aneurysm development (3.8 vs 11.1%) and more myocardial dysfunction (30.8 vs 1.6%) than PreCoV patients. Respiratory symptoms were not increased during the COVID-19 period (Table 1).

Conclusions

The KD CoV+ patients mostly meet PIMS-TC and MIS-C criteria. Around half of the KD patients presenting during the pandemic had confirmed SARS-COV-2 infection. Whether this is a novel entity or the same disease on different ends of the spectrum is yet to be clarified.

Clinical Trial Registration

Clinical trial registration: N/A

Background

COVID-19 manifests distinctively across different age groups. Robust, population-based data from active surveillance is necessary to understand and optimally handle this new infection in children. This prosopective nationwide study summarises key data on infants, children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in Switzerland.

Methods

Data were collected through the Swiss Paediatric Surveillance Unit (SPSU) from children with laboratory-confirmed SARS-CoV-2 infection presenting to 33 paediatric hospitals in Switzerland from March to October 2020 (during both epidemic peaks). All children aged less than 18 years old cared for at a Swiss hospital (ambulatory and hospitalised) were included.

Results

In total, 678 children were included. The median age was 12.2 (IQR 5.0-14.6) years, 316 (47%) were female and 106 (16%) had comorbidities. 126 (19%) children were hospitalised, 16 (2%) admitted to ICU. In children aged < 2 years, fever, cough and rhinorrhoea were the most common symptoms and in adolescents fever, cough and headache. Hospitalised children more often presented with fever (96 [76%] vs 209 [38%], p-value<0.01) and rash (16 [1%] vs 6 [1%], p-value<0.01). Anosmia/dysgeusia was more prevalent in ambulatory children (73 [13.3%] vs 3 [2.4%], p-value<0.01). 15 (2%) were treated with corticosteroids, nine (1%) with immunoglobulins and nine (1%) with inotropes. 28 (4%) children experienced complications, cardiovascular complications were the most frequnent (11 [2%]). A positive household-member was identified in 45% and community-acquired infection in 13%.

Conclusions

This study confirms that COVID-19 is mostly a mild disease in children and usually does not require specifiy treatment. However, children can present critically ill. With case numbers still rising, continuous observation is necessary to further understand the disease in children, guide therapy and evaluate the necessity for vaccination in children.

Clinical Trial Registration

The study has received ethical approval by the Ethikkommission Nordwest- und Zentralschweiz (EKNZ 2020-01130).

Background

Since COVID-19 pandemic started, preliminary evidence suggests that children are as likely as adults to get infected, but most of them have asymptomatic infection or mild disease. Pediatric multisystem inflammatory syndrome (PIMS) is a novel condition that emerged during this pandemic. The aim of this study was to describe clinical and epidemiological aspects of pediatric COVID-19 infection in 10 centers in Argentina.

Methods

Prospective, multicenter, observational and analytical cohort study. Confirmed cases between 0 to 18 years of age were included consecutively according to the case definition of the Argentina MOH, March to December 2020. Detection of SARS CoV-2 was confirmed by RT-PCR in nasopharyngeal aspirate/swab.

Results

A total of 1,517 COVID-19 confirmed cases were included, 90% between May-October (winter/spring). Median age:5.3 years (interquartile range-IQR-:1.1-10.9 years), 23.4% <1year; 49.8% male. Cases clasiffication: asymptomatic 24.3%, mild 64.4%, moderate 5.6%, severe 5%, critical 0.7%. Almost 70% (n=1,044) were hospitalized: median length of stay 7 days (IQR:3-9). . Cases characteristics in table 1. There were 3 fatal cases (0.2%) with underlying diseases (chronic kidney disease, myasthenia gravis). PIMS was diagnosed in 32 cases, median age 5.5 years (IQR:3-9), 78% received intravenous gamma-globulin, 62% systemic corticosteroids and 47% required intensive care.

Conclusions

In our study most cases were mild, had history of close contact with COVID-19 cases, PIMS was reported in 2% and COVID-19 lethality was 0.2%.

Background

It has been understood from worldwide reports that Coronavirus Disease 2019 (COVID-19) is a disease with a different course in children than adults. Studies investigating clinical and imaging findings of COVID-19 pneumonia and predictors for lung injury mostly focus on adults, and limited data are available for children. In this study, we aimed to evaluate the role of laboratory findings in predicting lung involvement in children with COVID-19.

Methods

Between March 11, 2020, and December 25, 2020, a total of 101 pediatric COVID-19 patients confirmed by RT-PCR or antibody test and who underwent chest CT scans were reviewed retrospectively. On admission absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC/ALC ratio, platelet count, D-dimer, fibrinogen, ferritin, procalcitonin, CRP and lactate dehydrogenase levels were compared in patients with normal and abnormal CT scans.

Results

Among the patients, 68 (67.3%) had normal CT scans, and 33 (32.7%) had pulmonary involvement. The median CRP, ferritin and fibrinogen levels were significantly higher in children with abnormal CT findings. The model of binary logistic regression based on the presence of cough, shortness of breath, fibrinogen, ferritin, and CRP levels showed that the possibility of having abnormal CT was 1.021 times likely to happen for every additional increase of fibrinogen levels.

Conclusions

In conclusion, while CRP, fibrinogen, and ferritin levels differ significantly in patients with pulmonary injury, ALC, ANC, LDH, D-dimer, PLT, procalcitonin, and ANC / ALC ratio were similar compared to the patients with no pulmonary findings. Only fibrinogen levels were found to be an independent risk factor for pulmonary involvement. Restricting radiological imaging to patients with significant symptoms and high fibrinogen levels might be rational in children with COVID-19 infections.

Background

Since April 2020, clusters of children with multisystem inflammatory syndrome (MIS-C) linked to SARS-CoV-2 infection have been described in Europe. The syndrome shares features with Kawasaki Disease (KD), toxic shock syndrome and macrophage activation syndrome. We aimed to describe and compare the epidemiologic, clinical and diagnostic findings, the therapeutic approach and the outcomes on MIS-C patients in our cohort.

Methods

Case series of children (0-18 years old) with MIS-C associated with SARS-CoV-2 enrolled from the 1^st March to the 31th of December 2020 in the Epidemiological Study of COVID-19 in Children (EPICO-AEP), a multicentre (49 hospitals) prospective registry cohort of children with SARS-CoV-2 infection in Spain. We describe different groups inside MIS-C spectrum: Kawasaki Disease (KD) or incomplete KD (IKD) were defined according the 2017 American Heart Association definition. For MIS-C definition, WHO's was used.

Results

85 hospitalized children were diagnosed with MIS-C by WHO criterial. 97% had microbiological or serological evidence of SARS-CoV-2 infection: 36/85 (42.3%%) positive RT-PCR, 23/68 (33.2%%) positive IgM and 60/68 (88%) positive IgG. 16/85 children (18.8%) fulfilled complete KD definition and 41/85 (48.2%%) IKD, while 28/85 (32.9%) did not meet either. Clinical and microbiological aspects of these groups are summarized in table 1.

Conclusions

MIS-C clinical and biomarker profile overlaps with KD and difficult its diagnosis and classification. MIS-C cases not fulfilling KD criteria differ in several characteristics as compared with KD SARS-CoV-2 related: patients are older, present more often with respiratory, gastrointestinal and neurological symptoms, and develop a more severe disease in terms of cardiovascular involvement (myocarditis and higher pro-BNP). Higher rates of leukopenia, lymphopenia and thrombocytopenia, as well as increased inflammation have been reported but were not statistically significant. Why a small fraction of SARS-CoV-2–infected children develop MIS-C remains unclear.

Background

One of the challenges in the management of Multisystem Inflammatory Syndrome in Children (MIS-C) is early diagnosis, as symptoms are non-specific and clinical features overlap with those of other infectious and inflammatory diseases. In order to establish how well the WHO criteria for a MIS-C diagnosis can distinguish the disorder from other febrile conditions, we compared patients fulfilling the diagnostic criteria for MIS-C to other febrile or inflammatory conditions, including bacterial and viral infections, and previously recognised inflammatory disorders.

Methods

Non-identifiable data was collected as part of the DIAMONDS study, an international consortium recruiting patients with fever and inflammation across 13 countries. Comparative analysis was performed on over 1000 children recruited from 2020 to 2021.

Results

Patients recruited to DIAMONDS were twice as likely to have an inflammatory diagnosis (6.2%) as those in PERFORM (2.8%), a study with similar inclusion and exclusion criteria that recruited children prior to the COVID-19 pandemic. More than half of patients (53%) with inflammatory conditions in DIAMONDS had a history of SARS-CoV-2 infection or exposure. Bacterial infections were identified in some patients fulfilling MIS-C criteria. A wide spectrum of SARS-CoV-2-related inflammation was observed, including patients who did not meet the WHO definition for MIS-C. Further analysis of this data is ongoing.

Conclusions

Early analysis of the DIAMONDS data has shown the impact of the COVID-19 pandemic on the burden of inflammatory conditions in children. There appears to be a wider spectrum of inflammatory diseases associated with SARS-CoV-2 than what has been identified by the current WHO diagnostic criteria. Further analysis of this data will help understand the impact of SARS-CoV-2 exposure on inflammatory disorders, as well as its impact on secondary infections.

Background

From April 2020, clinicians in multiple countries reported a novel and unusual inflammatory syndrome sharing features with Kawasaki Disease (KD), though occurring more in school-aged children, and with shock and abdominal symptoms common.

Treatment has been inspired by KD, with use of steroids and IVIg common.

Randomised trials are underway, but there is an urgent need to understand treatment efficacy.

Methods

In May 2020 we commenced the BATS study (bestavailabletreatmentstudy.co.uk), collecting data from paediatric units around the world on children presenting with PIMS-TS/MIS-C.

Data is collected in Redcap on demographics, presentation, exposure history, microbiological/serological results, outcomes and complications, with timecourse data on inflammatory markers, level of care, cardiological findings and treatments.

Exported data undergoes post-processing and QC. Patients are categorised by criteria for PIMS-TS/MIS-C and descriptive data on demographics, severity and treatment patterns is produced.

Propensity-score based methods will be used to compare effectiveness of initial treatments.

Results

At time of submission, 394 patient entries with admission/discharge dates are available from 49 hospitals in 25 countries. The majority (61%) of admissions come from the UK, Russia, Panama and USA.

Of 347 records where patients were previously untreated, initial immunomodulator treatment (two-day window) was steroids in 49 (14%), IVIG in 99 (29%) and both in 157 (45%). 15 (4%) had other treatment combinations and 27 (8%) received no immunomodulator.

Comparative analysis by treatment is underway.

Conclusions

Whilst randomised trials reduce bias, a low proportion of children globally are being recruited into trials. Low recruitment may lead to imprecise estimates of efficacy and uncertainty.

The depth, growing size and global reach of our study potentially offers the best available evidence of efficacy of primary treatments, as well as insight into treatment patterns, outcomes and complications.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of characteristics that range from asymptomatic seroconversion to severe cases, sometimes with prolonged symptoms. Only limited data are available about long-term consequences in pediatric population.

Objective of this research was to identify and compare long-term post-acute Covid-19 symptoms and sequelae in children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in various age groups.

Methods

This was a retrospective cohort study. From March 2020 to December 2020 ninety-two paediatric Covid-19 patients (age ≤ 18 years) and their parents were enrolled in the study. To identify the long-term consequences of SARS-CoV-2 infection, we defined post-acute covid-19 as extending beyond three weeks from onset of first symptoms. All patients were evaluated in a face-to-face visit according to specially designed post-COVID-19 symptom assessment protocol 1 to 3 months after COVID-19 onset. Descriptive statistics were used to present the data.

Results

During the first follow up visit 49% of all patients were asymptomatic and had returned to their previous level of health, but 51% had persistent symptoms after SARS-CoV-2 infection. From all the symptomatic children 19% had 1 symptom, 10% two, and 22% had 3 or more. Most often the complaints about long-term post-Covid-19 symptoms were seen among adolescents (age 15-18)-62%. In this age group the most common long-term symptoms were fatigue-31% and tiredness after good night sleep-31%, as well as headaches-15%, cognitive disturbances-12% and persistent loss of taste and/or smell-12%.

Conclusions

The long-term symptoms of SARS-CoV-2 infection are evident in paediatric population and affect children’s physical and emotional health. According to our data, the most common post-acute COVID-19 clinical features were noted in children from 15 to 18 years.

Background

Data on the clinical impact of immunocompromised children suffering from SARS-CoV-2 are limited.

The aim of this study is to describe the characteristics of children with primary (PID) or secondary Immunodeficiencies (SID) from a Spanish multicenter study.

Methods

EPICO-AEP is a multicenter cohort study conducted in Spain to assess the characteristics of children with COVID-19. In total, 75 hospitals are collecting data since the beginning of the epidemic in Spain in March 2020

This analysis includes children with PID and SID aged 0 to 18 years attending any of the participating hospitals between 12/03/20 to 23/01/2021, with a microbiologically confirmed SARS-CoV-2 infection.

Results

96 children were included (10% of patients recruited): 9 with PID and 87 with SID (42 secondary to immunosuppressive therapy and 42 to malignancy), 53(55.2%) males and a median age of 10.8 years (IQR:5-14.3years). Children with PID were younger compared to those with SID (34.7vs132.2 months,p=0.023). The most common diagnosis related to SARS-CoV-2 was pneumonia (24%), followed by upper respiratory tract infection (21.9%) and fever without a source (14.6%). Data related to laboratory findings, management and mortality is summarized in Table1; there were no statistically differences between PID and SID.

Conclusions

Of note, 4 (4,2%) died, all with SID, which represents 80% (4/5) of patients who died from the entire EPICO-AEP cohort.

In our cohort, patients with PID suffering from SARS-CoV-2 were younger and suffered from lower mortality compared to those with SID.

Data from larger cohorts is needed to better stratify risk groups and their management.

Background

In December 2019, a new coronavirus was identified and named SARS-CoV2. COVID-19 is a multisystemic disease caused by SARS-CoV-2. Pediatric patients represent only approximately 1% of total cases and usually present with less severe symptoms.

As of December 8, 2020, 6.623.911 cases were detected in Brazil and 177.317 deaths occurred.

This study describes the characteristic of children with COVID-19 and other respiratory viruses during the 2020 pandemic.

Methods

We analyzed clinical and laboratory data of patients aged 0-17 seeking care in the emergency department submitted to Real Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCT) for SARS-CoV-2. This was a single center study conducted in a private hospital in São Paulo, Brazil from February 25th to May 21st of 2020.

Laboratory results and clinical data were collected through patients' files. Viral testing was conducted by the hospital's laboratory independently from the research. Disease severity and Multisystem Inflammatory Syndrome (MIS-C) were defined according to World Health Organization criteria.

Results

We identified 885 patients submitted to RT-PCR for SARS-CoV-2, with 4.1% positive. 124 patients were included in the study, eight of them positive for SARS-CoV-2 and 38 positive for other respiratory pathogens. Cough (n=7, 87.5%) and fever (n=6, 75%) were the most common symptoms. Headache was significantly more common in children with COVID-19 (50%, p=0.03). No cases of MIS-C and no deaths were identified. No patients needed mechanical ventilation. There was one co-detection (SARS-CoV-2, Influenza B and HCoV-NL63). Disease severity was similar in children with COVID-19 and other respiratory viruses.

Conclusions

COVID-19 cannot be distinguished from other viral illnesses in the pediatric population. Other respiratory viruses were more frequent in children during the pandemic. Level of suspicion must always be high even in asymptomatic patients.