Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 Research Articles

Swissped-RECOVERY: masked independent adjudication for the interpretation of non-randomised treatment in a two-arm open-label randomised controlled trial (methylprednisolone vs immunoglobulins) in Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) involving 10 secondary and tertiary paediatric hospitals in Switzerland

ObjectivesIn trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of...

Clinical and Laboratory Biomarkers as Predictors of Severity in Pediatric Inflammatory Multisystem Syndrome-temporally Associated With SARS-CoV-2: Data From a Prospective Nationwide Surveillance Study in Switzerland.

PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention. To identify factors associated with increased PIMS-TS severity in children. In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support. A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group. The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients.

The Therapy of SARS-CoV-2 Infection in Children.

The impact of SARS-CoV-2 infections in children has fortunately been lower than what has been seen in adults. However, even previously healthy children have developed severe disease, sometimes with subsequent mortality, and those who are infants or adolescents, are from racial and ethnic minority groups, or have certain chronic conditions are at higher risk of these outcomes. During the pandemic, extensive studies of therapeutic agents, including antivirals and immunomodulators, were conducted in adults. Few trials included children, and most were in older children and adolescents. Thus, the potential benefits of therapies in children must be extrapolated from adult evidence. Despite these limitations, advisory committees of the National Institute of Health (NIH), the Infectious Disease Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS) were constituted, and expert consensus guidelines were developed. This review provides a synthesis of those comprehensive recommendations for therapy in children. These address treatment during the early infectious period with antiviral agents, including remdesivir and nirmatrelvir/ritonavir, as well as treatment in the later period of immune dysregulation with corticosteroids and immunomodulators. In addition, the therapeutic approach for multisystem inflammatory syndrome in children (MIS-C), also referred to as Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is also provided.

Cardiac assessment and inflammatory markers in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 (PIMS-TS) treated with methylprednisolone versus intravenous immunoglobulins: 6-month follow-up outcomes of the randomised controlled Swissped RECOVERY trial

Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI)-0.05 to 1.0; p=0.39). Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. NOMIS, Vontobel, and Gaydoul Foundation.

Demographic, clinical and laboratory differences between paediatric acute COVID-19 and PIMS-TS-results from a single centre study in the UK.

Paediatric symptomatic SARS-CoV-2 infections associate with two presentations, acute COVID-19 and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Phenotypic comparisons, and reports on predictive markers for disease courses are sparse and preliminary. A chart review of COVID-19 and PIMS-TS patients (≤19 years) admitted to Alder Hey Children's NHS Foundation Trust, a tertiary centre in the North-West of England, was performed (02/2020-09/2022). A total of 161 symptomatic COVID-19 and 50 PIMS-TS patients were included. Peaks in admissions of patients with PIMS-TS occurred approximately 4 weeks after those for acute COVID-19. The incidence of in-patients with PIMS-TS reduced over time, and there were no admissions after February 2022. When compared to acute COVID-19, PIMS-TS patients were older (median: 10.3 years vs. 2.03 years; p < 0.001). There were no differences in gender distribution, but minority ethnicities were over-represented among PIMS-TS patients. Regional ethnic distribution was reflected among acute COVID-19 patients (66% vs. 84.5% White Caucasian, p = 0.01). Pre-existing comorbidities were more common among acute COVID-19 patients (54.7% vs. 8%, p < 0.001). PIMS-TS patients more commonly presented with abdominal symptoms (92% vs. 50.3%), neurological symptoms (28% vs. 10.6%) and skin rashes (72% vs. 16.8%), (p ≤ 0.01) when compared with acute COVID-19, where respiratory symptoms were more common (51.6% vs. 32%, p = 0.016). PIMS-TS more frequently required intensive care admission (64% vs. 16.8%), and inotropic support (64% vs. 9.3%) (all p < 0.05). More deaths occurred among acute COVID-19 patients [0 vs. 7 (4.4%)], with 5/7 (71%) in the context of pre-existing comorbidities. When compared to acute COVID-19, PIMS-TS patients exhibited more lymphopenia and thrombocytopenia, a more pronounced acute phase reaction, and more hyponatraemia (p < 0.05). Partial least square discriminant analysis of routine laboratory parameters allowed (incomplete) separation of patients at diagnosis, and variable importance projection (VIP) scoring revealed elevated CRP and low platelets as the most discriminatory parameters. Admissions for PIMS-TS reduced with increasing seroconversion rates in the region. Young age and pre-existing comorbidities associate with hospital admission for acute COVID-19. While PIMS-TS may present more acutely with increased need for intensive care, acute COVID-19 had an increased risk of mortality in this cohort.

COVID-19 In Children

Diagnosis of SARS-CoV-2 infection is based on detection of viral RNA by RT-PCR of nasopharyngeal or oropharyngeal swabs. Consider alternative diagnoses in children who are unwell, even in the presence of a positive SARS-CoV-2 PCR result. Children with mild to moderate Covid19 do not routinely need admission or investigations such as blood tests and radiology, unless otherwise clinically indicated. Children with severe or critical disease as a minimum should have the following investigations: Blood cultures, Full Blood Count (FBC), Coagulation profile, D-dimer, Urea and Electrolytes, LFT, CRP, Troponin, Ferritin, Lactate dehydrogenase (LDH) and Blood Gas Analysis. Remdesivir may be considered for children &gt; 12 years and &gt;40kg with COVID-19 requiring supplemental oxygen. Consider chest x-ray in children who do not follow the expected clinical course, for example, those still requiring oxygen on day three of admission, those with worsening hypoxemia or those requiring respiratory support. Decision to escalate respiratory support to Non-Invasive Ventilation (NIV) should be made by a senior member of the pediatric team, in discussion with critical care. For children with clinical findings consistent with the Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS) should be managed as per specialized guidelines.&#x0D; Northern International Medical College Journal Vol. 12 No.2 Jan 2021, Page 548-554

Pediatric Hospitalizations and ICU Admissions Due to COVID-19 and Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 in England

Investigating how the risk of serious illness after SARS-CoV-2 infection in children and adolescents has changed as new variants have emerged is essential to inform public health interventions and clinical guidance. To examine risk factors associated with hospitalization for COVID-19 or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) among children and adolescents during the first 2 years of the COVID-19 pandemic and change in risk factors over time. This population-level analysis of hospitalizations after SARS-CoV-2 infection in England among children and adolescents aged 0 to 17 years was conducted from February 1, 2020, to January 31, 2022. National data on hospital activity were linked with data on SARS-CoV-2 testing, SARS-CoV-2 vaccination, pediatric intensive care unit (PICU) admissions, and mortality. Children and adolescents hospitalized with COVID-19 or PIMS-TS during this time were included. Maternal, elective, and injury-related hospitalizations were excluded. Previous medical comorbidities, sociodemographic factors, and timing of hospitalization when different SARS-CoV-2 variants (ie, wild type, Alpha, Delta, and Omicron) were dominant in England. PICU admission and death within 28 days of hospitalization with COVID-19 or PIMS-TS. A total of 10 540 hospitalizations due to COVID-19 and 997 due to PIMS-TS were identified within 1 125 010 emergency hospitalizations for other causes. The number of hospitalizations due to COVID-19 and PIMS-TS per new SARS-CoV-2 infections in England declined during the second year of the COVID-19 pandemic. Among 10 540 hospitalized children and adolescents, 448 (4.3%) required PICU admission due to COVID-19, declining from 162 of 1635 (9.9%) with wild type, 98 of 1616 (6.1%) with Alpha, and 129 of 3789 (3.4%) with Delta to 59 of 3500 (1.7%) with Omicron. Forty-eight children and adolescents died within 28 days of hospitalization due to COVID-19, and no children died of PIMS-TS (PIMS-S data were limited to November 2020 onward). Risk of severe COVID-19 in children and adolescents was associated with medical comorbidities and neurodisability regardless of SARS-CoV-2 variant. Results were similar when children and adolescents with prior SARS-CoV-2 exposure or vaccination were excluded. In this study of data across the first 2 years of the COVID-19 pandemic, risk of severe disease from SARS-CoV-2 infection in children and adolescents in England remained low. Children and adolescents with multiple medical problems, particularly neurodisability, were at increased risk and should be central to public health measures as further variants emerge.

Case report: Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 with severe myocardial dysfunction. Is there any hope in immunotherapy?

Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) develops in a small percentage of children after COVID-19, however, it might cause severe myocardial dysfunction. The pathogenesis of this disease includes systemic hyper-inflammation with cytokine storm. This case report concerns a 12-year-old boy with PIMS-TS who presented severe respiratory and circulatory failure with increased inflammatory markers and significant reduction of left ventricle ejaculatory fraction (LVEF) from 65% to 35%. The recommended therapy with the use of vasopressors, corticosteroids, intravenous immunoglobulins and mechanical ventilation was introduced and his condition gradually improved. However, after few days, aggravation of cardiac symptoms occurred again and among other treatment, the therapy with the use of anakinra - the human interleukin 1 receptor antagonist protein was introduced. This case highlights a satisfactory regression of cardiac disturbances and generally favorable outcome of the treatment in patients with PIMS-TS with the use of immunomodulatory therapy.

Epidemiological Profile and Management of Kawasaki Syndrome at Rabat Children’s Hospital: A retrospective study from Morocco

Kawasaki disease (KD) is a common pediatric vasculitis with a risk of coronary artery aneurysm. In this report, we review some particularities of KD disease, especially coronary involvement, and highlight its aspects during the COVID-19 epidemic which saw the emergence of a syndrome named multisystem inflammatory syndrome in children (MIS-C). Because of its many similarities with KD, MIS-C is often referred to as Kawasaki-like disease (KLD) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).We report on a retrospective study on the different epidemiological, clinical, and evolutionary aspects of KD and the coronary involvement resulting from this disease before and after the pandemic. The study is based on the echocardiography records of the P4 Department at Rabat Children’s Hospital, from January 2002 to December 2021. A total of 379 patients were diagnosed with KD during that period. This includes 47 cases that were reported during the first year of the COVID-19 epidemic in Morocco (March 2020). Echocardiography results for our series show that cardiac complications wererelatively more frequent among KD patients during the COVID-19 period, perhaps because they were relatively older (67 months on average) than classic KD patients (37 months on average). However, all patients had a favorable outcome after treatment with a combination of intravenous immunoglobulin (IVIG) and aspirin. The few patients who did not respond to standard treatment received corticosteroids, and no mortality occurred. We conclude that as far as cardiac complications,KD, KLD, and MIS-C are the same core disease that is triggered under different conditions for different age groups.The emergence of the Sars-Cov-2 virus changed the epidemiologic profile of KD but not its treatment. Insights from this study would help in the decision to initiate targeted immunotherapy quickly and reduce the risk factors associated with KD.

Role of Lung Ultrasonography (LUS) as a Tool for Evaluating Children with Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS).

Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a novel entity. The inflammatory process involves the circulatory, digestive, respiratory, and central nervous systems, as well as the skin. Making a diagnosis requires extensive differential diagnoses, including lung imaging. The aim of our study was to retrospectively assess the pathologies found in lung ultrasound (LUS) in children diagnosed with PIMS-TS and to evaluate the usefulness of the examination in diagnostics and monitoring. The study group consisted of 43 children diagnosed with PIMS-TS, in whom LUS was performed at least three times, including on admission to hospital, on discharge, and 3 months after disease onset. Pneumonia (mild to severe) was diagnosed in 91% of the patients based on the ultrasound image; the same number had at least one pathology, including consolidations, atelectasis, pleural effusion, and interstitial or interstitial-alveolar syndrome. By the time of discharge, the inflammatory changes had completely regressed in 19% of the children and partially in 81%. After 3 months, no pathologies were detected in the entire study group. LUS is a useful tool for diagnosing and monitoring children with PIMS-TS. Inflammatory lesions of the lungs resolve completely when the generalized inflammatory process subsides.

A brand new medical condition - 6 years old patient with neurological symptoms diagnosed with PIMS-TS (Paediatric Inflammatory Multisystem Syndrome – Temporally Associated with SARS-CoV-2) - case report

Children's multi-system inflammatory syndrome PIMS-TS is a completely new challenge for pediatricians, which has established a separate branch of the fight against the still active COVID-19 pandemic. It turns out that even a pediatric patient who has not suffered symptomatic infection with the SARS-CoV-2 virus, as a result of contact with this pathogen, can develop a severe systemic inflammatory reaction rich in symptoms originating in almost every system of the human body. The first reports of the inflammatory syndrome that is the subject of this work come from May 2020. It is known that the symptoms of PIMS are caused by a multi-system inflammatory response in the body, potentially related to the immune system. The course of this disease may bring to mind other inflammatory diseases in children, such as Kawasaki disease, toxic shock syndrome and MAS macrophage activation syndrome.

Impact of SARS-CoV-2 variants on the incidence of paediatric inflammatory multisystem syndrome (PIMS-TS).

Impact of SARS-CoV-2 variants on the incidence of paediatric inflammatory multisystem syndrome (PIMS-TS).

Responding to the psychological needs of children following admission to paediatric Intensive Care for paediatric inflammatory multisystem syndrome: A Narrative Therapy based Photography Workshop.

This article briefly describes the development of a novel narrative therapy-based photography workshop group for children following acute hospital admission for Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS). The workshop was a collaboration between the psychology team, an artist and the medical multi-disciplinary team (MDT) to develop a group during the COVID-19 pandemic. The aims were to reduce isolation and promote resilience and psychological recovery post discharge from hospital. Nine children aged 8-11 years joined the photography group. Parents (n = 8) and children (n = 8) provided feedback on the group through semi-structured telephone interviews. Thematic analysis of the interviews identified three narrative themes for parents: reducing isolation through shared experience, creative activity as a different experience of hospital, and the positive sharing of experiences after the day. The resulting narrative themes for the children included that the workshop was a fun and interactive day and an opportunity to share in hospital experience with peers.

Lower risk of multi-system inflammatory syndrome in children (MIS-C) with the omicron variant

Multi-system inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is an infrequent but severe post-infectious complication of COVID-19.1 The Paediatric Active Enhanced Disease Surveillance (PAEDS) network (www.paeds.org.au)2 initiated sentinel surveillance for MIS-C in May 2020. PAEDS used a case definition for MIS-C modified from the WHO definition (supplementary methods). PAEDS concurrently undertook surveillance for hospitalized COVID-19 and Kawasaki disease.

SARS-CoV-2 Seroprevalence Study in Pediatric Patients and Health Care Workers Using Multiplex Antibody Immunoassays.

SARS-CoV-2 infection has become a global health problem specially exacerbated with the continuous appearance of new variants. Healthcare workers (HCW) have been one of the most affected sectors. Children have also been affected, and although infection generally presents as a mild disease, some have developed the Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We recruited 190 adults (HCW and cohabitants, April to June 2020) and 57 children (April 2020 to September 2021), of whom 12 developed PIMS-TS, in a hospital-based study in Spain. Using an in-house Luminex assay previously validated, antibody levels were measured against different spike and nucleocapsid SARS-CoV-2 proteins, including the receptor-binding domain (RBD) of the Alpha, Beta, Gamma, and Delta variants of concern (VoC). Seropositivity rates obtained from children and adults, respectively, were: 49.1% and 11% for IgG, 45.6% and 5.8% for IgA, and 35.1% and 7.3% for IgM. Higher antibody levels were detected in children who developed PIMS-TS compared to those who did not. Using the COVID-19 IgM/IgA ELISA (Vircell, S.L.) kit, widely implemented in Spanish hospitals, a high number of false positives and lower seroprevalences compared with the Luminex estimates were found, indicating a significantly lower specificity and sensitivity. Comparison of antibody levels against RBD-Wuhan versus RBD-VoCs indicated that the strongest positive correlations for all three isotypes were with RBD-Alpha, while the lowest correlations were with RBD-Delta for IgG, RBD-Gamma for IgM, and RBD-Beta for IgA. This study highlights the differences in antibody levels between groups with different demographic and clinical characteristics, as well as reporting the IgG, IgM, and IgA response to RBD VoC circulating at the study period.

SARS-CoV-2 variants and the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 among children in Germany

PurposeTo investigate the relationship between the risk of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in children and the predominance of different SARS-CoV-2 variants of concern (VOC) over time.MethodsIn relation to the Alpha, Delta, and Omicron VOC phases of the pandemic, the risk of developing PIMS-TS was calculated by analyzing data for rtPCR-confirmed SARS-CoV-2 infections reported to the German statutory notification system, along with data captured by a separate, national PIMS-TS registry. Both overall infection rates and age group-specific ratios of PIMS-TS during the different pandemic phases were calculated using the Alpha period as the baseline.ResultsThe PIMS-TS rate changed significantly over time. When the Alpha VOC was dominant [calendar week (CW) 11 in March–CW 31 in August 2021], the PIMS-TS rate was 6.19 [95% confidence intervals (95% CI) 5.17, 7.20]. When Delta prevailed (CW 32 in August 2021–CW 4 in January 2022), the rate decreased to 1.68 (95% CI 1.49, 1.87). During the Omicron phase (CW 5 in January–CW 16 in April 2022), the rate fell further to 0.89 (95% CI 0.79, 1.00). These changes correspond to a decreased PIMS-TS rate of 73% (rate ratio 0.271, 95% CI 0.222; 0.332) and 86% (rate ratio 0.048, 95% CI 0.037; 0.062), respectively, in comparison to the Alpha period. Rate ratios were nearly identical for all age groups.ConclusionThe data strongly suggest an association between the risk for PIMS-TS and the prevailing VOC, with highest risk related to Alpha and the lowest to Omicron. Given the uniformity of the decreased risk across age groups, vaccination against SARS-CoV-2 does not appear to have a significant impact on the risk of children developing PIMS-TS.

Nationwide observational study of paediatric inflammatory multisystem syndrome temporally associated withSARS-CoV-2 (PIMS-TS) inthe Czech Republic.

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported.Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management. What is Known: • Preliminary evidence, majority from relatively small, and mostly single-centre patient cohorts, has shown some insights in the basic epidemiological and clinical data of children with a paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). What is New: • To our knowledge, this is the unique published national population-wide cohort allowing to study the epidemiology (including overall incidence), time gap between viral exposure and clinical symptoms of PIMS-TS, and clinical presentations and outcomes within the individual pandemic waves of COVID-19 that were characterised by various prevailing genetic variants of SARS-CoV-2.• We estimated 3-week interval as a most probable period between SARS-CoV-2 infection and PIMS-TS based on nationwide population data using cross-correlation method.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-022-04593-7.

Multisystem inflammatory syndrome in children related to COVID-19: Data from a Mexican national referral children's hospital.

ObjectivesTo describe characteristics of patients with the pediatric inflammatory multisystem syndrome, temporally associated with SARS-CoV-2 (PIMS-TS)/multisystem inflammatory syndrome in children (MIS-C) and to identify factors associated with admission to the pediatric intensive care unit (PICU) in the Mexican children without coronavirus disease 2019 (COVID-19) vaccination.MethodsThis was a cross-sectional study performed at Hospital Infantil de Mexico Federico Gomez, a referral children's hospital in Mexico. The study included all cases that met the criteria for PIMS-TS/MIS-C, unvaccinated, between March 2020 and January 2022. The primary outcome was the admission to PICU. Associations of PICU admission with demographic and clinical variables were estimated using logistic regression analyses.ResultsWe identified a total of 90 cases, with a median age of 7.5 years old, 47 (52.2%) girls. A previously healthy status was recorded in 76 (85%) children. All patients had positive PCR, serology test, or COVID-19 exposure. PICU admission was reported in 41 (45.6%) children. No deaths were reported. Patients received as treatment only corticosteroids in 53.3% of the cases. In univariable analyses, baseline factors associated with PICU admission were older age, hypotension or shock, positive PCR test, hypoalbuminemia, elevated procalcitonin, ferritin, and lymphopenia. Age, shock at admission, and hypoalbuminemia remained independently associated in the multivariable analysis adjusted by gender and previously healthy status.ConclusionWe found a high proportion of previously healthy children in patients with PIMS-TS/MIS-C in our center. Critical care attention was received by nearly half of the children. The main treatment used was steroids. Age, shock at admission, and hypoalbuminemia were factors associated with PICU admission.

Neurologic and radiographic findings associated with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS)

ObjectiveOur aim was to report neurological manifestations of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS).MethodsPatients (&lt;18yrs) presenting to Great Ormond Street Hospital between March 1, 2020, and June 21, 2020 fulfilling RCPCH PIMS-TS criteria, were included. Clinical and paraclinical features were retrieved retrospectively from electronic patient records.ResultsNew-onset neurological symptoms/signs were reported in 23/45 (51.1%); headaches (n=16), encephalopathy (n=7), dysarthria/dysphonia (n=6), hallucinations (n=4), ataxia (n=4), peripheral nerve involvement (n=3), and seizures (n=1). Five (21.7%) patients had CSF analysis; 1 patient had 118 leuko- cytes in CSF. Splenium signal changes were seen in 4/14 patients who had brain MRI. A mild excess of slow activity was found in 10/10 who had an EEG and mild myopathic and neuropathic changes were seen 4/5 who underwent nerve conduction studies and electromyography. Children with neurological involvement had higher peak inflammatory markers and were more likely to be ventilated and require inotropic support in PICU (p&lt;0.05).ConclusionsChildren with PIMS-TS presented with new neurological symptoms involving both the central and peripheral nervous systems, in the absence of respiratory symptoms. Neurological symptoms were seen more frequently in more severe presentations.o.abdel-mannan@ucl.ac.uk

Multicenter Randomized Trial of Methylprednisolone vs. Intravenous Immunoglobulins to Treat the Pediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS): Protocol of the Swissped RECOVERY Trial.

IntroductionIn 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG.Methods and AnalysisSwissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned.SignificanceCurrently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments.Ethics and DisseminationThe study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362).Registration DetailsThe study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT 04826588).