Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study.

BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85-1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 µg/L to 757 µg/L), whereas the lymphocyte count increased to more than 1·0 × 109 cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.

Association Between Treatments and Short-Term Biochemical Improvements and Clinical Outcomes in Post-Severe Acute Respiratory Syndrome Coronavirus-2 Inflammatory Syndrome.

OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs. DESIGN: Multicenter observational study. SETTING: Twenty-one U.K. PICUs. PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally recommended. CONCLUSIONS: We were unable to identify any short-term benefit from any of the treatments, or treatment combinations, administered. Despite a lack of evidence, treatment guidelines for multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 have become very similar in advising step-wise treatments. Retaining clinical equipoise regarding treatment will allow clinicians to enroll children in robust clinical trials to determine the optimal treatment for this novel important condition.

Acute Kidney Injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Experience From PICUs Across United Kingdom.

OBJECTIVES: To study the prevalence, evolution, and clinical factors associated with acute kidney injury in children admitted to PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. DESIGN: Multicenter observational study. SETTING: Fifteen PICUs across the United Kingdom. PATIENTS: Patients admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 between March 14, 2020, and May 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deidentified data collected as part of routine clinical care were analyzed. All children were diagnosed and staged for acute kidney injury based on the level of serum creatinine above the upper limit of reference interval values according to published guidance. Severe acute kidney injury was defined as stage 2/3 acute kidney injury. Uni- and multivariable analyses were performed to study the association between demographic data, clinical features, markers of inflammation and cardiac injury, and severe acute kidney injury. Over the study period, 116 patients with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 were admitted to 15 United Kingdom PICUs. Any-stage acute kidney injury occurred in 48 of 116 patients (41.4%) and severe acute kidney injury in 32 of 116 (27.6%) patients, which was mostly evident at admission (24/32, 75%). In univariable analysis, body mass index, hyperferritinemia, high C-reactive protein, Pediatric Index of Mortality 3 score, vasoactive medication, and invasive mechanical ventilation were associated with severe acute kidney injury. In multivariable logistic regression, hyperferritinemia was associated with severe acute kidney injury (compared with nonsevere acute kidney injury; adjusted odds ratio 1.04; 95% CI, 1.01-1.08; p = 0.04). Severe acute kidney injury was associated with longer PICU stay (median 5 days [interquartile range, 4-7 d] vs 3 days [interquartile range, 1.5-5 d]; p < 0.001) and increased duration of invasive mechanical ventilation (median 4 days [interquartile range, 2-6 d] vs 2 days [interquartile range, 1-3 d]; p = 0.04). CONCLUSIONS: Severe acute kidney injury occurred in just over a quarter of children admitted to United Kingdom PICUs with pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. Hyperferritinemia was significantly associated with severe acute kidney injury. Severe acute kidney injury was associated with increased duration of stay and ventilation. Although short-term outcomes for acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 appear good, long-term outcomes are unknown.