Investigation from London Provides Insight into New Post-Infectious Complication in Young Patients

A recent investigation from London examined a new and rare post-infectious complication of SARS-CoV-2 infection in children. The study provided insight on the outcomes of the complication during a 6-month period between April 4 – September 1, 2020.

The complication, later termed Pediatric inflammatory multisystem syndrome (PIMS-TS), was identified in April 2020. It was considered a distinct post-infectious entity by researchers, with clinical features that included fever, rash, conjunctivital injection, systemic inflammation, gastrointestinal symptoms, and occasionally multi-organ failure resulting in admissions to a pediatric intensive care unit (PICU).

More than 250 cases of PIMS-TS were recorded in the UK in the first 2 months.

In order to gain a better understanding of PIMS-TS, an investigative team lead by Justin Penner, MD, Department of Paediatric Infectious Diseases, Great Ormond Street Hospital,, monitored a group of 46 pediatric patients in the London area whose lives had been impacted by the complication.

All eligible participants were 18 years or younger and were admitted to the Great Ormand Street Hospital in London. Additionally, participants had to fulfill the UK Royal College of Pediatric and Child Health (RCPCH) criteria for PIMS-TS prior to admission.

Patients were visited by a multidisciplinary team on several occasions after being discharged from the hospital.

The investigators described the initial process.

“Recent SARS-CoV-2 infection was confirmed by RT-PCR of nasopharyngeal samples, positive serology, a clear epidemiological link to an infected contact, or a combination of the above,” the team wrote.

“Serology testing evaluated IgG antibodies to the SARS-CoV-2 nucleocapsid protein and, from June, 2020, to the spike protein (Epitope Diagnostics; San Diego). After June, 2020, anti-spike protein antibody tests were done on all patients presenting with PIMS-TS. Retrospective analysis of patients with negative nucleocapsid antibody

results was done on available stored samples. Follow-up serological assays were done on the anti-spike assay.”

Additional data was collected via patient-reported outcome measures and follow-ups by physicians and therapist during the 6-month period.

A myriad of complications due to PIMS-TS were recorded before and after hospitalization.

Physical complications included upper/lower respiratory symptoms (63%), gastrointestinal involvement (95%), neurological involvement (52%), and dermatological or mucous membrane involvement (85%).

However, improvement of inflammatory markers and systems involvement were recorded in patients at 6 weeks and 6 months of follow-up. Further improvements were cited by the team.

“Systolic function and concentrations of troponin and NT-proBNP were normal in all patients by 6 months,” the investigators wrote.

“By 6 months, echocardiograms in 44 (96%) of 46 patients had normalized. At 6 weeks, one patient had large coronary artery aneurysms (maximum Z-score 9·18), which remained stable at 6 months but required dual antiplatelet therapy, and one had a residual clinically insignificant pericardial effusion. One patient with underlying sickle-cell disease had marginally enlarged coronaries at 6 months (maximum Z-score 2·9), which were treated with aspirin and less evident at 6 weeks than at 6 months.”

Despite advancements, concerns with physical functioning in participants were recorded by parents for the Pediatric Quality of Life Inventory (PedsQL).

In addition to physical responses, emotional and social responses were also recorded.

“Emotional lability was reported in 12 (26%) of 46 patients at 6 weeks and in seven (15%) of 46 patients at 6 months,” the team wrote. “The median Paediatric Index of Emotional Distress score at 6 months was 6 (IQR 5–13), with three (7%) of 46 patients scoring above the clinical cutoff of 20, indicating a risk of clinically significant emotional distress.”

Additionally, parents reported anxiety about potential PIMS-TS relapses in their children and admitted to taking additional isolation precautions beyond UK Government guidance as a result. Despite hesitancy, 45 (98%) patients were back in full-time education after the 6-month period.

While further study of PIMS-TS was evident, as its impact was varied and concerning, researchers considered the 6-month study to be a success. They urged for longer-term prospective multicenter studies to aid in validating their findings and praised the multidisciplinary follow-up models utilized in the process.

“Irrespective of treatments received in the acute phase, our patients' outcomes were generally favorable, although severe sequelae did persist in some patients,” the team wrote. “The health outcomes reported in this study serve to provide guidance to families and health-care providers and outline general expectations as they relate to the natural history of PIMS-TS.”

The study, “6-month multidisciplinary follow-up and outcomes of patients with pediatric inflammatory multisystem syndrome (PIMS-TS) at a UK tertiary pediatric hospital: a retrospective cohort stud,” was published online in The Lancet Child & Adolescent Health.