Evaluation of long-term outcomes among survivors of pediatric critical illness has often lagged far behind the study of acute patient management and short-term outcomes such as inpatient mortality, length of stay, and organ dysfunction, with many postdischarge outcome studies not published until years to decades following reports of inpatient outcomes (1). Among the numerous commendable elements of the robust multicenter research collaborations that grew out of the COVID-19 pandemic (2–7) was the foresight to prioritize the study of long-term outcomes from the beginning. Within the first 18 months of the pandemic, literature was already beginning to emerge describing postdischarge outcomes for children surviving acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) (8–11).

Given the predominance of cardiovascular dysfunction and coronary anomalies identified in early reports of MIS-C (12), much of the initial literature describing postdischarge outcomes following MIS-C appropriately focused on cardiac outcomes. Reassuringly, studies evaluating patients 6 to 12 months following MIS-C have demonstrated normalization of cardiac function, resolution of coronary dilation or aneurysms, and no signs of persistent myocardial inflammation in most patients (2,4,8,9). Activity impairment and exercise intolerance have been more commonly reported in the months following hospitalization for MIS-C (4,6).

While cardiac impairment has remained the most prevalent organ system dysfunction in MIS-C, it has emerged that nearly two-thirds of PICU patients with MIS-C have neurologic involvement (13). It is within this context that Otten et al (14) examined neurocognitive, psychosocial, and quality of life outcomes among PICU patients surviving MIS-C in this issue of Pediatric Critical Care Medicine. The authors speculated that the pathogenesis of inflammation in the brain and throughout the body could contribute to long-term sequelae beyond cardiac and physical function.

Otten et al (14) conducted a prospective follow-up study as part of an ongoing nationwide cohort of children with COVID-19 in the Netherlands, one of the multiple large multicenter pediatric COVID-19 studies occurring throughout the world (2–7). They enrolled children admitted to seven university hospital PICUs with MIS-C from March 2020 to June 2021 and conducted in-person evaluations a median of 4 months following PICU admission. Of 56 eligible patients, 49 were seen through standardized multidisciplinary PICU follow-up programs present at each of the seven hospitals, a remarkable 88% follow-up rate. Patients and families participated in structured interviews with a pediatric intensivist and pediatric psychologist, underwent neurocognitive testing, and completed questionnaires assessing physical function, cognitive function, post-traumatic stress, emotional and behavioral problems, and quality of life. Most results were compared with Dutch general population norms collected prior to the COVID-19 pandemic (14).

The authors found that while general intelligence, verbal memory, and parent-reported executive function were comparable to general population norms, a subset of 29 children who underwent more extensive neurocognitive testing demonstrated deficits in visual memory, attention, and planning compared with the general population with at least half of the sample exhibiting abnormal memory and attention scores and one-third with abnormal planning scores. Children also had lower scores than population norms in the health-related quality of life domains of physical functioning, school functioning, and fatigue, and parents reported more emotional and behavioral problems. One-third of children scored at elevated risk for post-traumatic stress disorder, many reported that their sleep behavior and exercise tolerance had declined, and missed school days following discharge were common (14).

While these findings raise concerns about the potential effects of severe systemic inflammation on children’s neurocognitive and psychosocial recovery, it is also important to acknowledge the impact of the COVID-19 pandemic and associated social isolation and school closures on the mental health, behavior, quality of life, and school performance of children and young adults. When comparing patient outcomes to population norms, it is essential that the general population reflects the cohort of interest. This is often a major limitation in pediatric critical care research as PICU patients have a much higher prevalence of chronic illness (15), including neurodevelopmental, behavioral, and psychological comorbidities (16), compared with the general pediatric population.

While in this cohort only 38% of patients had preexisting comorbidities, making comparison to the general population more appropriate than for most PICU cohorts, the unique circumstances of the COVID-19 pandemic may have deemed pre-pandemic norms for typical child and adolescent psychosocial health nearly obsolete. Children in the general population have been found to have more emotional and behavioral difficulties compared with prior to the pandemic (17), with nearly 80% of children experiencing a negative impact on their behavior or psychological state (18). Multiple studies have demonstrated declines in health-related quality of life in children and adolescents during the pandemic (19), as well as frequent problems with sleep (18,20) and inattention (18) and worse school performance (21). Given that many of the impairments identified in the Otten et al (14) MIS-C cohort parallel problems in the general pediatric population during the pandemic, it is challenging to separate the potential effects of MIS-C itself or PICU exposure in general from challenges these children might have experienced regardless of their acute illness.

In considering how future studies could overcome this limitation, comparison of patients’ postdischarge outcomes to their own individual baseline status from immediately prior to the onset of critical illness would better reflect the impact of the illness itself, although would still be limited by an inability to distinguish the effects of the specific disease pathology from critical illness or PICU exposures in general. Furthermore, given how rapidly changes were observed in children’s and adolescents’ mental health, quality of life, and school performance after the onset of the pandemic, it is conceivable that changing environmental and social influences could differentially impact patients’ recovery during long follow-up periods. A study design that contrasts changes from baseline to follow-up between two different PICU cohorts (e.g., patients with MIS-C vs unplanned PICU admissions without MIS-C) over the same time period may be the most effective approach to addressing the question of the impact of a given illness process on patient outcomes.

Despite these limitations, the study by Otten et al (14) highlights the importance of comprehensive patient follow-up and the unique benefits of incorporating standardized PICU follow-up into routine clinical care. The Dutch Association for Pediatrics has implemented a guideline of care that recommends that every PICU in the Netherlands provide follow-up for patients with unplanned admissions, those who are previously healthy, and those who experience organ failure or receive PICU therapies such as mechanical ventilation or central venous access. The guidelines also provide recommendations for the types of evaluations performed including neuropsychologic testing (22).

At the onset of the pandemic, all of the Dutch PICUs collaborated to standardize their follow-up programs for COVID-19 and MIS-C patients such that the extensive neurocognitive and psychosocial assessments reported in the study by Otten et al (14) are considered a national standard of care. This comprehensive national approach is in stark contrast to the state of PICU follow-up in the United States, where few multidisciplinary follow-up programs exist, neuropsychologic testing is limited, and there is minimal integration across centers (23). While there are obvious differences in the feasibility of standardizing care across seven PICUs in the Netherlands compared with hundreds of PICUs in the United States or other large countries, the Dutch model confers a extremely valuable opportunity to study these important neuropsychologic outcomes with comprehensive, in-person assessments and high rates of patient follow-up.

Despite challenges in knowing the relative contribution of MIS-C pathology, the PICU experience, and the general pandemic environment to the patient outcomes described in the study by Otten et al (14), their findings that over one-third of children surviving MIS-C experienced deficits across a range of neurocognitive, psychosocial, and quality of life domains is alarming. The emerging literature describing physical, emotional, social, and psychological declines in both survivors of acute COVID-19 and MIS-C as well as children and adolescents in the general population living through the COVID-19 pandemic should be a call to action to improve support services for all children and families. For the PICU population in particular, this begins with recognition that the impact of critical illness extends beyond the hospital doors for most patients and families, and that comprehensive, multidisciplinary follow-up is essential to identify deficits and initiate targeted interventions. The early integration of postdischarge follow-up into the collaborative pediatric COVID-19 research networks around the world is a promising trend that hopefully will be replicated in future research protocols, with the ultimate goal that PICU follow-up becomes increasingly integrated into both research and clinical standard care as exemplified in the Dutch model.

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