Short- and mid-term outcomes of multisystem inflammatory syndrome in children: a longitudinal prospective single-center cohort study 2023 Roge et al

Background: Multisystem inflammatory syndrome in children (MIS-c) emerged during the coronavirus disease 2019 pandemic and is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the extensively studied clinical manifestation of acute condition, the short- and long-term effects of MIS-c on children's health are unknown.

Methods: This was a prospective longitudinal cohort study. Children aged <18 years who met the Centers for Disease Prevention and Control (CDC) diagnostic criteria and who were admitted to the Children's Clinical University Hospital of Latvia (CCUH) between July 1, 2020, and April 15, 2022, were enrolled in the study. An outpatient follow-up program was initiated in July 2020. All children were evaluated at 2 weeks, 2 months (1–3 months), and 6 months (5–7 months) after discharge. The face-to-face interviews comprised four domains as follows: symptom assessment, physical examination, laboratory testing, and cardiological investigation [including electrocardiogram (ECG) and echocardiography (echo)].

Results: Overall, 21 patients with MIS-c were enrolled. The median age of the study group was 6 years. At the 2-week follow-up, almost half of the patients (N = 10, 47.6%) reported exercise intolerance with provoked tiredness. Laboratory tests showed a considerable increase in blood cell count, with a near doubling of leukocyte and neutrophil counts and a tripling of thrombocyte levels. However, a decline in the levels of inflammatory and organ-specific markers was observed. Cardiological investigation showed significant improvement with gradual resolution of the acute-phase pathological findings. Within 2 months, improvement in exercise capacity was observed with 5-fold and 2-fold reductions in physical intolerance (N = 2, 9.5%) and physical activity-induced fatigue (N = 5, 23.8%), respectively. Normalization of all blood cell lines was observed, and cardiological investigation showed no persistent changes. At the 6-month visit, further improvement in the children's exercise capacity was observed, and both laboratory and cardiological investigation showed no pathological changes.

Conclusions: Most persistent symptoms were reported within the first 2 weeks after the acute phase, with decreased physical activity tolerance and activity-induced fatigue as the main features. A positive trend was observed at each follow-up visit as the spectrum of the children's complaints decreased. Furthermore, rapid normalization of laboratory markers and cardiac abnormalities was observed.

Open access, https://www.frontiersin.org/articles/10.3389/fped.2023.1223266/full

 

"Two weeks outcome
All children were examined 2 weeks after the MIS-c diagnosis was established. The patients were hemodynamically stable during the evaluation and showed significant clinical improvement after receiving immunomodulatory therapy. However, the most persistent complaint was decreased physical activity. Approximately half of the children (N = 10, 47.6%) reported exercise intolerance, which provoked tiredness after any exercise. Moreover, three children (14.3%) had difficulty walking for more than 15 min and climbing the stairs. Some of the patients also reported symptoms such as shortness of breath at rest (N = 5, 23.8%), fatigue (N = 4, 19%), irritability, and difficulty in concentrating (N = 2, 9.5% each). One patient (4.8%) reported persistent abnormal sensations on the scalp with accompanied headaches. However, no pathological clinical findings other than lymphadenopathy were observed during the physical examination."

 

From the discussion.

"According to our data, at the 2-week follow-up, almost half of the children (N = 10, 47.6%) experienced exercise intolerance with secondary-induced tiredness after any physical activity. Additionally, three children (14.3%) could not walk for more than 15 min or climb the stairs, and four (19%) had physical activity unrelated persistent fatigue. Within 2 months, improvement in exercise capacity was observed with a 5-fold and 2-fold reduction in physical intolerance (N = 2, 9.5%) and physical activity-induced fatigue (N = 5, 23.8%), respectively. However, no children reported physical activity-unrelated fatigue at the 2-month follow-up.

Similarly, post-inflammatory physical exercise intolerance was observed in other studies. Kahn et al. reported post-acute phase fatigue in 22% of the study population, with reduced exercise capacity in 7% of children at the 2-week follow-up. A significant reduction (14%) in fatigue was observed at the 8-week follow-up, whereas the reduced exercise capacity remained constant (18). Penner et al. also reported a significant reduction in functional exercise capacity, with 65% of the children scoring below the 3rd percentile in the 6-minute walking test 6 weeks after MIS-c. Alarmingly, continuous poor performance on the 6-minute walking test was observed in 45% of patients even 6 months post hyperinflammatory condition (19). Notably, a more positive outcome was recently reported by Ziebell et al., who analyzed cardiopulmonary exercise data with peak oxygen consumption (peak VO2) detection in children with MIS-c and viral/idiopathic myocarditis 3–6 months after an acute event. No statistically significant differences in exercise capacity were observed between the groups, indicating a possible return to the previous level of daily functioning after MIS-c (30). Similarly, a recent study by Chakraborty et al., showed normal exercise capacity in all patients who underwent a graded-exercise stress test (GXT) 4–6 months after acute MIS-c (31)."