To the best of our knowledge, this study is reporting one of the largest prospective case series of MISC syndrome published yet from India with a total of 78 cases. Our knowledge about the epidemiology, pathogenesis, clinical spectrum, and associated laboratory abnormalities seen in MISC syndrome is still evolving [7]. The diagnostic criteria of MISC are constantly revised with time as more evidence is being generated [7, 10].
Our study identified that the most commonly affected age group was 6 to 12 years accounting for more than 50% of the study population. This finding was in agreement with other similar published studies [9, 12,13,14]. We also noticed that girls were affected more than boys (M: F ratio of 1:1.9). Similar finding was also seen in another study by Dhanalakshmi et al. ( M:F ratio of 1:1.4 out of 19 cases) whereas most other studies showed male predisposition—Hoste et al. (M:F—1.4:1 out of 928 cases), Goldfred et al. (M:F—1.2:1 out of 570 cases), Sethy et al. (M:F—3.2:1 out of 21 cases), Kaushik et al. (M:F—1.6:1 out of 33 cases), and Sugunan et al. (M:F—1.9:1 out of 32 cases) [9, 12,13,14,15,16].
Though COVID RT-PCR was done in all patients, none were found to be positive. Rapid antigen test was positive in only one (1.3%) child. COVID-19 antibody was positive in 69 (88%) children. Fifty-four (69%) children had a history of contact with COVID positive cases. Other studies have shown RT-PCR positive in 19% to 31% of cases [9, 13, 15]. In our population, we noted a 2–6-week lag period for MIS-C presentation following COVID-19 infection or contact with COVID-19 case.
The most common presentations were lethargy (69%), poor oral intake (59%), rash (48%), vomiting (39.7%) and conjunctival congestion (39.7%). The presence of rash and conjunctival congestion were proportionately higher with the increasing age of children. Gastrointestinal system involvement was seen in 62% of our study population which was lower than global data of 86% as reported by recent systematic reviews [14, 17].
Leukocytosis, high N/L ratio and thrombocytopenia were found in 45%, 20%, and 37% of patients respectively. C-Reactive protein (CRP) was elevated in 58 (74%) patients. 38 (48%) had elevated ESR [18]. Serum Ferritin, d-dimer, and LDH were elevated in 21%, 34%, and 5% respectively. In contrast, elevated CRP, ferritin, and d-dimer were found in a higher proportion of children in the reported literature [17].
Fifty-four percent of patients had biochemical evidence of hepatic dysfunction as evidenced by elevated SGOT, SGPT, or both, similar to a study published from South India [9]. In our study, 25.7% of patients had renal dysfunction as evidenced by elevated serum urea or creatinine or both and 1 (1.3%) required hemodialysis. In a study by Williams et al., incidence of AKI was 35% and 2% required renal replacement therapy [17]. Epididymitis was seen in only 1 study subject. In a multi-center cohort study, 1 out of 232 children of MIS-C developed epididymitis [19].
Hypoxemia was observed in 15% of patients at presentation out of which 4% had SpO2 below 80%. Eight percent of patients had abnormal chest radiograph. Eleven (14%) children required respiratory support and 2 (2.6%) children needed invasive mechanical ventilation. The need for invasive mechanical ventilation was ranging from 0 to 39% in published studies [8, 9, 15].
Nine percent of our patients had serositis (5.4% had pleural effusion, 1.4% had ascites, and 2.7% had polyserositis). One systematic review revealed the incidence of pericardial effusion to be 22% [14].
Thirty-three percent of children were hypotensive at presentation. In one study, the incidence of hypotension at admission was found to be 47% [13]. Cardiac involvement was found in a significant number of cases in our population. The most common abnormality was coronary artery dilation which was observed in 19.2% of cases. Another study revealed the similar incidence of coronary artery involvement [15]. Incidence of myocardial systolic dysfunction was relatively less (7.7%) in our study compared to 63% in data from New York by Kaushik et al. [16]. Fifty-eight (74.3%) of children presented with shock out of which 28 (35.9%) were fluid refractory requiring inotropes. Similar results were reported by Hoste et al. [14]. In studies from New York by Kaushik et al., 51% required vasopressor support [16].
While neurological involvement was seen in up to 48% of cases in some studies, our population had only 5.1% of children presenting with seizures and altered sensorium [13].
Though IVIg, steroids, anticoagulation, and aspirin are the mainstay of therapy in MISC syndrome, there is limited evidence to support their use. Due to the striking similarities of this syndrome with Kawasaki disease, the same treatment is being recommended for MIS-C as well [7, 14, 17]. Our study group received IVIg as the first-line treatment followed by steroids, anticoagulation, and aspirin but we did not use biological agents. Seventy percent of our patients received both IVIg and steroids. There is no evidence-based consensus for managing MIS-C syndrome which reinforces the immediate need for such studies.
The overall prognosis was good in our patients when compared to global data. The mean duration of hospital stay was 4.7 days. And mean duration of ICU stay was 2.8 days.
Out of 78 children, 77 survived and 1 child (1.3%) died. Most of the other Indian and western studies also revealed similar incidence of mortality, ranging from 0 to 3%. Only one study from Odisha reported 9% mortality [13].
The main limitation of this study is the small sample size and lack of follow-up. Long-term follow-up can throw more light on chronic complications of MIS-C in children.
