Demographics and Clinical Presentation
During this 1-month study period, 15 patients met the case definition for PIMS-TS (Table 3). The median age was of 8.8 years (IQR 6.4–11.2 years). Notably 14 (93%) were over 5 years of age. Eleven out of 15 (73%) were male. All patients were from African/Afro-Caribbean, South Asian, Mixed or other minority ethnic groups (Table 3).
All 15 patients presented with pyrexia (median duration of 5 days). Thirteen (87%) had gastrointestinal symptoms and 8 (53%) had features of Kawasaki disease not fulfilling diagnostic criteria. Generalized myalgia and lethargy were also reported in 4 patients each (27%).
Two patients described typical COVID-19 symptoms in the previous two months, both of whom had positive SARS-CoV-2 PCR. Another 3 patients had family members with COVID-19 symptoms in the preceding 2 months.
Blood results (Table 3) showed raised inflammatory markers (C-reactive protein, ESR, ferritin) during the early part of the disease in keeping with published studies [5, 20]. Median peak C-reactive protein (CRP) was 154 (IQR 42–265)mg/L, median ESR was 75 (IQR 45–90)mm/h, and median peak ferritin 558 (IQR 31–2891)ng/mL. Cardiac markers were elevated in all patients with median peak Troponin I 396 (IQR 100–1280)ng/L, Creatine Kinase (CK) median peak 385 (IQR 117-1615)U/L and pro-B-type Natriuretic Peptide (pro-BNP) median peak 24,470 (IQR 17,212–26,655)pg/mL. The median peak for all three cardiac markers was on day 2 of hospital admission with gradual improvement thereafter.
Two patients had positive SARS-CoV-2 PCR, one at the time of admission and one four weeks previously. SARS-CoV-2 serology was available for 12 of 15 patients, all of whom were positive for the combined IgG, IgA and IgM ELISA.
Fourteen patients had chest radiographs; 7 were normal, 7 had abnormalities including pleural effusions (5), consolidation (3), cardiomegaly (2). Six patients had abdominal ultrasound due to persistent gastrointestinal symptoms, showing no abnormalities.
During their admission, two patients had non-coronary CT Angiograms and one had a MRI whole body, due to persisting inflammation despite treatment, all of which showed no evidence of vasculitis.
Nine patients (60%) had abnormalities on ECG (Table 4). Six of these had normalization of their ECG prior to discharge at median 5 days.
Fourteen patients (93%) had coronary artery abnormalities noted on echocardiography, which we have described as prominent, dilated or aneurysmal (Table 5). Of these:
1 had moderate fusiform aneurysm of right coronary artery (RCA) and small fusiform aneurysm of left anterior descending artery (LAD)
6 had ectatic dilated coronaries with increased z-scores of either left main coronary artery (2 patients) or left anterior descending artery (4 patients).
7 had prominent coronary arteries on echocardiogram but normal measurements.
Of the 14 patients with coronary changes, 13 (93%) had changes at presentation whilst 1 (7%) developed abnormal appearance on day 5 of admission. In 6 (43%) the coronary appearance normalized at a median 3 days, whilst the other 8 continued to have abnormal appearances at discharge.
Atrioventricular Valve Regurgitation (AVVR) (Table 6)
Thirteen patients had AVVR during admission, of which 10 had mitral regurgitation. There was serial improvement in 7 of these 10 patients, at median 2 days. Nine had non-physiological tricuspid regurgitation (mild-moderate), 5 of which improved at median 1 day after treatment. At discharge 7 patients had residual non-physiological AVVR. No patients had valve stenosis.
Ventricular Function (Tables 7 and 8)
Fractional Shortening was reduced in 8 patients, of whom 7 had changes on presentation and 1 developed subsequent changes. For those with impaired function, median FS at its nadir was 18% (IQR 17–20%) and all normalized before discharge (median 3 days).
LV ejection fraction was impaired in 12 patients (80%), 9 at presentation and in 3, there was a reduction after admission. For those with impaired function, the median of the lowest LVEF was 44% (IQR 38–50%). One patient had severe impairment on presentation (LVEF 28%) with improvement to mild impairment (LVEF 53%) at discharge. Three had moderate impairment which all normalized by discharge. The remaining 8 patients had mild impairment, of whom 7 had normalization of LVEF at discharge and 1 had an EF of 50%. Overall, normalization of LVEF took median 4 days in these 10 patients.
MAPSE z-score was reduced in 11 patients, of whom 10 had normalization after a median of 5 days.
MR dP/dt was available on admission echocardiograms in 7 patients, in whom 4 had impairment (2 mild, 2 moderate). In the 2 patients with mild impairment, mitral regurgitation resolved after the initial echocardiogram and so repeat assessment of dP/dt was not possible. For the other 2 patients with moderate impairment, MR was still present and they had normalized dP/dt at median 4 days.
In the 12 patients with LV dysfunction by ejection fraction, 9 also had reduced MAPSE on z-score, 8 had reduced fractional shortening, and 4 reduced MR dP/dt. Of these 12 with impaired LVEF, 10 normalized prior to discharge and the remaining 2 had mild impairment (LVEF 50% and 53%) at discharge.
Two patients had evidence of diastolic dysfunction with abnormal E/A and E/E′ ratios.
RV systolic function was assessed using tricuspid annular excursion (TAPSE). Using z-scores of TAPSE, 10 patients had impaired RV function with normalization in all at median 3 days. Subjective assessment of RV size and function did not show any abnormalities at any point.
Small pericardial effusion was present in 8 patients, half had complete resolution by discharge at median 5 days. The remaining 4 had small pericardial effusion at discharge.
Ten patients received intravenous immunoglobulin (IVIG), of whom 2 received a second dose. Five patients received IV methylprednisolone followed by weaning course of oral prednisolone. No patients needed Infliximab. None needed therapeutic anti-coagulation. Eleven patients (73%) were discharged on low dose aspirin with 2 requiring high doses initially. All patients were treated with broad-spectrum antibiotics for at least 5 days. Ten (67%) needed intensive care with a median stay of 4 days (IQR 3–5 days). Eight needed respiratory support, of whom half required mechanical ventilation (median 3 days) and others required high-flow nasal cannula support.
Ten patients (67%) needed fluid resuscitation with a median of 58 mL/kg (IQR 35-60 mL/kg) intravenous fluid boluses given. Ten (67%) required inotropes/vasopressors for a median of 3 days (IQR 2–3 days). Norepinephrine was used in 8 with additional support using vasopressin in 3 to treat systemic hypotension. Intravenous hydrocortisone was used for refractory hypotension in 8 patients. Nine required epinephrine to support LV dysfunction. One patient was transferred from an external hospital on milrinone, which was weaned off.
No patients needed extracorporeal life support (ECLS) in our cohort.
There were no deaths in our cohort. Median inpatient stay was 12 days (IQR 9–13 days). All 15 patients were discharged home clinically well with normal/improving biochemical and cardiac parameters. All are planned for clinical review one week after discharge in a multi-disciplinary clinic with repeat blood tests, ECG & echocardiogram.
Twelve patients (80%) have had their first clinic review with stable clinical and echocardiogram findings. There were no new coronary changes and no deterioration in cardiac function. Two patients have had outpatient CT coronary angiogram, both of which have mirrored echocardiographic findings with no new abnormalities.