Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step?
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analyses
3. Results
3.1. Distribution of Patients in the Study Period
3.2. Clinical Characteristics and COVID-19 Related Data of Patients
3.3. Laboratory and Cardiac Findings of Patients
3.4. Treatments of Patients with MIS-C
3.5. Evaluation of the Performance of Laboratory Tests in Distinguishing Cases According to Risk Groups
- An increase of 1000 units in BNP values increases the risk of being high-risk by 12.5%.
- A one-unit increase in total protein values reduces the risk of being high-risk by 36.8%.
- Those with a troponin value increased by ≥10-fold have a 9.5 times higher risk of being high-risk than those with a lower value.
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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All MIS-C | Low-Risk Group | High-Risk Group | p * | |
---|---|---|---|---|
Number of patients, n (%) | 99 (100) | 59 (59.6) | 40 (40.4) | |
Age, month, median (min.–max.) | 83 (3–205) | 73 (16–191) | 95.5 (3–205) | 0.07 |
Age groups, n (%) | 0.03 | |||
<72-month-old | 37 (37.4) | 27 (45.8) | 10 (25.0) | |
≥72-month-old | 62 (62.6) | 32 (54.2) | 30 (75.0) | |
Gender male, n (%) | 63 (63.6) | 38 (64.4) | 25 (62.5) | 0.84 |
Pre-existing medical condition, n (%) | 10 (10.1) | 1 (1.7) | 9 (22.5) | N/A ** |
Autoinflammatory diseases | 2 (2.0) | - | 2 (5.0) | |
Asthma | 2 (2.0) | 1 (1.7) | 1 (2.5) | |
Metabolic diseases | 2 (2.0) | - | 2 (5.0) | |
Malignancy | 2 (2.0) | - | 2 (5.0) | |
Congenital heart disease | 1 (1.0) | - | 1 (2.5) | |
Chronic kidney disease | 1 (1.0) | - | 1 (2.5) | |
Kawasaki Disease symptoms, n (%) | ||||
Fever | 99 (100) | 59 (100) | 40 (100) | - |
Conjunctivitis | 69 (69.7) | 41 (69.5) | 28 (70.0) | 0.97 |
Rash | 64 (64.6) | 41 (69.5) | 23 (57.5) | 0.22 |
Oral mucous membrane changes | 48 (48.5) | 27 (45.8) | 21 (52.5) | 0.51 |
Peripheral extremity changes | 30 (30.3) | 14 (23.7) | 16 (40.0) | 0.08 |
Cervical lymphadenopathy (>1.5 cm) | 13 (13.1) | 8 (13.6) | 5 (12.5) | 0.87 |
Number of positive criteria (instead of fever) for Kawasaki Disease, n (%) | 0.53 | |||
≤1 | 32 (32.3) | 20 (33.9) | 12 (30.0) | |
2–3 | 52 (52.5) | 32 (54.2) | 20 (50.0) | |
≥4 | 15 (15.2) | 7 (11.9) | 8 (20.0) | |
Other symptoms and findings, n (%) | ||||
Abdominal pain *** | 59 (67.8) | 36 (70.6) | 23 (63.9) | 0.51 |
Nausea/vomiting | 64 (64.6) | 38 (64.4) | 26 (65.0) | 0.95 |
Diarrhea | 47 (47.5) | 29 (49.2) | 18 (45.0) | 0.68 |
Headache *** | 22 (30.6) | 15 (37.5) | 7 (21.9) | 0.15 |
Respiratory distress | 15 (15.2) | 0 (0) | 15 (37.5) | N/A ** |
Arthralgia/arthritis | 14 (14.1) | 9 (15.3) | 5 (12.5) | 0.70 |
Organomegaly (hepatomegaly or splenomegaly) | 13 (13.1) | 5 (8.5) | 8 (20.0) | 0.09 |
Neurological symptoms/findings (except headache) | 7 (6.1) | 0 (0) | 7 (17.5) | N/A ** |
COVID-19 history, n (%) | 0.97 | |||
Previous SARS-CoV-2 infection § | 25 (25.3) | 15 (25.4) | 10 (25.0) | |
Close contact with a case but no infection | 43 (43.4) | 26 (44.1) | 17 (42.5) | |
No close contact or a history of infection | 31 (31.3) | 18 (30.5) | 13 (32.5) | |
The severity of previous SARS-CoV-2 infection †, n (%) | 0.15 | |||
Non-severe (no need for hospitalization) | 23 (92.0) | 15 (100) | 8 (80.0) | |
Need of hospitalization | 2 (8.0) | 0 (0) | 2 (20.0) | |
Duration between COVID-19 (or contact) and MIS-C ‡ week, median (min.–max.) | 4 (2–16) | 4 (2–16) | 4 (2–9) | 0.34 |
Duration between the onset of the MIS-C symptoms and admission, day median (min.–max.) | 5 (1–10) | 5 (1–10) | 5.5 (1–10) | 0.39 |
SARS-CoV-2 PCR and serology results at the admission, n (%) | 0.23 | |||
PCR and serology are both positive | 4 (4.0) | 1 (1.7) | 3 (7.5) | |
PCR positive—serology negative | 1 (1.0) | 0 | 1 (2.5) | |
PCR negative—serology positive | 93 (93.9) | 57 (96.6) | 36 (90.0) | |
PCR and serology are both negative | 1 (1.0) | 1 (1.7) | 0 | |
Chest X-ray abnormal findings, n (%) | 24 (24.2) | 5 (8.5) | 19 (47.5) | <0.001 |
Low blood pressure (hypotension/shock), n (%) | 13 (13.1) | 0 (0) | 13 (32.5) | N/A ** |
Respiratory support (high flow oxygen or invasive mechanical ventilation) need, n (%) | 15 (15.2) | 0 (0) | 15 (37.5) | N/A ** |
ICU admission, n (%) | 15 (15.2) | 0 (0) | 15 (37.5) | N/A ** |
Length of stay, day median (min.–max.) | 7 (3–24) | 6 (3–9) | 10,5 (6–24) | N/A ** |
Mortality, ratio (%) | ||||
General mortality | 3/99 (3.0) | 0 (0) | 3/40 (7.5) | 0.03 |
Mortality with a pre-existing medical condition | 2/10 (20) | 2/9 (22.2) | ||
Mortality in previously healthy children | 1/89 (1.1) | 1/31 (3.2) |
Variables * | Patients with MIS-C ** (n = 93) | Reference Ranges |
---|---|---|
WBC (cell/mm3) | 6281 ± 2592 | |
Absolute lymphocyte count (cell/mm3) | 930 (200–4920) | |
Absolute neutrophil count (cell/mm3) | 4365 ± 2255 | |
Platelet count (cell × 103/mm3) | 152 (27–490) | |
ESR (mm/h) | 42.6 ± 24.4 | 0–20 |
C-reactive protein (mg/dL) | 155.5 ± 90.0 | 0–0.5 |
Procalcitonin (ng/mL) | 6.0 (0.1–100) | 0–0.5 |
Ferritin (ng/mL) | 534 (108–7800) | 14–124 |
BNP (pg/mL) | 4611 (52–48050) | 0–125 |
LDH (U/L) | 343 (61–4285) | 120–300 |
ALT (U/L) | 39 (7–838) | 0–33 |
AST (U/L) | 45 (9–965) | 0–32 |
Total bilirubin (mg/dL) | 0.41 (0.1–8.37) | 0–0.9 |
Direct bilirubin (mg/dL) | 0.20 (0.06–7.06) | 0–0.3 |
Total protein (g/dL) | 5.84 ± 0.84 | 6–8 |
Albumin (g/dL) | 2.80 ± 0.49 | 3.2–4.5 |
Sodium (mEq/L) | 131.7 ± 3.7 | 136–145 |
BUN (mg/dL) | 13.4 (5.6–87.9) | 5–18 |
Creatinine (mg/dL) | 0.52 (0.24–3.19) | 0.4–0.9 |
aPTT (s) | 31.1 (22.3–58.0) | 25–36 |
PT (s) | 14.1 (11.4–62.3) | 10–14 |
INR | 1.26 (0.96–5.85) | 0.8–1.2 |
D-dimer (ng/mL) | 4620 (600–63000) | 0–500 |
Fibrinogen (mg/dL) | 486.9 ± 173.4 | 180–350 |
Findings n (%) * | All MIS-C (n = 99) | Low-Risk MIS-C (n = 59) | High-Risk MIS-C (n = 40) | p ** |
---|---|---|---|---|
Valvulitis | 72 (72.7) | 41 (69.49) | 31 (77.5) | 0.38 |
Valve involved Mitral Tricuspid Aortic Pulmonary | 71 (71.7) 25 (25.3) 10 (10.1) 3 (3.0) | 41 (69.5) 8 (13.6) 2 (3.4) 0 (0) | 30 (75.0) 17 (42.5) 8 (20.0) 3 (7.1) | 0.55 0.001 0.007 0.06 |
Number of valves involved None 1 2 >2 | 27 (27.3) 41 (41.4) 24 (24.2) 7 (7.1) | 18 (30.5) 30 (50.8) 11 (18.6) 0 (0) | 9 (22.5) 11 (27.5) 13 (32.5) 7 (17.5) | 0.004 |
Valvular maximum insufficiency degree None 1 2 3 | 27 (27.3) 65 (65.7) 6 (6.1) 1 (1.0) | 18 (30.5) 41 (69.5) 0 (0) 0 (0) | 9 (22.5) 24 (60.0) 6 (15.0) 1 (2.5) | 0.011 |
Left ventricular dysfunction | 10 (10.1) | 0 (0) | 10 (25.0) | N/A |
Troponin levels Normal or <10-fold of the upper limit Increased by ≥10-fold of upper limit | 90 (90.9) 9 (9.1) | 57 (96.6) 2 (3.4) | 33 (82.5) 7 (17.5) | 0.017 |
Myocarditis | 14 (14.1) | 3 (5.1) | 11 (27.5) | 0.002 |
Pericardial effusion | 12 (12.1) | 4 (6.8) | 8 (20.0) | 0.048 |
Coronary artery involvement | 10 (10.1) | 0 (0) | 10 (25.0) | N/A |
Transient sinus bradycardia | 62 (62.6) | 34 (57.6) | 28 (70.0) | 0.21 |
Duration between fever ending and bradycardia starting, median day (min.–max.) | 2 (0–6) | 1.5 (0–3) | 2 (0–6) | 0.15 |
Treatment Regime, n (%) | Low-Risk (n = 59) | High-Risk (n = 40) | p |
---|---|---|---|
IVIG plus steroid | 46 (78.0) | 39 (97.5) | 0.045 * |
IVIG only | 8 (13.6) | 1 (2.5) | |
Steroid only | 3 (5.1) | 0 (0) | |
IVIG or steroid not used | 2 (3.4) | 0 (0) |
Variable | OR | 95% CI for OR | p * |
---|---|---|---|
BNP (10−3) | 1.125 | 1.047–1.209 | 0.001 |
Total protein ** | 2.717 | 1.130–6.536 | 0.026 |
Troponin level (Increased by ≥10-fold upper normal limit) | 9.491 | 1.287–70.018 | 0.027 |
Method | Cut-Off Value | Accuracy | Sensitivity | Specificity | PPV | NPV | AUC |
---|---|---|---|---|---|---|---|
Univariate ROC Analysis | |||||||
Procalcitonin | 4.5 | 0.607 | 0.706 | 0.509 | 0.453 | 0.75 | 0.614 |
Platelet | 73,000 | 0.429 | 0.824 | 0.034 | 0.329 | 0.25 | 0.566 |
Ferritin | 546 | 0.721 | 0.765 | 0.678 | 0.578 | 0.833 | 0.742 |
BNP | 8332 | 0.77 | 0.676 | 0.864 | 0.742 | 0.823 | 0.772 |
ALC | 780 | 0.606 | 0.5 | 0.712 | 0.5 | 0.712 | 0.627 |
D-dimer | 2890 | 0.674 | 0.912 | 0.407 | 0.478 | 0.923 | 0.681 |
Total protein | 5.48 | 0.69 | 0.618 | 0.763 | 0.6 | 0.776 | 0.75 |
Combined Tests Analysis (Machine Learning) | |||||||
Decision Tree (CART) | 0.77 | 0.676 | 0.864 | 0.742 | 0.823 | ||
SVM w/radial basis function | 0.859 | 0.735 | 0.983 | 0.962 | 0.866 | ||
Logistic regression | 0.785 | 0.823 | 0.746 | 0.651 | 0.88 | ||
Naïve Bayes | 0.836 | 0.706 | 0.966 | 0.923 | 0.851 | ||
LDA | 0.746 | 0.559 | 0.932 | 0.826 | 0.786 |
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Cetin, B.S.; Kısaarslan, A.P.; Tekin, S.; Goksuluk, M.B.; Baykan, A.; Akyıldız, B.N.; Seçilmiş, Y.; Poyrazoglu, H.; on behalf of the Erciyes MIS-C Study Group. Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step? J. Clin. Med. 2022, 11, 4615. https://doi.org/10.3390/jcm11154615
Cetin BS, Kısaarslan AP, Tekin S, Goksuluk MB, Baykan A, Akyıldız BN, Seçilmiş Y, Poyrazoglu H, on behalf of the Erciyes MIS-C Study Group. Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step? Journal of Clinical Medicine. 2022; 11(15):4615. https://doi.org/10.3390/jcm11154615
Chicago/Turabian StyleCetin, Benhur Sirvan, Ayşenur Paç Kısaarslan, Sedanur Tekin, Merve Basol Goksuluk, Ali Baykan, Başak Nur Akyıldız, Yılmaz Seçilmiş, Hakan Poyrazoglu, and on behalf of the Erciyes MIS-C Study Group. 2022. "Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step?" Journal of Clinical Medicine 11, no. 15: 4615. https://doi.org/10.3390/jcm11154615
APA StyleCetin, B. S., Kısaarslan, A. P., Tekin, S., Goksuluk, M. B., Baykan, A., Akyıldız, B. N., Seçilmiş, Y., Poyrazoglu, H., & on behalf of the Erciyes MIS-C Study Group. (2022). Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step? Journal of Clinical Medicine, 11(15), 4615. https://doi.org/10.3390/jcm11154615