COVID-19 in Infants and Children under 2 Years—Could Lung Ultrasound Score Be Correlated with Biomarkers and Symptoms?
Abstract
:1. Introduction
- Transverse physiologic A-lines that depict healthy parenchyma;
- Isolated/sparse vertical B-lines are equivalent to interstitial edema;
- Confluent vertical B-lines correspond to alveolar edema;
- Subpleural/peripheral consolidations;
2. Patients and Methods
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- Infants with SARS-CoV-2 infection that were hospitalized for more than two days;
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- Children under 2 years of age with SARS-CoV-2 infection who had been hospitalized for more than two days.
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- Infants and children with SARS-CoV-2 infection that were hospitalized for less than two days;
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- Infants and children with chronic lung diseases such as bronchopulmonary dysplasia, cystic fibrosis, immunodeficiency, etc.;
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- Children over the age of 2 years with SARS-CoV-2 infection;
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- Infants and children lacking informed consent from parents or legal guardians.
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- Gender;
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- Age (months);
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- Anthropometric measurements (weight of children);
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- Number of positive PCR tests;
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- Days of hospitalization/days of convalescence;
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- Signs and symptoms of the infection (psychomotor agitation, asthenic syndrome, fever, cough, rhinorrhea, acute dehydration syndrome, vomiting, diarrhea, nasal obstruction, dysphagia, dysphonia, loss of appetite, dyspnea, oropharyngeal candidiasis, presence of inflammatory lymph nodes, presence of congestive pharynx);
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- Other associated pathologies;
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- Biological markers and inflammatory probes (hemoglobin, leukocytes, lymphocytes, neutrophils, monocytes, thrombocytes, erythrocyte sedimentation rate, procalcitonin, C-reactive protein, ferritin, LDH, hepatic transaminases, bilirubin, D-dimer level, fibrinogen, interleukin-6);
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- Bacterial and fungal cultures;
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- Imaging examinations;
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- Score of lung affection based on ultrasound.
3. Results
3.1. Demographic Data
3.2. Clinical and Biological Markers of COVID-19 Infection in Infants and Children under 2 Years
3.3. Lung ultrasound investigation, score and correlation
4. Discussion
4.1. Limitation of Study/Weakness
4.2. Further Directions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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LUSS = 0 Points | LUSS = 1 Point | LUSS = 2 Points | LUSS = 3 Points |
---|---|---|---|
Normal/physiological A-lines | More than 2 B-lines (sparse B-lines) with associated pleural abnormalities | Coalescent or confluent B-lines | Large peripheral consolidation (wider than 1 cm) in association or not with air bronchogram |
One or two B-lines per intercostal space | ‘White-lung’ aspect or small peripheral consolidation (smaller than 1 cm) |
Infants and Children’s Characteristics | Entire Lot n = 19 | Patients with Respiratory Involvement (n = 12) | Patients without Respiratory Involvement (n = 7) | Independent Samples Tests |
---|---|---|---|---|
Age (Months) Mean ± S.D. Min; Max | 11.21 ± 7.70 1; 24 | 13.16 ± 8.33 2; 24 | 7.87 ± 5.49 1; 18 | Test Statistic t = −1.49 p = 0.15 |
Weight (Kilograms) Mean ± S.D. Min; Max | 9.04 ± 3.08 3.5; 13.6 | 9.63 ± 2.95 4.5; 13.5 | 8.02 ± 3.26 3.5; 13.6 | Test Statistic t = −1.09 p = 0.28 |
Total PCR Tests Per Child Median; [IQR] Min; Max | 1; [1;2] 1; 3 | 1.5; [1;2] 1; 3 | 1; [1;2] 1; 3 | Mann–Whitney U = 39 p = 0.77 |
Days of Hospitalization Per Child Mean ± S.D. Min; Max | 4.68 ± 1.73 2; 9 | 5 ± 1.20 3; 7 | 4.14 ± 2.41 2; 9 | Test Statistic t = −1.04 p = 0.31 |
Days of convalescence per child Mean ± S.D. Min; Max | 7.68 ± 2.35 4; 13 | 7.75 ± 2.37 5; 13 | 7.57 ± 2.50 4; 12 | Test Statistic t = −1.55 p = 0.87 |
Second Positive PCR tests | 57.9% (n = 11) |
Signs and Symptoms in Infants and Children | n = 19 (Percentage %) | Patients with Respiratory Involvement n = 12 (Percentage % of the Entire Lot) | Patients without Respiratory Involvement n = 7 (Percentage % of the Entire Lot) |
---|---|---|---|
Moderately influenced general condition | 11 (57.89) | 8 (42.10) | 3 (15.78) |
Slightly influenced general condition | 8 (42.10) | 4 (21.05) | 4 (21.05) |
Psychomotor agitation | 3 (15.78) | 2 (10.52) | 1 (5.26) |
Asthenic syndrome | 8 (42.10) | 6 (31.57) | 2 (10.52) |
Fever (≥37.5 °C) | 16 (84.21) | 10 (52.63) | 6 (31.57) |
Rhinorrhea | 7 (36.84) | 3 (15.78) | 4 (21.05) |
Nasal obstruction | 8 (42.10) | 5 (26.31) | 3 (15.78) |
Congestive pharynx | 14 (73.68) | 8 (42.10) | 6 (31.57) |
Dysphonia | 4 (21.05) | 2 (10.52) | 2 (10.52) |
Dysphagia | 2 (10.52) | 2 (10.52) | 0 |
Red eyes and runny nose | 2 (10.52) | 2 (10.52) | 0 |
Mild acute dehydration syndrome (<5% of weight) | 15 (78.94) | 9 (47.36) | 6 (31.57) |
Episodes of diarrhea | 3 (15.78) | 3 (15.78) | 0 |
Diarrhea with bloody stools | 1 (5.26) | 1 (5.26) | 0 |
Vomiting | 4 (21.05) | 3 (15.78) | 1 (5.26) |
Loss of appetite | 11 (57.84) | 8 (42.10) | 3 (15.78) |
Lateral-cervical lymph nodes | 3 (15.78) | 2 (10.52) | 1 (5.26) |
Dyspnea | 1 (5.26) | 1 (5.26) | 0 |
Glottis spasm | 1 (5.26) | 1 (5.26) | 0 |
Associated pathologies and comorbidities | |||
Oral candidiasis | 3 (15.78) | 2 (10.52) | 1 (5.26) |
Lactose intolerance | 2 (10.52) | 2 (10.52) | 0 |
Egg intolerance | 1 (5.26) | 1 (5.26) | 0 |
Seizures | 1 (5.26) | 1 (5.26) | 0 |
Repeated otitis | 1 (5.26) | 1 (5.26) | 0 |
Atopic dermatitis | 1 (5.26) | 0 | 1 (5.26) |
History of whooping cough | 1 (5.26) | 1 (5.26) | 0 |
Urinary tract infection | 1 (5.26) | 0 | 1 (5.26) |
Biomarker (Unit Measurement) | Mean ± S.D. or Median; [IQR] | Patients with Respiratory Involvement (n = 12) | Patients without Respiratory Involvement (n = 7) | Independent Samples Tests |
---|---|---|---|---|
Hemoglobin (g/dL) Min; Max | 11.50; [10.92; 12.10] 9.7; 12.7 | 11.50; [10.35; 12.15] 9.7; 12.7 | 11.50; [11.22; 12.05] 9.7; 12.5 | Mann–Whitney U = 39 p = 0.79 |
Leukocytes (×109/L) Min; Max | 7890; [6400; 11062.50] 4230; 31,700 | 8695; [6170; 14760] 4230; 31,700 | 7380; [6697.50; 8100] 5440; 12,360 | Mann–Whitney U = 34 p = 0.49 |
Lymphocytes (×109/L) Min; Max | 3960; [2427.5; 5787.5] 1060; 12,460 | 4140; [2180; 5720] 1060; 12,460 | 3120; [2815; 5655] 1800; 7760 | Mann–Whitney U = 41 p = 0.93 |
Neutrophiles (×109/L) Min; Max | 2410; [1512.5; 4685] 720; 22,270 | 3755; [1700; 6010] 1220; 22,270 | 1710; [965; 3360] 720; 5050 | Mann–Whitney U = 23 p = 0.10 |
Monocytes (×109/L) Min; Max | 1260; [797.5; 1697.5] 360; 3440 | 1635; [700; 2635] 360; 3440 | 1210; [967.5; 1402.5] 640; 1700 | Mann–Whitney U = 33 p = 0.44 |
Thrombocytes (×109/L) Min; Max | 360,000.00 ± 124,869.26 138,000; 589,000 | 348,750.00 ± 106,279.32 222,000; 574,000 | 379,285.71 ± 159,316.99 138,000; 589,000 | Test statistic t = 0.50 p = 0.62 |
Erythrocyte Sedimentation Rate (mm/h) Min; Max | 10; [10; 15] 5; 70 | 12.50; [9; 17.50] 5; 70 | 10; [10; 15] 5; 60 | Mann–Whitney U = 40 p = 0.86 |
LDH (U/L) Min; Max | 279.10 ± 74.29 159; 461 | 278 ± 86.57 159; 461 | 281 ± 53.02 210; 361 | Test statistic t = 0.08 p = 0.93 |
AST (U/L) Min; Max | 53; [31.40; 65.35] 20.4; 160.1 | 60.40; [33.95; 81.15] 20.4; 160.1 | 34.70; [26.95; 57.87] 26.3; 60.6 | Mann–Whitney U = 23 p = 0.10 |
CRP (mg/L) Min; Max | 5.57 [2.63; 8] 0.4; 191 | 4.44 [2.65; 8.34] 0.4; 89.42 | 5.57 [2.96; 7.75] 0.66; 191 | Mann–Whitney U = 41 p = 0.93 |
Fibrinogen (g/L) Min; Max | 3.41; [2.90; 4.04] 1.8; 6.2 | 3.66; [3.37; 4.01] 1.8; 6.2 | 2.94; [2.78; 4.28] 2.67; 5.05 | Mann–Whitney U = 29.50 p = 0.29 |
Procalcitonin (ng/mL) Min; Max | 0.18; [0.08; 0.27] 0.05; 2.1 | 0.19; [0.09; 0.28] 0.07; 0.44 | 0.17; [0.09; 0.18] 0.05; 2.1 | Mann–Whitney U = 35 p = 0.55 |
Ferritin (μg/L) Min; Max | 91.68; [55.82; 147.17] 0.77; 1087 | 106.50; [58.73; 176.62] 0.77; 1087 | 91.68; [59.87; 122.37] 34.29; 524.87 | Mann–Whitney U = 35 p = 0.55 |
D-dimer (mg/L) Min; Max | 0.78; [0.53; 1.66] 0.32; 2.31 | 0.88; [0.54; 1.72] 0.49; 2.31 | 0.76; [0.40; 1.45] 0.32; 1.74 | Mann–Whitney U = 34 p = 0.49 |
IL-6 (pg/mL) Min; Max | 8.94; [ 1.73; 16.35] 1.32; 31.3 | 12.95; [ 5.08; 23.12] 1.40; 31.3 | 1.92; [ 1.55; 11.25] 1.32; 12.49 | Mann–Whitney U = 22 p = 0.09 |
ALT (U/L) Min; Max | 22.70; [14.27; 30.60] 9; 85 | 25.95; [13.50; 49.85] 9; 85 | 22.30; [16.47; 25.25] 13.10; 29.7 | Mann–Whitney U = 34.50 p = 0.52 |
Urea (mg/dL) Min; Max | 20.78 ± 6.36 12.3; 33.3 | 21.69 ± 6.70 13.4; 33.3 | 19.24 ± 5.89 12.3; 28.8 | Test statistic t = −0.80 p = 0.43 |
Total Bilirubin (mg/dL) Min; Max | 0.19; [0.11; 0.30] 0.07; 0.63 | 0.20; [0.15; 0.41] 0.11; 0.63 | 0.11; [0.09; 0.19] 0.07; 0.60 | Mann–Whitney U = 21.50 p = 0.08 |
Median LUSS, [IQR] | Average Rank LUSS | Mann–Whitney U Value | p-Value | |
---|---|---|---|---|
Patients with respiratory involvement (n = 12) vs. patients without (n = 7)—Figure 5a | 6 vs. 3 [3; 7.5] vs. [2;3.75] | 12.12 vs. 6.37 | 16.50 | 0.02 |
Patients with fever (n = 16) vs. patients without fever (n = 3) | 4.5 vs. 2 | 10.31 vs. 8.33 | 19 | 0.57 |
Correlation between | Rank Correlation/Coefficient | 95% CI | p-Value | Graphic Representation |
---|---|---|---|---|
LUSS and LDH at symptomatic patients (respiratory involvement) | rho = 0.60 | 0.04 to 0.87 | 0.03 | Figure 6a |
LUSS and D-dimer level | rho = 0.55 | 0.139 to 0.807 | 0.01 | Figure 6b |
LUSS and D-dimer level at symptomatic infants and children (with respiratory involvement present) | rho = 0.62 | 0.07 to 0.88 | 0.03 | Figure 6c |
LUSS and D-dimer level at symptomatic infants and children (with fever present) | rho = 0.50 | 0.01 to 0.80 | 0.04 | |
LUSS and IL-6 level | rho = 0.64 | 0.26 to 0.84 | 0.00 | Figure 6d |
LUSS and IL-6 level at symptomatic infants and children (with respiratory involvement present) | rho = 0.48 | −0.11 to 0.83 | 0.10 | |
LUSS and IL-6 level at symptomatic infants and children (with fever present) | r = 0.45 | −0.05 to 0.77 | 0.07 | |
LUSS and O2 saturation level | R = −0.65 | −0.865 to −0.28 | 0.00 | Figure 7 |
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Stoicescu, E.R.; Lovrenski, J.; Iacob, R.; Cerbu, S.; Iacob, D.; Iacob, E.R.; Susa, S.R.; Ciuca, I.M.; Bolintineanu, L.A.; Ciornei-Hoffman, A.; et al. COVID-19 in Infants and Children under 2 Years—Could Lung Ultrasound Score Be Correlated with Biomarkers and Symptoms? Biomedicines 2023, 11, 2620. https://doi.org/10.3390/biomedicines11102620
Stoicescu ER, Lovrenski J, Iacob R, Cerbu S, Iacob D, Iacob ER, Susa SR, Ciuca IM, Bolintineanu LA, Ciornei-Hoffman A, et al. COVID-19 in Infants and Children under 2 Years—Could Lung Ultrasound Score Be Correlated with Biomarkers and Symptoms? Biomedicines. 2023; 11(10):2620. https://doi.org/10.3390/biomedicines11102620
Chicago/Turabian StyleStoicescu, Emil Robert, Jovan Lovrenski, Roxana Iacob, Simona Cerbu, Daniela Iacob, Emil Radu Iacob, Septimiu Radu Susa, Ioana Mihaiela Ciuca, Laura Andreea Bolintineanu (Ghenciu), Andreea Ciornei-Hoffman, and et al. 2023. "COVID-19 in Infants and Children under 2 Years—Could Lung Ultrasound Score Be Correlated with Biomarkers and Symptoms?" Biomedicines 11, no. 10: 2620. https://doi.org/10.3390/biomedicines11102620