Table 3.
Characteristics of neonates and infants under six months of age with MIS-C with fully described cases.
| Subject Number | First Author | Age/Sex/Comorbidities | RT-PCR and Serology for SARS-CoV-2 | Parental SARS-CoV-2 Exposure | Fever | Organ Involvement | Laboratory Work-Up | Imaging | Treatment | ICU Admission/Need for MV/Length of Hospital Stay | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Acharyya [13] |
4 months/M/NA | RT-PCR pos/NA | YES—his mother was also subsequently found positive for SARS-CoV-2. | Yes | Diffuse ectasia of coronary arteries; Erythematous macular rash over the trunk, palm and sole on day 2; Red lips, congested throat and small cervical lymphadenopathy; Irritability | CRP 11.56, Albumin 3, Anemia | Perivascular brightness and diffuse ectasia of coronary arteries (echocardiogram) | IVIG, aspirin | No/No/NA | Favorable |
| 2 | Alharbi [47] |
1 month/F/No | RT-PCR pos/NA | NA | No | Hypotension, increase in troponin; respiratory distress requiring MV for 12 days | Tn 2410, NT-proBNP 1127, ferritin 6130, IL-6 9.1 | Ejection fraction 60%, normal coronary arteries (echocardiogram) | IVIG, Anakinra, inotropes (not specified) | Yes/Yes/13 days | Death |
| 3 | Alharbi [47] |
3 months/M/No | RT-PCR pos/NA | NA | No | Hypotension, increase in troponin; respiratory distress requiring MV for 15 days | Tn 1294, NT-proBNP 2241, ferritin 813, IL-6 9.3 | Ejection fraction 80,5%, normal coronary arteries (echocardiogram) | IVIG, Anakinra | Yes/Yes/73 days | Favorable |
| 4 | Cui [16] |
55 days/F/No | RT-PCR pos/IgM pos | YES—a week earlier (parents) | No | Tachycardia; productive cough and hypoxic respiratory failure requiring oxygen supplementation through a nasal cannula (day 7 of illness) | CRP 5.6, Tn 25,000, D-dimer 54,000 | Ground-glass opacity (CXR); Patchy shadows and ground-glass opacity in the right lung (day 4 of illness), pneumonia (day 9) at chest CT | Inhaled interferon α-1b, reduced glutathione, urso-deoxycholic acid, and traditional Chinese medicine lotus qingwen | No/No/20 days | Favorable |
| 5 | Del Barba [17] |
38 days/M/No | RT-PCR pos/NA | YES—Both parents diagnosed with COVID-19 | Yes | Increase in troponin; rhinitis; modest hypo-reactivity | Thrombocytosis (525 × 109/L), PCT 3.28, Tn 82, NT-proBNP 208, D-dimer 133,000, fibrinogen 128 | Mild thickening of broncho-vascular markings, but no pulmonary parenchymal opacities (CXR); minimal pericardial effusion (cardiac MRI) | None | No/No/14 days | Favorable |
| 6 | Diggikar [18] | 7 days/NA/No | RT-PCR pos/IgG neg/IgM neg | YES—the mother tested positive for SARS-CoV-2 infection one day before the presentation | Yes | Small coronary artery aneurysm; apnoea and respiratory distress requiring MV; reduced tone, sluggish reflexes and seizures | CRP 60, D-dimer 5000 | Small coronary artery aneurysm (echocardiogram); diffuse changes involving the periventricular white matter, external capsule and internal capsule, while peripheral bilateral thalami show T2 fluid-attenuated inversion recovery hyperintensity with diffusion restriction (brain MRI) | Steroids, remdesivir, enoxaparin, levetiracetam and phenobarbitone | Yes/Yes/NA | Favorable |
| 7 | Dugue [21] | 6 weeks/M/No | RT-PCR positive for SARS-CoV-2 and Rhinovirus/NA | NA | Yes | Cough; mottled appearance; brief episodes of upward gaze associated with bilateral leg stiffening and altered responsiveness | Leukopenia (5070) | Excess of temporal sharp transients for age and intermittent vertex delta slowing with normal sleep-wake cycling (long-term EEG) | None | No/No/1 day | Favorable |
| 8 | Esteve-Sole [52] |
3 months/M/NA | RT-PCR neg/serology neg | YES | Yes | Peripheral extremity changes; gastrointestinal symptoms (not specified); irritability | Leukopenia (4000), CRP 12.8, Albumin 2.3, NT-proBNP 3628, D-dimer 2000 | Coronary abnormalities (not specified at echocardiogram) | IVIG, steroids, aspirin, clopidogrel | No/No/NA | Favorable |
| 9 | Falah [53] |
4 months/M/No | RT-PCR pos/NA | NA | Yes | Isolated coronary artery disease; Rash, conjunctival injection, lips and oral cavity changes; Irritability, neurological symptoms (not specified) | Leukocytosis, CRP 11.56, Albumin 3 | Coronary artery dilation (echocardiogram) | IVIG, aspirin | No/No/NA | Favorable |
| 10 | Falah [53] |
6 months/F/No | RT-PCR pos/NA | NA | Yes | Rash, conjunctival injection, lips and oral cavity changes; Not specified GI symptoms, poor feeding; Irritability, neurological symptoms (not specified) | Leukocytosis, CRP 13.3, Albumin 2.8 | Faint opacity in the left mid-lung zone (CXR) | IVIG, aspirin | No/No/NA | Favorable |
| 11 | Frauenfelder [22] |
32 days (corrected age 37 + 3 weeks)/M/Prematurity | RT-PCR pos/NA | YES—recent contact with family members and asymptomatic healthcare workers | No | Need for inotropes, mildly elevated troponin; significant glottic swelling and copious airway secretions; hypoxic respiratory failure requiring HFOV and inhaled nitric oxide | Lymphopenia (1.45 × 109/L), CRP 4.2, Albumin 2, Tn 138, Ferritin 138, D-dimer 1143 | Mild bilateral ground-glass opacities (CXR); Small patent foramen ovale with left-to-right shunt, mild dilation left side structures, and mild MR (echocardiogram) | Steroids, remdesivir, not specified anticoagulation (not specified, because of a line-associated femoral arterial thrombus), inotropes (noradrenaline and adrenaline) | Yes/Yes/18 days | Favorable |
| 12 | García-Howard [23] |
3 months/F/No | RT-PCR pos/NA | YES | Yes | Rhinorrhea and cough; Diarrhea; Mild hypotonia, staring gaze, clonic movements of the face and right extremities, and repeating sucking movements of the mouth, lasting <5 min | CRP 0.67, Ferritin 385, Increased D-dimer, negative CSF culture | Normal interictal EEG, Normal cerebral MRI | Levetiracetam, Hydroxychloroquine | No/No/9 days | Favorable |
| 13 | Giacomet [24] |
2 months/F/No | RT-PCR pos/NA | YES— Father and older brother tested positive |
Yes | Intermittent tachycardia; mottled skin; non-bloody diarrhea and vomiting | Anemia (Hb 7.9), Tn 103, NT-proBNP 12,507, D-dimer 1918, IL-6 236 | Hypokinesia of the inferior left ventricular wall and the inferior interventricular septum, with a mild decrease in the left ventricular ejection fraction | IVIG, Packed red blood cells transfusion | Yes/No/NA | NA |
| 14 | Jones [27] |
6 months/F/No | RT-PCR pos/NA | YES—her 9-year-old sibling had upper respiratory symptoms 3 weeks before | Yes | Sinus tachycardia during fever; mild congestion and subcostal retractions; Prominent tongue papilla; a blanching, polymorphous, maculopapular rash, limbic sparing conjunctivitis, and dry cracked lips; Irritability | Left-shifted white blood cell count with bandemia, normocytic anemia, CRP 13.3, Albumin 2.8 | Faint opacity in the left midlung zone (CXR) | IVIG, aspirin | No/No/NA | Favorable |
| 15 | Lad [28] |
4 months/F/NA | RT-PCR neg/IgG pos | YES—Father with COVID-19 a month before | Yes | Compensated shock; Vomiting and fresh blood in stool; Lethargy | Neutrophilic leukocytosis; Anemia (Hb 8) | Both coronaries dilated with high z-score > 2.5; Abdominal CT showed dilated jejunum and proximal ileum suggestive of obstruction. | IVIG, steroids, exploratory laparotomy (showing extensively congested ileum and tiny fibrous band about 2.5 cm crossing from antimesenteric border to mesentery in proximal ileum, without any obvious volvulus), packed red blood cells transfusion | No/No/NA | Favorable |
| 16 | Luna Santiago [31] |
2 months/M/Griscelli syndrome type 2 | RT-PCR pos/NA | NA | Yes | Shock; respiratory distress; Hepatosplenomegaly | Pancytopenia (in the context of a familial hemophagocytic lympho-histiocytosis triggered by SARS-CoV-2 at bone marrow aspiration), with increased CRP, D-dimer, triglycerides and IL-6 | NA | Steroids, anticoagulation therapy (not specified); inotropes (not specified), multiple transfusions, cyclosporine, cytarabine and inhibitor of JAK signaling | Yes/Yes/NA | Death |
| 17 | Malle [41] |
6 months/F/Down syndrome and CHD | RT-PCR pos/serology neg | YES—her father had contracted COVID-19 | Yes | Heart dysfunction and distributive shock; cough; Maculopapular erythematous rash with peripheral desquamation, edematous hands; Vomiting; Fatigue | Lymphopenia and neutrophilic leukocytosis, increased CRP and PCT, Hypoalbuminemia, Increased Tn, ferritin, D-dimer, fibrinogen and IL-6; Increased STAT3 phosphorylation and increased FcɣRI and ICAM1 on neutrophils and monocytes | Myocarditis and coronary dilatation (echocardiogram) | IVIG, steroids, lopinavir/ritonavir and hydroxychloroquine | Yes/No/4 months | Favorable |
| 18 | Mariani [32] |
5 months/F/NA | RT-PCR pos/IgG pos | YES—five weeks earlier, her father had tested positive | Yes | Intermittent tachycardia | Thrombocytopenia (36 × 109/L) in the context of a Severe transient pancytopenia with dys-erythropoiesis and dys-megakaryopoiesis; hypoalbuminemia, NT-proBNP 3617, D-dimer 8060 | Mild to moderate TR with small pericardial effusion (echocardiogram) | Steroids | No/No/NA | Favorable |
| 19 | Marino [42] | 5 months/F/No | RT-PCR neg/NA | No | Yes | Isolated coronary artery disease; Erythematous rash at the trunk; Sterile pyuria; Diarrhea; Irritability | CRP 6.4 and PCT 0.96, Tn 13, NT-proBNP 1019, Ferritin 259, D-dimer 1053 | Dilatation of both right coronary artery (RCA) and left main coronary artery (LMCA); dim opacity of the left lung base (CXR); gallbladder hydrops (abdominal US); | IVIG, steroids, aspirin | No/No/NA | Favorable |
| 20 | Orlanski-Meyer [34] | 8 weeks/F/No | RT-PCR neg/IgG pos | YES—both parents tested positive at 2 weeks of age. The positive serology was unlikely to represent the passive transfer of maternal antibodies. | No | Tachycardia; Cracked lips; Profuse watery diarrhea, transient bloody stool, vomiting | Thrombocytosis (958 × 109/L), ALT 173 and AST 140, GGT 274, Albumin 1.4, NT-proBNP 1011, Ferritin 385, Fibrinogen 393, IL-6 37.5 | Mild-moderate MR with normal coronary arteries and systolic function (echocardiogram); nonspecific intestinal wall changes and mucosal flattening and splenomegaly (abdominal US); patchy erythema and scattered pinpoint (colonoscopy) | IVIG, steroids, anakinra | No/No/NA | Favorable |
| 21 | Rakha [43] | 5 months/NA/No | NA/IgG and IgM pos | NA | Yes | Isolated coronary artery disease; not specified respiratory and GI symptoms | Leukocytosis, increased CRP and ferritin | Diffuse ectasia of RCA and LCMA; initial fractional shortening 35% (echocardiogram) | IVIG, aspirin | NA/NA/from 6 to 14 days | Favorable |
| 22 | Rakha [43] | 5 months/NA/No | NA/IgG and IgM pos | NA | Yes | Isolated coronary artery disease; not specified respiratory and GI symptoms | Leukocytosis, increased CRP and ferritin | Medium aneurysm LMCA, ectasia of LAD and diffuse ectasia of RCA; initial fractional shortening 29% (echocardiogram) | IVIG, aspirin | NA/NA/from 6 to 14 days | Favorable |
| 23 | Rakha [43] | 3 months/NA/No | NA/IgG and IgM pos | NA | Yes | Isolated coronary artery disease; not specified respiratory and GI symptoms | Leukocytosis, increased CRP and ferritin | Multiple medium and giant aneurysms in left circumflex, and LAD; initial fractional shortening 28% (echocardiogram) | IVIG, aspirin | NA/NA/2 days | Death on second day of admission |
| 24 | Rakha [43] | 6 months/NA/No | NA/IgG and IgM pos | NA | Yes | Coronary artery disease with myopericarditis; not specified respiratory and GI symptoms | Leukocytosis, increased CRP and ferritin | Ectasia of RCA, LCA, and LAD with decreased contractility; initial fractional shortening 22% (vomiting) | IVIG, aspirin | NA/NA/from 6 to 14 days | Favorable |
| 25 | Rakha [43] | 36 days/NA/No | NA/IgG and IgM pos | NA | Yes | Supraventricular tachycardia; not specified respiratory and GI symptoms | Leukocytosis, increased CRP and ferritin | Initial fractional shortening 28% (echocardiogram) | None | NA/NA/from 6 to 14 days | Favorable |
| 26 | Raut [35] | 5 months/M/No | RT-PCR pos/NA | NA | Yes | Isolated coronary artery disease; Skin rash and bilateral non-purulent conjunctivitis; Irritability | CRP 21.5, PCT 8.6, Albumin 2.4, NT-proBNP 2025, Ferritin 975 | Normal left ventricular function, with coronary dilatation in LMCA and LAD (echocardiogram) | IVIG, aspirin | No/No/22 days | Favorable |
| 27 | Richardson [40] | 5 months/F/No | RT-PCR neg/IgG pos a week after hospitalization | NA | Yes | Isolated coronary artery disease; respiratory distress requiring high-flow oxygen on day 5 of illness; Erythematous rash on trunk and extremities (at presentation) with peeling skin on her hands and feet and cracked lips (day 10) | CRP 50, Albumin 2.2, Ferritin 937, D-dimer 6692, Fibrinogen 4700 | Coronary artery aneurysm (echocardiogram) | IVIG, steroids, Anakinra then Infliximab, aspirin | Yes/No/NA | Favorable |
| 28 | Rodriguez-Gonzalez [36] |
6 months/M/short bowel syndrome (secondary to multiple intestinal resections during the neonatal period), antithrombotic prophylaxis due to previous local thrombotic obstructions of the central line | RT-PCR neg/IgG pos on day 21 of illness | NA | Yes | Cardiogenic shock secondary to severe pulmonary hypertension and new onset right ventricular failure; respiratory distress requiring MV | Thrombocytopenia (98 × 109/L), PCT 3.46, Tn 90, NT-proBNP 26,000, Ferritin 7634, Fibrinogen 179, IL-6 198 | Massive pulmonary thromboembolism, with a pattern of ground glass and numerous consolidations of predominance in the posterior-basal segments of both lungs (chest CT); Severely dilated right chambers, severe right ventricular systolic dysfunction, and supra-systemic pulmonary hypertension (echocardiogram); irregular pleural line, B-lines, some coalescent, with bilateral patchy distribution, and small peripheral consolidations, which were larger in posterior-basal areas (lung US) | Steroids, Tocilizumab, previous antithrombotic prophylaxis, hydroxychloroquine and inotropic support (milrinone and norepinephrine) | Yes/Yes/21 days | Favorable |
| 29 | Saha [37] | 25 days/F/Previous hospitalization due to bacterial late-onset sepsis | RT-PCR pos/NA | NO—No family members had signs and symptoms suggestive of SARS-CoV-2. She was in 2 different hospitals previously and may have contracted the virus there. | Yes | Cardiogenic shock; respiratory distress requiring MV; disseminated maculopapular rash; acute kidney injury post-resuscitation; hepatosplenomegaly and greenish watery stool; short-duration seizures | Thrombocytopenia (100 × 109/L), PCR 2.9, Metabolic acidosis, increased NT-proBNP, Ferritin 16,000, D-dimer 16,500 | Atelectasis of both lower lobes of lung (chest CT); Significant systolic dysfunction, with ejection fraction of 40% and mild pericardial infusion (echocardiogram) | IVIG, steroids, enoxaparin, inotropes (adrenaline and milrinone), phenobarbitone, furosemide, packed red blood cells transfusion | Yes/Yes/50 days | Favorable |
| 30 | Shaiba [44] | 30 days/F/NA | RT-PCR pos/NA | NA | Yes | Increased cardiac enzymes; respiratory distress requiring MV; impaired renal function; not specified GI symptoms | Thrombocytopenia (43 × 109/L), CRP 1.1 and PCT 1.7, Hyponatremia (123), Cr 2.44, Tn 684, NT-proBNP 971, Ferritin 2316, D-dimer 5500, Fibrinogen 225, | NA | IVIG, steroids, anakinra, heparin, hydralazine, amlodipine | Yes/Yes/15 days | Death |
| 31 | Shaiba [44] | 90 days/M/NA | RT-PCR pos/NA | NA | Yes | Increased cardiac enzymes; respiratory distress requiring MV | CRP 5.6, ALT 1070 and 1178, Cr 0.89, Tn 108, NT-proBNP 1370, Ferritin 813, INR 1.49, D-dimer 1320 | NA | IVIG, steroids, anakinra, aspirin, enoxaparin, hydralazine, amlodipine, sildenafil | Yes/Yes/75 days | Favorable |
| 32 | Villacis-Nunez [45] | 4 months/M/Prematurity, twin | RT-PCR pos/IgG pos on day 19 of illness | NA | Yes | Isolated coronary artery disease; respiratory distress requiring non-invasive positive-pressure ventilation; rash, hand and foot swelling, conjunctivitis; diarrhea | Increased CRP (>3) | Giant LAD and RCA aneurysms identified on day 21 of illness (echocardiogram); coronary involvement with possible LAD artery mural thrombus (cardiac CT) | IVIG, steroids, infliximab, remdesivir, aspirin, enoxaparin, clopidogrel | Yes/No/ 26 days | Favorable |
Abbreviations: ALT = alanine transaminase, ASD = atrial septal defect; AST = aspartate transaminase, AVB = atrioventricular block; AXR = abdominal X-ray; CPAP = continuous positive airway pressure; Cr = serum creatinine; CRP = C-reactive protein; CSF = cerebrospinal fluid; CT = computed tomography; CXR = chest X-ray; EEG = electroencephalogram; F = female; FCɣRI = FCɣ receptor I; g = grams; GGT = gamma-glutamyl-transferase; Hb = Hemoglobin; HFOV = high frequency oscillator ventilation; ICAM1 = Intercellular Adhesion Molecule 1; IgG = immunoglobulin G; IgM = immunoglobulin M; IL-6 = interleukin-6; INR = International normalized ratio of prothrombin time; IVIG = intravenous immunoglobulin; IVS = interventricular septum; K+ = potassium; LAD = left anterior descending coronary artery; LMCA = left main coronary artery; LDH = lactate dehydrogenase; LMWH = low molecular weight heparin; LPA = left pulmonary artery; LV = left ventricle; M = male; MR = mitral regurgitation; MRI = magnetic resonance imaging; MV = mechanical ventilation; NA = not available; NEC = necrotizing enterocolitis; NT-proBNP = N-terminal pro–B-type natriuretic peptide; PCT = procalcitonin; PDA = patent ductus arteriosus; PPHN = persistent pulmonary hypertension of the new-born; QTc = corrected QT interval; RA = right atrium; RCA = right coronary artery; r-TPA = recombinant tissue plasminogen activator; RT- PCR = reverse transcription-polymerase chain reaction; RV = right ventricle; STAT3 = Signal Transducer And Activator Of Transcription 3 gene; SVT = supraventricular tachycardia; Tn = troponin; TR = tricuspid regurgitation; US = ultrasound; w = weeks. Measure units: Albumin = mg/dl; ALT and AST = U/L; Cr = mg/dl; CRP = mg/dl; D-dimer = mg/dl; Ferritin = ng/mL; fibrinogen = mg/dl; GGT = U/L; Hb = g/dl; IL-6 = pg/mL; K+ = mEq/L; LDH = U/L; NT-proBNP = pg/mL; PCT = ng/mL; Tn = ng/L.