A two weeks old female baby , born spontaneously at full term with a birth weight of 3.2kg in the maternity unit at the hospital. She presented with neonatal fever and admitted to pediatrics inpatient in May 2020. Initial laboratory workup was done to rule out neonatal sepsis, and she had full sepsis workup done for her, included Lumbar Puncture, at the third day of admission she was checked for COVID-19 polymerase chain reaction (PCR) and found to be positive, though she did not have any contact with COVID-19 patient, both parents were screened with a nasal swab after her diagnosis and were negative. After that, she was shifted to pediatrics COVID-19 inpatient area in the main and only pediatrics COVID-19 institution and stayed there for nine days, where her clinical and laboratory conditions were strictly observed.
The baby was continuously spiking high-grade fever throughout her stay with baseline tachycardia; although she clinically and hemodynamically continued to be stable, her inflammatory markers were increasing (table 2), declaring a state of acute inflammation. She was conscious alert and active and did not have any respiratory symptoms and was having normal oxygen saturation on room air despite her chest x-ray showing bilateral lungs infiltrates (pneumonitis), when consulted pulmonologist advised for starting Antibiotics. However, her clinical examination only revealed mild hepatosplenomegaly with no skin rash, lymph nodes enlargement, or Kawasaki disease signs. She had multiple laboratory investigations aiming to discover the source of infection and the degree of inflammation.
Complete blood counts (CBCs) were showing lymphocytic leukocytosis with (total WBC 31600/μL), she had normocytic normochromic anemia with hemoglobin level dropping up to (8.7 g/dL), With mild thrombocytopenia of (124 x10^3/ μL). Her C-reactive protein (CRP) was steadily rising from (6 to 84mg/dl), hypoalbuminemia (23g/l), hyponatremia (127mEq/L), and her lactic acid reached up to (6.4mmol/l) with normal PH and Kidney function. Liver functions showed a mild increment in liver transaminases, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were doubled with normal coagulation(table 2). All her cultures came back negative with CSF cell count showing increased RBC counts -deemed traumatic, and we decided to do an ultrasound head, which came to be normal.
The baby was screened again after first positive COVID-19 PCR on two consecutive days, eighth & ninth, and the results were negative COVID-19 PCR and other respiratory virus’s nasal swabs(table 2). When she continued to be febrile and tachycardic with increasing inflammatory markers and a drop in her hemoglobin, Baby was transferred to the main hospital in the pediatrics inpatient unit in an isolation room to complete the investigation as multisystem inflammatory syndrome of children (MIS-C) was suspected. Her ferritin level markedly raised (1773 ug/l),Troponin, and her Natriuretic peptide test (pro-BNP) were both increased (table 2),cardiac wise she had an Echocardiogram which was done twice, and it was showing normal coronary arteries and contractility. With her persistent tachycardia and low hemoglobin, the primary physician and upon pediatrics hematology consult both agreed to transfuse her packed red blood cells. On the same day, pediatrics rheumatologist reviewed the baby and advised to start (IVIG two grams per kilogram per dose)(table1),along with Aspirin high dose of 75 mg per dose every 6 hours per day, Same day she was given one dose of Dexamethasone(table 1)then commenced on Methylprednisolone as pulse steroid (30mg/kg) once daily for three days with tapering dose over the next days(table 1). After IVIG infusion, the baby continued to have high inflammatory markers; then, it was decided by a multidisciplinary team to admit her to the pediatric intensive care (PICU) unit to give the second line therapy , immunomodulatory therapy (Anakinra) as a refractory case.
Dose of Anakinra was (2mg/kg) loading dose(table1), followed by a continuous infusion of (0.02ml/kg/hour)12. Efficacy and safety-wise were the reasons to give continuous infusion, not subcutaneous (SC) injection, as there is no recommended dose for this age group as SC injection. She received Anakinra on day17 of illness and completed 9 days then was stopped. She was kept on antibiotics (Piperacillin/Tazobactam)(Table 1) for presumptive pneumonitis for 10 days and as pediatrics infectious diseases services were involved early, Baby was not started on any other COVID-19 medications, and especially she did not have any respiratory symptoms.
Baby was then re-spiked low grade fever on day 34 of admission and after around 24 hours from discontinued Anakinra , her primary team decided to give her a second dose of Intravenous immunoglobulins IVIG, unfortunately no laboratory investigations were taken before starting it, then was observed for three more days with inflammatory markers went back to normal . She was discharged home after total of five weeks of hospitalization in good general condition, she was then followed up by pediatric rheumatology and pediatric cardiology team along with general pediatrics . Echocardiogram was also repeated and continued to be normal.