key: cord-1009205-paa1tyqh
authors: Hamdy, Rana; El‐Mahallawy, Hadir; Ebeid, Emad
title: COVID‐19 infection in febrile neutropenic pediatric hematology oncology patients
date: 2020-10-16
journal: Pediatr Blood Cancer
DOI: 10.1002/pbc.28765
sha: 74d6e191f50f226e98bc117a213f7dec0d195f37
doc_id: 1009205
cord_uid: paa1tyqh

nan

itive result for COVID-19 by PCR. Other than the seven confirmed cases, there were no probable COVID-19 cases according to WHO criteria. 2 The diagnoses of the seven COVID-19 confirmed cases were acute lymphoblastic leukemia (n = 3), acute myeloid leukemia (n = 2), lymphoma (n = 1), and Wilms tumor (n = 1). Table 2 shows the laboratory findings of the patients. All the patients were neutropenic, thrombocytopenic, and had absolute lymphocytopenia. There was no significant difference in the total leucocyte count, absolute neutrophil count, and absolute lymphocyte count of COVID-19-positive or -negative patients. The median (range) Creactive protein (CRP) was 163 (1-268 mg/L) in COVID-19-positive patients and 72 (7-366 mg/L) in COVID-19-negative patients; P = .792.

The CRP levels were higher than 100 mg/L in five of seven of the positive versus 11/17 of the negative cases.

In the initial chest CT scan, two (28.5%) cases had bilateral focal ground-glass opacity as the predominant CT imaging pattern, while five patients (71.5%) had no abnormal findings. Follow-up CT, carried out 7-14 days after admission, showed patchy consolidation and interstitial abnormalities including reticular appearance and interlobular septal thickening in three patients (42.8%); normal scan of initially free three patients, and no imaging in one patient due to death.

Management was done as recommended by the local authorities' guidelines according to WHO 2020. 2 The medications used were hydroxychloroquine sulfate 6.5-10 mg/kg (max 400 mg) given every 12 h in the first day, then in two divided doses for 9 days, and azithromycin 12 mg/kg/day (max 500 mg) for 5 days. Oseltamivir was used in pediatric dose (twice daily for 5 days) according to the body weight: >40 kg: 75 mg; >23-40 kg: 60 mg; >15-23 kg: 45 mg; and empirical broad-spectrum antibiotics in the form of fourth-generation cephalosporin and carbapenem. Targeted antibiotic therapy according to blood culture results and voriconazole as prophylactic antifungal were administered. Three patients received methylprednisolone 1 mg/kg every 12 h for 5 days as they developed respiratory distress.

Nasopharyngeal swabs were repeated after 7 days and then every 72 h.

Duration to a negative PCR was 2 weeks in one case, and 5 weeks in three cases. Three cases were persistently positive and had unfavorable outcome. Admission to ICU was necessary in three cases, due to respiratory distress and desaturation in two patients; one of them due to cancer progression and septic shock in the third patient. Ventilation support was needed in one case. The mortality rate in COVID-19 cases was 43% (3/7), and 11% (2/17) in the negative cases. Additional contributing factors to mortality included progression of malignancy (n = 1) and bacterial sepsis (n = 1) among both COVID-19-positive and -negative cases.

The impact of COVID-19 in children with cancer is not yet clear. In the present study, a severe infection with ICU admission and unfavorable outcome was recorded in three of seven COVID-19-positive cases while receiving their chemotherapy. In another case series, COVID-19-positive cancer patients were more susceptible to a more severe infection and worse outcome. 3 In another study on 178 pediatric cases with cancer, mild symptoms were related to COVID-19 in 19/20 positive patients. 4 The different findings in the current case series could be related to the type of malignancy, as our patients were mostly cases with hematological malignant disorders.

Evidence suggested that a subgroup of COVID-19-infected cases develop a severe disease due to cytokine storm syndrome leading to a hyperinflammation state. 5 Serum ferritin levels were significantly increased in nonsurvivors, when compared to survivors in 191 COVID-19-positive patients. 6 In the current study, serum ferritin levels were remarkably elevated in COVID-19-positive pediatric cancer patients.

It was documented that elevated serum ferritin levels were closely related to poor prognosis in patients with hematological malignancies; with levels ≥1000 ng/mL denoting poor survival. 7 Thus, using ferritin to stratify the severity of COVID-19 infection is limited in patients with a diagnosis of hematological malignancies.

Though a reduced platelet count was encountered in our COVID- Total leucocyte count* 1075 (330-2700 × 10 9 /L) 1400 (160-3900 × 10 9 /L) 750 (500-1500 × 10 9 /L) Absolute neutrophil count* 150 (40-1600 × 10 9 /L) 150 (20-2800 × 10 9 /L) 150 (60-400 × 10 9 /L) Absolute lymphocyte count* 468 (160-1850 × 10 9 /L) 620 (120-2400 × 10 9 /L) 315 (200-1300 × 10 9 /L) ICU admission infection, 3.5% had a reduced lymphocyte count below 1.2 × 10 9 /L and CRP was elevated above 10 mg/dL in only 20% of the cases. 8 

World Health Organization. Clinical Management of COVID-19: Interim Guidance

COVID-19 and lung cancer: risks, mechanisms, and treatment interactions

COVID-19 in children with cancer in New York City

COVID-19: consider cytokine storm syndromes and immunosuppression

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

The impact of iron chelation therapy on patients with lower/intermediate IPSS MDS and the prognostic role of elevated serum ferritin in patients with MDS and AML: a meta-analysis

SARS-CoV-2 infection in children