COVID‐19 infection in children with cancer and stem cell transplant recipients in Turkey: A nationwide study

Abstract

To the Editor: Adultswith cancer are reported tohave ahigher risk for coronavirus disease (COVID-19) infection and more severe disease and mortality than the general population.1,2 Although children seem to be at a lower risk for COVID-19 than adults,3–5 data specifically addressing children with cancer are limited.6–12 Weconducted a retrospective,multicenter, cross-sectional studyon behalf of the Turkish Pediatric Hematology Society (TPHD) and Turkish Pediatric Oncology Group (TPOG) Society to analyze the characteristics of COVID-19 in all patients with cancer and stem cell transplant (SCT) recipients in all centers in Turkey, during March 11-May 31, 2020. Approval for the study was obtained by Turkish Ministry of Health (MoH), Istanbul University COVID Scientific Research Committee, and Istanbul University Ethics Committee. The study was carried out through the analysis of a questionnaire with 62 questions, which was sent to all members of the TPOG and TPHD Societies working in all 66 pediatric hematology/oncology departments in university, state, and private hospitals in Turkey. All replied and 53 patients were reported from the 24 centers. Following the national recommendations and guidelines of the MoH,13,14 centers tested all symptomatic patients or patients with contact history or patients who were planned to undergo transplantation or surgery. All patients and caregivers were questioned at the entrance of the hospital/oncology center and if there were any symptoms or contact history they were sent to the special clinics within the hospital that were allocated for suspected/proven COVID-19 patients. If a patient was suspected of having COVID-19 and found positive while in the oncology clinic, she/hewas transferred to theCOVID clinic and all staff, patients, and accompanying persons with whom she/he was in contact were tested for COVID-19. Samples from the naso-oropharyngeal swabs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction (PCR). Confirmed cases were defined as PCR-positive patients. Probable cases were defined according to guidelines of World Health Organization15 and MoH,13 as those who had typical symptoms and chest CT findings, or who had typical symptoms and contact history but negative PCR. Patients were classified into four groups regarding the severity of infection as asymptomatic/mild, moderate, severe, and critical on the basis of the clinical, laboratory, and radiological features.3,15 Patients were treated according to recommendations of the MoH.13,14 Statistical analyses were performed by IBM SPSS Statistics version 21.0. For comparison of mean of numerical variables Mann-Whitney U test was used. Categorical nominal variableswere comparedwith Fisher’s exact tests. There were 51 children with cancer, six of whom (four leukemia/lymphomas, two solid tumors) had undergone SCT (Table 1). The median age was 6 (0.3-17.8) years and 64.7% of the patients were male. Additional two patients with thalassemia major who underwent SCT were not included in the analyses. Chemotherapy courses were interrupted in 32 (62.7%) patients and delayed with a median of 15 (3-45) days. The most common presenting signs were fever and cough, while 37.25% of patients were asymptomatic. COVID-19 pneumonia was detected in 26 (50.9%) patients. Five of them had hypoxemia. Gastrointestinal system (17.6%) was the second most commonly involved site followed by central nervous, musculoskeletal systems and skin. Twenty-five patients had asymptomatic/mild, 17 patients moderate/severe, and nine patients critical disease. Thirty-eight patients were hospitalized and treated according to the severity of illness, six of whom were already hospitalized for reasons such as surgery or diagnostic workup when diagnosed with COVID-19. Nine patients with critical disease were in the intensive care unit (ICU) and three were intubated. Treatment consisted of hydroxychloroquine, azitromycine, antivirals either as a single agent or in combination (Table 1). Convalescent plasma was used in three patients, one of whom additionally received mesenchymal stem cell, tocizulumab, and granulocyte transfusions and was intubated. At the time of COVID-19 diagnosis, 26 patients had neutropenia and among them 15 had fever. In all patients with febrile neutropenia, broad-spectrum empirical antibiotics were initiated. In addition, 12 patients received antimicrobial therapy due to clinically and/or microbiologically documented infections. All patients, but one, fully recovered and the PCR tests became negative at a median of 7 (2-17) days. The patient who had received allogeneic SCT for relapsed leukemia/lymphoma and had progressive disease and fungal infection died due to COVID-19 infection. The incidence of critical care disease and need for ICU care were found tobehigher inpatientswithhematologicmalignancies (P= .012), patients post SCT (P = .001), patients with other infections (P = .005), and patients with abnormal findings on chest CT scan (P = .004). Age, gender, elevatedCRP, elevatedD-dimer, being neutropenic, and having relapsed/refractory disease were not significant for critical disease. It has been reported that children constitute about2%of all patients with COVID-19.15 In Turkey, children comprise 7.2% of all cases with COVID-19. The death rate for COVID-19 is 2.57% in Turkey and 0.19% of all deaths were in childhood.17