key: cord-0941740-rbhd1idv
authors: Mehrvar, Azim; Qaddoumi, Ibrahim; Tashvighi, Maryam; Naderi, Ali; Mousakhani, Hadi; Alasvand, Ramin; Shekarchi, Babak; Afsar, Negar; Nourian, Mahyar; Mehrvar, Narjes
title: Treatment and Outcomes of Pediatric Patients with Cancer and COVID-19 at MAHAK Pediatric Cancer Treatment and Research Center, Tehran, Iran
date: 2021-09-08
journal: Semin Oncol
DOI: 10.1053/j.seminoncol.2021.09.003
sha: 1ce564574f6f0b7a4229a42f2ea19cedc9b64818
doc_id: 941740
cord_uid: rbhd1idv

The COVID-19 pandemic has been particularly devastating for Iran. Children with cancer are generally immunosuppressed and especially vulnerable to SARS-CoV-2 infections. We report the treatment and outcomes of pediatric oncology patients with COVID-19 at the MAHAK Pediatric Cancer Treatment and Research Center (MPCTRC) in Tehran. We enrolled pediatric oncology patients who experienced SARS-CoV-2 infections from March 18, 2020, to January 28, 2021. The COVID-19 diagnostic criteria at MPCTRC were based on imaging and clinical presentation because of specific challenges diagnosing SARS-CoV-2 infections with molecular testing, which was locally developed and conducted at centers other than MPCTRC. We enrolled nine outpatients and eight inpatients (mean age = 9 years), seven of whom had a diagnosis of leukemias, and five who had brain tumors. COVID-19 symptoms were mild in fourteen patients, and three patients were asymptomatic. Of twelve patients who received molecular testing for SARS-CoV-2 infection, eight were negative and four were positive. Of nine patients tested for IgG and IgM antibodies, one was positive. Three patients died of COVID-19, all of whom were hospitalized. Mild COVID-19 symptoms did not appear to affect the outcomes of the pediatric patients with cancer who received treatment at MPCTRC during the study period.

IgG and IgM antibodies, one was positive. Three patients died of COVID-19, all of whom were 23 hospitalized. Mild COVID-19 symptoms did not appear to affect the outcomes of the pediatric patients 24 with cancer who received treatment at MPCTRC during the study period. Originating from Wuhan, China, 2 SARS-CoV-2 can easily transmit from person to person. 3 Initial reports 32 suggested that COVID-19 is uncommon in children. 1, [4] [5] [6] In April 2020, however, She et al. reported a 33 precipitous increase in the number of children infected with SARS-CoV-2. 7 The virus primarily targets 34 the respiratory system, which can lead to pneumonia. 8 The clinical features of children with are similar to those of adults but are generally milder. 9 36 From March 7 to March 30, 2020, SARS-CoV-2 infections were diagnosed in thirty-five children at 37

Tehran University of Medical Sciences. Of these children, 22 were boys, and their median age was 7.5 38 years (range, 4 months to 15 years old). Of these 35 pediatric COVID-19 cases in Tehran, 29 resulted 39 from family exposure to SARS-CoV-2. Nearly 86% of patients received oseltamivir, and 63% were 40 administered hydroxychloroquine. In addition, many patients received azithromycin, cefotaxime, and/or 41 ceftriaxone. 10 

Patients with cancer have a higher risk of morbidity and mortality than does the rest of the population 43 because of their compromised immune status secondary to cancer or its treatment. [11] [12] [13] [14] was developed locally at other hospitals and its quality assurance could not be confirmed or validated at 90 the time of diagnosis. CT imaging was performed at the time of diagnosis and at 14 days after treatment 91 or supportive care. Figure 1 depicts a schematic diagram of the diagnostic and treatment workflow for the 92 patients who were referred to MPCTRC during the study period. 93

Treatment of SARS-CoV-2 infections at MPCTRC was based on CT findings and clinical symptoms 95 rather than nasal swab/RT-PCR results. The inpatient cohort (n = 8, all symptomatic) consisted of patients 96 who were hospitalized and received oseltamivir, an antiviral medication used to treat influenza, and 97 hydroxychloroquine, in consultation with a pediatric infectious diseases specialist, 20 in addition to 98 azithromycin. 15 The outpatient cohort (n = 9, three asymptomatic and six symptomatic) consisted of 99 patients who were observed at home and received supportive care (i.e., intravenous fluids) with 100 azithromycin (10 mg/kg on the first day, then 5 mg/kg per day for 4 days). 15 

Oseltamivir was administered for 5 days according to body weight for patients older than 12 months: 102 15-23 kg received 45 mg twice per day; 24-40 kg received 60 mg twice per day; and ≥40 kg received 75 103 mg twice per day. 20 Hydroxychloroquine (5 mg/kg per day) was administered for 10 days, and 10 mg/kg 104 azithromycin was administered on the first day of treatment followed by 5 mg/kg per day for 4 days. 15 105

Hospitalization and treatment were offered for the six symptomatic patients in the outpatient cohort, but 106 the parents refused. Therefore, these six patients were treated at home with intravenous fluids and oral 107 azithromycin. Cancer-directed therapies (radiation and chemotherapy) were suspended for all patients 108 until recovery from COVID-19 symptoms, except for two patients who had finalized their treatment and 109

were receiving follow-up examinations. was suspected in two of these new cases at the time of admission. However, the parents of these children 120 preferred treatment at other centers closer to their homes and were therefore excluded from our analysis. 121 A total of 17 patients who received treatment at MPCTRC were eligible for our study. All 17 patients 122 had previous exposure to a person with COVID-19. Fourteen patients exhibited clinical symptoms 123 consistent with COVID-19, and three were asymptomatic. All 17 cases had CT findings consistent with 124 COVID-19. The most common cancer diagnoses in our cohort included leukemia (n = 7), brain tumors (n 125 = 5) and lymphoma (n = 3). The patients with leukemias had acute lymphoblastic leukemia (ALL, n = 4) 126 and acute myeloid leukemia (AML, n = 3). The patients with brain tumors had pilocytic astrocytoma (n = 127 2), ependymoma (n = 1), optic pathway glioma (n = 1), and medulloblastoma (n = 1). The patients with 128 lymphoma diagnoses comprised Burkitt lymphoma (n = 1), Hodgkin lymphoma (n = 1), and non-Hodgkin 129 lymphoma (n = 1). Finally, the two remaining cases had rhabdomyosarcoma (n = 1) and osteosarcoma (n 130 = 1). The clinical characteristics of the two patient cohorts (i.e., inpatient and outpatient) are summarized 131

in Table 2 . 

Laboratory test findings in the all patients and the inpatient and outpatient cohorts are provided in 143 Table 3 . The laboratory test findings were unremarkable for the total patient population and each cohort. 144 145

Chest CT imaging findings are summarized in Table 4 . These findings were based on chest axial 147 spiral CT scans without contrast. Representative CT images from cases 2 and 3 (inpatient cohort) and 148 case 10 (outpatient cohort) are shown in Figure 2 . (Table 5) . symptoms was mild in these cases. 26 The Memorial Sloan Kettering Cancer Center established a program 189 for screening COVID-19 in pediatric oncology patients (Table 6) . Over a brief one-month period from 190 March 10 to April 12, 2020, 20 of 178 patients who were screened for SARS-CoV-2 infections were 191 positive. The mean age of these patients was 15.9 years, and only three were female. One of the patients 192 was hospitalized for a noncritical condition, three asymptomatic patients were hospitalized because of 193 their cancer comorbidity, and the remaining 16 experienced mild COVID-19 symptoms and recovered at 194 home. 27 Finally through March 18, 2020, only five pediatric oncology cases exhibiting mild COVID- 19 195 symptoms were reported in the Lombardy region of Italy. These cases included patients with ALL in 196 second remission, osteosarcoma, hepatoblastoma, and rhabdoid tumors. Three patients recovered at home, 197 and two were hospitalized without any antiviral medications. 28 198 Our findings and those of others suggest that treatment in the outpatient setting without antivirals or 199 antibiotics is a viable option for pediatric oncology patients with COVID-19. Indeed, all of the patients in 200

our study with mild COVID-19 symptoms who refused hospitalization recovered at home. However, our 201 experience also demonstrates that COVID-19 can be fatal in a meaningful fraction of infected pediatric 202 patients, and it is hoped that going forward when these cases are recognized, the availability of novel 

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