The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the third large-scale epidemic caused by a coronavirus, after the SARS in 2002 and the Middle East respiratory syndrome (MERS) in 2012 [8]. Providing care to immunocompromised patients and those suffering from cancer during the first wave of the pandemic was extremely challenging. The pediatric oncology societies issued various guidelines on deciding the treatment for childhood cancers during the pandemic [9]. Few studies addressed pediatric patients with benign and malignant hematological disease with a large sample size as in our study which included 620 patients throughout the year of 2022 till 2023. In our study, 86 (14%) patients of the 620 studied children and adolescent patients were COVID-19 positive for omicron variant and its subvariants. The most common underlying disease among them was hematological malignancy followed by benign hematological disease, 9.3% of them were aplastic anemia, likely Bhayana et al. (2021) who tested 181 patients with hematological illnesses and cancer for COVID-19 found that 22 (12%) patients were COVID-19 positive and that the most common diagnosis among his cohort was acute leukemia (63.6%) [10]. In a study by Hammad and colleagues including children with malignancy from May 1, 2020, and November 30, 2020, including 76 patients with malignancy, hematological malignancies also constituted 86.8% of patients [11].

Another study done by Khaled et al. [12] mentioned that 79% of the studied aplastic anemia patients were at risk of acquiring COVID-19 and four of them died from the underlying disease complications and one patient died following allogeneic HSCT during the period of the study. Also in our study, there was a statistically significant increase in the percentage of patients with acquired aplastic anemia who died compared to survivors. Therefore, in the era of viral pandemic, hematologist had to think about revising the regimen of treatment of aplastic anemia patients and think of a regimen that boosts their immune system non-specifically maybe with adding growth factors. However, we cannot attribute the death to only COVID-19 infection but it was one of the contributing factors.

The analysis of the clinical presentation of our studied patients revealed that fever and dry cough were the most common presenting symptoms, similarly Aggarwal and his colleagues [13] reported that fever, cough followed by dyspnea were the most common presenting symptoms in their cohort of pediatric patients with hematological disease.

Neurological examination was abnormal in the form of hypotonia in 5 patients with COVID-19 infection and it was the most important factor associated with mortality. A study done by Abdel-Mannan et al. [14] reported that among 27 children with COVID-19, 4 patients (14.8%) who were previously healthy had new-onset neurological symptoms like encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes and were associated with mortality. However, Dufort et al. [15] reported that many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement but was mostly transient symptoms and that the range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred.

Analysis of the laboratory data of our patients showed that the neutrophil and lymphocytic count were significantly lower in COVID-19-positive patients compared to other patients with hemato-oncological disease; markers of inflammation like C-reactive protein were also elevated in COVID-19-positive patients. However, D-dimer and serum ferritin were high but not different between COVID-19-positive and COVID-19-negative patients. Ebeid and colleagues [16] reported that 50% of the hospitalized children with cancer and COVID-19 had lymphocytopenia, and that D-dimer and LDH were elevated in all patients. However, Wu et al. [17] reported that 30% of his pediatric population with COVID-19 infection had abnormal leukocyte count, where 6 (8.11%) patients had elevated lymphocytes, and 4 (5.41%) had reduced lymphocytes. CRP showed abnormal level in children with COVID-19 and has been identified as a probable biomarker for disease severity, this can be attributed to organ tissue damage as a result of the disease [18].

In our study, 73.3% of our COVID-19-positive patients had mild COVID-19 disease, 15.1% had a moderate disease, and 11.6% were considered to have a severe COVID-19 disease. Mukkada et al. [19] in their cohort study on cancer patients found that 45% were having mild or moderate and 19% were severe or critical; also, Ismail and colleagues in a study about COVID-19 and patients with hemoglobinopathy and inherited anemia found that 38 of 258 (14.7%) children had mild to moderate COVID-19, while there were no cases with severe form of COVID-19 [20]. This indicated that although the percentage of mild disease is high, yet a considerable percentage of immune suppressed patients with hemato-oncological diseases remain at risk for severe disease.

Twenty COVID-19-positive patients (23.3%) required ICU admission and 5.8% of all COVID-19-positive patients died. Similarly, Wang et al. [21] reported in his review of 226 published immunocompromised patients during the first wave of the COVID-19 pandemic that 47% of them were hospitalized requiring intensive care, and 4.9% died of COVID-19. While Haeusler et al. [22] reported in another multinational retrospective registry study of 131 pediatric hemato-oncological patients, the prevalence of severe critical COVID-19, intensive care unit (ICU) admission, and the mortality was 13, 11, and 3%, respectively.

Multisystem inflammatory syndrome in children (MIS-C) is a condition among pediatric patients that can occur with COVID-19, it causes inflammation of different body organs, including the heart, lungs, brain, kidneys, gastrointestinal system, skin, and eyes. Although fever and gastrointestinal symptoms are among the most common symptom yet neurologic and dermatologic abnormality are also frequently seen. A combination of clinical and laboratory testing are required to reach diagnosis [23]. In our study, 10.5% of COVID-19-positive patients with developed MIS-C.

Reports estimate the incidence of MIS-C in those under age 21 years to be 2 per 100,000 persons with an overall incidence among children with COVID-19 of 322 per 100,000 persons [24]. Similar to our finding, among 2035 children with cancer and COVID-19, 24 (1.2%) developed MIS-C, 20 patients (83.3%) had hematologic cancer where 54.2% (n = 13) needed intensive care unit admission [25].

When we compared our results of CT chest findings with other work involving children with hemato-oncological disease, Wang et al. (2021) did a multicenter study on clinical and imaging lesions of COVID-19 in cancer patients and showed that the typical pulmonary imaging lesions combined with consolidation were seen in 64.4% of his patients [26] and this was closely related to our CT chest findings. Similarly, Aygüneş et al. [27] reported that CT abnormalities were seen in 46.6% of the studied patients with ground-glass opacities (GGO), consolidation, pulmonary nodules surrounded by GGO, and air bronchograms, with pleural and pericardial effusion findings. For the echocardiographic evaluation, in most reports, changes have been observed mainly in the left ventricle, with a reduction in the ejection fraction (EF). Other findings included mitral regurgitation, pericardial effusion, and median hypokinesia of the inferoseptal and inferior walls and this was in line with our echocardiographic findings [28].

As regards mortality in COVID-19-positive patients, only 5 patients died and 18 patients survived, analysis of their data revealed that abnormal neurological was the most significant factor associated with mortality as in Table 3, patients who died were more neutropenic and lymphopenic and higher serum ferritin than others who survived but not reaching statistical significance as in Table 2; similarly, Fu and his colleagues reported that the relationship between baseline neutrophil count and mortality in COVID-19 is U-shaped with increased mortality risk for both neutropenia and neutrophilia [29]. Another study revealed that in patients with cancer undergoing chemotherapy, COVID-19 disease severity was associated with either high or low lymphocyte counts, low platelet count, or high neutrophil count [30], but in a systematic review done by Kim and his colleagues found no association was noted between any hematological parameter (leukocyte count, platelet count, lymphocyte or neutrophil counts) and mortality in COVID-19 among patients with hematological malignancy [31].

The findings of this study have to be seen in light of some limitations. It included only one center of experience in benign and malignant diseases in pediatrics in Egypt. It also coincided with the period of omicron variant of COVID-19 virus and its variants which are less virulent than the initial variant of COVID-19 virus. Therefore, more studies from Egypt about the same population have to be considered and compared to the initial wave of COVID-19 infection.