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Table of Contents
ORIGINAL ARTICLE: REAL WORLD DATA
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 262-269

Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India


Department of Pediatrics, Paediatric Hematology Oncology and BMT Unit, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission09-May-2021
Date of Decision05-Jun-2021
Date of Acceptance14-Jun-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Anupam Sachdeva
Paediatric Hematology Oncology and BMT Unit, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_98_21

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  Abstract 


Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging.
Objectives: This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer.
Materials and Methods: This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded.
Results: A total of 650 tests for COVID-19 were performed for 181 children; 22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support; all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%).
Conclusions: Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.

Keywords: Clinical profile, coronavirus disease-2019, first wave, India, outcome, pediatric, severe acute respiratory syndrome coronavirus 2, COVID-19, SARS-CoV-2


How to cite this article:
Bhayana S, Kalra M, Sachdeva P, Sachdeva A. Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India. Cancer Res Stat Treat 2021;4:262-9

How to cite this URL:
Bhayana S, Kalra M, Sachdeva P, Sachdeva A. Clinical profile and outcomes of COVID-19 infection during the first wave in children with hematological illnesses and cancer: An observational study from a tertiary care center in North India. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Jul 27];4:262-9. Available from: https://www.crstonline.com/text.asp?2021/4/2/262/320147




  Introduction Top


The world is amidst the coronavirus disease-2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[1] This is the third large-scale epidemic caused by a coronavirus, after the SARS in 2002 and the Middle East respiratory syndrome (MERS) in 2012.[2] Since its onset in December 2019 in Wuhan city in China, COVID-19 has spread extensively. With the second wave at its peak and the immense fear of an upcoming third wave, a better understanding of the disease and the impact of the first wave are of paramount importance.[3] The pandemic has affected different continents in different ways; the high-income countries have experienced more severe morbidity and mortality than most of the low-or middle-income countries.[3] Therefore, it is essential to study the impact of the pandemic on different geographical regions and subpopulations.

Reports on COVID-19 have shown that <1% of the affected individuals were children aged <10 years. Asymptomatic infections were reported in 15.8% of the infected children. Most critical cases were recorded in infants.[4] The risk factors for COVID-19 severity and mortality include advanced age, comorbidities like diabetes, renal disease, hypertension, and cardiovascular diseases.[5] Patients with cancer are at a particularly high risk of infection with SARS-CoV-2 owing to their immunocompromised status.[6] Data from China suggest that patients with cancer who are infected with SARS-CoV-2 have a significantly higher incidence of severe adverse events (39%) (including the need for intensive care unit admission, assisted ventilation, and death) than those without cancer (8%).[7] Although data on children with cancer are scarce, the incidence of COVID-19 among children with cancer appears to be low.[8] Studies on adult patients have shown that the risk of illness is higher in those who have received cancer-directed treatment (chemotherapy or radiation) 2–4 weeks before getting infected; the discontinuation of chemotherapy or dose modification is recommended in such patients.[9] Providing care to immunocompromised patients and those suffering from cancer, amidst 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.[10],[11],[12]

In this study, we evaluated the clinical profile and outcomes of the children who were treated for hematological illnesses or malignancies or recipients of hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 during the first wave of the COVID-19 pandemic in 2020. Our study was aimed at better understanding the outcomes of this vulnerable population and providing baseline data to compare the impact of the first wave with that of the future waves of the pandemic.


  Materials and Methods Top


General study details

This retrospective study was conducted at Sir Ganga Ram Hospital, a tertiary care center in Delhi, India, during the first wave of the COVID-19 pandemic between March and December 2020. The institutional ethics committee of Sir Ganga Ram Hospital approved the study [Project 1852; approved 8 Jun 2021; Supplementary Appendix 1: Study Protocol]. The need for obtaining written informed consent for retrospective data collection was waived by the Institutional Ethics Committee. No funding was obtained for this study. The study was conducted in accordance with the ethical guidelines established by the Declaration of Helsinki and the Indian Council of Medical Research. The study was not registered in a public clinical trials registry, given the retrospective nature of the study.

Participants

Children aged between 0 and 18 years, who were treated for a hematological illness or malignancy or those who underwent HSCT and were confirmed to be COVID-19 positive (as determined by COVID-19 antigen testing, COVID-19 reverse transcription-polymerase chain reaction [RT-PCR], or rapid real-time PCR [GeneXpert/BioFire]) were included in the study. In addition, patients who developed multisystem inflammatory syndrome of children (MIS-C) defined as per the World Health Organization (WHO) criteria[13] and had COVID-19 antibody positivity were also included.

Patient suspected to have COVID-19 infection without serological evidence were excluded from the study.

Variables

The primary objective of the study was to determine the prevalence of COVID-19 disease in pediatric patients with hematological illness or malignancy and those who underwent HSCT and to study their clinical outcomes

The secondary objective was to describe the symptoms, comorbidities, treatment, and complications in these patients.

Study methodology

During the initial phase of the pandemic (March to August 2020), the RT-PCR test kits for COVID-19 were not easily available and the turnaround time was high. Therefore, the institutional protocol and the Delhi government policy recommended COVID-19 antigen testing for patients with malignancies before administering chemotherapy, regardless of their symptoms. As the availability of testing kits and turnaround time improved, we shifted from antigen testing (antigen standard Q COVID-19 antigen kit) to RT-PCR testing (Argene kit) (August to December 2020) for COVID-19. Moreover, for emergency admissions, a rapid real-time PCR test (GeneXpert/BioFire-Xpert kit) was performed, which had a turnaround time of 1.5 hours. Repeat testing was performed every 3–4 days for the hospitalized patients and weekly or once in 2 weeks for patients in home quarantine. For asymptomatic patients, repeat testing was performed on a monthly basis as per the hospital policy. Baseline demographic data including the age, diagnosis, treatment status, and chemotherapy protocol used were collected from the hospital records and records maintained by the Department of Pediatric Hematology Oncology and the Bone Marrow Transplant Unit of our institution; these data were entered in Microsoft Excel. Patients with normal vital signs, maintained oxygen saturation, and temperature <100.4°F were managed at home, and an update was taken through teleconsultation twice a day. Patients received treatment for COVID-19 as per the institutional protocol and in accordance with the national guidelines for the management of COVID-19, issued by the government from time to time. Outcomes including the time required for a negative result on RT-PCR, morbidity, and sequelae were recorded.

Statistics

A sample size calculation was not performed for this study, and all patients fulfilling the eligibility criteria were included in the study. Data were entered in Microsoft Excel and were described as absolute numbers and percentages for categorical variables and as mean, standard deviation, and median with interquartile range (IQR) for continuous variables.


  Results Top


A total of 181 children were admitted to our hospital from March 2020 to December 2020. Of these, 22 (12.1%) were confirmed to be COVID-19 positive. A total of 650 tests were performed (190 COVID antigen tests, 332 COVID PCR tests, 86 COVID BioFire, 42 COVID antibody total, and IgG) for 181 children, with an average of 3 tests per patient [Figure 1]. The mean positivity rate in the first wave in our patients was 12.1%. The median age of the patients was 6 years (range: 3–13.25 years) and 17 (77.2%) were males. The baseline demographic characteristics of the 22 patients are provided in [Table 1].
Figure 1: Flowchart for patient recruitment

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Table 1: Demographic characteristics of patients with coronavirus disease-2019

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Clinical features

The majority of patients were asymptomatic (12 out of 22 patients, 54.5%), and testing was performed as a part of screening before admission for chemotherapy. Among the symptomatic patients, the most common symptoms were fever and cough, each reported by 7 out of 10 patients (70%). The median duration of hospitalization was 6 days (range: 3–49 days). The clinical profile of COVID-19-positive patients is described in [Table 2].
Table 2: Clinical profile of patients with coronavirus disease-2019

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Laboratory parameters

A total of 17 (77.2%) patients out of 22 were neutropenic (absolute neutrophil count [ANC] <1.5 × 109 cells/L) at the time of diagnosis with COVID-19, and 5 patients (23.8%) were severely neutropenic (ANC <0.2 × 109 cells/L). In addition, 2 patients were severely thrombocytopenic (platelet count <10,000/μl) at the time of diagnosis with COVID-19, of which one had newly diagnosed pre-B-cell acute lymphoblastic leukemia (ALL) and the other had severe aplastic anemia. None of the patients in our study had thrombocytosis [Table 3].
Table 3: Laboratory findings of patients with coronavirus disease-2019

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Noteworthy laboratory findings in COVID-19-positive pediatric patients in our cohort included elevated levels of interleukin-6 (IL-6) (n = 7; median – 22.53 pg/ml; IQR – 5.9–504 pg/ml) and serum ferritin (n = 7; median – 1123 mg/dl; IQR – 376–3245 mg/dl) in the majority of our patients.

Imaging

A chest X-ray was performed in eight patients. All but two patients had a normal chest X-ray. The two patients with abnormalities on the chest X-ray underwent high-resolution computed tomography (HRCT), which also revealed abnormal findings. One of the two patients had newly diagnosed pre-B-cell ALL. The computed tomography (CT) findings were suggestive of invasive pulmonary aspergillosis, and empirical therapy was administered to this patient. The other patient had CT findings suggestive of enlarged necrotic mediastinal and hilar nodes with a cavitary lesion in the left lower lobe indicating tubercular etiology. In addition, brocho-alveolar lavage positivity for acid-fast bacilli provided supportive evidence. The patients were administered anti-tubercular therapy along with chemotherapy.

Treatment

Of the 22 patients, 14 (63.6%) were managed at home, 8 (36.3%) needed hospitalization, and only 3 (13.6%) needed intensive care. The median duration of hospital stay was 6 days (range: 3–49 days). A total of 3 patients (13.6%) needed oxygen support, of which 2 (9%) were provided oxygen therapy by non-invasive ventilation; one patient with newly diagnosed pre-B-cell ALL with tubercular reactivation with MIS-C, cardiogenic shock, and posterior reversible encephalopathy syndrome received bilevel positive airway pressure. There was one patient in our cohort with relapsed T-cell lymphoblastic lymphoma with a mediastinal mass and massive pleural effusion who received palliative care. One patient with newly diagnosed pre-B-cell ALL with severe encephalopathy, candidemia, and invasive fungal infection was managed with oxygen administered through nasal prongs. None of the patients required invasive ventilation.

A total of 6 patients received steroids during active COVID-19 disease, 3 for the treatment of the underlying cancer (2 leukemia, 1 relapsed T-cell lymphoblastic leukemia), 1 for treatment of chronic graft versus host disease (GVHD), 1 for the treatment of autoimmune hemolytic anemia associated with Hodgkin's lymphoma, and 1 for the treatment of MIS-C (as per WHO criteria).[13] None of the patients received prophylactic anticoagulants or convalescent plasma therapy. No treatment-related adverse effects were noted in any patient. The treatment received by the patients with COVID-19 is highlighted in [Table 4].
Table 4: Treatment received by patients with coronavirus disease-2019

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Co-infection

Invasive candidiasis (blood culture positive for Candida tropicalis) was seen in 1 (4.5%) patient at the time of diagnosis of acute leukemia. The HRCT findings of this patient were suggestive of invasive fungal infection (pulmonary aspergillosis) at the time of diagnosis of COVID-19. Another patient with associated tubercular activation with MIS-C had to be managed with prolonged steroid and anti-tubercular therapy (switched to second-line anti-tubercular therapy in view of hepatitis).

Time required for negative coronavirus disease-2019 reverse transcription-polymerase chain reaction result

The average time required for a negative result on RT-PCR post-SARS-CoV-2 infection was 21.3 days (range: 7–63). In 16 patients, COVID-19 positivity was documented only once. Moreover, 1 patient remained COVID-19 positive for 6 consecutive tests performed over a period of 63 days. This patient had hemophagocytic lymphohistiocytosis (HLH), had undergone HSCT, and was on immunosuppression. He was home quarantined without any short- or long-term sequelae.

A total of 7 (31.8%) patients had come in contact with confirmed cases of COVID-19, while 2 had come in contact with suspected cases of COVID-19 (family members or close contacts).

Febrile neutropenia

Of the 22 patients with COVID-19, 6 (27.3%) had febrile neutropenia; 3 (13.6%) of these patients had very severe neutropenia (ANC <0.2 × 109 cells/L). These patients received empirical therapy for COVID-19 and antibiotics as per protocol. All the neutropenic patients except the two with newly diagnosed pre-B-cell ALL had a predicted course of hospital stay and fared well. Only 2 (9%) patients were on maintenance chemotherapy with stable blood counts; COVID-19 precipitated sudden neutropenia in these patients.

Delay in chemotherapy

Cancer treatment was modified in 15 patients (68.2%), the next cycle of chemotherapy was delayed in 7 out of 15 (46.7%) patients, maintenance chemotherapy was withheld in 2 out of 15 (20%), surgery after neoadjuvant chemotherapy was deferred in 1 out of 15 (6.6%), and chemotherapeutic such as daunorubicin and rituximab was omitted in 1 out of 15 (6.6%) and 2 out of 15 (13%) patients, respectively.

Sequelae

No treatment or disease-related adverse effects were observed in our patients. Only 2 (9%) patients developed a papular rash on the face which was self-limiting; 1 (4.5%) patient developed MIS-C based on the WHO criteria and had a prolonged hospital stay with prolonged use of steroids, complicated by uncontrolled hypertension leading to posterior reversible encephalopathy syndrome and tubercular reactivation. This patient developed cardiogenic shock with an ejection fraction of 25%, thus needing inotropes, which normalized after steroid and intravenous immunoglobulin therapy. COVID-19 antibody testing was performed in 10 patients on follow-up, of which 2 (9%) had a negative antibody titer. One of these patients had familial Burkitt leukemia with an underlying immunodeficiency. The antibody titer was checked in 10 patients; the mean antibody titer was 182.4 IU/ml (range: 0.1-638 IU/ml).

Outcomes

All the patients had favorable clinical outcomes, and there was no mortality.


  Discussion Top


In our study in children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT), the total percentage of COVID-19-positive tests (3.3%) indicated a generally low infection rate in our immunocompromised population. Our results are consistent with the rates previously reported in general pediatric patients. A documented contact with a COVID-19-positive individual was reported in 7 patients (31.8%), while contact with individuals suspected to be COVID-19 positive was reported in 3 patients (13.6%). This is in contrast with the findings of Lu et al.'s study on pediatric patients without cancer, in which a higher proportion of patients had exposure to a confirmed or suspected case of COVID-19.[14] This discrepancy could be attributed to the general isolated lifestyle of patients with cancer. Children with cancer and their families are advised to maintain a high level of hygiene and sanitation and to avoid socializing, being in crowded places, eating outside food, etc., The use of a mask and reverse barrier nursing is often practiced by children with cancer.

The median age of our patients at the time of diagnosis of COVID-19 was 6 years (range: 1.5–17 years). This is similar to the age at diagnosis reported by other published studies on patients with (6.7 years) [14,15] and without

(7 years)[16] cancer.[16] who are infected with SARS-CoV-2. The male-to-female ratio in our study was 3.4, suggesting a male preponderance. This bias has also been observed in most of the studies on patients with COVID-19.[17],[18] This suggests that besides socioeconomic factors, fundamental differences in the immune response between male and female patients are likely to be a factor contributing to this bias. Various studies have highlighted that higher counts of CD4+ T-cells, more robust CD8+ T-cell cytotoxic activity, increased production of immunoglobulins, increased production of type-1 interferon required for an initial response to SARS-CoV-2 infection, protective effect of estradiol against the development of hyperinflammatory immune responses could all have contributed to this observation.[19]

Asymptomatic disease was observed in 54.5% of the patients in our study. Testing for COVID-19 was performed as a part of routine screening before admission for chemotherapy. A similar observation was reported in Montoya et al.'s study in which 37 out of 69 patients (53.7%) had asymptomatic disease.[17] However, another study in pediatric patients showed that 16 out of 19 patients (84%) with COVID-19 had symptomatic disease.[18] Regular screening of patients before admission helped prevent the spread and outbreak of COVID-19 among our patients. In the symptomatic patients, the most common symptoms were fever and cough, each observed in 31.8% of the patients; these findings were similar to those of other studies.[20] Other symptoms included sore throat, coryza, and difficulty in breathing. Dermatological manifestations of COVID-19 were rare. A skin rash was an uncommon symptom in our cohort. It was typically generalized, evanescent, and maculopapular in nature and was present at the time of onset of COVID-19. Various studies have reported the occurrence of COVID-19-associated rashes such as morbilliform rash, urticaria, vesicular eruptions, acral lesions, and livedoid eruptions either at the onset or following hydroxychloroquine treatment. Cutaneous manifestations may serve as an indicator of infection, aiding in the timely diagnosis.[21] Only 1 (4.5%) patient in our cohort had gastrointestinal symptoms such as vomiting, diarrhea, and blood in stools. Among patients with COVID-19, the incidence of gastrointestinal symptoms reported during disease progression ranged from 3% to 79%.[22]

In our study, 14 (63.6%) patients were managed at home. This observation was similar to that reported by Boulad et al.'s study,[15] in which 1 patient (5%) requiredpediatric patients who were relatively asymptomatic for COVID-19 disease, noncritical care hospitalization for COVID-19 symptoms; 3 (15%) were admitted for the management of neutropenic fever, cancer-related issues or in-patient chemotherapy administration. Moreover, in our study, 8 (36.3%) patients needed hospitalization and only 3 (13.6%) needed oxygen support with admission to the intensive care unit. Higher IL-6 levels have been observed in patients requiring intensive care.

In our study, cancer treatment was modified in 15 (68.2%) patients. Such modifications have also been reported by other centers.[16],[20],[23] The majority of the delays were due to the decision to defer the planned treatment in view of the complications associated with COVID-19. Most of these delays were observed during the initial few months of the pandemic. Once data related to the safety of chemotherapy in patients with COVID-19 became available, the hesitation to administer chemotherapy decreased. The decision to delay critical, time-sensitive, anticancer therapy in pediatric patients is not easy to make. The risks of cancer relapse and COVID-19 should therefore be carefully weighed.[24]

Our cohort comprised some heavily immunosuppressed children. One of our patients had newly diagnosed pre-B-cell ALL and presented with severe encephalopathy and tested positive for COVID-19. This patient was ill with invasive pulmonary aspergillosis as detected by chest CT imaging and developed sepsis caused by C. tropicalis. With very aggressive supportive care, induction treatment for leukemia, and targeted treatment with antiviral and antifungal agents, this patient recovered well from the critical illness, with complete clearance of chest CT findings in 4 weeks. SARS-CoV-2 causes direct damage to the airway epithelium, enabling Aspergillus invasion. There have been several reports of COVID-19-associated pulmonary aspergillosis, raising concerns about this superinfection as an additional contributing factor to mortality. Consensus guidelines have been proposed for the management of this entity.[25] Another patient with relapsed T-cell lymphoblastic lymphoma receiving palliative care also recovered completely. Yet another patient with familial Burkitt lymphoma with ORAI1 gene-related immunodeficiency also recovered without any sequelae, despite the ongoing aggressive chemotherapy. The case of a severely immunocompromised child with relapsed refractory HLH who had received chemotherapy for 2 years followed by a haploidentical transplant from his mother was complicated by GVHD and adenovirus and SARS-CoV-2 infections; however, the patient recovered well. Another patient with juvenile myelomonocytic leukemia posttransplant from a matched sibling developed COVID-19 and chronic skin GVHD. He too responded well to supportive care. Yet another patient with very severe aplastic anemia who had received immunosuppressive therapy with antithymocyte globulin and cyclosporine, 4 months before SARS-CoV-2 infection, and received a transplant from a matched unrelated donor 3 weeks after SARS-CoV-2 infection, recovered without any sequelae.

Despite the severely immunocompromised state of the children in our cohort, the outcome of COVID-19 was excellent. Data from China, corroborated by other countries, suggest that adults with cancer are at a higher risk of getting infected with SARS-CoV-2 and are more likely to suffer from severe forms of COVID-19 disease as compared to the general population. In fact, mortality rates up to 40% have been reported by some studies in adult patients with cancer who are infected with SARS-CoV-2.[25] A systematic review of data from studies conducted in pediatric patients with cancer has reported poor outcomes and mortality rates of up to 4.9%.[20] Similarly, mortality rates of up to 50% have been recorded in pediatric patients with hemato-oncological illnesses in some studies.[27]

Our study was limited by the fact that it was conducted in a single center. However, given that the incidence of COVID-19 in patients with hematological and oncological illnesses is low, our analysis could help to understand the epidemiological and clinical data available for pediatric patients with COVID-19.

The outcomes in our study were excellent with 100% recovery rate, no mortality, and no long-term sequelae. The data from our study suggest that children with cancer were at no greater risk of severe COVID-19 disease than the general pediatric population during the first wave of the pandemic; these findings are in keeping with the emerging international data.[27] However, with the current COVID-19 outbreak and the second wave on its way, is essential that social distancing, home isolation, and good hygiene practices continue to be followed for immunosuppressed children. The adoption of these preventive measures will help reduce infection rates, avoid delays in cancer-directed treatment, and maintain good cure rates. At present, we are conducting a prospective study to assess the effects of COVID-19 during the second wave of the pandemic in the same patient population. The preliminary data have shown higher rates of infection and greater severity of COVID-19 among pediatric patients with cancer (unpublished data).


  Conclusions Top


Our study highlights the good outcomes of COVID-19 in children with hemato-oncological illnesses, with an excellent recovery rate. Their care amidst the rapidly spreading pandemic has been challenging. Therefore, it is essential that chemotherapy, supportive care, and prompt treatment must be carefully provided to these children to ensure good outcomes. Findings from our study can serve as baseline data for the future waves of the pandemic and could help strategize the way forward.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[28]


  Supplementary Appendix 1: Study protocol Top


The prevalence and clinical outcomes of coronavirus disease.2019 infection in pediatric hematology oncology and hematopoietic stem cell transplant patients from a tertiary care center

Anupam Sachdeva, Swati Bhayana1, Manas Kalra1

Institute of Child Health, Sir Ganga Ram Hospital, 1Sir Ganga Ram Hospital, New Delhi, India

Address for correspondence: Dr. Anupam Sachdeva, Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India. E.mail: [email protected]


  Background And Introduction Top


The world is experiencing a pandemic of coronavirus disease-2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is the third large-scale epidemic related to the coronavirus, after SARS-CoV in 2002 and Middle-East respiratory syndrome CoV in 2012. After its onset in December 2019 in Wuhan, China, the spread has been extensive with no limits on the counts of patients and deaths. With the second wave of COVID being reported in a lot of countries, better understanding of disease and its impact is very important.[1]

Severe COVID-19 disease usually affects adults sparing the children and is associated with presentations ranging from asymptomatic infections to severe viral pneumonia, acute respiratory distress syndrome, and death. Reports on COVID-19 disease showed that <1% of the cases were in children younger than 10 years of age. Asymptomatic infections were reported in 15.8% of infected children. The proportions of severe and critical cases were 10.6%, 7.3%, 4.2%, 4.1%, and 3.0% for the age groups <1, 1–5, 6–10, 11–15, and ≥16 years, respectively.[2]

Risk factors for COVID-19 severity and death include older age, along with comorbidities such as diabetes, hypertension, or cardiac disease.[3] Patients affected by cancer diseases are particularly at risk of SARS-CoV-2 infection due to higher morbidity and mortality associated with respiratory virus infections owing to immunocompromised status. The risk of hospitalization of cancer patients is four times higher compared to subjects of the same age. Data from China suggest that patients with cancer have a significantly higher incidence of severe events (including intensive care unit admission, need of assisted ventilation, death) after contracting the virus 39% versus 8% in patients without cancer.[4] Although information about children with cancer is scarce, data suggest a lower incidence of COVID-19 in children living with cancer.[5] The risk of morbidity and mortality is particularly increased in those who took cancer-directed treatment (chemotherapy or radiation) within the last 2–4 weeks in adult studies and emphasizes on discontinuation of chemotherapy or modification of doses.[6]

Providing care to immunocompromised patients and those suffering from cancer, amidst this pandemic, has been extremely challenging. The pediatric oncology societies have issued guidelines on deciding treatment of childhood cancer during the pandemic.[7]

We evaluated the clinical profile and outcomes of the children with cancer who developed COVID-19 infection regardless of stage and treatment status at our tertiary care center.

Review of literature

Boulad et al. screened 335 pediatric patients for symptoms or exposure to contacts. They also tested asymptomatic patients before deep sedation, myelosuppressive chemotherapy, or admission to the hospital. 20 (11.2%) had positive test results (mean [standard deviation] age: 15.9 [6.6] years). The rate of positivity for those with symptoms was 29.3% and those without symptoms were 2.5%. Only 1 patient with COVID-19 illness required noncritical care hospitalization for COVID-19 symptoms. All other pediatric patients had mild symptoms and were managed at home. Despite enrolling small number of patients, the study emphasized that the overall morbidity of COVID-19 in pediatric patients with cancer is low with only 5% required hospitalization for symptoms of COVID-19. Unrecognized SARS-CoV-2 infection in asymptomatic caregivers is a major infection control consideration.[8]

Ferrari et al. screened 286 pediatric cancer patients – 212 asymptomatic and 74 symptomatic (10 leukemias, 5 soft tissue or bone sarcomas, 2 lymphomas, 2 hepatoblastomas, 1 central nervous system tumor, and 1 colon carcinoma.) over an 8-week period. Twenty-one cases of COVID-19 infections were identified (48% of them males), with a median age of 6 years (range: 1–17). The cancer treatments were modified in 10 cases (delaying chemotherapy or reducing drug doses, postponing surgery). Two patients developed pneumonia. They advocated on the continuation of chemotherapy in patients.[9]

De Rojas et al. included 15 COVID-19-positive patients among pediatric cancer population (11 had hematological malignancies, 4 had solid tumors, 4 had HSCT). The COVID-19 infection rate in the study was 1.3%. Seven (47%) patients were hospitalized due to the COVID-19 infection, four (27%) were already hospitalized (nosocomial infection), and four (27%) were managed in the outpatient clinic. The most frequent symptoms were fever (67%, 10) and cough (40%, 6). Two patients were asymptomatic. Chemotherapy had to be interrupted or delayed in six (40%). Chest radiographs showed findings in 57% (8/14). Laboratory parameters showed median white blood cell count at diagnosis of 3195 (range: 90–10,690), median lymphocyte count of 580 (range: 0–6310), and median D-dimer 291 ng/mL (range: 0.7–2620). Most patients received hydroxychloroquine (73%, 11); four (29%) patients did not receive any treatment. No COVID-19 treatment-related severe adverse events were identified.[10]

Cooperative groups have provided management guidelines children with cancer during COVID-19 pandemic. Sullivan et al. presented the special report with contributions from the International Society for Pediatric Oncology, Children's Oncology Group, St Jude Global program, and Childhood Cancer International to summarize general principles for continuing multidisciplinary care during the SARS-CoV-2 (COVID-19) pandemic. Their area of focus was six most curable cancers that are part of the WHO Global Initiative in Childhood Cancer (acute lymphoblastic leukemia, Burkitt lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms' tumor, and low-grade gliomas). They provided advice for diagnostic and treatment protocols for children with cancer during the pandemic, the measures taken to contain it (e.g., extreme social distancing), and prepare for the anticipated recovery period.[7]

Aims and objectives

Aim

To study the prevalence and clinical outcomes of COVID-19 in Pediatric Hematology oncology patients from a tertiary care health center.

Primary objective

  1. To study the prevalence of COVID-19 virus in Pediatric Hematology Oncology, Hematopoietic stem cell transplantation, and Primary immunodeficiency deficiency patients
  2. To study the clinical outcomes of the above patients with documented COVID-19 infection.


Secondary objectives

  1. To describe the symptoms, treatment received, comorbidities, complications in patients with COVID-19 infection in Pediatric Hematology oncology patients.



  Materials and Methods Top


Hospital records were analyzed for patient presenting with COVID-19 infection in patients receiving treatment for any malignancy or recipients of HSCT.

The records were reviewed under following criteria

  1. Patient Demographic Profile – age, gender
  2. Symptomatology of the patients – duration, type
  3. Diagnosis of the patient
  4. CBC at admission
  5. COVID-19-specific investigations – Il-6, Ferritin, LDH, D Dimer, Pro BNP, Chest X-ray
  6. Treatment received
  7. Duration of treatment and hospitalization/intensive care requirements
  8. Delay in chemotherapy
  9. Post-COVID phenomenon – COVID antibody status, complications.


Study setting

  • Department of Pediatric hemato-oncology and BMT unit, Sir Gangaram Hospital
  • Department of Microbiology, Sir Gangaram Hospital.


Type of study

Observational study.

Study design

Retrospective study.

Time frame

March 2020 to December 2020.

Inclusion criteria

Study group

Children aged 0–18 years who were treated for a malignancy at the pediatric hemato-oncology and BMT unit in Sir Gangaram Hospital presenting with COVID-19 positivity (COVID antigen/COVID RTPCR/COVID Rapid BioFire) were enrolled.

Clinical data collection

Clinical data including the results of biochemical and microbiological analyses, patient's characteristics, treatment during the episode, duration of hospitalization, delay in chemotherapy were collected from the medical records.

Statistical analysis

Statistical analysis of the data will be done using SPSS software among various groups.


  References Top


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  2. Wolfs TF, Attarbaschi A, Balduzzi A, Bernardo ME, Bomken S, Borkhardt A, et al. COVID-19-Impact on childhood haematology patients. Hemasphere 2020;4:e465.
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