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Katato, G.K.; Sitaula, P.; Gupte, A.; Al-Antary, E.T. The Impact of COVID-19 on Pediatric Malignancy. Encyclopedia. Available online: https://encyclopedia.pub/entry/42856 (accessed on 18 July 2025).
Katato GK, Sitaula P, Gupte A, Al-Antary ET. The Impact of COVID-19 on Pediatric Malignancy. Encyclopedia. Available at: https://encyclopedia.pub/entry/42856. Accessed July 18, 2025.
Katato, Ghadir K., Prasiksha Sitaula, Avanti Gupte, Eman T. Al-Antary. "The Impact of COVID-19 on Pediatric Malignancy" Encyclopedia, https://encyclopedia.pub/entry/42856 (accessed July 18, 2025).
Katato, G.K., Sitaula, P., Gupte, A., & Al-Antary, E.T. (2023, April 06). The Impact of COVID-19 on Pediatric Malignancy. In Encyclopedia. https://encyclopedia.pub/entry/42856
Katato, Ghadir K., et al. "The Impact of COVID-19 on Pediatric Malignancy." Encyclopedia. Web. 06 April, 2023.
The Impact of COVID-19 on Pediatric Malignancy
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This entry is adapted from the peer-reviewed paper 10.3390/vaccines11030667

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare providers, hospital systems, and leading oncologic societies to quickly adapt and formulate new guidelines for the effective understanding, management, and treatment of patients with pediatric malignancy.

COVID-19 diagnosis management

1. Introduction

The outbreak of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan and soon thereafter was declared by the World Health Organization (WHO) as a global pandemic [1]. The coronavirus disease 2019 (COVID-19) has caused tremendous strain on the healthcare systems worldwide and has captivated the interest of pediatric oncologists in a unique way. Adults with COVID-19 were reported to have a severe course of disease with a significantly higher mortality rate [2]. However, we now have data to show that most of the children who tested positive for COVID-19 had either asymptomatic infection or mild symptoms, with only a handful presenting with severe disease requiring critical care [3]. A similar trend has also been noted in our pediatric oncology patients compared to their adult counterparts [2][4]. The COVID-19 pandemic has posed significant challenges in the healthcare sector, which has directly or indirectly impacted the care of pediatric cancer patients. From the challenges of diagnostic delay and delay in hospitalization to interrupted treatment in COVID-19-affected oncological patients, there have been substantial obstacles faced by providers and patients during the pandemic [5][6].

2. Management of the Malignancy during COVID-19 

Due to the COVID-19 pandemic, hospitals needed to change their practices due to surges causing overflow and limitations in resources. Oncology patients who typically received multimodal therapy and care had a limited ability to come to the hospital due to lockdowns in place. Early in the pandemic, leadership from the International Society for Pediatric Oncology (SIOP), Children’s Oncology Group (COG), SIOP-E (Europe), International Society of Pediatric Surgical Oncology (IPSO), Pediatric Radiation Oncology Society (PROS), Childhood Cancer International, (CCI), and St. Jude Global provided recommendations for the diagnosis and treatment of pediatric oncology patients. Care for pediatric oncology patients was not to be compromised due to the pandemic, and recommendations were made to establish normalcy during this time. They recommended that cancer centers have anticipatory and planned processes in the event hospitals became limited in resources, as evidenced in Lombardy, Italy [7]. Recommendations also came as an aid to low- and middle-income countries without adequate resources for the diagnosis and treatment of pediatric malignancies [8]. It was recommended to limit patient visits to clinics and hospital admissions and temporarily stop routine surveillance and survivorship clinics, especially in the event healthcare providers were needed in other departments for frontline critical care. Leadership had recommended that all aspects of cancer treatment would continue without any changes unless resources became limited [7][9].
Recommendations regarding anticipatory care in the setting of limited resources during the pandemic were modeled and adapted from the Lombardy experience in order to limit COVID exposures [7]. Factors included developing a standard operating procedure, COVID-19 viral testing of staff and patients prior to elective procedures or admission, appropriate hand washing and the use of appropriate personal protective equipment by staff and families entering and leaving clinical areas, restricting visitors to one per patient, cohorting staff, separation of oncology staff from staff working in COVID-19 areas, and an elective reduction of high-risk procedures, including CAR-T and stem cell therapies, to decrease the demand for intensive care services [7][9].
In certain instances where patients had advanced cancer with concurrent COVID-19, whether it is symptomatic or detected on screening, recommendations included interim therapy to control the disease and allow for recovery from COVID-19 before giving cancer-directed treatment. Similarly, in patients with new cancer diagnoses that were non-emergent, such as an abdominal mass or a low-stage Hodgkin’s lymphoma, deferring diagnostic approaches and treatment until recovery was deemed reasonable [9].
Leadership also provided recommendations in regard to ALL. It was recommended these patients undergo a full investigation to establish the diagnosis, risk stratification, and treatment plan according to guidelines, protocols, and trials. In patients who had COVID-19 alongside hyperleukocytosis, it was recommended that treatment include steroid prophase and supportive care and then initiating treatment-directed therapy once the patient had recovered from COVID-19 [10]. Typical diagnostics include age along with labs that include complete blood count, flow cytometry, molecular, bone marrow aspirate, and biopsy with cytomorphology to be interpreted. If flow cytometry and molecular diagnostics were unavailable, a diagnosis made without the use of these modalities was justifiable [11]. Patients would be treated with a morphologic response instead of molecular classification and minimal residual disease (MRD) status. No changes were recommended for maintenance therapy. Every attempt was to be made to minimize clinic visits in areas of high COVID-19 prevalence [9].
In regard to Burkitt Lymphoma, due to the aggressive nature of this disease, no modifications were recommended in fully resourced and high-income countries, especially in the setting of concurrent COVID-19. In settings where the disease was advanced with additional comorbidity, treatment prophase with stepped dosing corticosteroids and supportive care was recommended before initiating disease-directed therapy. In order to establish a diagnosis, baseline imaging such as chest X-ray, ultrasound, and biopsy were performed [12]. Hodgkin lymphoma recommendations included outpatient-based therapy without modifications in the protocol. Since low–middle-income countries may not have access to certain types of imaging for treatment stratification and radiotherapy access is limited, especially in the setting of COVID-19, a chemotherapy-only approach was recommended (in low- and intermediate-risk diseases) [13][14][15][16][17]. Several other modifications to the management of pediatric cancers were recommended [9].
It is also worth mentioning that, prior to major guidelines being released at the height of the pandemic, several countries released case reports of patients with altered chemotherapy regimens in the setting of COVID-19. Countries such as Japan, China, and Latin America had developed plans for AML with a milder treatment course [18][19]. Brazil followed their practices and treated nine patients with AML and COVID-19 with a less intensified induction regimen and showed excellent outcomes, with all achieving complete remission over the course of 4 months of follow-up [20]. Similarly, patients in China were followed over the course of 6 years and continued to have up to 4 years of follow-up at the time of the study completion. Their 4-year overall survival and event-free survival rate at 4 years were about 74% and 68%, respectively, with a cumulative incidence of relapse of about 25% [18]. A mild induction protocol regimen (MAG) consisted of mitoxantrone at 5 mg/m2 days 1, 3, and 5, cytarabine at 10 mg/m2 q12 for 10 days, and G-CSF 5 micrograms/kg once daily for 10 days [20][21]. Therefore, it was suggested that this regimen be used in low- and middle-income countries to overcome the induction mortality and try to improve outcomes of children and adolescents with AML, especially when in need of adapting a treatment regimen during an emerging health crisis when optimal therapy is not feasible.
In September 2020, the countries in Africa took recommendations from the Lombardy region in Italy to utilize on their own pediatric oncology patients. There were 25 pediatric oncology centers from 15 countries in Africa that showed a decrease in pediatric oncology treatment activity due to family fear of COVID-19, restricted travel, decrease in parental finances [22]. It was noted that 60% of centers experienced staff shortages and had postponed surveillance consultations as well, leading to a decrease in activity in pediatric oncology treatment. It was also reported that modifications in chemotherapy administration, surgery, and radiation occurred due to drug shortages, delays of cancer surgeries, radiotherapy due to schedules, and a shortage of blood products to be given in 50% of participants. The countries also understood an anticipatory approach needs to be taken in that there may be an increased risk of receiving patients with advanced-stage cancer, risk of treatment abandonment and relapses, and to continue to be aware of this and prepare [22].
In India, 30 centers reviewed treatment modalities of malignancy during COVID-19, which included chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplant, and noted that 36% of patients experienced delays in their care. Some of these centers in India modified treatment protocols, increased growth factor uses, and increased the use of support from social organizations [23]. Seventy percent of treatment centers in India continued to treat malignancies such as ALL, AML, and sarcomas without any changes based on recommendations by the leadership [23].
The Pediatric Oncology East and Mediterranean (POEM) group reported on the impact of the COVID-19 pandemic on patients with established oncologic diagnoses. In the majority of centers surveyed, it was noted that off-therapy surveillance was delayed to decrease clinic load as was recommended by leadership groups [9][24]. There were noted to be delays in chemotherapy administration in 29% of the centers in the Middle East, North Africa, and West regions. Modalities for local control, such as surgery and radiation, were also delayed in 44% of centers, raising concerns about tumor recurrences and treatment failures [25]. Lebanon, for instance, delayed local control surgery and administered neoadjuvant chemotherapy in the midst of the pandemic to minimize the risk of infection [26]. Further, it was noted that acceptance of new pediatric oncology patients was restricted in 24% of the centers, with the potential for more patients being referred to other centers and possibly some patients unable to obtain the necessary access to curative therapy [25].

3. Management of COVID-19 in Pediatric Oncology

The National Institutes of Health (NIH) established guidelines regarding criteria for patients with COVID-19 based on clinical type. Data were limited for pediatric patients, given the small subset of patients affected by COVID-19, and guidelines were largely based on adult data. These guidelines would allow providers to decide between supportive therapy vs. Symptomatology of COVID-19 included fever, cough, sore throat, malaise, headache, myalgias, nausea, vomiting, diarrhea, anosmia, and ageusia, among other symptoms, with or without supplemental oxygenation. Further guidelines were made regarding admitted patients with multisystem inflammatory syndrome in children (MIS-C), defined as a post-infectious complication of COVID-19 with symptoms including persistent fever, multisystem organ dysfunction, and systemic inflammation requiring care in the intensive care unit due to shock and the need for vasopressors and inotropes [27][28].
During the early phase of the pandemic, patients with a pediatric oncologic diagnosis needed to have a negative test by polymerase chain reaction (PCR) prior to the initiation of therapy. Poland has adopted European Centre for Disease Prevention and Control (ECDC) guidelines on ending COVID-19 isolation. In patients with mild–moderate disease, guidelines included no fever for 3 days and clinical improvement of symptoms as well as either 10 days having passed since isolation, or two negative COVID-19 PCR tests spaced 24 h apart [29]. In patients with severe disease, similar criteria were applied with the modification of a minimum of 14 days, and up to 20 days have passed since isolation. Similarly, in immunocompromised patients, a modification of 20 days needed to pass after the onset of symptoms was applied in order to leave isolation [29][30]. As these were guidelines developed earlier in the pandemic and with more knowledge and awareness of how COVID-19 affects patients, it is now recommended to begin treatment as soon as feasible, as delaying the induction phase could have an adverse effect on the outcome of the patient [31]. Further reports have also suggested not delaying treatment, especially as leukemia is curable, and it is noted that pediatric patients typically have a less severe infectious course with COVID-19 [32] and have shown success in treatment when receiving concurrent care with an active infection from COVID-19 [33].
The COVID-19 pandemic further affected procedures and surgeries that would take place for patients with malignancies. Institutions largely required patients to have a negative COVID-19 test prior to each sedated procedure. Positive test results potentially caused cancelations or delays in procedures until consecutive results yielded negative results [34].
Prior to a consensus, there were recommendations on the prevention or management of pediatric oncology patients in the setting of COVID-19. Recommendations include the patient being isolated to their home in between receiving treatment, and if they are to receive treatment, they stay in a single and nonshared room. Outpatient follow-up appointments were limited to an urgent basis, and there was an increase in the use of telemedicine or other communicative efforts [24]. COVID-19 screening of symptomatic patients was initiated, social distancing rules of at least 6 feet were enforced between individuals with no grouping, and a one-parent limit to stay with the child was recommended inpatient and outpatient. Recommended that, if possible, hospital settings could establish a COVID-19-free site to provide scheduled treatment [24]. Along the same lines, an inpatient setting dedicated just to COVID-19 pediatric oncology patients was trialed in Italy in order for patients who were infected by the virus to still continue their treatment under adequate medical and nursing assistance [35].
Limited data had previously suggested that patients with cancer and COVID-19 may have an increased risk of complications and mortality in comparison to the general population [36]. Lee et al. observed that patients with hematological malignancies were at increased risk of COVID-19 compared to those with solid tumors and exhibited a more severe clinical course [31]. However, as time passed, it was learned that children with malignancies were not necessarily at increased risk of severe COVID-19 [37], though symptomatic management was recommended in this high-risk group of patients. It is unclear about pediatric oncology patients’ increased risk for complications and mortality when there is associated COVID-19. Treatments have included the use of remdesivir due to in vitro activity against COVID-19 [36]. A first case report in the U.K. presented a pediatric patient with acute leukemia and COVID-19 who received concurrent treatment with remdesivir and induction chemotherapy and was shown to have not deteriorated or suffered severe complications from COVID-19 and was also in remission at the end of induction. This patient had a high risk of immunosuppression due to his chemotherapy regimen and was also at risk of worsening viral infection but was able to tolerate these regimens well [36]. Further cases revealed similar reports of patients with acute leukemia along with COVID-19 who were started on antiviral therapy following infection with COVID-19 and had successful outcomes [38][39].
Finally, in the setting of the COVID-19 pandemic, vaccines were developed to help prevent infection. AIEOP formulated a consensus report consisting of 21 statements and their rationale to specifically address the need for vaccination in this vulnerable immunocompromised population of pediatric oncology patients. It specifically addressed the questions regarding the need for vaccination, type and schedule, timing of vaccination, and eligibility criteria, among many other criteria that have been discussed in detail in this consensus report [40]. COVID-19 vaccines are now recommended in all patients older than 6 months who are undergoing chemotherapy and after a hematopoietic stem cell transplant. This is recommended to reduce the risk of therapy interruptions and complications that can occur from COVID-19 [41]. It is recommended to give vaccination at least 14 days prior to starting therapy treatment, but if this is not possible, then it is recommended to administer the vaccine when cytopenia from treatment is minimal. In bone marrow transplant patients, vaccines are recommended as soon as 100 days after the transplant and CAR-T cell therapy [42]. Once these patients have completed therapy, another dose is indicated to increase the immune response, as well as a booster dose every few months to maintain immunity [42]. The vaccine is noted to be safe and effective in children, especially those who are immunocompromised [43]. It is of note that the efficacy of the vaccine is lower in immunocompromised patients, and there have been no studies to date measuring vaccination efficacy in children with cancer [43][44], making it of utmost importance to continue taking protective measures such as vaccination.

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Subjects: Hematology; Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Ghadir K. Katato
,
Prasiksha Sitaula
,
Avanti Gupte
,
Eman T. Al-Antary
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Revisions: 2 times (View History)
Update Date: 07 Apr 2023
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