Discussion
Since the first SARS-CoV-2-positive case in March 2020, 8 935 746 cases have been confirmed in Argentina. Of these, 8% (720,147) were patients between 0 and 19 years of age26 and 0.1% (n= 888) were pediatric patients with concomitant oncological disease, who mostly presented with mild clinical manifestations or asymptomatic disease. The low incidence rate in our study is similar to that reported in other studies27,7but slightly higher than that estimated for the general pediatric population.8This low incidence could be related to the early implementation of social distancing and prevention measures,11 but may also suggest underreporting, given that children predominantly have mild or asymptomatic forms of COVID-19.27
Almost 60% of the children that tested positive for SARS-CoV-2 had leukemia or lymphoma, followed by central nervous system tumors in 13.5%, which is consistent with the distribution of cancer diagnoses in the general pediatric population. In addition, the distribution of diagnoses according to the ICCC-3 in children with SARS-CoV-2 infection was similar to that reported in previous series.5,7,8,10,14,17,28
In our series, 41.1% of patients were asymptomatic at the time of COVID-19 diagnosis. This is twice the rate published for the general population of patients under 18 years of age in Argentina.29This difference may be explained by the greater number of tests performed in cancer patients as a result of screening prior to admissions, procedures, and transfers.30
In the majority of patients, clinical manifestations consisted of mild respiratory symptoms with minimal requirement for hospital admission and not leading to an increase in COVID-19-related morbidity or mortality, coinciding with reports from other countries.12,31The symptoms most frequently observed were fever and cough, similar to those reported by other authors both in general pediatric population and in the pediatric population with cancer.2,5,7,8,10,12,17,28,32
Although these children are immunocompromised with greater susceptibility to infection, unlike what was initially thought for adults with cancer,33more than 70% of children with cancer and SARS-CoV-2 infection evolved favorably and remained asymptomatic or developed mild disease. Only 3 % of cases presented critical disease, consistent with those reported in other pediatric series.6,11,17,28
Madhusoodhan et al. found a higher rate of asymptomatic patients than in the general pediatric population in the same geographic region.7Similar to other series, our evaluation showed that only a small number of patients who were asymptomatic at diagnosis developed symptoms later. Although in our study mortality was high compared to previously published series.7,15,18,28,32when the causes of death in our population were analyzed, 88% were found to be due to progression of the underlying disease or to disease-associated complications2,7,14and not attributable to SARS-CoV-2. There was also no difference in COVID-19-related mortality (n=7) in children with leukemia or lymphoma when comparing the three waves, despite different circulating strains.
One of the major interrogatives during the pandemic was whether immunosuppressive treatment should be continued in patients with cancer and SARS-CoV-2 infection. In the first months of the pandemic, recommendations were developed to guide treating physicians in the management of cancer therapies. Different studies show that initially it was decided to discontinue or modify chemotherapies, immunotherapies, surgeries, and radiation therapies, motivated by uncertainty regarding outcome and prognosis of SARS-CoV-2 infections in cancer patients.2,3,8,17,20,21Due to a lack of data on treatment discontinuation or modification in our study, we cannot be sure if the same occurred in Argentina.
One of the strengths of our study is that ROHA has national coverage of more than 90% of pediatric cancer patients by including all PHOUs in the country. The creation of the epidemiological registry of patients with SARS-CoV-2 infection in the registry allowed for the dynamic and almost real-time reporting of positive cases. Based on this information, weekly epidemiological reports were prepared and sent back to each institution resulting in data-driven decision-making in the face of this new disease.
It should be noted that the unexpected outbreak of COVID-19 confronted us with a general population, including pediatric cancer patients and their families that had to comply with isolation protocols and restrictions and warranted the implementation of healthcare measures to combat the virus. Although changes in the management over time led to some delays, most patients were able to safely continue their treatment even during the most complicated moments of the pandemic.14,17,18,19,21
Future studies will be necessary to know the true impact of SARS-CoV-2 on the oncological disease of these patients.
Conclusion In conclusion, based on our data we may infer that the impact of SARS-CoV-2 in pediatric patients was low in terms of incidence and mortality exclusively attributed to SARS-CoV-2. The clinical course of COVID-19 was mild in the majority of cases.
The PHOU, which adapted to the epidemiological situation in each jurisdiction, continued to care for their patients. In all cases, changes in the hospital care model were reported.
The pediatric oncology units, adapted to the epidemiological reality of each jurisdiction, continued to assist their patients. In all cases, modifications in care attention model at the hospital were reported.
Based on the experience gained, which demonstrated the favorable evolution and the absence of severe complications in most cases of SARS-Cov2 in pediatric cancer patients and the increased risk associated with inadequate oncological management, the interruption of the treatments was limited to the small number of critically ill patients.
As lessons learned, we should include better preparation of health services to deal with infections, improved communication between centers and networking, as well as the use of telemedicine as an element of training that we should incorporate and continue to strengthen beyond the end of the pandemic.
Finally, it would be important to highlight the impact on the physical and psychological health of healthcare personnel, as well as the deaths caused by SARS-CoV-2. Social distancing, hand hygiene, greater awareness of infections, and the mandatory use of masks, which lead to a decrease in infections, were reflected in a decrease of non-covid-related infectious-contagious complications.
Based on the ROHA data, we may conclude that in pediatric oncology patients, contrary to what was initially expected, morbidity and mortality were not increased.