Abstract : The second wave of COVID 19, far outnumbered the
first, in cases and deaths. We report outcome of pediatric cancer
patients with COVID-19 during the second wave, from a tertiary center in
India. Out of 41 patients who tested positive; 51% were asymptomatic,
36% had mild symptoms, 12 required admissions in ward and 4 in
intensive care. Mechanical ventilation, systemic steroids, Remdesivir
and IVIG were required in those admitted to intensive care unit. Out of
4 deaths (9.7%), 3 occurred in adolescent age and 2 had superimposed
bacterial/viral infections. Other contributors to mortality were:
cachexia, airway obstruction, disease relapse.
Introduction : The second
wave of COVID 19, that hit India from April-June 2021, had far
outnumbered the first in terms of cases and deaths; resulting in 17
million cases and 0.2 million deaths (1). Children with a pre-existing
systemic disease might be at risk of getting severe COVID-19 (2) (3).
Data from various regions of the
world has demonstrated variable mortality rates in childhood cancer
patients contracting the virus. While the data from UK (4) reported 0%
mortality, that from regions of
USA (5) and Saudi Arabia (6) has reported 4.1% and 2.5% mortality
respectively. A systematic review (7) of 33 various studies from USA,
Italy, Egypt found that out of
6.6% COVID-19 deaths in 226
patients, 4.9% were attributable to the disease, while in others,
patients were incidentally COVID positive.
At the time of writing the manuscript, there was scarcity of literature
on the clinical spectrum and outcome of the novel viral infection in
childhood cancer patients from Indian subcontinent.
We report the outcome of patients
with COVID-19 during the second wave, from the pediatric oncology unit
of a tertiary center in India and highlight some of the factors
contributing to higher COVID -19 deaths in childhood cancer patients in
developing nations as compared to developed western countries.
Methods : This was a single institutional observational study.
Pediatric cancer patients, tested
positive for
SARS-CoV-2
by RT-PCR or CBNAAT or Rapid Antigen Test or CT- severity score during
the period of second wave of COVID 19 were included.
Patient data regarding symptoms,
treatment, hospitalization, outcome, hematologic and inflammatory
markers was collected. The severity of the disease was classified as
asymptomatic, mild, moderate, and severe/critical based on the criteria
by Dong et al (9). All patients were followed up till they tested
negative. Data analysis was done using MS-office excel.
Results : Forty-one
patients (23 ALL, 5 Ewing sarcoma, 3 retinoblastoma, 2 each of
AML/Neuroblastoma/Non-Hodgkin lymphoma and 1 each of Hodgkin
lymphoma/LCH/ Rhabdomyosarcoma/Nasopharyngeal carcinoma) tested positive
for SARS-CoV-2 by RT-PCR/ CBNAAT/Rapid Antigen Test/CT- severity score.
While more than half were asymptomatic, 36% had mild symptoms (TABLE
1). In the study population, 38 patients were without any co-morbidity.
One patient was relapsed ALL post HSCT, one Hodgkin lymphoma relapse and
one was CNS relapse of rhabdomyosarcoma. Hematological parameters were
normal in majority, but the median values of CRP, Ferritin, IL-6 and
D-dimer were elevated i.e., 11.7 mg/dl, 1024 ng/ml, 37.5 pg/ml, 1050
ng/ml respectively.
Twenty-five (60.9%) patients were sent on home isolation, 12 were
admitted in COVID ward and 4 in intensive
care.Out
of 5 patients that required supplemental oxygen, 4 needed mechanical
ventilation. Systemic steroids, IVIG and Remdesivir were given in 4, 2
and 2 patients respectively. Out of the 4 deaths (9.7%) one was a case
of rhabdomyosarcoma with CNS relapse admitted for end-of-life care, the
cause of death not attributed to the virus. Rest 3 deaths (7.3%)
occurred in adolescent age group with cancer cachexia, oncologic
emergencies and post HSCT period being additional risk factors for death
(TABLE 2).
The mean time to negativity was 18±11 days. While 8 patients tested
negative after 3 weeks, 5 did so only after one month. Maximum time to
negativity was 46 days found in a case of nasopharyngeal carcinoma.
Discussion :
Based on our observation 51% of cases were asymptomatic and 60%
improved with home isolation. Out of those who were symptomatic, only
80% had manifested fever, while classical symptom of anosmia was
reported by none. Meena JP et al. (8) in their systematic review had
analyzed data from 33 studies (226 patients) from various countries and
reported 6.6% COVID-19 positive deaths, of which 4.9% were
attributable to the disease itself, while in the rest SARS-CoV-2 was an
incidental finding, not contributing to death. Due to widespread
infection by the virus during the second wave in India, we made a
similar observation where incidental positive tests were evident, by the
finding that, half of the cases were asymptomatic.
Pre-existing co-morbidities might increase the risk of severe COVID in
children. Graff et al report that, age 0–3 months or >20
years, preterm birth or comorbidities including immunocompromise,
gastrointestinal condition, diabetes, asthma and raised CRP were
predictors for hospitalization and severe outcome (3). Out of three
COVID attributed deaths in our study population, while severe bacterial
sepsis was a major contributory cause of death in one patient, another
had Adenoviral infection, with MIS-C being a common contributor for
deterioration in both. This observation highlights that COVID deaths in
LMICs could be compounded by superimposed bacterial and viral
infections. Recent IDSA finding also suggest that bacterial
superinfections were evident at postmortem examination in 32% of
COVID-19 deaths (12). Musuuza JS et al. (13) in their meta-analysis also
found that 19% of patients with COVID-19 have co-infections and 24%
have superinfections. The presence of either co-infection or
superinfection was associated with increased mortality.
Though UNICEF India enlists malignancy as one of the risk factors (2)
for getting severe COVID 19 in children, data from various regions of
the world are quite variable. Data from United Kingdom published by
Millen GC et al. reports 0% mortality with 28% asymptomatic, 63% mild
and 10% moderate, severe or critical infections in a cohort of 54
pediatric cancer patients. They concluded that children with cancer who
contract COVID-19 are not at any additional risk of serious infection
than general children (4). Registries from regions of USA (5) and Saudi
Arabia (6) have reported 4.1% and 2.5% mortality respectively in
pediatric cancer patients with COVID-19, which is more than the general
population (10) (11). Although the rate of severe COVID 19 in our study
(10%), is somewhat similar to other developed countries, 7.3% COVID
related death in our cohort is higher than those of the above-mentioned
developed nations. However, the mortality and severity rates were
similar to that in adult cancer patients reported by another apex cancer
hospital in the country (14). Ramaswamy et al. from TMC, Mumbai reported
11% severe COVID and 10% death in 230 adult cancer patients, but no
death was encountered in pediatric population that comprised 14% of
their cohort. While our patient
population comprised of patients from 7 months to 17 years, deaths
attributable to COVID were mostly in adolescent age groups. Additional
co-morbidities were present in these patients. While one patient had
severe thinness, another one had airway obstruction due to superior
mediastinal syndrome. One patient also died of Adenoviral infection plus
COVID MIS-C, who was one-year post-HSCT. Hence patients
with cancer cachexia, oncologic
emergencies and those who are less than one year post HSCT, might be at
increased risk of severe disease and death.
In our study while the mean time
to negativity was 18 days, 5 patients became negative only after one
month, with maximum time to negativity being 46 days. A Ramaswamy et al
from TMC, Mumbai have also reported similar median time to negativity of
17 days (14). Using viral culture, Teresa Aydillo etal (15) had reported
that viral RNA was detected for up to 78 days after the onset of
symptoms during immunosuppressive therapy in adult cancer patients. This
prolonged period of viral shedding in these cancer patients emphasizes
the need for extending the period of isolation in this population.
Conflict of Interest statement: The authors declare no conflict
of interest.
Acknowledgement: We sincerely acknowledge our nursing staffs
Tincy Jobin and Riya for helping in data collection