key: cord-0815162-tk95rj2l
authors: Rahmadhan, Mustaqim Apriyansa; Parenrengi, M. Arifin; Suryaningtyas, Wihasto
title: A case report of pediatric germinoma with SARS-CoV-2: Lessons learned from an academic tertiary referral hospital in Asian COVID epicentrum
date: 2022-01-17
journal: Int J Surg Case Rep
DOI: 10.1016/j.ijscr.2022.106774
sha: 5cdebaed4937a998c443a5b51dab12c9d379c543
doc_id: 815162
cord_uid: tk95rj2l

BACKGROUND: Patients often present with one or more pre-existing underlying chronic diseases that will affect their prognoses and mortality. A study revealed that the majority of children with SARS-CoV-2 infection presented with either no or a single symptom. Meanwhile, multiple other studies reported of more severe disease in SARS-CoV-2 infected children with brain tumor and/or cancer as a whole. CASE REPORT: The patient was a 15-year-old male who was referred to our hospital with complaints of vomiting, headache, and signs of worsening right hemiparesis. Initial MRI suggested of a high-grade astrocytoma and hydrocephalus, but a subtotal tumor resection and external ventricular drainage gave light to a histopathological examination conclusive of germinoma. After adhering to radiotherapy and recovering well, the patient fell into unconsciousness 9 months later and tested positive for SARS-CoV-2 infection. The patient deteriorated on the third day of admission with respiratory failure, shock, arrythmias, fever, and increased d-dimer. After multiple attempts stabilization with ventilatory, defibrillator, and medical support, the patient deceased at the 6th day of admission. DISCUSSION: Cancer patients with COVID-19 have been reported to have relatively higher mortality rate when compared to the non-infected patients. Moreover, malignancies were also reported to increase the risk of developing more severe disease in children. Although rare, patients may develop a condition called multisystem inflammatory syndrome in children (MIS-C), which is a state of hyperinflammatory and severe illness temporally associated with COVID-19 infection. No observations have been evident in indicating the influence of COVID-19 on the neurological state of the patient, but we believe that it may be reasonable to not yet exclude the possibility of it of exacerbating the CNS malignancy our patient suffered from. CONCLUSION: Children with intracranial brain tumor infected by SARS-CoV-2 may fall into a worse condition with poor prognosis, exacerbated by severe acute respiratory distress and the need for breathing support in intensive care unit. Multidisciplinary tumor boards have to convene regularly, including through call-conferences and telemedicine platforms.

The Coronavirus Disease caused by a novel zoonotic coronavirus (SARS-CoV-2) emerged from Wuhan, China and rapidly escalated into a global pandemic. A systematic review conducted by Christophers et al. revealed that the majority of children with SARS-CoV-2 presented with either no symptoms or a single symptom, with 75% of asymptomatic children exhibiting abnormal chest radiography or computed tomography findings 1 .

The first case reported in Indonesia was on March 2020, and ever since then the number of active cases of COVID-19 has grown exponentially with a mortality rate of 8,9 %. As the top referral hospital in the East Java province, The Dr. Soetomo Academic General Hospital (DSAGH) gives a standard health care of tertiary referral hospital 2 . East Java, in August 2021, based on the data of East Java Province Goverment, has 383.209 cumulative cases with 28.204 death cases. Indonesia have become a large epicentrum in Asia.

The Indonesian Pediatrician Society have reported 2,712 confirmed paediatric cases of COVID-19 with 51 deaths on 20 th of July 2020. The highest mortality rate was seen in patients aged >10 years and those placed in severe category upon admission. Most patients presented with generalized or systemic symptoms such as fever, malaise, myalgia and fatigue. This condition is interchangeably referred to as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 1 .

As an academic centre is a national tertiary referral hospital, patients often present with one or more pre-existing underlying chronic diseases that will affect their prognoses and mortality. The present findings differ from those of another study which reported that 86% of patients had at least one comorbidity, with the most prevalent pre-existing conditions being medically complex conditions (40%), immunosuppression or malignancy (23%), and obesity (15%). There were two deaths reported in this study, and both of the patients who died had comorbidities 3 .

Children with delayed brain cancer diagnosis have a higher risk for developing irreversible neurological disabilities from acquired brain lesions, such as loss of vision and endocrinopathies. Changes in the decision-making process for children with brain tumors due to fear and pressure of SARS-CoV-2 infection could negatively influence their final outcome 3 .

We report a case of a 15-year-old male with germinoma, who tested positive for SARS-CoV-2 on June 19 th , 2021. This case report is in accordance with the SCARE Guideline. 4 The problem began a year earlier, with a worsening right hemiparesis. The patient already received a medical support from a remote hospital far from ours, and was diagnosed with a brain abscess without any surgical intervention. In September 2020, he was referred to our hospital, as one of the tertiary medical centre in Indonesia, with a chief complaint of vomiting for 4 times in the last 3 hours. The vomiting was accompanied with a headache. He was given dexamethasone with a loading dose of 10 mg, continued with a maintenance dose of 5 mg 3 times a day. Scheduled brain magnetic resonance imaging revealed high grade astrocytoma and obstructive hydrocephalus ( Figure. J o u r n a l P r e -p r o o f Surgical intervention was performed through a subtotal tumor resection and external ventricular drainage to relief the hydrocephalus. The histopathological examination of the tumor sample was conclusive of germinoma. A month after the surgery, the patient began undergoing a radiotherapy protocol of total 40 Gy for 27 times. Due to the operation and patient's adherence to the radiation protocol, the patient recovered well.

On June 2021, he was admitted to the emergency department after experiencing a seizure for 30 minutes followed by decreased consciousness. Since March 2020, a "lockdown" for all Indonesian citizen was adopted; and a screening program through nasopharyngeal swab (NPS) for every patient with any kind of intervention, emergency or elective, was encouraged. The patient underwent NPS and revealed a positive result for SARS-CoV-2. Upon admission, he weighed 54 kg, with a heart rate of 88 bpm, blood pressure of 110/80 mm Hg. The patient also presented with no catarrhal inflammation of the mucous membranes, no hepatosplenomegaly, no abnormalities upon auscultation of both the heart and lungs, and a tracheostomy status from previous admission. His body temperature was 36.8°C. Laboratory studies were normal except for a white blood cell count of 20,46 x 10 3 cells/μL, 73,5% neutrophils and 21,7% lymphocytes, and a CRP of 4,6. Chest x-ray revealed a right hemithorax infiltrate suggestive of pneumonia ( Figure. 2). Oxygen saturation (SpO 2 ) was 96-99%. Neurological status in the emergency room was E 3 M 5 V x (tracheostomy), symmetrical pupils with normal light reflexes, and spastic limbs. Patient received an antiviral treatment of remdesivir 100 mg/ 24 hours.

On the third day of admission, the patient started to develop a fluctuating fever up to 39°C. Decreased condition occurred with a hypovolemic shock caused by massive diarrhea. The vital signs were 131/71 mmHg (supported by 50 nanograms of nor-epinephrine), HR 200x/mins, and an ECG indicative of vent---ricular tachycardia. Neurological status revealed a GCS of E 1 M 4 V x with asymmetrical pupils. In regards to the ventricular tachycardia and unstable condition, a cardioversion with 150 joules was performed. After three times of cardioversion with DC shock, the heart rate began to slow down (174 x/min), although the ECG still showed a VT. Amiodarone was administrated for maintenance. Laboratory evaluation were within normal limits, but we found an increased D-Dimer of 2980, and blood gas analysis revealed a severe respiratory acidosis and failure. The SARS CoV-2 pandemic made it hard to find a ventilator to support the respiratory failure of the patient.

On the fourth day, the patient's condition worsened with arythmias (refractory VT) that cannot be overcome by medical and direct cardioversion (Picture 4.). Neurological condition revealed a motor posturing, decerebrated, bilaterally dilate pupils, and no light reflexes. Breathing problem of the patient was indicated by the increased respiratory rate and decreased saturation of 90% with maximum oxygen delivery using Jackson-Rees Circuit (15 lpm). We still administrated redemsivir, dexamethgp789-asone, and amidodarone with a maintenance dose of 550 mg/24 hours.

On the fifth day, evaluation of continuous monitoring ECG showed a sinus rhytm with slower heart rate 135-144x/ mins (Picture 5). Unfortunately, the vital signs and neurological status got worse. Saturation of patient was 85-90% with Jackson Rees 15 lpm. We found hematin on the patient indicative of a GI tract bleeding suspected to be caused by administration of corticosteroids and the SARS-CoV-2 status. Laboratory evaluation revealed an elevated leukocyte of 19,78 x 10 3 cells/μL, without blood coagulation abnormalities.

On the sixth day, the vital signs of the patient was unstable with a blood pressure of 70/40 mmHg (supported by dopamine 10 mcg), heart rate and respiration rate was slowing down 80x/ mins and 16x/ mins, while saturation remained at 50%. Monitoring of ECG showed a sinus rhytm. Hematin was still produced. The condition did not improve for some time, and after a several hours of observation, the patient died. The intracranial lesion could not therefore be confirmed nor hospitalized with MIS-C may develop central and/or peripheral nervous system involvement. 22, 23 The frequency itself is still unclear, but the range of severity and various clinical course may be somewhat of a challenge for neurosurgeons and other physicians of various specialties to deal with. As in our case, no observations have been evident in indicating the influence of COVID-19 on the neurological state of the patient, but we believe that it may be reasonable to not yet exclude the possibility of it of exacerbating the CNS malignancy our patient suffered from. 23 Radiotherapy (RT) plays an important role in the management of oncologic patients, including those of neurosurgical malignancies. 24 The scope of RT may vary from its elective use to emergency ones, which may vary from neurologic injury from cord compression, brain metastases, airway compromise, and bleeding. [25] [26] [27] Radiotherapy with palliative intent are suited for patients with limited functional status and is effective for providing care and limiting morbidity due to the disease progression. 24 COVID-19 pandemic has led to the importance in our developing more meticulous patient selection, as this situation may affect patients from an individual level, especially in neuro-oncologic cases, and to a more administrative and public health issues. This should also prompt healthcare facilities to create guidelines on whether it is crucial to delay treatments and set priorities for cases that are clinically urgent or not. 28 The Royal College of Radiologists (RCR) defined several aspects of prioritization amidst the COVID-19 pandemic for neuro-oncology patients. 29 They stressed the importance of knowing the context of delineation normal, non-pandemic suggestions and COVID-19 based advice, and physicians will need to be clear on the difference between them. Patients and their family members should always be consulted with proper documentation and performed by consultants. The RCR noted that the highest priority of care should be addressed towards those diagnosed with large benign tumours with acute symptoms (pressure, loss of sight) and posterior fossa tumours (malignant or non-malignant) causing life-threatening hydrocephalus. The next, which they noted as highintermediate priority, include medulloblastoma and grade 3 glioma in younger patients. The other two, intermediate and low, are reserved for high-grade glioma in young fit patients, and those with small benign tumours, high grade glioma in elderly, and low-grade glioma of any age, respectively. They also stressed that age plays a significant factor in treatment response and prognosis, which should also influence a physician's choice in which patients should get which appropriate modalities. For patients whom are already on treatment, the continuation of any RT and chemotherapy, with the changing risk, should be documented and discussed comprehensively with other specialties and the patients. 29 The influence of age and COVID-19 highlighted through multiple relevant studies may help understand the state of the patient in our case and how to further manage cases such as this. Although one could not accurately point out which factor accounts for the most deleterious effect on the patient's condition, it is proven that COVID-19 and brain tumors in pediatric cases do not mix well. The hyperinflammatory state of COVID-19 infection and tumoral environment may be believed to have exacerbated the patient's general condition indicated by the increased D-dimer and possibly due to a cytokine storm. The patient's condition deteriorated at the third day of admission, and ultimately died after experiencing an atrial fibrillation, ventricular tachycardia, and multiple attempts of DC-shocks. This case may help elucidate the importance of patient selection in the case of RT in pediatric neuro-oncology cases, and what to monitor to further decide the appropriate management for similar cases. Although no clear distinction whether the condition of the patient was due to the tumor, COVID-19, or both, the current evidence suggests links between them. Moreover, age also plays a factor in the exacerbation of the clinical condition of these patients.

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Children with intracranial brain tumor infected by SARS-CoV-2 may fall into a worse condition with poor prognosis, excacerbated by severe acute respiratory distress and the need for breathing suppport in intensive care unit. The pandemic situation may lead us to make tough decision in taking care of multiple paediatric patients. Multiple organ complications, especially those of cardiovascular, shorten the rate and time of survival. These should be a major concern, aside from the breathing problems caused by SARS-CoV-2 infection. Multidisciplinary tumor boards have to convene regularly, including through call-conferences and telemedicine platforms.Provenance and peer review Not commissioned, externally peer-reviewed

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