*2.4.1 Testing of patients with cancer*

Symptoms of COVID-19 (fever, cough, dyspnea, diarrhea, etc.) and suspected exposure are essential for testing cancer patients. According to IDSA (Infectious Diseases Society of America) guidelines, the first higher priority includes unexplained viral pneumonia or respiratory failure in critically ill patients in ICU. Also, fever or lower respiratory tract illness in immunosuppressed, older, or have underlying chronic health conditions is an indication. The other symptoms in the first higher priority are fever or lower respiratory tract illness in patients with COVID-19 contact within 14 days or in health care workers, public health care workers, and other essential leaders. Non-ICU hospitalized patients with unexplained fever, and lower tract illness are in the second level of priority. The third priority consists of outpatients with criteria of influenza testing (chronic diseases and immunocompromising conditions), pregnant women, and children with similar risk factors. Public health and infectious diseases authorities' decisions are the fourth priority [25]. Before cytotoxic chemotherapy, solid organ and stem cell transplantation, cellular immunotherapy, or high-dose corticosteroids, SARS-CoV2 RNA testing is recommended in several guidelines [26].

#### **2.5 Treatment and outcome of SARS-CoV2 infection in children with cancer**

#### *2.5.1 Guideline recommendations for children*

Treatment recommendations of COVID-19 for childhood cancer are the same with children without cancer. Supportive treatment (hydration, nutrition, oxygen supplementation) is essential in COVID-19 treatment. In the COVID-19 treatment guidelines panel, remdesivir is recommended for hospitalized children ≥12 years with risk factors of severe disease and increasing demand for oxygen. In addition, this panel recommends dexamethasone for children with high flow oxygen, mechanical ventilation, or extracorporeal membrane oxygenation in COVID-19 disease. If dexamethasone is not available, other glucocorticoids can also be given. The dose of dexamethasone is 0.15 mg/kg/dose (maximum 6 mg) for up to ten days. Convalescent plasma is used for mechanical ventilated COVID-19 positive children. Anti-SARS-CoV2 monoclonal antibodies (bamlanivumab plus etesevimab or casarivimab plus imdevimab) studies are insufficient in the pediatric population. However, ≥ 16 aged and hospitalized patients having at least one high risk of severe disease can be consulted for pediatric infectious disease. The safety of baricitinib has not been evaluated in pediatric patients; the data of baricitinib and remdesivir combination is insufficient for hospitalized children who have a contraindication for corticosteroids. The use of tocilizumab for severe pediatric cases has been described; there is inadequate data for recommending tocilizumab in MIS-C or hospitalized children with COVID-19. All of these therapies can be discussed for selected patients [23]. Increased D-dimer and high risk of thrombosis are indications for anticoagulation in childhood cancer with COVID-19 disease [27].

In MIS-C, IVIG (intravenous immunoglobin) and corticosteroids are in the first-line treatment. High-dose IVIG (typically 2 g/kg, based on ideal body weight) is used. In severe cases, low-moderate dose glucocorticosteroids (1-2 mg/kg/ day) should be given with IVIG. Interleukin-1 antagonists are given in refractory instances in patients with MIS-C. Features of macrophage activation syndrome or contraindications for glucocorticosteroids are indications of it. Therefore, highdose steroids are used for refractory patients. Antiplatelet therapy is used at least for weeks after diagnosis. In case of indefinite treatment and documented thrombosis, anticoagulation is recommended [23, 28].

### *2.5.2 The COVID-19 treatment guideline panel recommendations for adult patients with cancer*

Vaccination for COVID-19 is recommended for adults with active cancer and those receiving treatment for cancer. The vaccination should be done at least two weeks before starting chemotherapy. In adults with hematologic malignancies, vaccination should be done after neutrophil recovery for those receiving intensive chemotherapy. Vaccination should be done at least after three months of hematopoietic stem cell transplantation and chimeric T-cell therapy.

For signs and symptoms of COVID-19 and before chemotherapy, radiotherapy, and all invasive procedures, testing with PCR should be performed. Treatment delays for curable cancers like pediatric lymphoblastic leukemia should be avoided. If regimens with similar results are preferable, orally administered drugs or regimens with fewer days should be chosen. Regimens should not be altered even in COVID-19 patients with cancer. In radiotherapy guidelines, the daily dose by a fraction is increased to lower the days of treatment. For patients with febrile neutropenia, a PCR test for COVID-19 should be performed. National Comprehensive Cancer

Network guidelines should be followed. Treatment of COVID-19 in cancer patients is the same with the general population. Drug interactions are essential [23].
