Introduction:
People with cancer are more prone to COVID-19 infections compared to those without cancer, and people being treated with cancer are at increased risk of severe COVID-19. A systematic review of more than 40,000 patients with COVID-19 showed an increase in mortality rates in cancer patients, and these cancer patients with COVID-19 are more likely to get admitted to intensive care units. This increased risk for SARS-CoV-2 infection and immunosuppression varies from:
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Cancer types.
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Treatments administered.
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Stages of therapy - Patients under active treatment.
Cancer patients under active treatment are a at higher risk of death of COVID-19, where cancer patients under remission are at lower risk. Although cancer survivors do not share an increased risk of developing COVID-19, once infected the complications they develop can be severe that require hospitalization as compared to other patients. So, start to focus on the following to prevent the risks.
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Test for SARS-CoV-2 if any symptoms.
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Manage COVID-19 in patients with cancer.
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Manage cancer-directed therapies during the COVID-19 pandemic.
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Get the vaccination at your turn with the advice of the treating oncologist.
Can Cancer Patients Be Administered COVID-19 Vaccines?
COVID-19 vaccines that have received approval and emergency use authorization (EUA) excluded the immunocompromised patients in the clinical trials. These vaccines are live vaccines, and they can be administered safely on immunocompromised patients, says the advisory committee on immunization practices.
The COVID-19 treatment guidelines recommend SARS-CoV-2 vaccination for cancer patients and patients under treatment for cancer by considering the effectiveness of this vaccine on the general population.
Some patients show severe anaphylactic reactions to ingredients like:
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Polyethylene glycol - mRNA vaccine.
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Polysorbate - Johnson, and Johnson vaccine or Janssen vaccine.
So patients with severe anaphylactic reactions can undergo allergy testing before getting vaccinated.
How to Determine the Time for Vaccination in Cancer Patients
The patients should consider the following factors before deciding to get vaccinated.
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The patients who are planning to receive chemotherapy should complete vaccination before two weeks of starting the treatment.
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The vaccination is to be delayed until there is a neutrophil recovery for patients undergoing intensive chemotherapy for hematologic malignancy.
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At least after three months of therapy, the SARS-CoV-2 vaccination can be offered to hematopoietic stem cell and chimeric antigen receptor T cell recipients.
How Does Vaccine Respond in Cancer Patients?
Better understanding is required to assess the response of vaccines in cancer patients.
Immune Response with SARS-CoV-2 Vaccination - It is not clear whether there will be a risk of graft-versus-host disease or other immune-related complications on SARS-CoV-2 vaccination.
Immune Response with Influenza Vaccination - Immune response in cancer patients on influenza virus is based on the following:
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Type of cancer.
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Whether the patient has received chemotherapy recently.
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Type of chemotherapy.
Non-Recommendations with SARS-CoV-2 Vaccination - Antibody testing to assess immunity to SARS-CoV-2 following vaccination is not recommended in patients with cancer. Also, revaccination after regaining immune competence is not recommended for people who received COVID vaccination during:
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Treatment with other immunosuppressive drugs.
Recommendations on SARS-CoV-2 Vaccination - Healthcare providers provide care for immunocompromised patients to protect them from infection, and all close contacts to immunocompromised individuals such as family members, healthcare professionals are strongly recommended to get vaccinated as soon as possible.
How COVID-19 Testing Is Done in Cancer Patients?
The COVID-19 treatment guidelines panel recommends that cancer patients undergo molecular diagnostic testing when they develop signs and symptoms of COVID-19. Cancer patients who are receiving chemotherapy are at an increased risk of developing neutropenia (low count of white blood cells). In turn, cancer patients with neutropenia have a high mortality rate if they develop COVID-19. Granulocyte colony-stimulating factor (G-CSF) should be given chemotherapy regimens to prevent the risk of febrile neutropenia.
What Is Febrile Neutropenia?
The NCCN (National Comprehensive Cancer Network) guidelines outline that cancer patients with febrile neutropenia should undergo:
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Molecular diagnostic testing for SARS-CoV-2.
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Evaluation for other infectious agents.
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Take empiric antibiotics.
Test Positive For SARS-CoV-2 - Patients who test positive for SARS-CoV-2 should be given empiric antibiotics.
Low-Risk Febrile Neutropenia - To limit nosocomial exposure to SARS-CoV-2, these patients are treated at home with,
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Oral antibiotics.
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Intravenous infusions of antibiotics.
High-Risk Febrile Neutropenia - These patients are hospitalized per standard of care.
So, the panel recommends undergoing molecular diagnostic testing for SARS-CoV-2 due to the risk of outcomes during the:
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The setting of neutropenia.
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The perioperative period.
Also, molecular diagnostic testing for SARS-CoV-2 is done prior to procedures:
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That requires anesthesia.
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Before the initiation of cytotoxic chemotherapy.
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Long-acting biologic therapy.
How Medical Care Can Be Given to Cancer Patients During the COVID-19 Pandemic?
Cancer patients are always in contact with the healthcare professionals for supportive care. However, during this pandemic, telemedicine is helpful for people who are at risk medically and socially and helps to reduce:
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The risk of SARS-CoV-2 exposure in cancer patients.
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The number of in-person visits to the hospital.
Principles for in-Person Interactions - The prevention strategies to be applied during in-person visits are,
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Social distancing.
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Wearing masks (patients and health care workers).
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Practicing hand hygiene.
To make this more clear to clinicians, the Center for Disease Control and Prevention (CDCP) has published a framework to decide whether a patient should visit the hospital for treatment or to have virtual health care from the comfort of the bed during this COVID-19 pandemic. Decisions regarding the treatment (in-person or virtual care) are made on an individual basis depending on the biology and malignancy of cancer as:
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Treatment regimens.
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Surgery.
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Radiation therapy.
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Need for hospitalization.
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The number of clinical visits required.
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Anticipated degree of immunosuppression.
Also, this framework explains the complications of delayed care and SARS-CoV-2 transmission in the patient's community.
What Are the General Guidelines for Cancer Patients During the COVID-19 Pandemic?
The key points to be considered during the COVID-19 pandemic are:
1. If possible, do not hold up the treatment for the cancers that may get worse if the treatment is delayed.
2. Prefer regimens that can be orally administered or that require fewer infusions.
3. Maintain a balance on the risks of drug-related lung toxicity (from using Bleomycin or PD-1 inhibitors) with alternative regimens.
4. During the COVID-19 pandemic, preventing neutropenia decreases the risk of:
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Neutropenic fever.
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Emergency department evaluation.
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Hospitalization.
5. In order to minimize the number of hospitals visits, the radiation therapy guidelines suggest to:
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Reduce the number of daily treatments.
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Increase the dose per fraction.
6. In cancer patients lowering blood transfusion products should be considered, and at this time, there is no evidence of COVID-19 getting transmitted through blood and blood products. But there are blood supply shortages due to:
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Social distancing.
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Cancellation of blood drives.
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Infection among donors.
How to Treat and Manage Chemotherapy in Cancer Patients With COVID-19?
Higher death rates are seen in cancer patients (mostly in hematologic malignancies than solid tumors) admitted to the hospitals due to SARS-CoV-2 exposure. The treatment recommendations are the same for cancer patients as the general population.
Dexamethasone-
Uses: It has a low mortality rate in COVID-19 patients who require supplemental oxygen or mechanical ventilation. It is used in cancer patients to,
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Prevent chemotherapy-induced nausea as a part of tumor-directed therapy.
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Treat inflammation associated with brain metastasis.
Side Effects: The side effects are the same in patients with or without cancer. Also, treatments that are not recommended for SARS-CoV-2 infection should now be included in the clinical trials as the efficacy and safety of these agents are not known in cancer patients.
Managing Chemotherapy-
A case-by-case basis treatment decision should be made on,
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Cancer-directed therapy to acute COVID-19 patients.
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Patients recovering from COVID-19.
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Indication for chemotherapy.
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Goals of care.
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History of tolerance to the treatment by the patient.
The duration between infection and cancer-directed therapy initiation is not clear, and stop the treatment until the COVID-19 symptoms subside. Also, viral shedding occurs in cancer patients, and it is unknown how it is related to infectious viruses and how it impacts outcomes. So, the COVID-19 treatment guidelines panel recommends that clinicians consult a hematologist or oncologist before prescribing cancer-directed medications to COVID-19 cancer patients.
Drug Interactions:
The clinicians should be very cautious about drug interactions and toxicities on,
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COVID-19 and cancer-directed therapies.
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Prophylactic antimicrobials.
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Corticosteroids.
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Other medications.
Additional challenges have been faced in treating COVID-19 with cancer patients through the use of antiviral or immune-based therapies. The use of antineoplastic medications for COVID-19 is still being investigated as it is known to interact with different drug therapies; for example, Tocilizumab interacts with Vincristine and Doxorubicin.
Dexamethasone-
It is used as an antiemetic for cancer patients and is also recommended to treat COVID-19 patients. It is a weak to moderate cytochrome, so drug interactions with any CYP3A4 substrates should be carefully monitored.
Lopinavir or Ritonavir-
It is not recommended for the treatment of COVID-19, but it may be received in clinical trials. Lopinavir or Ritonavir is a CYP3A4 inhibitor increasing the concentrations of,
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Methotrexate.
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Vincristine.
Suppose Lopinavir or Ritonavir is used in combination with a cytotoxic drug (with CYP3A4 substrate). In that case, monitoring is necessary regarding drug toxicities, and generally, Lopinavir or Ritonavir and CYP3A4 substrates combination should be avoided.
Conclusion:
Pediatric patients with cancer also have milder COVID-19 manifestations when compared to adult COVID-19 cancer patients. The guidance for managing and providing relevant care for pediatric cancer patients during the COVID-19 pandemic is available in two publications namely, guidance for managing specific malignancies and guidance for supportive care.
Also, multicenter guidance for using antivirals in immunocompromised children (patients also with malignancy) is now available. In addition, follow the COVID-19 safety protocols everywhere, irrespective of the age group, to beat this pandemic.