What should medical oncologists know about COVID-19?

Coronaviruses are a group of related viruses that cause diseases in mammals and birds. Coronaviruses are named for the crown-like spikes on their surface. They were first identified in the mid-1960s and are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry.

Coronaviruses that infect animals can evolve and become a new human coronavirus. There are to date seven coronaviruses that can infect humans. Severe Acute Respiratory Syndrome related coronavirus (SARSr-CoV) is a viral species including hundreds of different strains that mostly circulate in bats and civets. COVID-19 stands for Coronavirus Disease 2019, the present fast spreading novel coronavirus infectious disease due to SARS-CoV-2 - initially called 2019-nCov for Novel Coronavirus 2019 -, was first identified in December 2019 in China. Before SARS-CoV-2, responsible for the current COVID-19 pandemic, SARS-CoV resulted in the SARS 2002-2004 outbreak, while MERS-Co-V caused three waves of epidemics in 2012, 2015 and 2018 notably in Saudi Arabia and South Korea. In humans, coronaviruses cause respiratory tract infections that can be mild and others that can be lethal, such as SARS, MERS, and COVID-19. Human-to-human transmission of coronaviruses is primarily thought to occur among close contacts via respiratory droplets generated by sneezing and coughing. The interaction of the coronavirus spike protein with its complement host cell receptor is central in determining the tissue tropism, infectivity, and species range of the virus. The SARS coronavirus of 2002, for example, infected human cells by attaching to the angiotensin-converting-enzyme-2 (ACE-2) receptor.

Coronaviruses vary significantly in pathogenicity. Some can kill more than 30% of those infected (such as MERS-CoV), and some are relatively harmless, resulting in the common cold. The later became endemic in the human population, while the SARS Coronavirus of 2002 to 2004 is no longer circulating in humans. Coronaviruses can cause pneumonia (either direct viral pneumonia or a secondary bacterial pneumonia) and bronchitis. The first published human coronavirus discovered in 2003, SARS-CoV, caused severe acute respiratory syndrome (SARS), and had a unique pathogenesis because it caused both upper and lower respiratory tract infections. In contrast, SARS-CoV-2 spread rapidly around the world and has been declared a pandemic by the World Health Organization. Transmission of SARS-CoV-2 appears to be similar to that of the related SARS and MERS coronaviruses, but with a lower fatality rate. SARS-CoV-2 can still cause serious and life-threatening infections - particularly in older people and those with pre-existing health conditions. The incubation period (time between when a person is exposed to the virus and when symptoms first appear) is typically between 4 to 6 days, although may range from 2 to 14 days.

Most COVID-19 cases appear to be spread from people who are symptomatic. However, similarly to the other respiratory viruses, a certain proportion of patients may have been infectious before their symptoms developed. Contagiousness seems to be quite high even if the estimated basic reproduction number (Ro) is rather low (2.2), meaning that an average of two people will be contaminated by one infected person.

Whole genome sequencing approaches have enabled rapid development of molecular diagnostic tests for SARS-CoV-2. Presently, treatment is supportive and no specific antiviral medications are available.

Many therapeutic approaches are currently being tested, including protease inhibitors used in HIV (lopinavir/ritonavir), an anti-malaria drug (chloroquine), a new nucleotide analog (remdesivir) and a monoclonal anti-IL6 antibody (tocilizumab). Several approaches are also being considered for development of vaccines — some targeting a "spike glycoprotein", which is involved in interactions between coronaviruses and cells. Until such treatment and preventive measures are available, researchers are emphasising the importance of the full range of strategies for controlling SARS-CoV-2 — as for the "highly effective global public health response" that led to containment of the SARS epidemic.

This perfectly justifies the present measures of containment including social distancing and other mitigation strategies, isolation of ill patients, school closure, avoiding crowds of people, avoiding travel, and actions to improve sanitary behaviour to prevent spreading. Moreover, the potential role of long-lasting immunity after recovery from coronavirus infection is as yet speculative.

So far, no systematic reports are available about a higher incidence of COVID-19 infections in patients with cancer. However, available data indicate that older people are more vulnerable, particularly when there are underlying health conditions such as chronic lung disease, cardiovascular disease, diabetes, chronic kidney disease and active cancer.

People at risk include:

• Patients having chemotherapy, or who have received chemotherapy in the last 3 months
• Patients receiving extensive radiotherapy
• People who have had bone marrow or stem cell transplants in the last 6 months, or who are still taking immunosuppressive drugs
• People with some types of blood or lymphatic system cancer which damage the immune system, even if they have not needed treatment (for example, chronic leukaemia, lymphoma or myeloma).

Specific risk groups are cancer patients with an impaired immune system such as those with:

• Leukocytopenia
• Low immunoglobulin levels
• Long lasting immunosuppression (steroids, antibodies)

The impact of immunotherapy, i.e. administration of PD-1 pathway blockade or CTLA-4 monoclonal antibodies, on risk is a matter of debate. There is no clear evidence that allows us to define the specific impact of such drugs (administered previously or actively) on SARS-CoV-2 susceptibility, or on the course of the COVID-19 disease.

Co-infections of the upper airways may increase the risk of an adverse outcome in patients with viral infections. Specifically, co-infections caused by bacteria and fungi have a significant impact on the outcome of the primary viral infection. Chronic inflammatory and obstructive pulmonary disease probably increase the risk of major respiratory complications. Patients are advised to discuss their individual risk profiles, due to the primary hemato-oncological disease and the above-mentioned factors and comorbidities, with their treating oncologist.

All measures to prevent the risk of infection with SARS-CoV-2 and COVID-19 disease outbreak, as published by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO), do also apply for cancer patients.

Important actions are:

PREVENT:

• Clean your hands often
• Wash your hands with soap and water or, if not available, use an alcohol-based hand sanitizer
• Avoid contact with sick people, in particular with those with a cough
• Avoid touching your face, nose and eyes
• Avoid meetings, events and other social gatherings in areas with ongoing community transmission
• Practice social distancing

RECOGNISE first coronavirus infection such as:

• Fever
• Coughing
• Sore throat
• Difficulty breathing
• Muscle pain
• Tiredness

TAKE ACTION:

Telephone your doctor or national health care services when returning from a risk region, after contact with an infected person, or when feeling symptoms suspicious for COVID-19.

DO NOT go directly to your doctor, clinic/hospital if you have a fever or other symptoms, to avoid potential spread of the infection. Telephone the clinic first and follow the instructions they give to you.

The principles of evidence-based medicine and patient-involved care continue to be cornerstones of medical practice.

Additionally, cancer health care professionals are recommended to:

• Promptly liaise with local administrators in order to set up proactive action and contingency plans for provision of cancer care in the setting of the COVID-19 pandemic.
• Together with local administrators, explore strategies for splitting cancer healthcare personnel to operating and back-up crews rotating in “shifts” epidemiologically compatible with the COVID-19 incubation time of 14 days.
• Explore telephonic or web-conferencing capabilities for consultation of stable patients, especially applicable for patients on oral therapies.
• Implement strategies for “previous day” telephone triage for identification of patients with flu-like symptoms and for reducing mass gathering of patients in waiting rooms.
• Discuss the benefits and risks of palliative therapy in the setting of the COVID-19 pandemic and local constraints, weighing in all relevant factors: disease prognosis, patient comorbidities, patient preferences, probability and risks from COVID-19 infection.
• Similarly, discuss the benefits and risks of maintenance therapies and the options of “therapy holidays” during the pandemic.
• Prioritize adjuvant therapies in patients with resected high-risk disease who are expected to derive a significant absolute survival benefit.
• Discuss with the patient options of regimens and schedules that reduce the number of hospital visits during the pandemic (three or two-weekly as opposed to weekly, oral or subcutaneous alternatives as opposed to intravenous administration).
• Discuss shorter/accelerated or hypo-fractionated radiation schemes with radiation oncologists, where scientifically justified and appropriate for the patient.
• Use blood product transfusions when strictly necessary, in view of the risk of shortages. Donors should be encouraged to continue donating blood under appropriate precautions.
• Cite reliable information from scientifically driven sources, and refrain from using or sharing social media accounts and rumours.
• Develop information material for cancer patients as well as psychosocial support projects for health care professionals and patients.