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Cumulative Risk Factors for COVID-19 Complications in Patients with Lung Cancer

An accurate COVID-19 screening model could allow early detection and potentially reduce the risk of severe complications and mortality
10 Apr 2020

An article authored by Dr Antonio Passaro of the Division of Thoracic Oncology of the European Institute of Oncology (IEO) IRCCS in Milan, Italy, and a group of lung cancer experts from Switzerland, Hong Kong - China, Italy and Japan, and published in the Annals of Oncology, describe pathophysiological-, clinical- and treatment-related factors which contribute that lung cancer, among all cancer types, represents a specific clinical scenario of cumulative risk factors for COVID-19 disease complications.

The authors underlined that despite the current lack of robust data, it is of paramount importance to come-up with an international consensus on SARS-CoV-2 testing among patients with lung cancer, as early identification of infection with this novel virus may result in tailored management.

The authors wrote that a case fatality rate, defined as number of deaths among patients with COVID-19 divided by number of those tested positive, is significantly higher in those with comorbidities, such as cardiovascular disease, diabetes, chronic respiratory disease and cancer, as well as older age. This phenomenon appears to be more pronounced in the Caucasian population.

Different approaches towards SARS-CoV-2 testing could partly explain the difference in incidence and case fatality rate. Initially, Italy adopted testing among both symptomatic and asymptomatic patients. However, just after 6 days, when large numbers of patients suffered from severe COVID-19-related acute respiratory distress syndrome (ARDS), the Italian Ministry of Health decided to test only symptomatic patients who were potential candidate for hospitalisation. The authors speculate that such decision may have resulted in a biased selection and delayed treatment.

The authors emphasise in their article that lung cancer patients represent a specific population for COVID-19 testing prioritisation. While all types of cancers seem to be associated with high COVID-19 prevalence, morbidity and mortality, lung cancer represents a specific scenario of cumulative risk factors for COVID-19 complications, including older age, significant cardiovascular and respiratory co-morbidities, smoking-related lung damage, as well as treatment-related immune impairment or suppression. 

In smokers, the risk of severe symptoms of COVID-19 is 1.4 times higher than in non-smokers, and risks of admission to intensive care unit, mechanical ventilation or death is 2.4 times higher. Structural and immunologic-induced modifications are the two main tobacco-related damages related to susceptibility to infections. It has been postulated that prior tobacco-related lung damage, including chronic obstructive pulmonary disease and lung cancer, additionally predispose to more severe COVID-19 complications.

Mechanical tumour obstruction and previous lung surgery contribute to defective lung architecture that may predispose to infection. Changes in the airway anatomy and pulmonary tissue lead to intra- and peri-tumoral microenvironment alteration. The presence of macrophage infiltration in lung tissue poses a higher risk for cytokine release. In particular, massive cytokine release has been highlighted as a major step leading to the development of ARDS.

Furthermore, patients with lung cancer show similar clinical symptoms including cough, fever and dyspnoea with SARS-CoV-2 infection compared to other individuals. Therefore, an accurate COVID-19 screening model could allow for early detection and potentially reduce the risk of severe complications and mortality. 

The authors wrote that a significant number of patients with lung cancer need corticosteroids for prophylaxis, treatment and symptom control related to cancer or chronic obstructive pulmonary disease. Corticosteroids are possibly deleterious in the management of ARDS in COVID-19 and they may mask some of the early symptoms of infection, arguing for routine SARS-CoV-2 testing in patients treated with steroids.

Among patients with lung cancer there is a predisposing risk of immunosuppression by chemotherapy, immunotherapy and molecular targeted therapy. While the impact of immune checkpoints inhibitors or tyrosine kinase inhibitors on the risk and course of COVID-19 remains unknown, radiological features of lung cancer or related to these treatments may be characterised by ground-glass opacities, mimicking COVID-19 radiological characteristics.

Data about higher sensitivity of radiologic imaging compared to nasopharyngeal/oropharyngeal swab are emerging. Considering that lung cancer patients periodically undergo computed tomography scans, the authors predicted an emerging amount of increased COVID-19-suspicious imaging, even in the absence of new symptoms in coming weeks.

The authors wrote that suspending or delaying cancer treatment seems logical in some patients with cancer. However, the risks/benefits and final outcomes of treatment adaptations in such circumstances remain unknown. Therefore, they underline importance of collecting data within a TERAVOLT global registry for development of a tailored risk assessment strategy for patients with lung cancer. 

As announced in this article published on 9 April 2020 in the Annals of OncologyESMO released on its website the management and treatment adapted recommendations for lung cancer in the COVID-19 era.


Passaro A, Peters S, Mok TSK, et al. Testing for COVID-19 in lung cancer patients. Annals of Oncology; Published online 9 April 2020. DOI: https://doi.org/10.1016/j.annonc.2020.04.002

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