Lung Cancer in COVID-19 Era

 Lung Cancer in COVID-19 Era 

The outbreak of COVID-19 was first observed in Wuhan, China, in December 2019, and since then the infection Thas been spreading throughout the world. The symptoms of COVID-19 infection are related to other respiratory infections such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome and influenza. The symptoms include fever, sore throat, nasal congestion, body ache and dry cough. Some of COVID-19- infected patients develop severe clinical conditions such as chest pain, breathlessness and diarrhoea. This article covers the characteristics of SARS-CoV-2 infection in lung cancer patients in terms of transmission, pathophysiology, risk assessment and addressing clinical needs associated with the management of patients with thoracic carcinoma during the COVID-19 pandemic .

Since November 2020, the United States has reported the greatest number of COVID-19-infected patients, followed by India, Brazil, Russia, etc., with 75+ million infected and 1.7+ million deaths. Senior citizens and patients with comorbid conditions, such as diabetes, cardiovascular disorder, respiratory diseases and cancer, are more likely to contract life-threatening COVID-19-related conditions, including pneumonia, multi-organ failure and various 1 neurological disorders. 

SARS-CoV-2 is a member of family coronaviridae and observed to be related with numerous coronavirus-associated diseases. This virus can affect almost every organ but specifically causes acute respiratory disorder as illustrated in Figure 1. Numerous viral infections act as causative agents to carcinogenesis. Various reports suggest that viral infection-associated inflammation initiates cellular transformation through activating/modulating several oncogenic signal transduction pathways. Although there is no clinical and experimental data available, SARS-CoV-2 infection 1 can activate some oncogenic pathways that remain active even after the infection subsides.

Infection of Lungs by SARS-CoV-2 

 

The viruses of the coronavirus family mainly enter the human body through the nasal mucosa and oropharynx and eventually get deposited in the lungs. Other organs expressing angiotensin-converting enzyme 2 (ACE2) receptors on the surface of the cells, such as heart, kidney and intestine, are also prone to get infected by SARSCoV-2. Immature cells have a very low level of ACE2 expression compared to matured/differentiated cells, which makes matured cells more susceptible to the virus. Figure 2 illustrates the schematic representation of sequential intracellular events in alveolar epithelial cells 1 due to SARS-CoV-2 infection.

Pathophysiology of SARS-CoV-2 Lung Injury 

Cancer patients are more prone to COVID-19 infection compared to the general population due to systemic immunosuppression caused by tumour and anti-cancer treatments. Severe COVID-19 is considered as a hyperinflammatory disorder characterised by a massive activation of the immune system, thus explaining the worse survival outcomes observed in both elderly people and cancer patients. The pathophysiology of COVID-19 yet remains unclear. In some cases, SARSCoV-2 induces an excessive aberrant ineffective host immune response, resulting in a potentially fatal lung injury. On the other hand, in severe cases, infection may be associated with the hyperactivation of tissue macrophages that release a storm of cytokines, leading to rapidly progressive organ dysfunction. Macrophage activation syndrome can be fatal due to tissue hemophagocytosis, disseminated intravascular coagulation, pancytopenia and the dysfunction of hepatobiliary system and central nervous system.

Recent studies explored the critical role of reactive oxygen species-associated inflammation pathways,

specifically redox-sensitive transcription factor - Nuclear Factor Erythroid 2–related factor 2 (NRF2) in both COVID-19 and lung cancer, manifesting some similarities but relevant variations. Indeed, NRF2 is usually activated in lung cancer, facilitating the immune escape of tumour cells, whereas it is downregulated in COVID-19-positive patients, causing immunosuppressive effects that worsen COVID-19 symptoms in 2 lung cancer patients.

Management of Lung Cancer Patients in Pandemic 

The oncology community has been pushed to find a balance between protecting cancer patients from the risk of COVID-19 infection and ensuring adequate anticancer treatment since the beginning of the pandemic. To comply with social distancing and general public health measures for mitigating the spread of SARS-CoV2, outpatient oncology services have been thoroughly reorganised. Triage areas have been set up at hospital entrances to record body temperature. Non-essential outpatient visits were conducted via telemedicine or postponed. Several leading global professional organisations, including the European Society of Medical Oncology, provided recommendations for the diagnosis, treatment and follow-up of lung cancer patients during the COVID-19 pandemic, as a guide for prioritising cancer care issues and mitigating potential harm related to the state of health emergency. Taking into consideration the risk of SARS-CoV-2 infection in surgically resected patients and the potential immunosuppressive status induced by peri-operative chemotherapy, it has been recommended that the role of adjuvant treatment be reconsidered following thorough discussion with patients. The indication should be always denied in frail elderly patients who are affected 2 by significant comorbidities.

The American Society for Radiation Oncology and European Society for Radiation Oncology consensus conference of 32 experts in lung cancer radiotherapy produced some practical recommendations on radiotherapy treatment delivery, considering two discrete pandemic scenarios: Mitigation of infectious risk and Reduced radiotherapy resources. The first expert recommendation aimed to not compromise a patient's prognosis by deviating from recommended practice guidelines. Secondly, radiotherapy discontinuation or postponement for COVID-19- positive patients should always be considered to avoid the exposure of negative patients and healthcare personnel to the risk of infection. In a severe pandemic scenario with limited resources, it has been recommended to consider a patient’s triage which includes patient cure potential, treatment benefit, life 2 expectancy and performance status.

COVID-19 and Lung Cancer Treatment Delays  

Lung cancer patients represent a central concern in clinical diagnosis and therapeutic decision-making in the context of the contagious COVID-19 pandemic. The estimated increase in cancer deaths up to 5 years after diagnosis ranges from 4–8% for lung cancer to 16% for colorectal cancer. Chemotherapy, radiation therapy, surgery and molecular targeted therapy are keystones in the treatment of early and locally advanced lung cancer with good prognosis. Chemotherapy plus targeted therapy or immunotherapy has also brought substantial survival benefit to recurrent or metastatic advanced lung cancer patients. However, frequent visits to hospital during the COVID-19 pandemic and receiving anticancer treatments with immunosuppressive properties might considerably increase the risk of getting infected. Therefore, balancing the benefit from in-hospital anticancer treatments and the risk of infection may be crucial 2 to the care of lung cancer patients.

Impact of Anti-cancer Treatment on COVID-19 Cancer Patients 

Evaluating the impact of COVID-19 on cancer diagnosis and treatment delays remains an alluring and challenging topic. Some studies indicated that COVID19-positive patients receiving anti-cancer therapy were at higher risk of reporting severe clinical outcomes than patients not receiving any anti-cancer treatment. A major challenge for cancer patients is the potential impact of immune checkpoint inhibition (ICI) during the clinical course of COVID-19. Immunotherapeutic agents, like programmed death-1 inhibitors, programmed death ligand-1 inhibitors and cytotoxic T lymphocyteassociated antigen-4 inhibitors, act by enhancing T-cell functions against virus or tumour cells. The adaptive + immune cells involved in this process, specifically CD8 + and CD4 T-cells, are crucial for regulating immunity against viruses, thus immune checkpoint inhibitors may improve the immunological control of viral infections and potentially offer protection against the development of severe COVID-19 disease. Another challenge for lung cancer patients receiving ICI-based therapy during the COVID-19 pandemic is the differential diagnosis between COVID-19-related pneumonia and ICI-induced pneumonia. Indeed, there is a wide range of radiological features and clinical symptoms that overlap, sometimes 2 complicating the clinical management of these patients .

SARS-CoV-2 Vaccination: The Saviour 

SARS-CoV-2 vaccine has emerged as the main weapon to fight the COVID-19 pandemic. Over 9 billion doses of vaccines have been administered worldwide as of February 2022. The rate of positivity, hospitalizations and mortality from SARS-CoV-2 is significantly decreasing over the time, allowing the reopening of 2 major services and healthcare borders .

Conclusion 

SARS-CoV-2 infection has dramatically impacted the real-world management of patients with cancer. Oncological services have been profoundly re-organised considering the higher risk of severe COVID-19 in lung cancer patients. The world’s leading organisations have provided new recommendations for the diagnosis, treatment and follow-up of lung cancer patients during this pandemic. Telemedicine was preferred for nonurgent visits, and screening programs were temporarily suspended to prevent the spread of infection. The vaccination campaign has definitively inverted COVID19 trend with the administration of booster dose prioritised in frail immune-depressed patients. The efficacy and duration of humoral imnemu response in cancer patients still represents an open question, requiring further investigation in dedicated studies to 2 monitor the trends in large cohorts of cancer patients.