COVID-19 and lung cancer: risks, mechanisms and treatment interactions

Abstract

Cases of the 2019 novel coronavirus also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to rise worldwide. To date, there is no effective treatment. Clinical management is largely symptomatic, with organ support in intensive care for critically ill patients. The first phase I trial to test the efficacy of a vaccine has recently begun, but in the meantime there is an urgent need to decrease the morbidity and mortality of severe cases. It is known that patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments. Therefore, these patients might be at increased risk of pulmonary complications from COVID-19. The SARS-CoV-2 could in some case induce excessive and aberrant non-effective host immune responses that are associated with potentially fatal severe lung injury and patients can develop acute respiratory distress syndrome (ARDS). Cytokine release syndrome and viral ARDS result from uncontrolled severe acute inflammation. Acute lung injury results from inflammatory monocyte and macrophage activation in the pulmonary luminal epithelium which lead to a release of proinflammatory cytokines including interleukin (IL)-6, IL-1 and tumor necrosis factor-α. These cytokines play a crucial role in immune-related pneumonitis, and could represent a promising target when the infiltration is T cell predominant or there are indirect signs of high IL-6-related inflammation, such as elevated C-reactive protein. A monoclonal anti-IL-6 receptor antibody, tocilizumab has been administered in a number of cases in China and Italy. Positive clinical and radiological outcomes have been reported. These early findings have led to an ongoing randomized controlled clinical trial in China and Italy. While data from those trials are eagerly awaited, patients' management will continue to rely for the vast majority on local guidelines. Among many other aspects, this crisis has proven that different specialists must join forces to deliver the best possible care to patients.

Keywords: T-Lymphocytes; immunity; lung neoplasms.

Figure 1

Chest CT showing typical ground glass opacities in acute respiratory distress syndrome, in this case in a lung cancer patient with COVID-19.

Figure 2

Autocrine macrophage activation. The hallmark of pathogenesis of macrophage activation syndrome, as can be seen in COVID-19, is the overproduction of IL-1β by tissues macrophages. IL-1β, as well as other proinflammatory cytokines, acts through autocrine stimulation on macrophages leading to a vicious cycle of cytokine production and hyperinflammation. gp130, glycoprotein 130; IFN, interferon; IL, interleukin; R, receptor; TLR, toll-like receptor; TNF, tumor necrosis factor.

Figure 3

Acute inflammation in COVID-19 and treatment strategies. In response to the viral infection, inflammatory monocyte and macrophage activation in the pulmonary luminal epithelium leads to a massive release of proinflammatory cytokines including IL-6, IL-1 and TNF-α (the different treatment strategy should be highlighted). These are potential targets currently under investigation. DAMPS, damage-associated molecular patterns; gp130, glycoprotein 130; IFN, interferon;IL, interleukin; JAK, Janus kinase; R, receptor; sIL-6R, soluble IL-6 receptor;TNF, tumor necrosis factor.