Pathophysiology of Lung Cancer in the Context of SARS-CoV-2 Variants of Concern

Many retrospective cohort studies have revealed that patients with cancer are at increased risk of severe complications and mortality from COVID-19 due to a multitude of factors, including advanced age in this cohort, high incidence of underlying comorbidities, and immunosuppression caused by cancer and its treatments. It has been futher demonstrated that individuals with lung cancer face a disproportionately higher risk of mortality compared to other cancer types following SARS-SoV-2 infection. However, several questions remain unanswered regarding the understanding of the pathophysiology of lung cancer in the context of COVID-19, as well as the effects of SARS-CoV-2 variants of concern on patient outcomes. The article aims to investigate the following gaps the clinical manifestation of SARS-CoV-2 infection in patients with lung cancer: the molecular characteristics of lung cancer driving the development of severe COVID-19, and the role of COVID-19-induced inflammation in accelerating the development and increasing the severity of lung cancer, particularly with respect to the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) variants. Understanding the crosstalk between lung cancer and COVID-19, particularly concerning the early variants of concern, will reveal the unique mechanisms contributing to poor outcomes following SARS-CoV-2 in patients with lung cancer, including the maintenance of a hyperinflammatory state, TMPRSS2 expression patterns, and tumor-associated immune evasion, among others. This work will be valuable in the development of improved antivirals and vaccines against SARS-CoV-2 in the cancer population and will help provide insight into the pathogenesis of current and emerging variants of concern in this at-risk cohort. Additional studies and a high degree of caution are essential in understanding the impacts of newer and emerging variants of concern such as Omicron (B.1.1.529) and its subvariants on patients with lung cancer.