Assessing vulnerability of patients with lung cancer to SARS-CoV-2 infection based on serological antibody analyses

ABSTRACT

COVID-19 presents a unique threat to patients with lung cancer, with mortality rates as high as ∼32%. Given the convergence of these two deadly diseases, the lung cancer research and advocacy communities rapidly mobilized in early 2020 to create the COVID Lung Cancer Consortium (CLCC), a global assembly of leading experts in thoracic oncology, immunology, virology, vaccines and patient advocacy. With ongoing robust exchange of data and shared learning and rational planning for clinical and laboratory investigations, the CLCC is bringing its collective expertise to bear on beginning to address the question of why patients with lung cancer are at such elevated risk of worse outcomes from COVID-19. These efforts led to a recently funded U54 CA260560 grant as part of the National Cancer Institute's SeroNet initiative to study the magnitude, quality and duration of antibody responses to SARS-CoV-2 infection in patients with lung cancer compared to healthy controls. In the first project, our Mt. Sinai U54 Serological Center of Excellence will follow a prospective lung cancer cohort (750 patients) and a matched non-lung cancer control group (750 individuals) to determine if there are differences in antibody responses related to age, gender, tobacco history, and race/ethnicity. Given that effective SARS-CoV-2 vaccines are now being deployed, the study will also analyze antibody responses to vaccination across these two patient cohorts. The second project will examine biological determinants correlating with susceptibility to infection, including analysis of both ACE2 and TMPRSS2 levels, and antibody-mediated neutralization in pre-clinical models of established lung cancer and normal lung epithelial cell lines. In order to capture a diverse and inclusive patient population, this effort will be supported by GO2 Foundation for Lung Cancer through its national network of Centers of Excellence. This rapid global mobilization of the lung cancer community through the CLCC and the resulting Serological Center of Excellence is positioned to answer fundamental questions regarding the susceptibility of patients with lung cancer to SARS-CoV-2 infection and severe COVID-19 disease and provide information to allow assessment of the value of vaccination and the utility of specifically designed vaccine programs for this high-risk patient population.