Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses

OVERALL Abstract: The overarching research theme for the Mount Sinai U54 Serological Center of Excellence "Vulnerability ofSARS-CoV-2 Infection in Lung Cancer Based on Serological Antibody Analyses," is to fill the vital knowledgegap in factors contributing to the great vulnerability of lung cancer patients to morbidity and mortality from SARS-CoV-2 infection through serological analysis of antibody responses and studies of inter-individual variation inpatient-derived lung tumor and epithelial cells to SARS-CoV-2 infection. We will characterize and compare lungcancer patients' antibody responses to SARS-CoV-2 infection or SARS-CoV-2 vaccines with a matched non-lung cancer control group; quantitate differences in SARS-CoV-2 viral replication in lung cancer and normal lungepithelial cells from different lung cancer patients; and quantitate differences in neutralizing antibody responsesin lung cancer patients. This information is urgently needed to enact vaccine and other strategies for protectinglung cancer patients against development of COVID-19. While antibodies, induced by infection or vaccines, areprotective against many viruses, it has not yet been established if antibodies to SARS-CoV-2 are protective, howmuch and what types of antibody are needed for protection, and how long protection will last are unknown.Likewise, we do not know if lung cancer patients can mount an effective immune response and if different aspectsof lung cancer or its treatment influences this immune response. Our overall hypothesis is that lung cancerpatients have a different (e. g. weaker) antibody response to SARS-CoV-2 infection compared to persons withoutlung cancer, and that their lung cancer or lung epithelial cells play a role in viral replication of host responses,which together could explain the aggressive course and high fatality rate demonstrated in lung cancer patientswith COVID-19. Our U54 will determine whether natural infection or SARS-CoV-2 vaccines (forecast fordeployment) will give comparable serological antibody responses longitudinally in 1,000 lung cancer patientsand a matched non-lung cancer control group (1,000 individuals); and determine if there are differences inantibody responses related to age, gender, tobacco history, and race/ethnicity. The U54 proposal has twoProjects and three Cores (Administrative, Clinical, and Data Sciences). Project 1: "Characterization of theAntibody Response to SARS-CoV-2 in Lung Cancer Patients" quantitatively characterizes anti-SARs-CoV-2antibody responses and their functionality longitudinally in lung cancer patients compared to a control populationafter natural infection and vaccination, and relates the serological response characteristics to key clinical,demographic information. Project 2: "Susceptibility of Lung Cancer Cells to SARS-CoV-2 Infection and Antibody-Mediated Neutralization," determines the inter-individual variation in lung cancers and lung epithelial cells tosupport SARS-CoV-2 viral replication, the inter-individual variation of antibodies to neutralize viral infection, andhow these host viral responses relate to host cell characteristics and important clinical demographic information.