Project Summary/Abstract The Mount Sinai U54 continues to accrue new lung cancer (LC) patients to its large, highly annotated longitudinal cohort with routine specimen collection. Updated research focus areas include: 1) the ability of patients with lung cancer to maintain robust immune responses to infections and/or vaccinations related to novel variants; 2) the long-term health consequences of SARS-CoV-2 infection in patients with lung cancer; and 3) biologic factors that influence SARS-CoV-2 susceptibility using in vitro modeling. The magnitude, quality, breadth and durability of the systemic and mucosal immune responses elicited by influenza virus and RSV vaccinations will be determined in comparison to SARS-CoV-2 in LC patients. Key areas to be addressed here include the effects of: vaccine platform, timing of vaccination, concordance or discordance of patient immune response to differing vaccines, a more detailed understanding of the effects of cancer treatment, and the correlation between cellular and antibody response. The Mount Sinai finding that vaccination for influenza was associated with a subsequent induction of SARS-CoV-2 anti- spike Abs in our patients will be validated using patient specimens from collaborators within the Pooling Project. The Mount Sinai clinical team will continue to Investigate socioeconomic and demographic associations with the risk of compromised immune responses and/or severe infection. Additionally, residual plasma from select patients will be used to determine whether patients who experienced a SARS-CoV-2 infection retain molecular evidence of viral infection. Evidence for a persistent reservoir of viral RNA and/or proteins will be determined by highly sensitive RT-qPCR and ELISA-based assays, and the duration of persistence after infection will be correlated with specific clinical symptoms.

Project Narrative The overarching research theme for the Mount Sinai U54 is to understand factors that may compromise the immune response of lung cancer patients following SARS-CoV-2 infection or vaccination in comparison to a matched “healthy” control group. Comprehensive serologic and cellular analyses of serially collected blood samples from consented patients coupled to a highly annotated database of patient clinical and demographic factors will be used to identify vulnerabilities inherent to this patient population, augmented by in vitro modeling.