Abstract PO-067: Tissue banking from patients with SARS-CoV-2 (COVID-19) infection
Authors: Higgs Emily F. , Flood Blake A. , Pyzer Athalia R. , Rouhani Sherin J. , Trujillo Jonathan A. , Cron Kyle R. , Cabanov Alexandra , Fessler Jessica , Bloodworth Jeffrey , Beavis Kathleen , Yeo Kiang-Teck J , Sweis Randy F. , Zha Yuanyuan , Gajewski Thomas F. 
Published: December 2020

The clinical spectrum of SARS-CoV-2 (COVID-19) infection ranges from asymptomatic infection to fatal pneumonia, but the determinants of outcome are not well understood. To characterize the immune response to COVID-19, we established a protocol to collect biologic specimens from patients with confirmed or suspected COVID-19. Between April 9th and June 8th, 2020, we enrolled 146 inpatients and 169 outpatients at the University of Chicago. We hypothesized that the complex interplay of viral, environmental, and host genetic factors may influence disease severity in patients with COVID-19. To probe for genetic predispositions that may influence outcomes, we collected germline DNA from 140 patients spanning the breadth of clinical severity, which will be sequenced for SNPs in genes previously implicated in immune responsiveness and ARDS. To determine whether a pattern of commensal bacteria correlates with disease severity, we will analyze the composition of airway microbiota from 226 nasopharyngeal swabs, using viral quantification and 16S sequencing. Longitudinal serum samples from 156 patients were obtained to probe for the presence of antibodies using an ELISA against the spike protein of SARS-CoV-2. In tandem, 36-color flow cytometry on PBMCs, from the same patients, will characterize immune cell phenotypes influenced by infection. We also hypothesized that by characterizing mechanisms of immune-hyperresponsiveness, we may elucidate key biologic pathways that inform the development of novel therapeutics. To determine if severity of disease and response to therapy correlates with soluble factors, we are performing 44-plex cytokine Luminex assays on serum samples. We will probe the adaptive immune response using an ELISA against the SARS-CoV-2 RBD domain, and by performing IFN-g ELISPOT analysis against peptide pools from SARS-CoV-2 proteins. We developed a bioinformatic pipeline to integrate clinical data with the results from the diverse data types and will adopt a machine learning approach to identify parameters contributing to disease severity, response to therapies, and outcomes. In establishing this protocol, there were significant biosafety considerations. To limit potential exposure and virus transmission, research coordinators contacted inpatients by phone for an informed consent discussion, and patients completed the consent form electronically using REDCap (n=61). Inpatients who were unable to navigate the electronic consent were visited with a paper consent (n= 85). Samples were processed in a BSL2 laboratory with enhanced biosafety precautions. Where feasible, samples were collected into reagents such as Zymo DNA/RNA shield to immediately inactivate the virus. Other safety measures included heat inactivation of some samples and use of a laminar flow washer to minimize aerosolization during FACS staining. In summary, we have established a biorepository of specimens from patients with COVID-19, including a subset with active cancer or a history of the disease (n=22).

Citation Format: Emily F. Higgs, Blake A. Flood, Athalia R. Pyzer, Sherin J. Rouhani, Jonathan A. Trujillo, Kyle R. Cron, Alexandra Cabanov, Jessica Fessler, Jeffrey Bloodworth, Kathleen Beavis, Kiang-Teck J Yeo, Randy F. Sweis, Yuanyuan Zha, Thomas F. Gajewski. Tissue banking from patients with SARS-CoV-2 (COVID-19) infection [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-067.