Abstract 787: SARS-COV-2 P.1 strain infection in lung, breast and colon tumoral patient-derived organoids

Abstract

Abstract Coronavirus 2019 disease (COVID-19), caused by the newly identified strain of the coronavirus family capable of inducing acute respiratory syndrome, rapidly escalated into a pandemic, triggering a public health emergency. Throughout this period, it became evident that increased attention should be addressed towards at-risk groups, particularly individuals with chronic illnesses, including cancer. World widely, lung, breast, and colon cancer stand as the most prevalent types of cancer exhibiting high mortality rates in both men and women. Epidemiological data demonstrate that cancer patients, particularly those with lung, breast, and colon cancer, face elevated risk and severity when infected by SARS-CoV-2, resulting in even higher mortality rates. However, there is a knowledge gap concerning the interaction between COVID-19 and cancer patients, and thus, the current proposal evaluated SARS-CoV-2 infection in biopsy cells extracted from lung, breast, and colon cancer patients, cultivated as a patient-derived organoid (PDOs). Additionally, we also evaluated SARS-CoV-2 infection in a 3D model of spheroids in LC319, CALU-3, A549, H460, MRC-5, MDA-MB-231, MCF-10A and CACO-2 cell lines. Both PDOs and spheroids were infected with the SARS-Cov-2 P.1 strain with a multiplicity of infection (MOI) of 0.01 for 24 hours. We observed that PDOs and tumoral and non-tumoral spheroids were equally permissive to SARS-CoV-2 infection showing similar viral load levels. However, we observed a cytopathic effect after SARS-CoV-2 P.1 strain infection only in tumoral cells in comparison to non-tumoral cells from the same tissue. Furthermore, we explored the cytopathic effects caused by SARS-CoV-2 infection in PDOs and in tumoral and non-tumoral spheroids by scanning electron microscopy (SEM). Interestingly, we observed morphological alterations on the surface of SARS-CoV-2 P.1 strain -tumoral infected cells, with the occurrence of surface projections after 1 hour infection. Finally, we performed an exome sequencing analysis of PDOs and tumoral and non-tumoral cells which preliminarily indicated an intriguing and informative crosstalk between cancer-related genes and SARS-CoV-2 infection pathways. Here we have identified missense and nonsense mutations in genes involved in PI3K pathway, immune function, and cell cycle regulation. In summary, our study showed that SARS-CoV-2 P.1 strain can infect and directly induce cytopathic effects in lung, breast, and colon tumors. Citation Format: Tayanne F. Sassaro, Anael Viana, Mariano Zalis, Carlos Gil Moreira Ferreira, Jorge Canedo, Danielle Ferreira, Aline S. Moreira, Elen Mello, Fabiana Rondão, Beatriz I. Ferreira, Otacilio C. Moreira, Daniel A. Moreira, Bruno Souza, Mariana C. Waghabi, Tatiana M. Tilli. SARS-COV-2 P.1 strain infection in lung, breast and colon tumoral patient-derived organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 787.