key: cord-0924344-4rzpde7m authors: Kvistborg, P.; Gangaev, A.; Ketelaars, S.; Patiweal, S.; Dopler, A.; Isaeva, O.; Hoefakker, K.; De Biasi, S.; Mussini, C.; Guaraldi, G.; Girardis, M.; Talavera Ormeno, C.; Hekking, P.; Lardy, N.; Toebes, M.; Balderas, R.; Schumacher, T. N.; Ovaa, H.; Cossarizza, A. title: The ORF1ab of SARS-CoV-2 encodes an immunodominant epitope restricted by HLA-A*01:01 date: 2020-09-30 journal: Annals of Oncology DOI: 10.1016/j.annonc.2020.08.2314 sha: 4b4e1056dba5e6a8feee56e62c9cf1674b783a7e doc_id: 924344 cord_uid: 4rzpde7m Background: A large global effort is ongoing to develop vaccines against SARS-CoV-2, the causative agent of COVID-19. While there is accumulating information on the antibody response against SARS-CoV-2, less is known about the SARS-CoV-2 antigens that are targeted by CD8 T cells. Such knowledge will be of high value to gain fundamental insights into the antigenic landscape of SARS-CoV-2 recognized by CD8 T cells, to develop tool allowing focused analysis of the SARS-CoV-2 specific T cell responses directly ex vivo, and to understand whether current vaccine designs are covering the CD8 T cell recognized antigens. Methods: To address this issue, we have analyzed samples from 18 COVID-19 patients for CD8 T cell recognition of 500 predicted SARS-CoV-2-derived epitopes restricted to 10 common HLA-A and HLA-B alleles. For each HLA allele, the top 50 epitopes were selected based on predicted binding affinity and likelihood of successful proteasomal processing. To probe for CD8 T cell recognition of the selected epitope-HLA complexes, we made use of our in-house technology based on multiplexing of peptide HLA (pHLA) multimers conjugated to fluorescent dyes. Results: In addition to previous studies showing CD8 T cell reactivity towards epitopes derived from the spike protein of SARS-CoV-2, we have identified several CD8 T cell recognized epitopes derived from the ORF1ab, including one epitope displaying clear immunodominant properties across patients positive for HLA-A*01:01. Investigation of the functional status of part of the identified responses (including 4 responses specific for the immunodominant epitope) revealed that the T cell responses were highly dysfunctional. In addition the SARS-CoV-2 specific CD8 T cell responses displayed an increased expression of NKG2A in comparison with bulk CD8 T cells, which may explain their dysfunctional state. Conclusions: Our data suggest that part of the ORF1ab encodes multiple CD8 T cell antigens including one immunodominant epitope. Noteworthy these epitopes were derived from a part of the viral genome that is not included in the majority of vaccine candidates in development, and this may potentially influence their clinical activity and safety profile. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Background: A large global effort is ongoing to develop vaccines against SARS-CoV-2, the causative agent of COVID-19. While there is accumulating information on the antibody response against SARS-CoV-2, less is known about the SARS-CoV-2 antigens that are targeted by CD8 T cells. Such knowledge will be of high value to gain fundamental insights into the antigenic landscape of SARS-CoV-2 recognized by CD8 T cells, to develop tool allowing focused analysis of the SARS-CoV-2 specific T cell responses directly ex vivo, and to understand whether current vaccine designs are covering the CD8 T cell recognized antigens. Methods: To address this issue, we have analyzed samples from 18 COVID-19 patients for CD8 T cell recognition of 500 predicted SARS-CoV-2-derived epitopes restricted to 10 common HLA-A and HLA-B alleles. For each HLA allele, the top 50 epitopes were selected based on predicted binding affinity and likelihood of successful proteasomal processing. To probe for CD8 T cell recognition of the selected epitope-HLA complexes, we made use of our in-house technology based on multiplexing of peptide HLA (pHLA) multimers conjugated to fluorescent dyes. Results: In addition to previous studies showing CD8 T cell reactivity towards epitopes derived from the spike protein of SARS-CoV-2, we have identified several CD8 T cell recognized epitopes derived from the ORF1ab, including one epitope displaying clear immunodominant properties across patients positive for HLA-A*01:01. Investigation of the functional status of part of the identified responses (including 4 responses specific for the immunodominant epitope) revealed that the T cell responses were highly dysfunctional. In addition the SARS-CoV-2 specific CD8 T cell responses displayed an increased expression of NKG2A in comparison with bulk CD8 T cells, which may explain their dysfunctional state. Conclusions: Our data suggest that part of the ORF1ab encodes multiple CD8 T cell antigens including one immunodominant epitope. Noteworthy these epitopes were derived from a part of the viral genome that is not included in the majority of vaccine candidates in development, and this may potentially influence their clinical activity and safety profile. Legal entity responsible for the study: The authors. Background: The COVID-19 pandemic has rapidly altered cancer care. However, the ways in which it has done so and the associated impact at the individual and societal levels remains poorly defined. Methods: CCOS is a multicenter prospective cohort study designed to define the impact of the pandemic on cancer care delivery and outcomes. The CCOS cohort comprised consecutive outpatients with cancer seen at two US cancer centers from March 2 to March 6, 2020 (index visit). Data was collected at baseline, retrospectively from the preceding 3 months, and prospectively at 3-month follow up. Per patient changes in numbers of visits were compared using Wilcoxon signed rank tests. Correlates of increases in telehealth visits and decreases in in-person visits were evaluated using multivariable logistic regression models. Adjusted Odds ratios [aOR] and 95% confidence intervals (CI) were reported. Results: Of 2365 included patients, 1219 (51.6%) had a decrease in in-person visit frequency during the pandemic period relative to the preceding 3 months. Conversely, 760 (32.2%) had an increased frequency of telehealth visits (decrease in in-person and increase in telehealth visits; both p<0.01). 128 (5.4%) patients developed COVID-19. Compared to White patients, Black and Hispanic patients were less likely to have telehealth visits, had no significant change in frequency of in-person visits, and were more likely to develop COVID-19 (Table) . Conclusions: Significant disruptions to routine cancer care were observed during the pandemic period relative to the prior 3 months. Racial and ethnic barriers to the adoption of telehealth, and related socioeconomic factors, place these vulnerable populations simultaneously at disproportionate risk for decreased cancer-related visits and COVID infection, thereby exacerbating existing racial and ethnic health disparities. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: D. Doroshow: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Ex- Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Athenaeum Partners Advisory/Consultancy: Boston Healthcare Associates. A.L. Schmidt: Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Astellas. Z. Bakouny: Non-remunerated activity/ies: Bristol Myers Squibb Research grant/Funding (self): Lilly Research grant/Funding (self): AstraZeneca Research grant/ Funding (self): Genentech; Advisory/Consultancy: Merck; Advisory/Consultancy: Achilles; Advisory/ Consultancy: AbbVie. R. Haddad: Advisory/Consultancy, Research grant/Funding (self) Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self Research grant/Funding (self): Genentech; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy Honoraria (self): BioMotiv Honoraria (self): Janssen; Honoraria (self): Dendreon Honoraria (self): Merck Honoraria (self): GlaxoSmithKline; Honoraria (self): Lilly; Honoraria (self) Honoraria (self): Genentech Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): EMD Serono; Honoraria (self): AstraZeneca; Honoraria (self): Seattle Genetics; Honoraria (self): Incyte; Honoraria (self): Alleron Therapeutics; Honoraria (self): Dracen; Honoraria (self): Inovio Pharmaceuticals Honoraria (self): Dragonfly Therapeutics; Honoraria (institution): Janssen Oncology; Honoraria (institution): Dendreon Honoraria (institution): Novartis Bristol-Myers Squibb; Honoraria (institution): Merck; Honoraria (institution): AstraZeneca; Honoraria (institution): Genentech/Roche. T.K. Choueiri: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Honoraria (self), Advisory/Consultancy Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): BristolMyersSquibb; Honoraria (self), Advisory/ Consultancy, Research grant/Funding (self Research grant/Funding (self): Exelixis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ipsen; Research grant/Funding (self): 16 Tracon; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Genentech; Honoraria (self), Advisory/ Consultancy, Research grant/Funding (self): Roche; Honoraria (self) Advisory/Consultancy, Research grant/ Funding (self): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self Advisory/Consultancy, Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy Advisory/Consultancy, Research grant/Funding (self): Corvus; Research grant/Funding (self): Calithera; Research grant/ Funding (self) Research grant/Funding (self): Sanofi/Aventis; Research grant/Funding (self): Takeda; Honoraria (self) Healthcare Communications Company with several brands such as OnClive, PeerView and PER) LBA75 Defining COVID-19 outcomes in thoracic cancer patients: TERAVOLT (Thoracic cancERs Department of Medicine, Division of Medical Oncology, Mount Sinai Pediatric Associates Practice Cliniche Humanitas Gavazzeni N (%); aOR (95% CI)* Increase in telehealth visits Decrease in in-person visits COVID-19 diagnosis 0%) 1.86 (1.10 e 3.11) Hispanic 65 Adjusted for cancer disease group, cancer center, cancer status, and receipt of systemic therapy (during index week)