The adaptive immune response to severe acute respiratory coronavirus 2 (SARS-CoV-2) is important for vaccine development and in the recovery from coronavirus disease 2019 (COVID-19). Men and cancer patients have been reported to be at higher risks of contracting the virus and developing the more severe forms of COVID-19. Prostate cancer (PCa) may be associated with both of these risks. We show that CD4+ T cells of SARS-CoV-2-unexposed patients with hormone-refractory (HR) metastatic PCa had decreased CD4+ T cell immune responses to antigens from SARS-CoV-2 spike glycoprotein but not from the spiked glycoprotein of the 'common cold'-associated human coronavirus 229E (HCoV-229E) as compared with healthy male volunteers who responded comparably to both HCoV-229E- and SARS-CoV-2-derived antigens. Moreover, the HCoV-229E spike glycoprotein antigen-elicited CD4+ T cell immune responses cross-reacted with the SARS-CoV-2 spiked glycoprotein antigens. PCa patients may have impaired responses to the vaccination, and the cross-reactivity can mediate antibody-dependent enhancement (ADE) of COVID-19. These findings highlight the potential for increased vulnerability of PCa patients to COVID-19.

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czechia

Department of Technical Operations SOTIO a s Prague Czechia

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Dyer O. Covid-19: Black People and Other Minorities are Hardest Hit in US. BMJ (2020) 369:m1483.   10.1136/bmj.m1483 PubMed DOI

Chen J, Qi T, Liu L, Ling Y, Qian Z, Li T, et al. Clinical Progression of Patients With COVID-19 in Shanghai, China. J Infect (2020) 80(5):e1–6.   10.1016/j.jinf.2020.03.004 PubMed DOI PMC

Zhang L, Zhu F, Xie L, Wang C, Wang J, Chen R, et al. Clinical Characteristics of COVID-19-infected Cancer Patients: A Retrospective Case Study in Three Hospitals Within Wuhan, China. Ann Oncol: Off J Eur Soc Med Oncol ESMO (2020).   10.1016/j.annonc.2020.03.296 PubMed DOI PMC

Mehta V, Goel S, Kabarriti R, Cole D, Goldfinger M, Acuna-Villaorduna A, et al. Case Fatality Rate of Cancer Patients With COVID-19 in a New York Hospital System. Cancer Discovery (2020).   10.1158/2159-8290.CD-20-0516 PubMed DOI PMC

Jin JM, Bai P, He W, Wu F, Liu XF, Han DM, et al. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health (2020) 8:152.   10.3389/fpubh.2020.00152 PubMed DOI PMC

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2019. CA: Cancer J Clin (2019) 69(1):7–34.   10.3322/caac.21551 PubMed DOI

Sama IE, Ravera A, Santema BT, van Goor H, Ter Maaten JM, Cleland JGF, et al. Circulating Plasma Concentrations of Angiotensin-Converting Enzyme 2 in Men and Women With Heart Failure and Effects of Renin-Angiotensin-Aldosterone Inhibitors. Eur Heart J (2020) 41(19):1810–7.   10.1093/eurheartj/ehaa373 PubMed DOI PMC

Paces J, Strizova Z, Smrz D, Cerny J. Covid-19 and the Immune System. Physiol Res (2020).   10.33549/physiolres.934492 PubMed DOI PMC

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical Features of Patients Infected With 2019 Novel Coronavirus in Wuhan, China. Lancet (2020) 395(10223):497–506.   10.1016/S0140-6736(20)30183-5 PubMed DOI PMC

Braciale TJ, Hahn YS. Immunity to Viruses. Immunol Rev (2013) 255(1):5–12.   10.1111/imr.12109 PubMed DOI PMC

Kang SM, Compans RW. Host Responses From Innate to Adaptive Immunity After Vaccination: Molecular and Cellular Events. Mol Cells (2009) 27(1):5–14.   10.1007/s10059-009-0015-1 PubMed DOI PMC

Grifoni A, Weiskopf K, Ramirez SI, Mateus J, Dan J M, Moderbacher C R, et al. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans With COVID-19 Disease and Unexposed Individuals. Cell (Forthcoming 2020).   10.1016/j.cell.2020.05.015. PubMed DOI PMC

Subramaniam KS, Lant S, Goodwin L, Grifoni A, Weiskopf D, Turtle L. Two Is Better Than One: Evidence for T-Cell Cross-Protection Between Dengue and Zika and Implications on Vaccine Design. Front Immunol (2020) 11:517.   10.3389/fimmu.2020.00517 PubMed DOI PMC

Balz K, Trassl L, Hartel V, Nelson PP, Skevaki C. Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development. Front Immunol (2020) 11:513.   10.3389/fimmu.2020.00513 PubMed DOI PMC

Hotez PJ, Corry DB, Bottazzi ME. Covid-19 Vaccine Design: The Janus Face of Immune Enhancement. Nat Rev Immunol (2020).   10.1038/s41577-020-0323-4 PubMed DOI PMC

Ricke D. Ricke, Darrell and Malone, Robert W., Medical Countermeasures Analysis of 2019-nCoV and Vaccine Risks for Antibody-Dependent Enhancement (Ade) (2/27/2020). (2020). Available at: https://ssrn.com/abstract=3546070 10.2139/ssrn.3546070. DOI

Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of Spike Glycoprotein of SARS-CoV-2 on Virus Entry and its Immune Cross-Reactivity With SARS-Cov. Nat Commun (2020) 11(1):1620.   10.1038/s41467-020-15562-9 PubMed DOI PMC

Li Z, Tomlinson AC, Wong AH, Zhou D, Desforges M, Talbot PJ, et al. The Human Coronavirus HCoV-229E s-Protein Structure and Receptor Binding. eLife (2019) 8.   10.7554/eLife.51230 PubMed DOI PMC

Podrazil M, Horvath R, Becht E, Rozkova D, Bilkova P, Sochorova K, et al. Phase I/II Clinical Trial of Dendritic-Cell Based Immunotherapy (DCVAC/Pca) Combined With Chemotherapy in Patients With Metastatic, Castration-Resistant Prostate Cancer. Oncotarget (2015) 6(20):18192–205.   10.18632/oncotarget.4145 PubMed DOI PMC

Taborska P, Bartunkova J, Smrz D. Simultaneous In Vitro Generation of Human CD34(+)-derived Dendritic Cells and Mast Cells From non-Mobilized Peripheral Blood Mononuclear Cells. J Immunol Methods (2018) 458:63–73.   10.1016/j.jim.2018.04.005 PubMed DOI

Taborska P, Stakheev D, Strizova Z, Vavrova K, Podrazil M, Bartunkova J, et al. Personalized Ex Vivo Multiple Peptide Enrichment and Detection of T Cells Reactive to Multiple Tumor-Associated Antigens in Prostate Cancer Patients. Med Oncol (2017) 34(10):173.   10.1007/s12032-017-1035-x PubMed DOI

Currier JR, Kuta EG, Turk E, Earhart LB, Loomis-Price L, Janetzki S, et al. A Panel of MHC Class I Restricted Viral Peptides for Use as a Quality Control for Vaccine Trial ELISPOT Assays. J Immunol Methods (2002) 260(1-2):157–72.   10.1016/s0022-1759(01)00535-x PubMed DOI

Stakheev D, Taborska P, Strizova Z, Podrazil M, Bartunkova J, Smrz D. The WNT/beta-catenin Signaling Inhibitor XAV939 Enhances the Elimination of LNCaP and PC-3 Prostate Cancer Cells by Prostate Cancer Patient Lymphocytes In Vitro. Sci Rep (2019) 9(1):4761.   10.1038/s41598-019-41182-5 PubMed DOI PMC

Wu SQ, Su H, Wang YH, Zhao XK. Role of Tumor-Associated Immune Cells in Prostate Cancer: Angel or Devil? Asian J Andrology (2019) 21(5):433–7.   10.4103/aja.aja_47_19 PubMed DOI PMC

Zou L, Dai L, Zhang Y, Fu W, Gao Y, Zhang Z, et al. Clinical Characteristics and Risk Factors for Disease Severity and Death in Patients With Coronavirus Disease 2019 in Wuhan, China. Front Med (2020) 7:532.   10.3389/fmed.2020.00532 PubMed DOI PMC

Cohen JF, Korevaar DA, Matczak S, Chalumeau M, Allali S, Toubiana J. Covid-19-Related Fatalities and Intensive-Care-Unit Admissions by Age Groups in Europe: A Meta-Analysis. Front Med (2020) 7:560685.   10.3389/fmed.2020.560685 PubMed DOI PMC

Saletti G, Gerlach T, Jansen JM, Molle A, Elbahesh H, Ludlow M, et al. Older Adults Lack SARS CoV-2 Cross-Reactive T Lymphocytes Directed to Human Coronaviruses OC43 and NL63. Sci Rep (2020) 10(1):21447.   10.1038/s41598-020-78506-9 PubMed DOI PMC

Amanat F, Krammer F. SARS-Cov-2 Vaccines: Status Report. Immunity (2020) 52(4):583–9.   10.1016/j.immuni.2020.03.007 PubMed DOI PMC

Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell (2020) 181(2):281–92.e286.   10.1016/j.cell.2020.02.058 PubMed DOI PMC

DiPiazza A, Richards KA, Knowlden ZA, Nayak JL, Sant AJ. The Role of CD4 T Cell Memory in Generating Protective Immunity to Novel and Potentially Pandemic Strains of Influenza. Front Immunol (2016) 7:10.   10.10.3389/fimmu.2016.00010 PubMed DOI PMC

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of Immune Response in Patients With COVID-19 in Wuhan, China. Clin Infect Dis: an Off Publ Infect Dis Soc America (2020).   10.1093/cid/ciaa248 PubMed DOI PMC

Giwa AL, Desai A, Duca A. Novel 2019 Coronavirus SARS-CoV-2 (Covid-19): An Overview for Emergency Clinicians. Pediatr Emergency Med Pract (2020) 17(5):1–24. PubMed

Cai C, Ahmed OA, Shen H, Zeng S. Which Cancer Type has the Highest Risk of COVID-19 Infection? J Infect (2020).   10.1016/j.jinf.2020.05.028 PubMed DOI PMC

Reber AJ, Music N, Kim JH, Gansebom S, Chen J, York I. Extensive T Cell Cross-Reactivity Between Diverse Seasonal Influenza Strains in the Ferret Model. Sci Rep (2018) 8(1):6112.   10.1038/s41598-018-24394-z PubMed DOI PMC

Iwasaki A, Yang Y. The Potential Danger of Suboptimal Antibody Responses in COVID-19. Nat Rev Immunol (2020).   10.1038/s41577-020-0321-6 PubMed DOI PMC

Tetro JA. Is COVID-19 Receiving ADE From Other Coronaviruses? Microbes Infect Institut Pasteur (2020) 22(2):72–3.   10.1016/j.micinf.2020.02.006 PubMed DOI PMC

Bajaj V, Gadi N, Spihlman AP, Wu SC, Choi CH, Moulton VR. Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections? Front Physiol (2020) 11:571416.   10.3389/fphys.2020.571416 PubMed DOI PMC

Chen Y, Klein SL, Garibaldi BT, Li H, Wu C, Osevala NM, et al. Aging in COVID-19: Vulnerability, Immunity and Intervention. Ageing Res Rev (2021) 65:101205.   10.1016/j.arr.2020.101205 PubMed DOI PMC

Cao X. Covid-19: Immunopathology and its Implications for Therapy. Nat Rev Immunol (2020) 20(5):269–70.   10.1038/s41577-020-0308-3 PubMed DOI PMC

Effectiveness and Durability of mRNA Vaccine-Induced SARS-CoV-2-Specific Humoral and Cellular Immunity in Severe Asthma Patients on Biological Therapy

SARS-CoV-2 spike glycoprotein-reactive T cells can be readily expanded from COVID-19 vaccinated donors