T-Cell-Dominated Immune Response Resolves Protracted SARS-CoV-2 Infection in the Absence of Neutralizing Antibodies in an Immunocompromised Individual
Abstract
:1. Introduction
2. Case Report
3. Results
3.1. SARS-CoV-2 Whole-Genome Sequencing
3.2. Profiling of SARS-CoV-2-Specific Immunity
4. Discussion
5. Materials and Methods
5.1. SARS-CoV-2 Whole-Genome Sequencing
5.2. Isolation of Peripheral Blood Mononuclear Cells (PBMCs)
5.3. Multi-Parameter IFN-γ /IL-2/TNF/Granzyme B Fluorospot Assay
5.4. Flow-Cytometry-Based Ex Vivo Detection of SARS-CoV-2-Reactive T-Cells
5.5. Serum SARS-CoV-2 Neutralization Activity
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Erber, J.; Kappler, V.; Haller, B.; Mijočević, H.; Galhoz, A.; Prazeres da Costa, C.; Gebhardt, F.; Graf, N.; Hoffmann, D.; Thaler, M.; et al. Infection Control Measures and Prevalence of SARS-CoV-2 IgG among 4554 University Hospital Employees, Munich, Germany. Emerg. Infect. Dis. 2022, 28, 572–581. [Google Scholar] [CrossRef] [PubMed]
- Aschenbrenner, A.C.; Mouktaroudi, M.; Krämer, B.; Oestreich, M.; Antonakos, N.; Nuesch-Germano, M.; Gkizeli, K.; Bonaguro, L.; Reusch, N.; Baßler, K.; et al. Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients. Genome Med. 2021, 13, 7. [Google Scholar] [CrossRef] [PubMed]
- Schulte-Schrepping, J.; Reusch, N.; Paclik, D.; Baßler, K.; Schlickeiser, S.; Zhang, B.; Krämer, B.; Krammer, T.; Brumhard, S.; Bonaguro, L.; et al. Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell 2020, 182, 1419–1440.e23. [Google Scholar] [CrossRef] [PubMed]
- Belsky, J.A.; Tullius, B.P.; Lamb, M.G.; Sayegh, R.; Stanek, J.R.; Auletta, J.J. COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. J. Infect. 2021, 82, 329–338. [Google Scholar] [CrossRef] [PubMed]
- Choi, B.; Choudhary, M.C.; Regan, J.; Sparks, J.A.; Padera, R.F.; Qiu, X.; Solomon, I.H.; Kuo, H.-H.; Boucau, J.; Bowman, K.; et al. Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host. N. Engl. J. Med. 2020, 383, 2291–2293. [Google Scholar] [CrossRef] [PubMed]
- Avanzato, V.A.; Matson, M.J.; Seifert, S.N.; Pryce, R.; Williamson, B.N.; Anzick, S.L.; Barbian, K.; Judson, S.D.; Fischer, E.R.; Martens, C.; et al. Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer. Cell 2020, 183, 1901–1912.e9. [Google Scholar] [CrossRef] [PubMed]
- Kemp, S.A.; Collier, D.A.; Datir, R.P.; Ferreira, I.A.T.M.; Gayed, S.; Jahun, A.; Hosmillo, M.; Rees-Spear, C.; Mlcochova, P.; Lumb, I.U.; et al. SARS-CoV-2 evolution during treatment of chronic infection. Nature 2021, 592, 277–282. [Google Scholar] [CrossRef] [PubMed]
- Koerber, N.; Priller, A.; Yazici, S.; Bauer, T.; Cheng, C.-C.; Mijočević, H.; Wintersteller, H.; Jeske, S.; Vogel, E.; Feuerherd, M.; et al. Dynamics of spike-and nucleocapsid specific immunity during long-term follow-up and vaccination of SARS-CoV-2 convalescents. Nat. Commun. 2022, 13, 153. [Google Scholar] [CrossRef] [PubMed]
- Robrt Koch Institut. Täglicher Lagebericht des RKI zur Coronavirus-Krankheit-2019 (COVID-19). Available online: https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Situationsberichte/Sept_2020/2020-09-16-de.pdf?__blob=publicationFile (accessed on 19 March 2023).
- Niessl, J.; Sekine, T.; Buggert, M. T cell immunity to SARS-CoV-2. Semin. Immunol. 2021, 55, 101505. [Google Scholar] [CrossRef] [PubMed]
- Bange, E.M.; Han, N.A.; Wileyto, P.; Kim, J.Y.; Gouma, S.; Robinson, J.; Greenplate, A.R.; Porterfield, F.; Owoyemi, O.; Naik, K.; et al. CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer. Res. Sq. 2021. [Google Scholar] [CrossRef]
- Riise, J.; Meyer, S.; Blaas, I.; Chopra, A.; Tran, T.T.; Delic-Sarac, M.; Hestdalen, M.L.; Brodin, E.; Rustad, E.H.; Dai, K.Z.; et al. Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination. Br. J. Haematol. 2022, 197, 697–708. [Google Scholar] [CrossRef] [PubMed]
- Bange, E.M.; Han, N.A.; Wileyto, P.; Kim, J.Y.; Gouma, S.; Robinson, J.; Greenplate, A.R.; Hwee, M.A.; Porterfield, F.; Owoyemi, O.; et al. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat. Med. 2021, 27, 1280–1289. [Google Scholar] [CrossRef] [PubMed]
- Apostolidis, S.A.; Kakara, M.; Painter, M.M.; Goel, R.R.; Mathew, D.; Lenzi, K.; Rezk, A.; Patterson, K.R.; Espinoza, D.A.; Kadri, J.C.; et al. Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. Nat. Med. 2021, 27, 1990–2001. [Google Scholar] [CrossRef] [PubMed]
- Bellucci, G.; Rinaldi, V.; Buscarinu, M.C.; Reniè, R.; Bigi, R.; Pellicciari, G.; Morena, E.; Romano, C.; Marrone, A.; Mechelli, R.; et al. Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started? Front. Immunol. 2021, 12, 755333. [Google Scholar] [CrossRef] [PubMed]
- Böttcher, J.P.; Beyer, M.; Meissner, F.; Abdullah, Z.; Sander, J.; Höchst, B.; Eickhoff, S.; Rieckmann, J.C.; Russo, C.; Bauer, T.; et al. Functional classification of memory CD8+ T cells by CX3CR1 expression. Nat. Commun. 2015, 6, 8306. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bunse, T.; Koerber, N.; Wintersteller, H.; Schneider, J.; Graf, A.; Radonic, A.; Thuermer, A.; von Kleist, M.; Blum, H.; Spinner, C.D.; et al. T-Cell-Dominated Immune Response Resolves Protracted SARS-CoV-2 Infection in the Absence of Neutralizing Antibodies in an Immunocompromised Individual. Microorganisms 2023, 11, 1562. https://doi.org/10.3390/microorganisms11061562
Bunse T, Koerber N, Wintersteller H, Schneider J, Graf A, Radonic A, Thuermer A, von Kleist M, Blum H, Spinner CD, et al. T-Cell-Dominated Immune Response Resolves Protracted SARS-CoV-2 Infection in the Absence of Neutralizing Antibodies in an Immunocompromised Individual. Microorganisms. 2023; 11(6):1562. https://doi.org/10.3390/microorganisms11061562
Chicago/Turabian StyleBunse, Till, Nina Koerber, Hannah Wintersteller, Jochen Schneider, Alexander Graf, Aleksandar Radonic, Andrea Thuermer, Max von Kleist, Helmut Blum, Christoph D. Spinner, and et al. 2023. "T-Cell-Dominated Immune Response Resolves Protracted SARS-CoV-2 Infection in the Absence of Neutralizing Antibodies in an Immunocompromised Individual" Microorganisms 11, no. 6: 1562. https://doi.org/10.3390/microorganisms11061562