Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients

• Main Authors: Constantin J. Thieme, Moritz Anft, Krystallenia Paniskaki, Arturo Blazquez-Navarro, Adrian Doevelaar, Felix S. Seibert, Bodo Hoelzer, Margarethe Justine Konik, Marc Moritz Berger, Thorsten Brenner, Clemens Tempfer, Carsten Watzl, Toni L. Meister, Stephanie Pfaender, Eike Steinmann, Sebastian Dolff, Ulf Dittmer, Timm H. Westhoff, Oliver Witzke, Ulrik Stervbo, Toralf Roch, Nina Babel
• Format: Article
• Language: English
• Published: Elsevier 2020-09-01
• Series: Cell Reports Medicine
• Subjects: COVID-19; SARS-CoV-2; immunity; spike; nucleocapsid; S/M/N protein-reactive T cells
• Online Access: http://www.sciencedirect.com/science/article/pii/S266637912030118X
• ISSN: 2666-3791

Summary: T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4+ over CD8+ T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4+ T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients.