Potent SARS-CoV-2-Specific T Cell Immunity and Low Anaphylatoxin Levels Correlate With Mild Disease Progression in COVID-19 Patients

Abstract

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.

Low anti‐SARS‐CoV‐2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID‐19 patients

“…Previous studies have shown that critical COVID-19 patients develop higher titers of SARS-CoV-2 antibodies than those with milder disease, suggesting that antibody response alone is insufficient to avoid severe disease [10]. Our results support nonetheless that critical COVID-19 patients would need to mount a robust anti-S antibody response to survive.…”

Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine

“…CV2CoV induced both antigen-specific memory B cell responses and T cell responses. While the correlates of protection in this study were binding and neutralizing antibodies 34,35 , it is likely that CD8 + T cells contribute to viral clearance in tissues 36,37 . We previously reported that depletion of CD8 + T cells partially abrogated protective efficacy against SARS-CoV-2 re-challenge in convalescent macaques 22 .…”

ChAdOx1‐S adenoviral vector vaccine applied intranasally elicits superior mucosal immunity compared to the intramuscular route of vaccination

“…It is also well established that intranasal vaccination promotes the induction of virus‐specific T lymphocytes in the lungs [ 7 , 8 ]. Clinical studies have shown a good correlation between disease resolution and T lymphocyte response [ 22 , 23 ]. We, therefore, compared CD8 T‐cell response in mice upon intranasal or intramuscular immunization with ChAdOx1‐S (Fig.…”