T-cell-Mediated Immunity to Sars-cov-2 Defines Covid-19 Risk and Severity in Transplanted and Non-Transplanted Individuals and Associates with Myeloid-Derived Suppressor Cells
1Plexision, Pittsburgh, PA, 2Medical University of South Carolina, Charleston, SC, 3MedStar Georgetown Transplant Institute, Georgetown, DC, 4DHR Health Institute for Research and Development, Texas, TX, 5University of Pittsburgh, Pittsburgh, PA, 6University of California, San Diego, CA, 7University of Pittsburgh, pittsburgh, PA
Meeting: 2021 American Transplant Congress
Abstract number: 12
Keywords: FACS analysis, High-risk, Infection, T cells
Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes
Session Information
Session Name: Biomarkers, Immune Assessment and Clinical Outcomes - I
Session Type: Rapid Fire Oral Abstract
Date: Saturday, June 5, 2021
Session Time: 4:30pm-5:30pm
Presentation Time: 4:35pm-4:40pm
Location: Virtual
*Purpose: We assessed whether COVID-19-risk is enhanced by chronic immunosuppression, and is associated with suppressor cells.
*Methods: We tested 66 COVID-19 patients, including 26 with solid organ transplants at median 11 days after diagnosis, and 64 unexposed healthy subjects including 21 with transplants, who were sampled pre-pandemic. T- and B-cells, which express CD154 were measured after stimulation with peptide mixtures representing the spike protein S, its conserved C-terminal S2, and less conserved N-terminal S1 components. Monocytic myeloid-derived suppressor cells (M-MDSC) were measured in an independent cohort of 47 COVID-19 patients
*Results: Frequencies (%) of S-reactive T-cells (Mean±SEM 2.0±0.3 vs 3.8±0.3, p=5.6E-05) and B-cells (3.0±0.4 vs 5.1±0.4, p=0.0003) were significantly lower in COVID-19 compared with healthy subjects, but were measurable in all samples. Transplanted and non-transplanted subjects demonstrated similar within group frequencies of S-reactive T-cells (4.1±0.3 vs 3.7±0.5, p=NS in healthy and 1.5±0.4 vs 2.4±0.3, p=NS in the COVID-19 group) and other S-reactive cells. Among COVID-19 patients, intubated patients showed lower S-reactive CD8 frequencies compared with non-intubated patients. (1.4±0.5 vs 3.5±0.5, p=0.003). In logistic regression analysis using training and test sets, S-reactive CD3 and CD8 cells, age, race, and transplantation status distinguished COVID-19 from healthy subjects (test set negative and positive predictive values 75% and 85% respectively, AUC 0.9). Among 66 COVID-19 patients, S-reactive CD8 cells and age predicted respiratory failure with NPV 62%, PPV 86%, AUC 0.73. S2-reactive T-cells demonstrated similar predictive performance. S1 antigen elicited minimal cellular responses. Transplanted COVID-19 patients show lower cytomegalovirus-specific CD154+CD3 frequencies compared with non-transplanted patients (0.5±0.1 vs 1.3±0.2, p=0.006). Frequencies of CD14+CD33+CD11b+HLADR-ve M-MDSC (14.5±2.9 vs 3.3±1.5, p=0.002) were higher in 47 independent COVID-19 patients compared with 6 healthy subjects.
*Conclusions: Conserved SARS-CoV-2-spike antigen drives T-cell immunity to COVID-19 in unexposed transplanted and non-transplanted subjects. This immunity declines with COVID-19 infection, is accompanied by increased myeloid derived suppressor cells, and can predict infection-risk and disease severity. Transplant patients demonstrate increased COVID-19-risk and co-infection-risk.
To cite this abstract in AMA style:
Ashokkumar C, Rohan V, Kroemer AH, Rao S, Mazariegos G, Higgs BW, Nadig S, Ningappa M, Fishbein T, Subramaniam S, Sindhi R. T-cell-Mediated Immunity to Sars-cov-2 Defines Covid-19 Risk and Severity in Transplanted and Non-Transplanted Individuals and Associates with Myeloid-Derived Suppressor Cells [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/t-cell-mediated-immunity-to-sars-cov-2-defines-covid-19-risk-and-severity-in-transplanted-and-non-transplanted-individuals-and-associates-with-myeloid-derived-suppressor-cells/. Accessed May 16, 2025.« Back to 2021 American Transplant Congress