Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2023 Aug 1:14:1179620.
doi: 10.3389/fimmu.2023.1179620. eCollection 2023.

T cell immune response predicts survival in severely ill COVID-19 patients requiring venovenous extracorporeal membrane oxygenation support

Zsuzsanna Ulakcsai  1 , Liliana Szabo  1   2 , Zsofia Szabo  3 , Eva Karaszi  4 , Tamas Szabo  3 , Levente Fazekas  1 , Alexandra Vereb  1 , Nora Fanna Kovacs  1 , Dora Nemeth  5   6 , Eniko Kovacs  1 , Endre Nemeth  1 , Gyorgy Nagy  1   5   7 , Hajnalka Vago  1   8 , Bela Merkely  1   8
Affiliations
Observational Study

T cell immune response predicts survival in severely ill COVID-19 patients requiring venovenous extracorporeal membrane oxygenation support

Zsuzsanna Ulakcsai et al. Front Immunol. .

Abstract

Introduction: There is a critical gap in understanding which SARS-CoV-2 patients would benefit most from venovenous extracorporeal membrane oxygenation (VV-ECMO) support. The potential role of a dysregulated immune response is still unclear in this patient population.

Objectives: To assess the potential predictive value of SARS-CoV-2 specific cellular and humoral immune responses for survival in critically ill COVID-19 patients requiring VV-ECMO.

Methods: We conducted a prospective single-center observational study of unvaccinated patients requiring VV-ECMO support treated at the intensive care unit of Semmelweis University Heart and Vascular Center between March and December 2021. Peripheral blood samples were collected to measure the humoral and cellular immune statuses of the patients at the VV-ECMO cannulation. Patients were followed until hospital discharge.

Results: Overall, 35 COVID-19 patients (63% men, median age 37 years) on VV-ECMO support were included in our study. The time from COVID-19 verification to ECMO support was a median (IQR) of 10 (7-14) days. Of the patients, 9 (26%) were discharged alive and 26 (74%) died during their hospital stay. Immune tests confirmed ongoing SARS-CoV-2 infection in all the patients, showing an increased humoral immune response. SARS-CoV-2-specific cellular immune response was significantly higher among survivors compared to the deceased patients. A higher probability of survival was observed in patients with markers indicating a higher T cell response detected by both QuantiFeron (QF) and flow cytometry (Flow) assays. (Flow S1 CD8+ ≥ 0.15%, Flow S1 CD4+ ≥ 0.02%, QF CD4 ≥ 0.07, QF whole genome ≥ 0.59). In univariate Cox proportional hazard regression analysis BMI, right ventricular (RV) failure, QF whole genome T cell level, and Flow S1 CD8+ T cell level were associated with mortality, and we found that an increased T cell response showed a significant negative association with mortality, independent of BMI and RV failure.

Conclusion: Evaluation of SARS-CoV-2 specific T cell response before the cannulation can aid the risk stratification and evaluation of seriously ill COVID-19 patients undergoing VV-ECMO support by predicting survival, potentially changing our clinical practice in the future.

Keywords: COVID-19; ECMO; SARS-COV-2; T cell response; antibody response; immune dysregulation; serological test.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Boxplots depicting the comparison between survivors (green) and deceased (red) patients. The comparison was performed using the Wilcoxon test, and immune markers are shown on a logarithmic scale to account for the skewness of the data. NC, nucleocapsid; SP, spike protein; QF, quantiferon. The cutoff value for each immune marker: QF: >0.15 IU/ml; Roche IgG: >0.8 U/ml; Flow: >0.02%; SP1 IgA >1.1 U/ml; NCP IgM: >1.1 U/ml – positive. A detailed description of the applied methodology and grading system is found in Supplementary Table 1 .
Figure 2
Figure 2
Correlation matrix showing the associations between markers of the SARS-CoV-2 immune response among critically ill COVID-19 patients. Color-coded boxes in the upper part of the figure illustrate the strength of the correlation between immune markers, whereas Rho values calculated from Spearman rank correlation are shown in the lower segment. Each box depicts the results from correlations; positive values signify positive correlations and negative values show negative correlations. Asterix (*) shows significant correlations.
Figure 3
Figure 3
ROC curves are drawn for markers of the cellular immune response. ROC curves were drawn to ascertain the ideal cutoff point for each marker of the cellular immune response. AUC values suggest that Flow S1 CD8+ and QF whole genome levels measured at ECMO initiation can help identify patients at risk with high accuracy.
Figure 4
Figure 4
Kaplan Meier curves showing the associations between T cell response intensity and all-cause mortality among critically ill COVID-19 patients. Patients were categorized according to the intensity of their immune response.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Zhou G, Chen S, Chen Z. Back to the spring of 2020: facts and hope of COVID-19 outbreak. Front Med (2020) 14:113–6. doi: 10.1007/s11684-020-0758-9 - DOI - PMC - PubMed
    1. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. . Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med (2020) 382:1708–20. doi: 10.1056/nejmoa2002032 - DOI - PMC - PubMed
    1. Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, et al. . Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med (2018) 378:1965–75. doi: 10.1056/nejmoa1800385 - DOI - PubMed
    1. Ramanathan K, Shekar K, Ling RR, Barbaro RP, Wong SN, Tan CS, et al. . Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis. Crit Care (2021) 25:1–11. doi: 10.1186/s13054-021-03634-1 - DOI - PMC - PubMed
    1. Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, et al. . Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care (2020) 24:1–10. doi: 10.1186/s13054-020-03120-0 - DOI - PMC - PubMed

Publication types

Grants and funding

This study was supported by the National Research, Development, and Innovation Office of Hungary (NKFIA; NVKP_16-1-2016-0017 National Heart Program). Project no. RRF-2.3.1-21-2022-00003 has been implemented with the support provided by the European Union.