Persistent Exhausted T-Cell Immunity after Severe COVID-19: 6-Month Evaluation in a Prospective Observational Study

Elena Vazquez-Alejo; Laura Tarancon-Diez; Maria de la Sierra Espinar-Buitrago; Miguel Genebat; Alba Calderón; Guillermo Pérez-Cabeza; Esmeralda Magro-Lopez; Manuel Leal; Mª Ángeles Muñoz-Fernández

doi:10.3390/jcm12103539

Persistent Exhausted T-Cell Immunity after Severe COVID-19: 6-Month Evaluation in a Prospective Observational Study

J Clin Med. 2023 May 18;12(10):3539. doi: 10.3390/jcm12103539.

Authors

Affiliations

¹ Immunology Section, Molecular Immuno-Biology Laboratory, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28007 Madrid, Spain.
² Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
³ Internal Medicine Department, Hospital Fátima, 41012 Sevilla, Spain.
⁴ Urgency Department, Hospital Viamed Santa Ángela de la Cruz, 41013 Sevilla, Spain.
⁵ Internal Medicine Department, Hospital Viamed Santa Ángela de la Cruz, 41013 Sevilla, Spain.

Abstract

Introduction: Severe COVID-19 can result in a significant and irreversible impact on long-term recovery and subsequent immune protection. Understanding the complex immune reactions may be useful for establishing clinically relevant monitoring.

Methods: Hospitalized adults with SARS-CoV-2 between March/October 2020 (n = 64) were selected. Cryopreserved peripheral blood mononuclear cells (PBMCs) and plasma samples were obtained at hospitalization (baseline) and 6 months after recovery. Immunological components' phenotyping and SARS-CoV-2-specific T-cell response were studied in PBMCs by flow cytometry. Up to 25 plasma pro/anti-inflammatory cytokines/chemokines were assessed by LEGENDplex immunoassays. The SARS-CoV-2 group was compared to matched healthy donors.

Results: Biochemical altered parameters during infection were normalized at a follow-up time point in the SARS-CoV-2 group. Most of the cytokine/chemokine levels were increased at baseline in the SARS-CoV-2 group. This group showed increased Natural Killer cells (NK) activation and decreased CD16^high NK subset, which normalized six months later. They also presented a higher intermediate and patrolling monocyte proportion at baseline. T cells showed an increased terminally differentiated (TemRA) and effector memory (EM) subsets distribution in the SARS-CoV-2 group at baseline and continued to increase six months later. Interestingly, T-cell activation (CD38) in this group decreased at the follow-up time point, contrary to exhaustion markers (TIM3/PD1). In addition, we observed the highest SARS-CoV-2-specific T-cell magnitude response in TemRA CD4 T-cell and EM CD8 T-cell subsets at the six-months time point.

Conclusions: The immunological activation in the SARS-CoV-2 group during hospitalization is reversed at the follow-up time point. However, the marked exhaustion pattern remains over time. This dysregulation could constitute a risk factor for reinfection and the development of other pathologies. Additionally, high SARS-CoV-2-specific T-cells response levels appear to be associated with infection severity.

Keywords: SARS-CoV-2; SARS-CoV-2-specific T-cell response; hospitalization; immune exhaustion profile; long-term evolution; severe COVID-19.

Abstract

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