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

Author:

Vazquez-Alejo Elena12ORCID,Tarancon-Diez Laura12ORCID,Espinar-Buitrago Maria de la Sierra12,Genebat Miguel3,Calderón Alba3,Pérez-Cabeza Guillermo4ORCID,Magro-Lopez Esmeralda12ORCID,Leal Manuel5,Muñoz-Fernández Mª Ángeles12ORCID

Affiliation:

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 CD16high 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.

Funder

Instituto de Salud Carlos III

Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine

European Cooperation in Science and Technology

Insituto de Investigación Sanitaria Gregorio Marañón

Publisher

MDPI AG

Subject

General Medicine

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