Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome

Max Augustin; Ferdinand Heyn; Stella Ullrich; Ute Sandaradura de Silva; Marie-Christine Albert; Viktoria Linne; Maike Schlotz; Philipp Schommers; Elisabeth Pracht; Carola Horn; Isabelle Suarez; Alexander Simonis; Lea Katharina Picard; Alexander Zoufaly; Christoph Wenisch; Gerd Fätkenheuer; Henning Gruell; Florian Klein; Michael Hallek; Henning Walczak; Jan Rybniker; Sebastian J Theobald; Clara Lehmann

doi:10.3389/fmed.2023.1129288

Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome

Front Med (Lausanne). 2023 Apr 24:10:1129288. doi: 10.3389/fmed.2023.1129288. eCollection 2023.

Authors

Max Augustin^{1

2

3}, Ferdinand Heyn^{1

2

3}, Stella Ullrich^{1

2

3}, Ute Sandaradura de Silva^{1

2

3}, Marie-Christine Albert^{4

5}, Viktoria Linne¹, Maike Schlotz^{2

6}, Philipp Schommers^{1

2

3

6}, Elisabeth Pracht¹, Carola Horn^{1

2

3}, Isabelle Suarez^{1

3}, Alexander Simonis^{1

2

3}, Lea Katharina Picard^{1

2}, Alexander Zoufaly^{7

8}, Christoph Wenisch⁷, Gerd Fätkenheuer^{1

3}, Henning Gruell^{2

6}, Florian Klein^{2

3

6}, Michael Hallek¹, Henning Walczak^{4

5

8}, Jan Rybniker^{1

2

3}, Sebastian J Theobald^{1

2

3}, Clara Lehmann^{1

2

3}

Affiliations

¹ Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany.
² Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
³ German Center for Infection Research (DZIF), Bonn-Cologne, Germany.
⁴ Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
⁵ Institute for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁶ Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁷ Department IV of Internal Medicine, Klinik Favoriten, Vienna Healthcare Group, Vienna, Austria.
⁸ Faculty of Medicine, Sigmund Freud University, Vienna, Austria.

Abstract

Background: Symptoms lasting longer than 12 weeks after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection are called post-coronavirus disease (COVID) syndrome (PCS). The identification of new biomarkers that predict the occurrence or course of PCS in terms of a post-viral syndrome is vital. T-cell dysfunction, cytokine imbalance, and impaired autoimmunity have been reported in PCS. Nevertheless, there is still a lack of conclusive information on the underlying mechanisms due to, among other things, a lack of controlled study designs.

Methods: Here, we conducted a prospective, controlled study to characterize the humoral and cellular immune response in unvaccinated patients with and without PCS following SARS-CoV-2 infection over 7 months and unexposed donors.

Results: Patients with PCS showed as early as 6 weeks and 7 months after symptom onset significantly increased frequencies of SARS-CoV-2-specific CD4⁺ and CD8⁺ T-cells secreting IFNγ, TNF, and expressing CD40L, as well as plasmacytoid dendritic cells (pDC) with an activated phenotype. Remarkably, the immunosuppressive counterparts type 1 regulatory T-cells (TR1: CD49b/LAG-3⁺) and IL-4 were more abundant in PCS⁺.

Conclusion: This work describes immunological alterations between inflammation and immunosuppression in COVID-19 convalescents with and without PCS, which may provide potential directions for future epidemiological investigations and targeted treatments.

Keywords: PCS; immune activation; immunological fingerprint; immunosuppression; long COVID; post-COVID syndrome.

Copyright © 2023 Augustin, Heyn, Ullrich, Sandaradura de Silva, Albert, Linne, Schlotz, Schommers, Pracht, Horn, Suarez, Simonis, Picard, Zoufaly, Wenisch, Fätkenheuer, Gruell, Klein, Hallek, Walczak, Rybniker, Theobald and Lehmann.