Heterogenous CD8+ T Cell Maturation and 'Polarization' in Acute and Convalescent COVID-19 Patients

Igor V Kudryavtsev; Natalia A Arsentieva; Zoia R Korobova; Dmitry V Isakov; Artem A Rubinstein; Oleg K Batsunov; Irina V Khamitova; Raisa N Kuznetsova; Tikhon V Savin; Tatiana V Akisheva; Oksana V Stanevich; Aleksandra A Lebedeva; Evgeny A Vorobyov; Snejana V Vorobyova; Alexander N Kulikov; Maria A Sharapova; Dmitrii E Pevtsov; Areg A Totolian

doi:10.3390/v14091906

Heterogenous CD8+ T Cell Maturation and 'Polarization' in Acute and Convalescent COVID-19 Patients

Viruses. 2022 Aug 28;14(9):1906. doi: 10.3390/v14091906.

Authors

Igor V Kudryavtsev^{1

2}, Natalia A Arsentieva³, Zoia R Korobova^{2

3}, Dmitry V Isakov², Artem A Rubinstein¹, Oleg K Batsunov^{2

3}, Irina V Khamitova³, Raisa N Kuznetsova^{2

3}, Tikhon V Savin^{2

3}, Tatiana V Akisheva¹, Oksana V Stanevich^{2

4}, Aleksandra A Lebedeva², Evgeny A Vorobyov², Snejana V Vorobyova², Alexander N Kulikov², Maria A Sharapova², Dmitrii E Pevtsov², Areg A Totolian^{2

3}

Affiliations

¹ Institute of Experimental Medicine, Akademika Pavlova 12, 197376 Saint Petersburg, Russia.
² Medical Faculty, First Saint Petersburg State I. Pavlov Medical University, L'va Tolstogo St. 6-8, 197022 Saint Petersburg, Russia.
³ Laboratory of Immunology, Saint Petersburg Pasteur Institute, Mira 14, 197101 Saint Petersburg, Russia.
⁴ Smorodintsev Research Institute of Influenza, Prof. Popov St. 15/17, 197376 Saint Petersburg, Russia.

Abstract

Background: The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited.

Methods: . Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry.

Results: Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on 'naïve', CM, EM4, and pE1 2-3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients.

Conclusions: We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on 'naïve' and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.

Keywords: CD3+CD8+; COVID-19; COVID-19 convalescent; IL-27; SARS-CoV-2; Tc1; Tc17; Tc2; chemokine receptors; memory CD8+ T cells; post-COVID-19 syndrome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / metabolism
CD8-Positive T-Lymphocytes
COVID-19* / complications
Humans
Immunoglobulin G
Interleukin-27*
Post-Acute COVID-19 Syndrome
SARS-CoV-2

Substances

Antiviral Agents
Immunoglobulin G
Interleukin-27

Grants and funding

This research was funded by the Saint Petersburg Pasteur Institute within the framework of the State Task (Registration No 121030200299-3), as well as by the Institute of Experimental Medicine within the framework of State Task No. 075-01135-22-00.