T-cell immune response to SARS-CoV-2 in healthcare workers 2.5–3 years after COVID-19

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Abstract

BACKGROUND: The T cell adaptive immune response is an important factor in the formation of antiviral defense against SARS-CoV-2.

AIM: Тo study T cell immunity to the SARS-CoV-2 in healthcare workers of a temporary infectious diseases hospital in Kazan — COVID-19 convalescents 2.5–3 years after the infection using the IGRA-ELISPOT technology.

MATERIALS AND METHODS: The immune response to the most SARS-CoV-2 immunogenic peptides S, N, ORF-3a, ORF-7a was studied in 91 healthcare workers of the city of Kazan 2.5–3 years after suffering from COVID-19 of varying severity and varying vaccine status. The results were recorded by the number of formed spots: imprints of one T cell secreting interferon γ in response to antigenic stimulation. The number of obtained spots characterized the content of peripheral blood CD4+ and CD8+ T cells specific for SARS-CoV-2 antigens and made it possible to assess individual immune response. Statistical processing wasperformed using variation statistics methods using the statistical package Excel 2016 and WinPepi Version 11, 65. The relative frequency of a trait (P) and the error in the relative frequency value (m) were calculated. The study results were compared using the χ2-test when the number of observations was more than 5 and Fisher’s exact method when the number of observations was 5 or less. Differences were considered significant at p <0.05.

RESULTS: 2.5–3 years after experiencing COVID-19 infection, T-cell immune response to S protein peptides is recorded in 72.53 ± 5.50 %, and to structural peptides N, M, ORF3a and ORF7a in 86.81 ± 3.81 % (χ2-test 5.733; p = 0.017) of medical workers. A higher level of T cell immunity to S protein peptides of the SARS-CoV-2 virus is observed in healthcare workers who have had moderate/severe COVID-19. The preservation of the parameters of hybrid immunity compared to post-infectious immunity is higher, which is significant both for groups with a history of clinical manifestations of COVID-19 and for the group with asymptomatic forms.

CONCLUSION: Our empirically established ranking of the number of spots in classes can be used to assess individual cellular immunity and stratify the risks of re-infection in healthcare workers. A negative result of the T cell immune response to the spike S protein antigen may be the basis for deciding whether to re-vaccinate healthcare workers.

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About the authors

Irina D. Reshetnikova

Kazan Scientific Research Institute of Epidemiology and Microbiology; Kazan Federal University

Author for correspondence.
Email: reshira@mail.ru
ORCID iD: 0000-0002-3584-6861
SPIN-code: 3255-0088

MD, Cand. Sci. (Medicine), Assistant Professor

Россия, Kazan; Kazan

Yuriy A. Tyurin

Kazan Scientific Research Institute of Epidemiology and Microbiology; Kazan State Medical University

Email: tyurin.yurii@yandex.ru
ORCID iD: 0000-0002-2536-3604
SPIN-code: 5089-5565

MD, Dr. Sci. (Medicine), Assistant Professor

Россия, Kazan; Kazan

Rustem S. Fassakhov

Kazan Scientific Research Institute of Epidemiology and Microbiology; Kazan Federal University

Email: farrus@mail.ru
ORCID iD: 0000-0001-9322-2689
SPIN-code: 1748-7760

MD, Dr. Sci. (Medicine), Professor

Россия, Kazan; Kazan

Elena V. Agafonova

Kazan Scientific Research Institute of Epidemiology and Microbiology; Kazan State Medical University

Email: agafono@mail.ru
ORCID iD: 0000-0002-4411-8786
SPIN-code: 4897-1326

MD, Cand. Sci. (Medicine)

Россия, Kazan; Kazan

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Supplementary files

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2. Fig. 1. Results of T-cell response study for one subject using the TIGRA-Test SARS-CoV-2. Photos of the wells after incubation: a — with a pool of S-protein peptides (35 spots); b – with a pool of peptides N, M, a ORF3a, ORF7a (23 spots); с — without specific antigenic inducer to determine spontaneous production of interferon γ (negative control, 2 spots); d — with monoclonal antibody OCT-3 to determine functional activity of T-lymphocytes (positive control, >100 spots).

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3. Fig. 2. Distribution of medical workers by class level of T-cell immune response to S-protein peptides in “TIGRA-Test SARS-CoV-2” depending on the severity COVID-19 infection.

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4. Fig. 3. Distribution of medical workers by class level of T-cell immune response to N, M, ORF3a and ORF7а protein peptides in “TIGRA-Test SARS-CoV-2” depending on the severity COVID-19 infection.

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5. Fig. 4. Distribution of medical workers by class level of T-cell immune response to S-protein peptides depending on the severity of COVID-19 infection and vaccine status.

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6. Fig. 5. Distribution of medical workers by class level of T-cell immune response to N, M, ORF3a и ORF7a protein peptides depending on the severity of COVID-19 infection and vaccine status.

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