Intracellular level of HIF-1α as an indicator of the delayed impact of COVID-19 on peripheral blood lymphocytes metabolism

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Abstract

BACKGROUND: COVID-19 infection triggers metabolic alterations that are crucial for both the replication of SARS-CoV-2 and the regulation of the immune response. HIF-1α, which is one of the effectors in the PI3K/Akt/mTOR signal transmission pathway, promotes the reprogramming of metabolism by enhancing aerobic glycolysis.

AIM: To assess whether the intracellular level of HIF-1α can reflect changes in the metabolism of peripheral blood lymphocytes after a COVID-19 infection.

MATERIAL AND METHODS: The sample consisted of 59 volunteers. Thirty eight of them had no history of COVID-19 while 21 reported having COVID-19 infection 2–8 months prior to the study. Serum concentrations of IgG antibodies to SARS-CoV-2 were assessed in both groups. Absolute content of lymphocytes was measured in whole blood, and the concentration of HIF-1α was determined in the lymphocyte lysate by enzyme immunoassay. All data were analyzed using IBM SPSS software (v. 26). Means and standard deviations were calculated for all numeric variables. Normality of the distributions were assessed using Kolmogorov–Smirnov test. Differences between the groups were studied by unpaired Student's t-tests. The differences at p <0.05 were considered statistically significant. Receiver operative characteristic curve was constructed to assess the prognostic value of HIF-1α.

RESULTS: Volunteers with a history of COVID-19 infection had significantly lower concentrations of HIF-1α in peripheral blood lymphocytes compared to their counterparts with no history of COVID-19. Intracellular concentration of HIF-1α was significantly associated with the likelihood of changes in lymphocyte metabolism. HIF-1α concentration of 1.25 ng/106 cells was the most optimal cut-off value.

CONCLUSION: The intracellular level of HIF-1α can serve as an indicator of the potential delayed impact of COVID-19 on the metabolic activity of peripheral lymphocytes. Our research findings hold significant value in monitoring and assessing metabolic alterations in individuals recovering from COVID-19.

About the authors

Olga V. Zubatkina

Laverov Federal Center for Integrated Arctic Research

Author for correspondence.
Email: ozbiochem@gmail.com
ORCID iD: 0000-0002-5039-2220
SPIN-code: 1581-5178

Dr. Sci. (Biol.), professor, senior research associate

Russian Federation, 249 Lomonosova avenue, 163000 Arhangel'sk

Lilia K. Dobrodeeva

Laverov Federal Center for Integrated Arctic Research

Email: dobrodeevalk@mail.ru
ORCID iD: 0000-0001-5080-6502
SPIN-code: 4518-6925

MD, Dr. Sci. (Med.), professor

Russian Federation, Arkhangelsk

Sergey D. Kruglov

Laverov Federal Center for Integrated Arctic Research

Email: stees67@yandex.ru
ORCID iD: 0000-0002-4085-409X
SPIN-code: 2532-9912
Russian Federation, Arkhangelsk

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2. Fig. 1. Intracellular concentration of HIF-1α (ng/106 cells) across subgroups by the time elapsed after COVID-19 infection and in the control group (M±SD): * differences are statistically significant between subgroup 1 and subgroup 2; ** differences are statistically significant between subgroup 1 and control group.

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3. Fig. 2. ROC curve for HIF-1α concentration.

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