Investigating the relationship between lymphocyte cells apoptosis and DNA damage and oxidative stress and therapeutic and clinical outcomes of COVID-19 elderly patients

Abstract

Background: While COVID-19 has been controlled and deaths have decreased, the long-term consequences of COVID-19 remain a challenge we face today. This study was conducted to determine the relationship between the apoptosis of lymphocyte cells with DNA damage and oxidative stress and the therapeutic and clinical outcomes of elderly patients with COVID-19.

Methods: This study was conducted from April 2020 to May 2021 (the period of severe attacks of the epidemic peak of COVID-19) and September 2022 (the post-COVID-19 period). The study groups included elderly patients with COVID-19 hospitalized in the ICU and normal wards of the hospital as well as elderly patients with influenza. A polymerase chain reaction was used to check the validity of the studied diseases. The Annexin V/Propidium Iodide method was used to evaluate the level of apoptosis. Genotoxic effects and DNA damage were assessed by the comet assay method. Total antioxidant status (TAS), total oxidant status (TOS), and myeloperoxidase activity (MPO) were measured by photometric methods.

Results: The highest level of apoptosis in peripheral blood lymphocytes and the highest level of DNA damage were observed at both times in the intubated-ICU and non-intubated-ICU groups. In all groups, there was a significant increase in peripheral blood lymphocyte apoptosis levels and DNA damage levels compared to the healthy control group (p < 0.01). The level of apoptosis and DNA damage decreased significantly in the post-COVID-19 period (p < 0.01). In the investigation of oxidative stress biomarkers, the oxidative stress index, including TOS and MPO levels, increased in patients (p < 0.01), and the TAS level decreased (p < 0.01).

Conclusion: It shows that the apoptosis of lymphocyte cells, DNA damage, and oxidative stress can be effective in prognostic decisions and is a suitable predictor for diagnosing the condition of patients with viral infections such as COVID-19 and influenza.

Keywords: Apoptosis; COVID‐19; DNA damage; Flow cytometry; Influenza virus; Lymphocyte; Lymphopenia; MPO; Pandemic; TAS; TOS.

Fig. 1

A Average of the comet assay indices in the COVID-19 and influenza groups (*P-value < 0.01). B Schematic figure of DNA damage obtained by the comet assay technique

Fig. 2

Comparison of apoptosis in elderly patients with COVID-19 in 2020: significant difference in different flow cytometry levels of apoptosis in the 2 control groups and the intubated groups (p < 0.01). Analysis of apoptosis levels in peripheral blood mononuclear cells (PBMC) from controls and all elderly patients hospitalized with COVID-19 in non-intubated ICU and intubated ICU and non-ICU departments

Fig. 3

Col: one-way ANOVA. The mean apoptosis cell percentage obtained from all elderly patients with COVID-19 and elderly controls in 2020 and 2022 is shown. This comparison was done in 3 stages of the flow cytometry technique, including A early apoptosis, B late apoptosis, and C necrosis, and showed that the apoptosis cell percentage increases with the progress of the disease. Differences between mild and severe cases are by * indicating significance (p < 0.01)

Fig. 4

Col: one-way ANOVA. The average percentage of oxidative damage found in all aged COVID-19 patients, elderly controls, and influenza patients in 2020 and 2022 is displayed. Three oxidative stress biomarkers were compared: A total oxidant status (TOS), B myeloperoxidase (MPO), and C total antioxidant status (TAS). Significant differences (p < 0.01) between mild and severe cases are indicated by an asterisk (*)