Labilization of the DNA structure in peripheral blood lymphocytes of COVID-19 patients

Introduction. Available data indicate the SARS-CoV-2 coronavirus to be potent of impairing DNA repair processes and cause oxidative stress, which can lead to the accumulation of DNA damage in human cells. However, the DNA-damaging effect of the virus has not yet been sufficiently studied.

The purpose of the research was to study the ability of SARS-CoV-2 to cause DNA damage in human peripheral blood lymphocytes.

Materials and methods. One hundred forty COVID-19 patients and 24 donors of the control group are included in the study. The level of DNA fragmentation in lymphocytes was determined by alkaline DNA-comet assay. Statistical differences between the mean medians of the «%DNA in the comet tail» (tail DNA%) were assessed using Student’s t-test. The Jeffers test was used to compare the proportions of cells with different levels of DNA-damage. Statistical differences between groups were assessed using the Mann-Whitney test.

Results. In the COVID-19 patients, an increase in the level of breaks and alkali-labile sites in DNA was revealed when compared to controls (p = 0.025).
In the group of patients infected with SARS-CoV-2, the proportion of comets with DNA damage of up to 5% decreased (p = 0.009), while the proportion of comets containing more than 10% DNA tail increased (p = 0.000). The number of atypical comets compared to the control increased by 3.7 and 5.9 times with mild and moderate severity of the disease, respectively (r = 0.993; p = 0.001). In the association with diseases — coronary heart disease (CHD) and diabetes mellitus type II (DM type 2), the level of DNA fragmentation in lymphocytes statistically significantly increased compared to the group of patients without these diseases.

Limitations. A limitation is the lack of data on DNA-structure damage in severe COVID-19 disease.

Conclusion. SARS-CoV-2 infection leads to labilization of the DNA structure in human peripheral blood lymphocytes. The level of DNA damage depends on the severity of COVID-19 and the presence of comorbid diseases: CHD and DM type 2. The results of the study are important for understanding the mechanisms of action of the virus on human immunocompetent cells.

Compliance with ethical standards. The study was conducted in accordance with the ethical standard of the World Medical Association Declaration of Helsinki “Ethical Principles for Medical Research Involving Human Subjects” as amended in 2000. The study was approved by the local ethics committee (protocol No. 8 of September 29, 2022). All donors gave informed consents to participate in the study.

Contribution:
Popova A.Yu., Kuzmin S.V. — concept of the study;
Ilyushina N.A. — concept of the study, collection of material, data processing, writing text;
Gorenskaya O.V. — laboratory research, statistical processing, text writing;
Egorova O.V. — laboratory research, text writing;
Kotnova A.P. — laboratory research, data processing;
Averianova N.S. — laboratory research;
Ignatyev S.D. — statistical processing;
Kuznetsova N.E., Kobelevskaya N.V. — collection of material.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: December 15, 2023 / Accepted: April 9/ Published: May 8, 2024