Clinical Physiology of Circulation

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery

Association between functional variants of the genes involved into immune response and vascular regulation, and severity of SARS-CoV-2 pneumonia

Authors: Titova O.N., Kuzubova N.A., Volchkova E.V., Chukhlovin A.B., Barkhatov I.M., Alexandrovich Y.S., Bug D.S., Aleksandrov A.L.

1 ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Минздрава России, Санкт-Петербург, Российская Федерация

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UDC: 616.1:616.24-002-06]+616.98

Link: Clinical Physiology of Blood Circulaiton. 2022; 4 (19): 372-382

Quote as: Titova O.N., Kuzubova N.A., Volchkova E.V., Chukhlovin A.B., Barkhatov I.M., Alexandrovich Y.S., Bug D.S., Aleksandrov A.L. Association between functional variants of the genes involved into immune response and vascular regulation, and severity of SARS-CoV-2 pneumonia. Clinical Physiology of Circulation. 2022; 19 (4): 372–82 (in Russ.). DOI: 10.24022/1814-6910-2022-19-4-372-382

Received / Accepted:  28.11.2022 / 16.12.2022

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АIntroduction. Susceptibility to COVID-19 and the severity of clinical manifestations depend both on the pathogenic properties of SARS-CoV-2, and on the patient's age, physical condition. Moreover, some gene variants have been found that affect severity and outcome of COVID-19.

Objective. The aim of our work was to evaluate genetic associations between a number of gene variants previously identified during the COVID-19 pandemic, and clinical parameters of viral infection in the patients admitted to specialized pulmonological department.

Material and methods. We examined 181 patients aged 20 to 85 years with verified SARS-CoV-2 infection. Inflammation markers included quantitative assays of C-reactive protein, interleukin-6, fibrin D-dimer, fibrinogen, and ferritin in blood samples. The disease severity was determined by complex assessment of clinical and laboratory parameters. 113 patients (63%) had a severe course, 67 (37%) had an average severity of the disease. 97 patients (53.6%) were referred for treatment to the intensive care unit. Mortality rate in the entire cohort was 37%. Genotyping of DNA from blood leukocytes was performed using allele-specific PCR assays. Allelic variants of the following genes were genotyped: OAS1 (rs10774671); ACE1 (rs 4343); VEGF (rs3025039); TLR3 (rs3775291); IL-6 (rs1800795); IL-10 (rs1800896); triallelic polymorphism of the ApoE gene (rs429358/rs7412). The results were evaluated using the methods of parametric and nonparametric statistics (STATISTICA 5.0).

Results. In the primary correlation analysis, we found significant correlations between the 7 gene variants, and disease severity for only 3 allelotypes, i.e., OAS1, VEGF, and ApoE2/3/4. At the same time, harboring G allele of the OAS1 gene (including heterozygous AG genotype) was more common in the patients requiring intensive care, as well as in fatal outcomes of the disease. Assessment of the VEGF genotype frequencies showed that the CC genotype is associated with lower incidence of severe clinical forms. The less common TT genotype was not detected in the group of surviving patients (0/84). Among the deceased patients, its frequency was 10% (5/67, p = 0.003. The ApoE 3/3 genotype was somewhat less common in the group of patients with severe disease (p = 0.05). A significant correlation was noted between the GC genotype of the IL-6 gene (rs1800795) and the levels of IL-6 in blood at the peak of disease.

Conclusion. The data obtained allow us to recommend further studies of OAS1 (rs10774671) and VEGF (rs3025039) as candidate markers of the clinical course and outcome of COVID-19.


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About Authors

  • Olga N. Titova, Dr. Med. Sci., Professor, Director of Pulmonology Research Institute; ORCID
  • Natalia A. Kuzubova, Dr. Med. Sci., Deputy Director of Pulmonology Research Institute; ORCID
  • Elizaveta V. Volchkova, Postgraduate, Anesthesiologist-resuscitator; ORCID
  • Alexey B. Chukhlovin, Dr. Med. Sci., Professor, Head of Laboratory of Transplantology; ORCID
  • Ildar M. Barkhatov, Dr. Med. Sci., Professor, Leading Researcher; ORCID
  • Yury S. Аlexandrovich, Dr. Med. Sci., Professor, Head of the Department of Anesthesiology, Reanimatology and Emergency Pediatrics; ORCID
  • Dmitry S. Bug, Physician of Clinical Diagnostics Laboratory; ORCID
  • Albert L. Aleksandrov, Dr. Med. Sci., Professor, Head of the Department of Clinical and Experimental Pathology of the Respiratory System; ORCID

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