Comparative study of Wuhan-like and omicron-like variants of SARS-CoV-2 in experimental animal models

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Abstract

Introduction. The variability of SARS-CoV-2 appeared to be higher than expected, the emergence of new variants raises concerns.

The aim of the work was to compare the pathogenicity of the Wuhan and BA.1.1/Omicron variants in BALB/c mice and Syrian hamsters.

Materials and methods. The study used strains of SARS-CoV-2: Dubrovka phylogenetically close to Wuhan-Hu-1, and LIA phylogenetically close to Omicron, BALB/c mice, transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/HEMI Hemizygous for Tg(K18-ACE2)2Prlmn, Syrian golden hamsters. Animals were infected intranasally, pathogenicity was estimated by a complex of clinical, pathomorphological and virological methods.

Results. Comparative studies of SARS-CoV-2 Dubrovka and LIA strains on animal models demonstrated their heterogeneous pathogenicity. In parallel infection of BALB/c mice with Dubrovka and LIA variants, the infection proceeded without serious clinical signs and lung damage. Infection with the LIA strain resulted to a systemic disease with a high concentration of viral RNA in the lungs and brain tissues of animals. The presence of viral RNA in mice infected with the Dubrovka strain was transient and undetectable in the lungs by day 7 post-infection. Unlike the mouse model, in hamsters, the Dubrovka strain had a greater pathogenicity than the LIA strain. In hamsters infected with the Dubrovka strain lung lesions were more significant, and the virus spread through organs, in particular in brain tissue, was observed. In hamsters infected with the LIA strain virus was not detected in brain tissue.

Conclusion. The study of various variants of SARS-CoV-2 in species initially unsusceptible to SARS-CoV-2 infection is important for monitoring zoonotic reservoirs that increase the risk of spread of new variants in humans.

About the authors

Irina A. Leneva

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Author for correspondence.
Email: wnyfd385@yandex.ru
ORCID iD: 0000-0002-7755-2714

PhD (Bio.), head of Laboratory of Experimental Virology

Russian Federation, 105064, Moscow

Daria I. Smirnova

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: daria.sm.1995@mail.ru
ORCID iD: 0000-0001-7325-0834

junior researcher, Laboratory of Molecular Virology

Russian Federation, 105064, Moscow

Nadezhda P. Kartashova

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: nadezdakartasova10571@gmail.com
ORCID iD: 0000-0003-2096-5080

researcher, Laboratory of Experimental Virology

Russian Federation, 105064, Moscow

Anastasiia V. Gracheva

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: anastasiia.gracheva.95@mail.ru
ORCID iD: 0000-0001-8428-4482

junior researcher, Laboratory of Molecular Virology

Russian Federation, 105064, Moscow

Anna V. Ivanina

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: ivanina.anna97@mail.ru
ORCID iD: 0000-0002-7289-693X

research laboratory assistant, Laboratory of Experimental Virology

Russian Federation, 105064, Moscow

Ekaterina A. Glubokova

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: eaglubokova@yandex.ru
ORCID iD: 0000-0002-5925-9733

junior researcher, Laboratory of Experimental Virology

Russian Federation, 105064, Moscow

Ekaterina R. Korchevaya

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: c.korchevaya@gmail.com
ORCID iD: 0000-0002-6417-3301

junior researcher, Laboratory of Molecular Virology

Russian Federation, 105064, Moscow

Andrey A. Pancratov

Herzen Moscow Research Institute of Oncology of the Ministry of Health of Russia

Email: andreimnioi@yandex.ru
ORCID iD: 0000-0001-7291-9743

PhD, Head of the Department of Experimental Pharmacology and Toxicology

Russian Federation, 125284, Moscow

Galina V. Trunova

Herzen Moscow Research Institute of Oncology of the Ministry of Health of Russia

Email: gtrunovamnioi@mail.ru
ORCID iD: 0000-0003-2917-4496

PhD, senior researcher of the Department of Experimental Pharmacology and Toxicology

Russian Federation, 125284, Moscow

Varvara A. Khokhlova

Herzen Moscow Research Institute of Oncology of the Ministry of Health of Russia

Email: nostocus@yandex.ru
ORCID iD: 0000-0002-0339-2068

junior researcher of the Department of Experimental Pharmacology and Toxicology

Russian Federation, 125284, Moscow

Oksana A. Svitich

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: svitichoa@yandex.ru
ORCID iD: 0000-0003-1757-8389

D. Sci. (Med.), Prof., Corresponding Member of RAS, Head, Laboratory of molecular immunology, Director

Russian Federation, 105064, Moscow

Vitaly V. Zverev

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: vitalyzverev@outlook.com
ORCID iD: 0000-0001-5808-2246

D. Sci. (Biol.), Prof., Academician of RAS, Head, Laboratory of molecular biotechnology

Russian Federation, 105064, Moscow

Evgeny B. Faizuloev

Mechnikov Research Institute of Vaccines and Sera, Department of Virology

Email: faizuloev@mail.ru
ORCID iD: 0000-0001-7385-5083

PhD (Biol.), Head of Molecular Virology Laboratory

Russian Federation, 105064, Moscow

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2. Fig. 1. Parameters of BALB/c and K18-hACE2 mice infected with Dubrovka and LIA strains: а – the body weight (the line shows the weight value M ± SD); b – survival rate; c – average values of SARS-CoV-2 RNA concentrations in tissues of various organs of BALB/c mice infected with Dubrovka and LIA strains; d – viral titer (lg TCID50/ml) and the concentration of viral RNA (lg copies of RNA/ml) of SARS-CoV-2 Dubrovka strain in the lungs of K18-hACE2 mice on days 4 and 7 days post-infection.

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3. Fig. 2. Morphological characteristics of the lungs of mock-infected BALB/c (a, b) mice and infected with the Dubrovka strain (Wuhan-like) (c, d): a – the bronchial lumen are free, the organ parenchyma looks airy; b – the alveolar lumen is uniformly airy, the interalveolar septa are thin, the vessels and capillaries with moderately hyperemia; c – the histostructure of the lung corresponds to the variant of the norm; d – a small lymphoid accumulation (bronchoassociated lymphoid tissue) in the area of contact between the bronchus and the blood vessel. Magnifcation: a, c – 40 ×; b – 400 ×; d – 200 ×. Staining: hematoxylin and eosin.

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4. Fig. 3. Indicators of golden Syrian hamsters infected with Dubrovka and LIA strains: a – body weight (the line shows the weight value M ± SD); b – average values of SARS-CoV-2 RNA concentrations in tissues of various organs.

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5. Fig. 4. Alterative and inflammatory changes in the lungs of Syrian hamsters on day 4 post-infection with SARS-CoV-2 strain Dubrovka (Wuhan): a – focies of viral pneumonia; b – peribronchial airless focus of pneumonia: bronchial lumen is free; epithelial lining is preserved, weak inflammatory infiltration of the bronchial wall; in the adjacent parenchyma, the interalveolar septa are destroyed due to inflammatory infiltration, edema and death of the respiratory epithelium; с – section of the lung parenchyma with reduced airiness: pronounced perivascular edema, slit-like lumen of the alveoli, in them – exudate fluid, desquamated epithelium, macrophages, erythrocytes, lymphocytes; d – section of the lung parenchyma with reduced airiness: intraalveolar swelling, intraalveolar hemorrhages, thickened interalveolar septa due to lymphohistiocytic infiltration and interstitial swelling, hyperemia of capillaries. Magnifcation: a – 40 ×; с – 200 ×; b, d – 200 ×. Staining: hematoxylin and eosin.

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Copyright (c) 2022 Leneva I.A., Smirnova D.I., Kartashova N.P., Gracheva A.V., Ivanina A.V., Glubokova E.A., Korchevaya E.R., Pancratov A.A., Trunova G.V., Khokhlova V.A., Svitich O.A., Zverev V.V., Faizuloev E.B.

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