Infected Syrian Hamsters Research Articles

Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection.

Since the emergence of SARS-CoV-2 and the COVID-19 pandemic, a wide range of treatment options have been evaluated in preclinical studies and clinical trials, with several being approved for use in humans. Immunomodulatory drugs have shown success in dampening the deleterious inflammatory response seen in severe COVID-19 patients, but there remains an urgent need for development of additional therapeutic options for COVID-19 treatment. A potential drug target is the CCR5-CCL5 axis, and blocking this pathway may protect against severe disease. Here we evaluated whether OB-002, an analog of human CCL5 and a potent antagonist of CCR5, provides therapeutic benefit in SARS-CoV-2 infected Syrian hamsters. Daily treatment with OB-002 altered immune gene transcription in the lungs, and reduced pathology following infection, but did not prevent weight loss or viral replication in the lungs of infected animals, even in combination with the antiviral drug remdesivir. Our data suggest that targeting the CCR5-CCL5 pathway in SARS-CoV-2 infection in hamsters is insufficient to significantly impact disease development in this model.

Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology

The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluate the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compare in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assess differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicate efficiently in the URT but display limited pathology in the lungs compared to previous variants and fail to replicate in human lung organoids. JN.1 is attenuated in both URT and LRT compared to other Omicron variants and fails to transmit in the male hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.

Wild Brazilian Yellow Fever Virus infection in Syrian hamsters (Mesocricetus auratus): Clinical and histopathological analyses

The Yellow Fever virus (YFV) wild-type strains studied until now have little or no ability to evade the Syrian hamster interferon antiviral response. Thus, evaluating the susceptibility of this model to new YFV isolates is paramount to aid in the understanding of their viscerotropic phenotype. To this end, Syrian hamsters were inoculated intraperitoneally with two Brazilian wild-type YFV isolates originated from dying or dead howler monkeys obtained during outbreaks in the states of Rio Grande do Sul in 2008 (PR4408) and Rio de Janeiro in 2019 (RJ155). The results were compared with a YFV experimental vaccine strain (17DDexp). The main findings observed for animals infected with the PR4408 strain were progressive weight loss and persistent viremia (at least up to day seven post-infection), associated with viral RNA detection in the liver, and hepatic, splenic, and pancreatic histological alterations consistent with YF. The infection was eliminated seven days post-infection in animals inoculated with the RJ155 strain. No changes were observed for animals infected with 17DDexp virus. The findings indicate that both Brazilian isolates are able to infect Syrian hamsters, resulting in histopathological changes compatible with the YF pathology observed in humans. Furthermore, the PR4408 strain exhibited increased virulence in this mammalian model, despite causing a non-fatal infection.

Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides.

Extracellular vesicles (EVs) released by virus-infected cells have the potential to encapsulate viral peptides, a characteristic that could facilitate vaccine development. Furthermore, plasma-derived EVs may elucidate pathological changes occurring in distal tissues during viral infections. We hypothesized that molecular characterization of EVs isolated from COVID-19 patients would reveal peptides suitable for vaccine development. Blood samples were collected from three cohorts: severe COVID-19 patients (G1), mild/asymptomatic cases (G2), and SARS-CoV-2-negative healthcare workers (G3). Samples were obtained at two time points: during the initial phase of the pandemic in early 2020 (m0) and eight months later (m8). Clinical data analysis revealed elevated inflammatory markers in G1. Notably, non-vaccinated individuals in G1 exhibited increased levels of neutralizing antibodies at m8, suggesting prolonged exposure to viral antigens. Proteomic profiling of EVs was performed using three distinct methods: immunocapture (targeting CD9), ganglioside-capture (utilizing Siglec-1) and size-exclusion chromatography (SEC). Contrary to our hypothesis, this analysis failed to identify viral peptides. These findings were subsequently validated through Western blot analysis targeting the RBD of the SARS-CoV-2 Spike protein's and comparative studies using samples from experimentally infected Syrian hamsters. Furthermore, analysis of the EV cargo revealed a diverse molecular profile, including components involved in the regulation of viral replication, systemic inflammation, antigen presentation, and stress responses. These findings underscore the potential significance of EVs in the pathogenesis and progression of COVID-19.

Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in SARS-CoV-2 and H1N1 influenza-induced acute lung injury.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown anti-inflammatory potential in multiple inflammatory diseases. In the March 2022 issue of the Journal of Extracellular Vesicles, it was shown that EVs from human MSCs can suppress severe acute respiratory distress syndrome, coronavirus 2 (SARS-CoV-2) replication and can mitigate the production and release of infectious virions. We therefore hypothesized that MSC-EVs have an anti-viral effect in SARS-CoV-2 infection in vivo. We extended this question to ask whether also other respiratory viral infections could be treated by MSC-EVs. Adipose stem cell-derived EVs (ASC-EVs) were isolated using tangential flow filtration from conditioned media obtained from a multi-flask cell culture system. The effects of the ASC-EVs were tested in Vero E6 cells in vitro. ASC-EVs were also given i.v. to SARS-CoV-2 infected Syrian Hamsters, and H1N1 influenza virus infected mice. The ASC-EVs attenuated SARS-CoV-2 virus replication in Vero E6 cells and reduced body weight and signs of lung injury in infected Syrian hamsters. Furthermore, ASC-EVs increased the survival rate of influenza A-infected mice and attenuated signs of lung injury. In summary, this study suggests that ASC-EVs can have beneficial therapeutic effects in models of virus-infection-associated acute lung injury and may potentially be developed to treat lung injury in humans.

The influence of exogenous and endogenous nitric oxide on the human and animal body

It has been shown that the inhalation of gaseous NO (exogenous nitric oxide) leads to the formation of nitrosonium cations (NO+) in the circulating blood of humans and animals during the oxidation of NO, which can have a detrimental effect on pathogenic viruses and bacteria. When thiols enter the blood simultaneously with NO inhalation, they form S-nitrosothiols with NO+ and cause hypotensive effect in animals. The biological effect of endogenous NO, which is produced in cells and tissues with the participation of NO synthases in animals and humans, is mediated by the dinitrosyl iron complexes (DNIC) formed with thiol-containing ligands. As NO and NO+ donors, these complexes have a variety of regulatory and cytotoxic effects on the animal and human body. In particular, the NO+ released by DNIC was shown to suppress SARS-CoV-2 infection in Syrian hamsters.

A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

Assessment of the therapeutic effect of the drug Molixan in the treatment of Syrian hamsters experimentally infected with the SARS-CoV-2 virus

Background. Studying the characteristics of the course of coronavirus infection caused by SARS-CoV-2 remains relevant due to the high mutagenicity of the virus and the prevalence of the disease in the world. The search for new drugs to eliminate clinical manifestations of COVID-19, as well as against its agent, is essential. During the pandemic caused by SARS-CoV-2, dexamethasone was recognized as the only effective anti-inflammatory drug for the treatment of patients with severe form of the disease, but its use leads to a large number of side effects.The aim. To study the therapeutic effect of the drug Molixan in the treatment of coronavirus infection in model animals – Syrian hamsters.Methods. To assess the effectiveness of the drug Molixan, we carried out a visual assessment of the condition of the lungs using light microscopy and the morphometry of the lung tissue of experimentally infected Syrian hamsters on the day 6 after infection under different Molixan treatment regimens and during dexamethasone therapy. The test drug was administered using three different doses (22.2 mg/kg, 44.4 mg/kg and 88.8 mg/kg, which are equivalent to doses of 3 mg/kg, 6 mg/kg and 12 mg/kg of human body weight) once daily or dividing the dose into two within 12 h interval in case of multiple (5 days) intramuscular administration. Dexamethasone (comparison drug) was administered at a dose of 20 mg/kg once daily for 5 days.Results. The studies showed statistically significant effectiveness of using Molixan at a dose of 44.4 mg/kg, divided into two doses, during 5 days. When compared with untreated hamsters, this treatment regimen reduces the degree of generalization and severity of the inflammatory process in the lungs; and the pathomorphological picture is similar to that observed during treatment with Dexamethasone.Conclusion. The studied drug Molixan is effective as an anti-inflammatory drug in the treatment of the disease caused by SARS-CoV-2.

Some Specific Biological Risks of SARS-CoV-2 Infected Syrian Hamsters at Animal Biosafety Level - Lab 3

The emergence of novel severe acute respiratory syndrome 2 (SARS-CoV-2) has prompted extensive research to identify its pathogenesis, transmission, and reservoir entry in animals. Syrian hamsters (Mesocricetus auratus) are being identified as an ideal animal model for the study of SARS-CoV-2 infection due to their susceptibility and respiratory symptoms similar to that observed in humans. This study focused on the specific biological risks associated with the use of infected Syrian hamsters in animal biosafety level 3 (ABSL-3) laboratories. The professional and psychological training of professionals working with laboratory animals should be a priority. Biological safety requires the involvement of all parties from technical staff to top management. The COVID-19 pandemic has shown a limitation in experimental studies when obtaining the right strain of mice proved difficult. A rare experimental model of Syrian hamsters started to be used in the work, which Syrian hamsters have several distinctive characteristics associated with increased aggressiveness of females, leading to a requirement to keep them isolated and some technical difficulties during manipulations in the biological safety cabinet. Therefore, a risk-based approach must be introduced to reduce the additional risks to workers to an acceptable level. This includes enhanced accuracy in the use of personal protective equipment (PPE), rigorously following biosecurity protocols, and monitoring staff health to detect potential risk of zoonotic transmission. The implementation of international standards and regulations on biological safety and biosecurity is of paramount importance.

Hepatic vascular changes associated with Opisthorchis felineus infection in Syrian hamsters and humans

The liver fluke Opisthorchis felineus is a foodborne zoonotic pathogen endemic to Russia, Kazakhstan, and several European countries. The adult flukes affect the hepatobiliary system of piscivorous mammals and humans, thereby causing numerous complications, including liver fibrosis. Detailing the mechanisms of progression of the fibrotic complications is a hot topic in the field of research on opisthorchiasis pathogenesis. Pathologic angiogenesis appears to be associated with the fibrogenic progression due to active participation in the recruitment of inflammatory cells and many factors involved in the modulation of the extracellular matrix. The aim of the study was to evaluate neoangiogenesis and amyloid deposits in liver tissues of model animals and patients with confirmed chronic opisthorchiasis. In addition, we assessed a possible correlation of neoangiogenesis with liver fibrosis. We found a significant increase in the number of newly formed vessels and amyloid deposits in the liver of people with chronic opisthorchiasis compared to that of uninfected ones. Thus, for the first time we have demonstrated neoangiogenesis and amyloid deposits during O. felineus infection in a Mesocricetus auratus model. Regression analysis showed that CD34+ newly formed vessels correlate with fibrosis severity in the course of the infection. Our results indicate the potential contribution of angiogenesis to the progression of liver fibrosis, associated with O. felineus infection.

Dinityrosyl Iron Complexes with Thiol-Containing Ligands as a Functionally Active “Working Form” of Nitric Oxide System in Living Organisms: A Review

Experimental data were summarized to assume that dinitrosyl iron complexes (DNICs) with thiol-containing ligands are an endogenous “working form” of the nitric oxide (NO) system in living organisms. DNICs can function as donors of both neutral NO molecules, which are responsible for positive regulatory effects of the NO system on various physiological and biochemical processes in humans and animals, and nitrosonium cations (NO+), which are responsible mostly for negative cytotoxic activity of the system. Special attention is paid to the finding that DNICs, especially in combination with dithiocarbamate derivatives, suppress SARS-CoV-2 infection in Syrian hamsters.

SARS-CoV-2 Spike Protein-Expressing Enterococcus for Oral Vaccination: Immunogenicity and Protection.

The declaration of the conclusion of the COVID-19 pandemic notwithstanding, coronavirus remains prevalent in circulation, and the potential emergence of novel variants of concern introduces the possibility of new outbreaks. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters.

Dinityrosyl Iron Complexes with Thiol-Containg Ligands as a Funcionally Active “Working Form” of Nitric Oxide System in Living Organisms

The experimental data are summarized which allow to suggest that dinitrosyl iron complexes (DNIC) with thiol-containing ligands can be considered as an endogenous “working form” of nitric oxide (NO) system in living organisms. The complexes can function as donors of both neutral NO molecules as well as nitrosonium cations (NO+) which exert respectively positive (regulatory) or negative (cytotoxic) effect on human and animal organisms. A special attention is paid to DNIC capacity to block (especially in combination with dithiocarbamate derivatives) coronavirus SARS-CoV-2 infection in Syrian hamsters.

Antiviral Nanobiologic Therapy Remodulates Innate Immune Responses to Highly Pathogenic Coronavirus.

Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR-MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR-MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR-MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7-dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re-modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS-CoV-2 and all tested variants.

Combination of the parent analogue of remdesivir (GS-441524) and molnupiravir results in a markedly potent antiviral effect in SARS-CoV-2 infected Syrian hamsters.

Remdesivir was the first antiviral drug to be approved for the treatment of severe COVID-19; followed by molnupiravir (another prodrug of a nucleoside analogue) and the protease inhibitor nirmatrelvir. Combination of antiviral drugs may result in improved potency and help to avoid or delay the development of resistant variants. We set out to explore the combined antiviral potency of GS-441524 (the parent nucleoside of remdesivir) and molnupiravir against SARS-CoV-2. In SARS-CoV-2 (BA.5) infected A549-Dual™ hACE2-TMPRSS2 cells, the combination resulted in an overall additive antiviral effect with a synergism at certain concentrations. Next, the combined effect was explored in Syrian hamsters infected with SARS-CoV-2 (Beta, B.1.351); treatment was started at the time of infection and continued twice daily for four consecutive days. At day 4 post-infection, GS-441524 (50mg/kg, oral BID) and molnupiravir (150mg/kg, oral BID) as monotherapy reduced infectious viral loads by 0.5 and 1.6 log10, respectively, compared to the vehicle control. When GS-441524 (50mg/kg, BID) and molnupiravir (150mg/kg, BID) were combined, infectious virus was no longer detectable in the lungs of 7 out of 10 of the treated hamsters (4.0 log10 reduction) and titers in the other animals were reduced by ∼2 log10. The combined antiviral activity of molnupiravir which acts by inducing lethal mutagenesis and GS-441524, which acts as a chain termination appears to be highly effective in reducing SARS-CoV-2 replication/infectivity. The unexpected potent antiviral effect of the combination warrants further exploration as a potential treatment for COVID-19.

Tissue replication and mucosal swab detection of Sosuga virus in Syrian hamsters in the absence of overt tissue pathology and clinical disease

Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. We demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues.

Biological characterization of cold-adapted SARS-CoV-2 variants

Introduction. The emergence of new epidemiologically significant variants of SARS-CoV-2 has shifted emphasis to development of a live vaccine, which would be able to provide protection against a wide range of antigenic variants of the virus. The aim of the study was to obtain SARS-CoV-2 variants attenuated through cold adaptation and to provide their biological characterization.Materials and methods. The Dubrovka laboratory strain of SARS-CoV-2 and its variants were cultured on Vero and Calu-3 cells. The virus quantification was performed by virus titration in Vero cells and by real-time reverse transcription-polymerase chain reaction. SARS-CoV-2 virions were analyzed using transmission electron microscopy. Genome sequences of the virus were identified by nanopore sequencing. The attenuation (att) phenotype of SARS-CoV-2 variants was identified using Syrian hamsters as an animal model for COVID-19. Results. Cold-adapted (ca) SARS-CoV-2 variants – Dubrovka-ca-B4 and Dubrovka-ca-D2 were produced by continued passaging of the Dubrovka strain in the Vero cell culture at the temperature being gradually decreased to 23ºC and by subsequent cloning. Up to 20 nucleotide substitutions and 18 amino acid substitutions were detected in genomes of ca-variants. Ca-variants, as distinct from the parent Dubrovka strain, actively replicated at 23ºC, while the Dubrovka-ca-D2 variant had a temperature-sensitive (ts) phenotype (did not replicate at 39ºC). Ca-variants of the virus replicated poorly at 37ºC in the Calu-3 human lung cell culture, which, along with the ts-phenotype, can be a marker of virus attenuation for humans. In the intranasally infected Syrian hamsters, ca-variants of the virus demonstrated an attenuation phenotype: they did not cause loss of appetite, fatigue, drowsiness, did not slow down weight gain, replicating much more slowly in the lungs and brain compared to the virulent Dubrovka strain. Conclusion. The obtained attenuated SARS-CoV-2 ca-variants, Dubrovka-ca-B4 and Dubrovka-ca-D2, should be studied further as candidate vaccine strains for a live attenuated vaccine against COVID-19.

SARS-CoV-2 Virus Culture, Genomic and Subgenomic RNA Load, and Rapid Antigen Test in Experimentally Infected Syrian Hamsters.

ABSTRACTThe duration of SARS-CoV-2 genomic RNA shedding is much longer than that of infectious SARS-CoV-2 in most COVID-19 patients. It is very important to determine the relationship between test results and infectivity for efficient isolation, contact tracing, and post-isolation. We characterized the duration of viable SARS-CoV-2, viral genomic and subgenomic RNA (gRNA and sgRNA), and rapid antigen test positivity in nasal washes, oropharyngeal swabs, and feces of experimentally infected Syrian hamsters. The duration of viral genomic RNA shedding is longer than that of viral subgenomic RNA, and far longer than those of rapid antigen test (RAgT) and viral culture positivity. The rapid antigen test results were strongly correlated with the viral culture results. The trend of subgenomic RNA is similar to that of genomic RNA, and furthermore, the subgenomic RNA load is highly correlated with the genomic RNA load.IMPORTANCE Our findings highlight the high correlation between rapid antigen test and virus culture results. The rapid antigen test would be an important supplement to real-time reverse transcription-RCR (RT-PCR) in early COVID-19 screening and in shortening the isolation period of COVID-19 patients. Because the subgenomic RNA load can be predicted from the genomic RNA load, measuring sgRNA does not add more benefit to determining infectivity than a threshold determined for gRNA based on viral culture.

SARS‐CoV‐2 infection impacts carbon metabolism and depends on glutamine for replication in Syrian hamster astrocytes

COVID‐19 causes more than million deaths worldwide. Although much is understood about the immunopathogenesis of the lung disease, a lot remains to be known on the neurological impact of COVID‐19. Here we evaluated immunometabolic changes using astrocytes in vitro and dissected brain areas of SARS‐CoV‐2 infected Syrian hamsters. We show that SARS‐CoV‐2 alters proteins of carbon metabolism, glycolysis, and synaptic transmission, many of which are altered in neurological diseases. Real‐time respirometry evidenced hyperactivation of glycolysis, further confirmed by metabolomics, with intense consumption of glucose, pyruvate, glutamine, and alpha ketoglutarate. Consistent with glutamine reduction, the blockade of glutaminolysis impaired viral replication and inflammatory response in vitro. SARS‐CoV‐2 was detected in vivo in hippocampus, cortex, and olfactory bulb of intranasally infected animals. Our data evidence an imbalance in important metabolic molecules and neurotransmitters in infected astrocytes. We suggest this may correlate with the neurological impairment observed during COVID‐19, as memory loss, confusion, and cognitive impairment.

Specific features of the pathology of the respiratory system in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus: Sarbecovirus) infected Syrian hamsters (Mesocricetus auratus)

Verification of histological changes in respiratory system using Syrian (golden) hamsters (Mesocricetus auratus) as experimental model is an important task for preclinical studies of drugs intended for prevention and treatment of the novel coronavirus infection COVID-19.The aim of this work was to study pathological changes of pulmonary tissue in SARS-CoV-2 (Coronaviridae: Coronavirinae: Betacoronavirus; Sarbecovirus) experimental infection in Syrian hamsters. Male Syrian hamsters weighting 80-100 g were infected by intranasal administration of culture SARS-CoV-2 at dose 4 × 104 TCID50/ml (TCID is tissue culture infectious dose). Animals were euthanatized on 3, 7 and 14 days after infection, with gravimetric registration. The viral load in lungs was measured using the polymerase chain reaction (PCR). Right lung and trachea tissues were stained with hematoxylin-eosin and according to Mallory. The highest viral replicative activity in lungs was determined 3 days after the infection. After 7 days, on a background of the decrease of the viral load in lungs, a pathologically significant increase of the organ's gravimetric parameters was observed. Within 3 to 14 days post-infection, the lung histologic pattern had been showing the development of inflammation with a succession of infiltrative-proliferative, edematousmacrophagal and fibroblastic changes. It was found that initial changes in respiratory epithelium can proceed without paranecrotic interstitial inflammation, while in the formation of multiple lung parenchyma lesions, damage to the epithelium of bronchioles and acinar ducts can be secondary. The appearance of epithelioid large-cell metaplastic epithelium, forming pseudoacinar structures, was noted as a pathomorphological feature specific to SARS-CoV-2 infection in Syrian hamsters. As a result of the study, the specific features of the pathology of the respiratory system in SARSCoV-2 infected Syrian hamsters were described. These findings are of practical importance as reference data that can be used for preclinical studies to assess the effectiveness of vaccines and potential drugs.