Apoptosis and pyroptosis in the nasal mucosa of Syrian hamster during SARS-CoV-2 infection and reinfection.

In SARS-CoV-2 infection, it has been observed that viral replication lasts longer in the nasal mucosa than in the lungs, despite the presence of a high viral load at both sites. In hamsters, we found that the nasal mucosa exhibited a mild inflammatory response and minimal pathological injuries, whereas the lungs displayed a significant inflammatory response and severe injuries. The underlying cellular events may be induced by viral infection in three types of cell death: apoptosis, pyroptosis, and necroptosis. Our findings indicate that apoptosis was consistently activated during infection in the nasal mucosa, and the levels of apoptosis were consistent with the viral load. On the other hand, pyroptosis and a few instances of necroptosis were observed only on 7 dpi in the nasal mucosa. In the lungs, however, both pyroptosis and apoptosis were prominently activated on 3 dpi, with lower levels of apoptosis compared to the nasal mucosa. Interestingly, in reinfection, obvious viral load and apoptosis in the nasal mucosa were detected on 3 dpi, while no other forms of cell death were detected. We noted that the inflammatory reactions and pathological injuries in the nasal mucosa were milder, indicating that apoptosis may play a role in promoting lower inflammatory reactions and milder pathological injuries and contribute to the generation of long-term viral replication in the nasal mucosa. Our study provides valuable insights into the differences in cellular mechanisms during SARS-CoV-2 infection and highlights the potential significance of apoptosis regulation in the respiratory mucosa for controlling viral replication.

Advanced glycation end product-modified low-density lipoprotein promotes pro-osteogenic reprogramming via RAGE/NF-κB pathway and exaggerates aortic valve calcification in hamsters.

BACKGROUND: Advanced glycation end product-modified low-density lipoprotein (AGE-LDL) is related to inflammation and the development of atherosclerosis. Additionally, it has been demonstrated that receptor for advanced glycation end products (RAGE) has a role in the condition known as calcific aortic valve disease (CAVD). Here, we hypothesized that the AGE-LDL/RAGE axis could also be involved in the pathophysiological mechanism of CAVD. METHODS: Human aortic valve interstitial cells (HAVICs) were stimulated with AGE-LDL following pre-treatment with or without interleukin 37 (IL-37). Low-density lipoprotein receptor deletion (Ldlr-/-) hamsters were randomly allocated to chow diet (CD) group and high carbohydrate and high fat diet (HCHFD) group. RESULTS: AGE-LDL levels were significantly elevated in patients with CAVD and in a hamster model of aortic valve calcification. Our in vitro data further demonstrated that AGE-LDL augmented the expression of intercellular cell adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and alkaline phosphatase (ALP) in a dose-dependent manner through NF-κB activation, which was attenuated by nuclear factor kappa-B (NF-κB) inhibitor Bay11-7082. The expression of RAGE was augmented in calcified aortic valves, and knockdown of RAGE in HAVICs attenuated the AGE-LDL-induced inflammatory and osteogenic responses as well as NF-κB activation. IL-37 suppressed inflammatory and osteogenic responses and NF-κB activation in HAVICs. The vivo experiment also demonstrate that supplementation with IL-37 inhibited valvular inflammatory response and thereby suppressed valvular osteogenic activities. CONCLUSIONS: AGE-LDL promoted inflammatory responses and osteogenic differentiation through RAGE/NF-κB pathway in vitro and aortic valve lesions in vivo. IL-37 suppressed the AGE-LDL-induced inflammatory and osteogenic responses in vitro and attenuated aortic valve lesions in a hamster model of CAVD.

Expression of the SARS-CoV-2 receptor-binding domain by live attenuated influenza vaccine virus as a strategy for designing a bivalent vaccine against COVID-19 and influenza.

Influenza and SARS-CoV-2 are two major respiratory pathogens that cocirculate in humans and cause serious illness with the potential to exacerbate disease in the event of co-infection. To develop a bivalent vaccine, capable of protecting against both infections, we inserted the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein into hemagglutinin (HA) molecule or into the open reading frame of the truncated nonstructural protein 1 (NS1) of live attenuated influenza vaccine (LAIV) virus and assessed phenotypic characteristics of the rescued LAIV-RBD viruses, as well as their immunogenicity in mouse and Syrian hamster animal models. A panel of 9 recombinant LAIV-RBD viruses was rescued using the A/Leningrad/17 backbone. Notably, only two variants with RBD insertions into the HA molecule could express sufficient quantities of RBD protein in infected MDCK cells. Intranasal immunization of mice induced high levels of anti-influenza antibody responses in all chimeric LAIV-RBD viruses, which was comparable to the LAIV virus vector. The RBD-specific antibody responses were most pronounced in the variant expressing RBD194 fragment as a chimeric HA protein. This candidate was further tested in Syrian hamsters and was shown to be immunogenic and capable of protecting animals against both infections.

Comparative analysis of optional hunting behavior in Cricetinae hamsters using the data compression approach.

Research into the hunting behavior in members of the Cricetidae family offers an opportunity to reveal what changes in the predatory behavioral sequences occur when a rodent species shifts from an omnivorous to a predatory lifestyle. The study tests the following hypotheses: are there phylogenetic differences in the divergence of species' predatory lifestyles in hamsters or do ecological factors lead to shaping their hunting behavior? We applied the data compression approach for performing comparative analysis of hunting patterns as biological "texts." The study presents a comparative analysis of hunting behaviors in five Cricetinae species, focusing on the new data obtained for the desert hamster Phodopus roborovskii whose behavior has never been studied before. The hunting behavior of P. roborovskii appeared to be the most variable one. In contrast, behavioral sequences in P. campbelli and Allocricetulus curtatus display more significant order and predictability of behavior during hunting. Optional hunting behavior in the most ancient species P. roborovskii displayed similarities with obligate patterns in "young" Allocricetulus species. It thus turned out to be the most advanced hunter among members of the Phodopus genus. Differences in hunting sequences among Phodopus representatives suggest that the hunting behavior of these species, despite its optional mode, was subject to selection during species splitting within the genus. These results did not reveal the role played by phylogenetic differences in the divergence of species' predatory lifestyles. They suggested that ecological conditions are the main factors in speciation of the hunting behavior in hamsters.

Fat accumulation in striped hamsters (Cricetulus barabensis) reflects the temperature of prior cold acclimation.

BACKGROUND: Proper adjustments of metabolic thermogenesis play an important role in thermoregulation in endotherm to cope with cold and/or warm ambient temperatures, however its roles in energy balance and fat accumulation remain uncertain. Our study aimed to investigate the effect of previous cold exposure (10 and 0 °C) on the energy budgets and fat accumulation in the striped hamsters (Cricetulus barabensis) in response to warm acclimation. The body mass, energy intake, resting metabolic rate (RMR) and nonshivering thermogenesis (NST), serum thyroid hormone levels (THs: T3 and T4), and the activity of brown adipose tissue (BAT), indicated by cytochrome c oxidase (COX) activity and uncoupling protein 1 (ucp1) expression, were measured following exposure to the cold (10 °C and 0 °C) and transition to the warm temperature (30 °C). RESULTS: The hamsters at 10 °C and 0 °C showed significant increases in energy intake, RMR and NST, and a considerable reduction in body fat than their counterparts kept at 21 °C. After being transferred from cold to warm temperature, the hamsters consumed less food, and decreased RMR and NST, but they significantly increased body fat content. Interestingly, the hamsters that were previously exposed to the colder temperature showed significantly more fat accumulation after transition to the warm. Serum T3 levels, BAT COX activity and ucp1 mRNA expression were significantly increased following cold exposure, and were considerably decreased after transition to the warm. Furthermore, body fat content was negatively correlated with serum T3 levels, BAT COX activity and UCP1 expression. CONCLUSION: The data suggest that the positive energy balance resulting from the decreased RMR and NST in BAT under the transition from the cold to the warm plays important roles in inducing fat accumulation. The extent of fat accumulation in the warm appears to reflect the temperature of the previous cold acclimation.

Understanding hypergammaglobulinemia in experimental or natural visceral leishmaniasis.

Nonspecific hypergammaglobulinemia (HGG) occurs in symptomatic human visceral leishmaniasis (VL) caused by L. L. infantum. This study assessed this finding in experimental infection in hamsters and natural infection in dogs. The serum concentration of proteins, albumin and globulins was determined through the biuret and bromocresol green reaction, where the HGG was better expressed through the albumin/globulin (A/G) ratio. HGG was associated with a higher concentration of specific anti-glycan antibodies (BSA-G)/promastigote soluble extract (PSE) and the presence of circulating immune complexes (IC) by dissociative enzyme-linked immunoassay (ELISA). The study found monovalent IC in 37.9% (PSE) and 50% (BSA-G) of sera from infected hamsters, with increased frequency as the disease progressed. HGG was found in >60% of the samples in dogs with VL, associated with higher levels of specific immunoglobulin (Ig)A and IgM, but not IgG, determined using the PSE and BSA-G ELISA. HGG was associated with the presence of monovalent IC in 58.9% (PSE) and 63.4% (BSA-G) positive dog samples. HGG may result not only from the nonspecific activation of B cells, with greater production of specific and nonspecific antibodies, but also due to lower IgG excretion due to the presence of soluble monovalent IC. HGG correlates to the progression of VL and may be a marker for manifested disease.

Characterization of a new SARS-CoV-2 variant that emerged in Brazil.

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.

The Abundant Distribution and Duplication of SARS-CoV-2 in the Cerebrum and Lungs Promote a High Mortality Rate in Transgenic hACE2-C57 Mice.

Patients with COVID-19 have been reported to experience neurological complications, although the main cause of death in these patients was determined to be lung damage. Notably, SARS-CoV-2-induced pathological injuries in brains with a viral presence were also found in all fatal animal cases. Thus, an appropriate animal model that mimics severe infections in the lungs and brain needs to be developed. In this paper, we compared SARS-CoV-2 infection dynamics and pathological injuries between C57BL/6Smoc-Ace2em3(hACE2-flag-Wpre-pA)Smoc transgenic hACE2-C57 mice and Syrian hamsters. Importantly, the greatest viral distribution in mice occurred in the cerebral cortex neuron area, where pathological injuries and cell death were observed. In contrast, in hamsters, viral replication and distribution occurred mainly in the lungs but not in the cerebrum, although obvious ACE2 expression was validated in the cerebrum. Consistent with the spread of the virus, significant increases in IL-1ß and IFN-γ were observed in the lungs of both animals. However, in hACE2-C57 mice, the cerebrum showed noticeable increases in IL-1ß but only mild increases in IFN-γ. Notably, our findings revealed that both the cerebrum and the lungs were prominent infection sites in hACE2 mice infected with SARS-CoV-2 with obvious pathological damage. Furthermore, hamsters exhibited severe interstitial pneumonia from 3 dpi to 5 dpi, followed by gradual recovery. Conversely, all the hACE2-C57 mice experienced severe pathological injuries in the cerebrum and lungs, leading to mortality before 5 dpi. According to these results, transgenic hACE2-C57 mice may be valuable for studying SARS-CoV-2 pathogenesis and clearance in the cerebrum. Additionally, a hamster model could serve as a crucial resource for exploring the mechanisms of recovery from infection at different dosage levels.

Reduced Pathogenicity and Transmission Potential of Omicron BA.1 and BA.2 Sublineages Compared with the Early Severe Acute Respiratory Syndrome Coronavirus 2 D614G Variant in Syrian Hamsters.

BACKGROUND: The epidemiological advantage of Omicron variant is evidenced by its rapid spread and the ability to outcompete prior variants. Among Omicron sublineages, early outbreaks were dominated by BA.1, while BA.2 has gained dominance since February 2022. The relative pathogenicity and transmissibility of BA.1 and BA.2 have not been fully defined. METHODS: We compared viral loads and clinical signs in Syrian hamsters after infection with BA.1, BA.2, or D614G variant. A competitive transmission model and next-generation sequencing were used to compare the relative transmission potential of BA.1 and BA.2. RESULTS: BA.1 and BA.2 caused no apparent clinical signs, while D614G caused more than 10% weight loss. Higher viral loads were detected in nasal wash samples and nasal turbinate and lung tissues from BA.1-inoculated hamsters compared with BA.2-inoculated hamsters. No aerosol transmission was observed for BA.1 or BA.2 under the experimental condition in which D614G transmitted efficiently. BA.1 and BA.2 were able to transmit among hamsters via direct contact; however, BA.1 transmitted more efficiently than BA.2 under the competitive transmission model. No recombination was detected from direct contacts exposed simultaneously to BA.1 and BA.2. CONCLUSIONS: Omicron BA.1 and BA.2 demonstrated attenuated pathogenicity and reduced transmission potential in hamsters compared with early SARS-CoV-2 strains.

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

The 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.

Transmission of HCoV-OC43 to pet hamsters.

Coronaviruses (CoVs) are a significant group of pathogens that pose a serious threat to both human and animal health, with some being zoonotic and displaying frequent cross-species transmission. Human CoV-OC43 (HCoV-OC43) is one of the four common human CoVs that can cause seasonal mild to moderate respiratory diseases in humans. In this study, we identified HCoV-OC43 for the first time in two asymptomatic pet hamsters, which share a high similarity with the human-derived HCoV-OC43 strain, suggesting potential cross-species transmission of HCoV-OC43 to pet hamsters. The finding emphasizes the need to strengthen pathogen monitoring of livestock and pets in close contact with humans to provide early warning of public safety.

Liposomal Phytosterols as LDL-Cholesterol-Lowering Agents in Diet-Induced Hyperlipidemia.

The high blood level of low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for cardiovascular disease. Plant sterols, known as phytosterols (PSs), can reduce LDL-C in a range of 8-14%. The extent of LDL-C reduction depends on its formulation. Encapsulation into liposomes is one formulation strategy to enhance the efficiency of PSs. PSs (campesterol, stigmasterol, and ß-sitosterol) have frequently been assessed alone or in combination for their LDL-C-lowering ability. However, one naturally abundant PS, brassicasterol, has not yet been tested for its efficacy. We have previously developed a novel liposomal formulation containing the PS mixture present naturally in canola that is composed of brassicasterol, campesterol, and ß-sitosterol. In this work, the efficacy of our novel liposomal PS formulation that includes brassicasterol was assessed in a hamster model. Animals were divided into five groups: (i) liposomal PS in orange juice, (ii) liposomal PS in water, (iii) marketed PS in orange juice, (iv) control orange juice, and (v) control water. The animals were fed a high-fat, cholesterol-supplemented (0.5%) diet to induce hypercholesterolemia. The treatment was administered orally once daily for 4 weeks. Fasting blood samples were collected at baseline, week 2, and week 4. The extent of the reduction of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides was compared among the groups. Liposomal PSs in both orange juice and water significantly reduced LDL-C compared to their controls. Furthermore, the liposomal PS was as effective as a marketed PS-containing product in reducing LDL-C. Liposomal PSs in both orange juice and water showed similar efficacy in LDL-C reduction, highlighting that these vehicles/food matrices do not affect the efficacy of PSs. The liposomal formulation of a natural PS mixture extracted from canola oil, with brassicasterol as a major component, exhibited a significant LDL-C reduction in a hamster model.

Pentoxifylline reduces inflammation and prevents myocardial perfusion derangements in experimental chronic Chagas' cardiomyopathy.

BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.

Evaluating the sensitivity of newborn rats and newborn hamsters to oncogenic DNA.

To evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cell lines, we have been establishing in vivo assays to quantify the oncogenic activity of DNA. We had generated three oncogene-expression plasmids: pMSV-T24-H-ras, which expresses activated H-ras; pMSV-c-myc, which expresses c-myc; and pMSV-T24-H-ras/MSV-c-myc, which expresses both oncogenes. Tumors were induced in mice by pMSV-T24-H-ras plus pMSV-c-myc or by pMSV-T24-H-ras/MSV-c-myc. Because newborn hamsters and newborn rats have been recommended for oncogenicity testing of the DNA from tumorigenic mammalian cell-substrates used for vaccine production, we evaluated their sensitivity. Newborn hamsters and rats were inoculated with different doses of pMSV-T24-H-ras/MSV-c-myc to determine their sensitivity to tumor induction and with the single-oncogene-expression plasmids to determine whether single oncogenes could induce tumors. Newborn rats were more sensitive than newborn hamsters, and activated H-ras but not c-myc induced tumors in newborns of both rodent species. DNA from four cell lines established from tumors induced by pMSV-T24-H-ras/MSV-c-myc was inoculated into newborn rats. Because no tumors were induced by this cellular DNA, which should be optimal as it contains both oncogenes linked and present in several copies, we conclude that available in vivo models are not sensitive enough to detect the oncogenicity of cellular DNA.

Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development.

At the end of 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was detected in Wuhan, China, that spread rapidly around the world, with severe consequences for human health and the global economy. Here, we assessed the replicative ability and pathogenesis of SARS-CoV-2 isolates in Syrian hamsters. SARS-CoV-2 isolates replicated efficiently in the lungs of hamsters, causing severe pathological lung lesions following intranasal infection. In addition, microcomputed tomographic imaging revealed severe lung injury that shared characteristics with SARS-CoV-2-infected human lung, including severe, bilateral, peripherally distributed, multilobular ground glass opacity, and regions of lung consolidation. SARS-CoV-2-infected hamsters mounted neutralizing antibody responses and were protected against subsequent rechallenge with SARS-CoV-2. Moreover, passive transfer of convalescent serum to naïve hamsters efficiently suppressed the replication of the virus in the lungs even when the serum was administrated 2 d postinfection of the serum-treated hamsters. Collectively, these findings demonstrate that this Syrian hamster model will be useful for understanding SARS-CoV-2 pathogenesis and testing vaccines and antiviral drugs.

Probable Animal-to-Human Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta Variant AY.127 Causing a Pet Shop-Related Coronavirus Disease 2019 (COVID-19) Outbreak in Hong Kong.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect human and other mammals, including hamsters. Syrian (Mesocricetus auratus) and dwarf (Phodopus sp.) hamsters are susceptible to SARS-CoV-2 infection in the laboratory setting. However, pet shop-related Coronavirus Disease 2019 (COVID-19) outbreaks have not been reported. METHODS: We conducted an investigation of a pet shop-related COVID-19 outbreak due to Delta variant AY.127 involving at least 3 patients in Hong Kong. We tested samples collected from the patients, environment, and hamsters linked to this outbreak and performed whole genome sequencing analysis of the reverse transcription polymerase chain reaction (RT-PCR)-positive samples. RESULTS: The patients included a pet shop keeper (Patient 1), a female customer of the pet shop (Patient 2), and the husband of Patient 2 (Patient 3). Investigation showed that 17.2% (5/29) and 25.5% (13/51) environmental specimens collected from the pet shop and its related warehouse, respectively, tested positive for SARS-CoV-2 RNA by RT-PCR. Among euthanized hamsters randomly collected from the storehouse, 3% (3/100) tested positive for SARS-CoV-2 RNA by RT-PCR and seropositive for anti-SARS-CoV-2 antibody by enzyme immunoassay. Whole genome analysis showed that although all genomes from the outbreak belonged to the Delta variant AY.127, there were at least 3 nucleotide differences among the genomes from different patients and the hamster cages. Genomic analysis suggests that multiple strains have emerged within the hamster population, and these different strains have likely transmitted to human either via direct contact or via the environment. CONCLUSIONS: Our study demonstrated probable hamster-to-human transmission of SARS-CoV-2. As pet trading is common around the world, this can represent a route of international spread of this pandemic virus.

Pharmacokinetics and Efficacy of Human Hyperimmune Intravenous Immunoglobulin Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Adult Syrian Hamsters.

BACKGROUND: After the failure of antibody therapies in treating hospitalized patients with coronavirus disease 2019 (COVID-19), we investigated the impact of viral replication on the pharmacokinetics and efficacy of a hyperimmune severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (CoVIG) product in treating SARS-CoV-2 infection using an adult Syrian hamster model. METHODS: The CoVIG was manufactured from plasma donors who had recovered from COVID-19. The dose used (400 mg/kg) was based on the dose given in clinical trials to hospitalized patients with COVID-19. Hamsters were given a single dose of CoVIG 2 days after challenge with the SARS-CoV-2 virus (isolate NY/PV08410/2020), followed by sampling of blood, nasal, tracheal, and lung tissues at different time points. The blood samples were assayed for anti-SARS-CoV-2 spike binding and used to calculate pharmacokinetic (PK) parameters. Nasal wash, tracheal, and lung tissue samples were assayed for viral replication by polymerase chain reaction (subgenomic messenger RNA). RESULTS: CoVIG-treated hamsters showed a reduction in viral replication in the lower respiratory tract, but minimal reduction in the upper respiratory tract, after challenge with SARS-CoV-2. Challenge resulted in altered PK parameters proportionate to viral replication, resulting in decreased area under the curve, accelerated clearance, and shorter half-life of CoVIG. CONCLUSIONS: These data indicate that in the presence of actively replicating SARS-CoV-2 virus, PK parameters are altered and should trigger an adjustment in CoVIG dosing.

Severe Acute Respiratory Syndrome Coronavirus-2 Delta Variant Study In Vitro and Vivo.

At the end of 2019, an outbreak of a new severe acute respiratory syndrome caused by a coronavirus occurred in Wuhan, China, after which the virus spread around the world. Here, we have described the adaptive capacity and pathogenesis of the SARS-CoV-2 Delta variant, which is widespread in Armenia, in vitro and vivo on Syrian hamsters. We have studied the changes in the SARS-CoV-2genome using viral RNA sequencing during virus adaptation in vitro and in vivo. Our findings revealed that SARS-CoV-2 in Syrian hamsters causes a short-term pulmonary form of the disease, the first symptoms appear within 48 h after infection, reach 5-7 days after infection, and begin to disappear by 7-9 days after infection. The virus induces pathogenesis in the blood and bone marrow, which generally corresponds to the manifestation of the inflammatory process. The pulmonary form of the disease passes faster than changes in blood cells and bone marrow. Our data show that hamster organs do not undergo significant pathological changes in the Delta variant of SARS-CoV-2 infection.

Siberian hamsters nonresponding to short photoperiod use fasting-induced torpor.

Nonresponding Siberian hamsters (Phodopus sungorus) do not develop the winter phenotype of white fur, low body mass (Mb) and spontaneous torpor in response to short photoperiod. However, their thermoregulatory response to fasting remains unknown. We measured body temperature and Mb of 12 nonresponders acclimated to short photoperiod and then to cold and fasted four times for 24 h. Four individuals used torpor, and in total, we recorded 19 torpor bouts, which were shallow, short and occurred at night. Moreover, fasting increased the heterothermy index in all hamsters. Low Mb was not a prerequisite for torpor use and Mb loss did not correlate with either heterothermy index or torpor use. This is the first evidence that individuals which do not develop the winter phenotype can use torpor or increase body temperature variability to face unpredictable, adverse environmental conditions. Despite the lack of seasonal changes, thermoregulatory adjustments may increase the probability of winter survival in nonresponders.

Leptin mediates the suppressive effect of partial fat removal on cellular and humoral immunity in striped hamsters.

Leptin secreted mainly by white adipose tissues (WAT) plays an important role in immune responses. To understand the role of energy status and leptin in immunity, bilateral perigonadal fat pads were removed or sham-removed in male striped hamsters (Cricetulus barabensis). Half of these hamsters were injected with sterile saline, and another half were administrated with exogenous leptin each day, which lasted for 20 days. Fat removal reduced total body fat mass and leptin titers significantly, leptin administration increased leptin levels in the fat removed hamsters to the control levels, but did not affect total body fat mass. Body mass and gross energy intake were not affected by fat removal, leptin supplement or their interaction. Fat removal decreased thymus mass, phytohaemagglutinin (PHA) response at 12 h, and the levels of immunoglobin (Ig) G 5, IgG10, IgM5, IgM10, IL-2, IL-4, and TNF-α, indicating a reduction in fat mass suppressed cellular and humoral immunity and the production of cytokines. However, fat removal had no effect on spleen mass, bacteria killing activity and IFN-γ titers. Leptin supplement increased PHA response at 6 h and 12 h, and the levels of IgG5, IgG10, IL-4, and IFN-γ to the control levels, implying its boosting effects on these parameters. In addition, leptin level was positively correlated with body fat mass, PHA 6 h, 12 h, Ig G10, Ig M5, Ig M10, IL-2, IL-4, and TNF-α. Collectively, these findings implied leptin was a link between energy status and immunity, and leptin mediated the suppressive effects of reduced energy storage on cellular and humoral immunity.