On day 4 post infection, Syrian hamsters infected with the D614G strain and the omicron SARS-CoV-2 variant had a cumulative lung pathology score of 7.5 and 1.75 (close to the baseline score of untreated, non-infected hamsters), respectively.
In comparison to the ancestral D614G strain and other variants of concerns, the omicron is unable to proliferate well in the lower respiratory tract of Syrian hamsters.
Hamsters infected with 103 TCID50 of BavPat
(D614G) strain showed median viral RNA copies of 4 x 106/mg of lung tissue, infectious viral loads of 2 x 104/mg of lung tissue , and weight change of 0.65%.
Hamsters infected with 103 TCID50 omicron (B.1.1.529) SARS-CoV-2 variant showed median viral RNA copies of 3 x 103/mg of lung tissue, no infectious viral loads, and weight gain of about 3.8%.
Highly mutated spike of the omicron variant is better adapted to human ACE2 receptor when compare to ACE2 receptor of the hamster.
Instilling the S1 subunit of SARS-CoV-2 Spike protein (400 µg/kg in 2ml/kg body weight) in K18-hACE2 transgenic mice exhibited a decline in body weight, increase in white blood cells and protein concentrations in bronchoalveolar lavage fluid (BALF), upregulation of multiple inflammatory cytokines in BALF and serum, histological evidence of lung injury, and activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways in the lung.
A single exposure of K18-hACE2 mice to SARS-CoV-2 Spike Protein S subunit S1 may represent a valid model of COVID-19, allow the study of the molecular mechanisms of SARS-CoV-2 induced lung injury and be useful in the investigation of potential new therapeutic approaches to the management of COVID-19 as well as future coronavirus-dependent respiratory diseases.
Single intratracheal exposure to SARS-CoV-2 S1 spike protein induces acute lung injury in K18-hACE2 transgenic mice
Author(s) name
Colunga Biancatelli RML, Solopov PA et al.
Affiliations
Pavel Solopov (Old Dominion University)| Ruben Colunga Biancatelli (Old Dominion University)| Elizabeth Sharlow (University of Virginia)| John Lazo (University of Virginia)| John Catravas (Old Dominion University, Old Dominion University)
Journal
Am J Physiol Lung Cell Mol Physiol
Impact factor
3.78
Citation count: 27
Date of Entry
2021 Jun 15
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Colunga Biancatelli RML, Solopov PA, Sharlow ER, Lazo JS, Marik PE, Catravas JD. Single intratracheal exposure to SARS-CoV-2 S1 spike protein induces acute lung injury in K18-hACE2 transgenic mice. Am J Physiol Lung Cell Mol Physiol. 2021 Aug 1;321(2):L477-L484. PMID:34156871
The virus titers in the tracheal and lung tissues of infected Hamsters showed higher virus replication in the lung tissues of hamsters infected with WT SARS-CoV-2 than Del-mut-1 variant infected hamsters.
Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction
Author(s) name
Lau SY, Wang P et al.
Journal
Emerg Microbes Infect
Impact factor
5.84
Citation count: 142
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NLM format
Lau SY, Wang P, Mok BW, Zhang AJ, Chu H, Lee AC, Deng S, Chen P, Chan KH, Song W, Chen Z, To KK, Chan JF, Yuen KY, Chen H. Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction. Emerg Microbes Infect. 2020 Dec;9(1):837-842. PMID:32301390
4 Hamsters infected with Del-mut-1 SARS-CoV-2 viruses showed diffuse alveolar wall thickening and peribronchiolar infiltration in the lungs and no bodyweight loss.
Del-mut-1 (a 30 bp deletion at S1/S2 junction) attenuated variant has reduced its ability to cause disease in the hamster animal model
Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction
Author(s) name
Lau SY, Wang P et al.
Journal
Emerg Microbes Infect
Impact factor
5.84
Citation count: 142
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NLM format
Lau SY, Wang P, Mok BW, Zhang AJ, Chu H, Lee AC, Deng S, Chen P, Chan KH, Song W, Chen Z, To KK, Chan JF, Yuen KY, Chen H. Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction. Emerg Microbes Infect. 2020 Dec;9(1):837-842. PMID:32301390
4 Hamsters infected with WT SARS-CoV-2 viruses (Wuhan-1) showed extensive alveolar wall destruction, alveolar space haemorrhage, and mononuclear cell infiltration in the lungs and bodyweight loss.
WT virus has led to disease severity in the hamster animal model
Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction
Author(s) name
Lau SY, Wang P et al.
Journal
Emerg Microbes Infect
Impact factor
5.84
Citation count: 142
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NLM format
Lau SY, Wang P, Mok BW, Zhang AJ, Chu H, Lee AC, Deng S, Chen P, Chan KH, Song W, Chen Z, To KK, Chan JF, Yuen KY, Chen H. Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction. Emerg Microbes Infect. 2020 Dec;9(1):837-842. PMID:32301390
Hamsters infected with mutant SARS-CoV-2 (G614 virus) showed higher viral load in the nasal washes and the tracheae, but not in the lungs, than those of Hamsters infected with WT SARS-CoV-2 (D614 virus).
Infected hamsters from both groups showed similar weight loss.
Plante JA, Liu Y, Liu J, Xia H, Johnson BA, Lokugamage KG, Zhang X, Muruato AE, Zou J, Fontes-Garfias CR, Mirchandani D, Scharton D, Bilello JP, Ku Z, An Z, Kalveram B, Freiberg AN, Menachery VD, Xie X, Plante KS, Weaver SC, Shi PY. Spike mutation D614G alters SARS-CoV-2 fitness. Nature. 2021 Apr;592(7852):116-121. PMID:33106671
Transgenic type I interferon knockout (IFNAR/-) mice, inoculated intranasally with SARS-CoV-2 showed infections in tissues including lungs, heart, stomach, intestines, liver, spleen and kidneys. Lungs with hyperemia, regional consolidation and subpleural air accumulation was observed on necropsy.
Characterization of local SARS-CoV-2 isolates and pathogenicity in IFNAR-/-mice
Author(s) name
Hanifehnezhad A, Kehribar EÅž et al.
Journal
Heliyon
Impact factor
1.65
Citation count: 7
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NLM format
Hanifehnezhad A, Kehribar EŞ, Öztop S, Sheraz A, Kasırga S, Ergünay K, Önder S, Yılmaz E, Engin D, Oğuzoğlu TÇ, Şeker UÖŞ, Yılmaz E, Özkul A. Characterization of local SARS-CoV-2 isolates and pathogenicity in IFNAR-/-mice. Heliyon. 2020 Sep;6(9):e05116. PMID:33015402
2 aged cynomolgus macaques infected with SARS-CoV-2 had 0-5% of lungs affected, and leukocyte infiltration with type I & II pneumocytes affected at 4 days post-infection.
Organs affected were also noticed for SARS-CoV and MERS-CoV.
Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model
Author(s) name
Rockx B, Kuiken T et al.
Journal
Science
Impact factor
20.57
Citation count: 468
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NLM format
Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, de Meulder D, van Amerongen G, van den Brand J, Okba NMA, Schipper D, van Run P, Leijten L, Sikkema R, Verschoor E, Verstrepen B, Bogers W, Langermans J, Drosten C, Fentener van Vlissingen M, Fouchier R, de Swart R, Koopmans M, Haagmans BL. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020 May 29;368(6494):1012-1015. PMID:32303590
2 young cynomolgus macaques infected with SARS-CoV-2 had 0-10% of lungs affected, hyaline membranes, alveolar oedema and leukocyte infiltration with type I & II pneumocytes affected at 4 days post-infection.
Organs affected were also noticed for SARS-CoV and MERS-CoV.
Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model
Author(s) name
Rockx B, Kuiken T et al.
Journal
Science
Impact factor
20.57
Citation count: 468
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NLM format
Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, de Meulder D, van Amerongen G, van den Brand J, Okba NMA, Schipper D, van Run P, Leijten L, Sikkema R, Verschoor E, Verstrepen B, Bogers W, Langermans J, Drosten C, Fentener van Vlissingen M, Fouchier R, de Swart R, Koopmans M, Haagmans BL. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020 May 29;368(6494):1012-1015. PMID:32303590
2 out of 6 12-24 months old male and female ferrets in indirect contact with infected ferrets had viral RNA in nasal washes and fecal specimens.
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Author(s) name
Kim YI, Kim SG et al.
Journal
Cell Host Microbe
Impact factor
10.45
Citation count: 442
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NLM format
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 May 13;27(5):704-709.e2. PMID:32259477
12-24 months old male and female ferrets infected through direct contact with infected ferrets had viral RNA in nasal washes, saliva, fecal and urine samples.
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Author(s) name
Kim YI, Kim SG et al.
Journal
Cell Host Microbe
Impact factor
10.45
Citation count: 442
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NLM format
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 May 13;27(5):704-709.e2. PMID:32259477
12-24 months old male and female ferrets inoculated with SARS-CoV-2 virus had highest viral RNA in nasal washes. Viral RNA was also detected in saliva specimens.
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Author(s) name
Kim YI, Kim SG et al.
Journal
Cell Host Microbe
Impact factor
10.45
Citation count: 442
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NLM format
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 May 13;27(5):704-709.e2. PMID:32259477
12-24 months old male and female ferrets in indirect contact with infected ferrets had no change in body temperature and body weight.
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Author(s) name
Kim YI, Kim SG et al.
Journal
Cell Host Microbe
Impact factor
10.45
Citation count: 442
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NLM format
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 May 13;27(5):704-709.e2. PMID:32259477
12-24 months old male and female ferrets infected through direct contact with infected ferret had elevated body temperatures and reduced activity.
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Author(s) name
Kim YI, Kim SG et al.
Journal
Cell Host Microbe
Impact factor
10.45
Citation count: 442
×
NLM format
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 May 13;27(5):704-709.e2. PMID:32259477
12-24 months old male and female ferrets inoculated with SARS-CoV-2 virus had elevated body temperatures and reduced activity.
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Author(s) name
Kim YI, Kim SG et al.
Journal
Cell Host Microbe
Impact factor
10.45
Citation count: 442
×
NLM format
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 May 13;27(5):704-709.e2. PMID:32259477
Nasal turbinate, trachea, lungs, kidney, and intestine with acute bronchiolitis was present in infected lungs of ferrets intranasally infected with SARS-CoV-2 virus.
After 12 dpi, viral RNA and virus recovery failed to be detected in all tested tissues.
Infection and Rapid Transmission of SARS-CoV-2 in Ferrets
Author(s) name
Kim YI, Kim SG et al.
Journal
Cell Host Microbe
Impact factor
10.45
Citation count: 442
×
NLM format
Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, Chang JH, Kim EJ, Lee S, Casel MAB, Um J, Song MS, Jeong HW, Lai VD, Kim Y, Chin BS, Park JS, Chung KH, Foo SS, Poo H, Mo IP, Lee OJ, Webby RJ, Jung JU, Choi YK. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 May 13;27(5):704-709.e2. PMID:32259477