SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

Francis, Magen E.; Goncin, Una; Kroeker, Andrea; Swan, Cynthia L.; Ralph, Robyn; Lu, Yao; Etzioni, Athema L.; Falzarano, Darryl; Gerdts, Volker; Machtaler, Steven; Kindrachuk, Jason; Kelvin, Alyson A.

doi:10.1101/2021.04.07.438843

Cited by 10 publications

(16 citation statements)

References 120 publications

(132 reference statements)

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“…33 IL-6 is an important cytokine in host responses against viral infection. 33 The increase observed here could have contributed to the host response in control of infection.…”

Section: Discussionmentioning

confidence: 99%

“…IL-6, IL1beta, and TNF increase has been reported in hamsters infected with SARS-CoV-2. 33 IL-6 is an important cytokine in host responses against viral infection. 33 The increase observed here could have contributed to the host response in control of infection.…”

Section: Discussionmentioning

confidence: 99%

“…33 IL-6 is an important cytokine in host responses against viral infection. 33 The increase observed here could have contributed to the host response in control of infection. Other inflammatory cytokines like IL-4, IFN-Gamma, TNF-alpha also showed slight increase in comparison to control animals during the acute phase of infection.…”

Section: Discussionmentioning

confidence: 99%

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Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters

Mohandas

Yadav

Shete

et al. 2021

Preprint

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Delta variant has evolved to become dominant SARS-CoV-2 lineage worldwide and there are reports of secondary infections with varying severity in vaccinated and unvaccinated naturally recovered COVID-19 patients. As the protective immunity following the infection wanes within few months, studies of re-infection after prolonged duration is needed. Hence we assessed the potential of re-infection by Delta, Delta AY.1 and B.1 in COVID-19 recovered hamsters after 3 months of infection. Re-infection with Delta and B.1 variants in hamsters showed reduced viral shedding, lung pathology and lung viral load, whereas the upper respiratory tract viral load remained similar to that of first infection. The reduction in viral load and lung pathology after re-infection with Delta AY.1 variant was not marked. Further we assessed the disease characteristics of Delta AY.1 to understand whether it has any replication advantage over Delta variant and B.1 variant, an early isolate in Syrian hamsters. Body weight changes, viral load in respiratory organs, lung pathology, cytokine response and neutralizing antibody response were assessed. Delta AY.1 variant produced milder disease in comparison to Delta variant and the neutralizing response was similar against Delta, B.1 and B.1.351 variant in contrast to Delta or B.1 infected hamsters which showed a significant reduction in neutralization titres against B.1.351. Elevation of IL-6 levels was observed post infection in hamsters after primary infection. The prior infection could not produce sterilizing immunity but the protective effect was evident following reinfection. This indicates the importance of the transmission prevention efforts even after achieving herd immunity.Research in contextEvidence before this studySecondary infections with Delta variant are being widely reported and there are reports of increased disease severity. Delta sub lineages with K417N substitution has caused concern worldwide due to the presence of the same substitution in Beta variant, a Variant of Concern known for its immune evasion. The information on the biological characteristics of this sub lineage is also scanty.Added value of this studyThe present study showed that the secondary infection with Delta variant does not show any evidence of increased disease severity in hamster model. Delta AY. 1 variant produces mild disease in Syrian hamsters in contrast to severe disease caused by Delta variant. Delta, B.1 and AY.1 variant infected hamster sera showed comparable cross neutralizing response against each other. In contrast to the lower neutralizing response shown by B.1 and Delta variant infected animals against B.1.351 variant, Delta AY.1 showed comparable response as that with other variants.Implications of the available evidenceSARS-CoV-2 infections do not produce sterilizing immunity but protect from developing severe disease in case of Delta variant re-infection indicating the importance of the transmission prevention efforts even after achieving herd immunity. Delta AY. 1 infection in hamsters did not show any evidence of speculated immune evasion.

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“…33 IL-6 is an important cytokine in host responses against viral infection. 33 The increase observed here could have contributed to the host response in control of infection.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters

Mohandas

Yadav

Shete

et al. 2021

Preprint

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“…On the other hand, several limitations of the hamster model exist. SARS-CoV-2 infection in humans affects multiple organ systems including the heart, kidneys, liver, spleen and large intestine (83, 84) whereas in hamsters live virus mainly replicates in respiratory tracts with little evidence of infectious virus in other organs, despite the detection of viral RNA in non-respiratory tissues (55, 85). Furthermore, a lack of hamster-specific biological reagents makes it difficult to characterize immune responses and the mechanisms of pathogenesis in hamsters.…”

Section: Discussionmentioning

confidence: 99%

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

Kulkarni

Chen

Lee

et al. 2021

Preprint

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COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10-15% of infected individuals and mortality in 2-3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the cold chain transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS-CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.

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“…Images were obtained by 200× magnification using a digital microscope system (IX81; Olympus, Japan). The characteristics and severity of the pathologic lesions were scored using lungspecific inflammation parameters as previously reported (Francis et al, 2021). Three different scores were used that included the following parameters: (i) lung inflammation score including severity of interstitial pneumonia, bronchitis, epithelial necrosis of the bronchi and alveoli, and hyperplasia of type II-alveolar epithelial cells; (ii) immune cell infiltration score taking into account the presence of neutrophils, macrophages, and lymphocytes in the lungs as well as perivascular lymphocytic cuffing; and (iii) edema score, including alveolar edema and perivascular edema.…”

Section: Histopathological Examinationmentioning

confidence: 99%

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

Peng

Ding

Jiang

et al. 2021

Sci. China Life Sci.

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis. Clinical candidates with high efficacy, ready availability, and that do not develop resistance are in urgent need. Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture, there are few confirmed antiviral candidates in vivo . In this study, 94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs. Among them, 24 compounds with low cytotoxicity were selected, and of these, 17 compounds also effectively suppressed SARS-CoV-2 infection in HeLa cells transduced with human ACE2. Six compounds disturb multiple processes of the SARS-CoV-2 life cycle. Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2 infection. Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant. Except for cisatracurium, six compounds reduced hamster pulmonary viral load, and IL-6 and TNF -α mRNA when assayed at 4 d postinfection. In particular, sertraline, salinomycin, and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro , suggesting promising application for COVID-19 treatment. Supporting Information The supporting information is available online at 10.1007/s11427-021-2031-7. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

Cited by 10 publications

References 120 publications

Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters

Protective immunity of the primary SARS-CoV-2 infection reduces disease severity post re-infection with Delta variants in Syrian hamsters

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

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