Design and validation of an exposure system for efficient inter-animal SARS-CoV-2 airborne transmission in Syrian hamsters

Kuehl, P.; Dearing, Justin; Werts, Adam D.; Cox, Jason M.; Irshad, Hammad; Barrett, Edward G.; Tucker, Sean N.; Langel, Stephanie N.

doi:10.1101/2022.11.18.517035

Cited by 1 publication

(1 citation statement)

References 10 publications

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“…However, none of the models recapitulate prolonged infection of an immunocompromised host. Ferrets and Syrian golden hamsters are highly permissive for SARS-CoV-2, supporting efficient viral replication in the upper (20)(21)(22)(23) or upper and lower (24,25) respiratory tract, respectively, in each case combined with efficient viral transmission to uninfected contact animals (20,(26)(27)(28). Clinical signs in either model remain mild, and infection is fully cleared within 5 to 10 days (23,26,29,30).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of late-onset antiviral treatment in immune-compromised hosts with persistent SARS-CoV-2 infection

Lieber,

Kang,

Sobolik

et al. 2024

Preprint

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The immunocompromised are at high risk of prolonged SARS-CoV-2 infection and progression to severe COVID-19. However, efficacy of late-onset direct-acting antiviral (DAA) therapy with therapeutics in clinical use and experimental drugs to mitigate persistent viral replication is unclear. In this study, we employed an immunocompromised mouse model, which supports prolonged replication of SARS-CoV-2 to explore late-onset treatment options. Tandem immuno-depletion of CD4+ and CD8+ T cells in C57BL/6 mice followed by infection with SARS-CoV-2 variant of concern (VOC) beta B.1.351 resulted in prolonged infection with virus replication for five weeks after inoculation. Early-onset treatment with nirmatrelvir/ritonavir (paxlovid) or molnupiravir was only moderately efficacious, whereas the experimental therapeutic 4'-fluorourdine (4'-FlU, EIDD-2749) significantly reduced virus load in upper and lower respiratory compartments four days post infection (dpi). All antivirals significantly lowered virus burden in a 7-day treatment regimen initiated 14 dpi, but paxlovid-treated animals experienced rebound virus replication in the upper respiratory tract seven days after treatment end. Viral RNA was detectable 28 dpi in paxlovid-treated animals, albeit not in the molnupiravir or 4'-FlU groups, when treatment was initiated 14 dpi and continued for 14 days. Low-level virus replication continued 35 dpi in animals receiving vehicle but had ceased in all treatment groups. These data indicate that late-onset DAA therapy significantly shortens the duration of persistent virus replication in an immunocompromised host, which may have implications for clinical use of antiviral therapeutics to alleviate the risk of progression to severe disease in highly vulnerable patients.

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