Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Bessière, Pierre; Wasniewsk, Marine; Servat, Alexandre; Figueroa, Thomas; Foret‐Lucas, Charlotte; Coggon, Amelia; Lesellier, Sandrine; Boué, Frank; Cebron, Nathan; Gausserès, Blandine; Trumel, Catherine; Foucras, Gilles; Salguero, Francisco J.; Monchâtre-Leroy, Élodie; Volmer, Romain

doi:10.1101/2021.02.09.430458

Cited by 11 publications

(4 citation statements)

References 39 publications

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“…The IFN-pretreated animals that did become infected had only limited virus titers, indicating that IFN pre-treatment reduced viral transmission and the infectivity of treated animals (Hoagland et al, 2021). Meanwhile, treating hamsters with IFN-⍺ at 3 dpi, coincident with symptom onset, did not change clinical outcomes (Bessie `re et al, 2021). By contrast, when non-human primates were infected with SARS-CoV-2, it resulted in significant upregulation of IFN-I and -II expression in bronchoalveolar lavage (BAL) fluid and induced robust ISG expression in the lungs, indicating that non-human primates mount a stronger IFN response to SARS-CoV-2 infection than that observed in other animal models (Chandrashekar et al, 2020;Singh et al, 2021).…”

Section: Sars-cov-2 Induction Of Ifn Pathways In Vitromentioning

confidence: 96%

“…The infection of other animal models with SARS-CoV-2, including of hamsters, ferrets, and non-human primates, results in mild clinical disease, with a lethal infection only observed in aged hamsters (Selvaraj et al, 2021). The infection of hamsters and ferrets with SARS-CoV-2 does not result in an IFN-b response (Bessie `re et al, 2021;Blanco-Melo et al, 2020;Hoagland et al, 2021), although ISG15 expression was observed after infection and remained elevated to 8 dpi, by which time the virus had already fully cleared (Hoagland et al, 2021). These data indicate that non-classical, IFN-independent induction of ISGs occurred in these animals after SARS-CoV-2 infection.…”

Section: Sars-cov-2 Induction Of Ifn Pathways In Vitromentioning

confidence: 99%

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Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19

Lowery

Sariol

Perlman

2021

Cell Host & Microbe

237

176

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COVID-19 can result in severe disease characterized by significant immunopathology that is spurred by an exuberant, yet dysregulated, innate immune response with a poor adaptive response. A limited and delayed interferon I (IFN-I) and IFN-III response results in exacerbated proinflammatory cytokine production and in extensive cellular infiltrates in the respiratory tract, resulting in lung pathology. The development of effective therapeutics for patients with severe COVID-19 depends on our understanding the pathological elements of this unbalanced innate immune response. Here, we review the mechanisms by which SARS-CoV-2 both activates and antagonizes the IFN and inflammatory response following infection, how a dysregulated cytokine and cellular response contributes to immune-mediated pathology in COVID-19, and therapeutic strategies that target elements of the innate response.

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Section: Sars-cov-2 Induction Of Ifn Pathways In Vitromentioning

confidence: 96%

Section: Sars-cov-2 Induction Of Ifn Pathways In Vitromentioning

confidence: 99%

Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19

Lowery

Sariol

Perlman

2021

Cell Host & Microbe

237

176

View full text Add to dashboard Cite

show abstract

“…Interestingly, Stat2 -/- (lacking both type I and III IFN responses) hamsters fail to control SARS-CoV-2 infection, whereas this infection is successfully controlled by Il-28r -/- (deficient for the type III IFN response only) animals [ 84 ]. Moreover, intranasal treatment with universal IFN-α within one to three days of infection can protect hamsters from severe disease [ 85 , 86 ].…”

Section: Type I Ifn Immunity In Animal Models Naturally Susceptible To Sars-cov-2mentioning

confidence: 99%

Type I interferons and SARS-CoV-2: from cells to organisms

Bastard

Zhang

et al. 2022

Current Opinion in Immunology

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Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro . In various animal species infected in vivo , type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The early administration of exogenous type I IFNs improves infection control. In humans, inborn errors of, and auto-antibodies against type I IFNs underlie life-threatening COVID-19 pneumonia. Overall, type I IFNs are essential for host defense against SARS-CoV-2 in individual cells and whole organisms.

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“…Moreover, as global efforts are underway to identify and develop new anti-viral and immunomodulatory therapeutics that reduce COVID-19 related hospitalization and deaths, need arises for the right timing (38). Indeed, early type I IFN treatment seemed to be critical for therapeutic success (39). However, prophylactic immunomodulation might not be feasible for most COVID-19 patients due to high costs and potential adverse events.…”

Section: Figurementioning

confidence: 99%

Distinguishing Incubation and Acute Disease Stages of Mild-to-Moderate COVID-19

Müller

Volzke

Subin

et al. 2021

Preprint

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Objective: While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Methods: Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Results: Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched whereas all other parameters returned to baseline. Conclusion: Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcome.

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Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Cited by 11 publications

References 39 publications

Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19

Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19

Type I interferons and SARS-CoV-2: from cells to organisms

Distinguishing Incubation and Acute Disease Stages of Mild-to-Moderate COVID-19

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