COVID-19 and emerging viral infections: The case for interferon lambda

Prokunina‐Olsson, Ludmila; Alphonse, Noémie; Dickenson, Ruth E.; Durbin, Joan E.; Glenn, Jeffrey S.; Hartmann, Rune; Kotenko, Sergei V.; Lazear, Helen M.; O’Brien, Thomas R.; Odendall, Charlotte; Onabajo, Olusegun O.; Piontkivska, Helen; Santer, Deanna M.; Reich, Nancy C.; Wack, Andreas; Zanoni, Ivan

doi:10.1084/jem.20200653

Cited by 192 publications

(162 citation statements)

References 20 publications

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“…IFN-λ treatment early during influenza virus infection was shown to be protective, owing to its ability to confer antiviral protection without generating the proinflammatory responses associated with IFN-α/β (68,69). For these reasons, IFN-λ is therefore 20 being implemented as a candidate therapy for COVID-19 (70). However, our findings here identify a mechanism by which IFN-λ exacerbates respiratory virus disease acting specifically through the respiratory epithelium, independent of immunomodulation.…”

Section: Discussionmentioning

confidence: 74%

Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

Major

Crotta

Llorian

et al. 2020

Preprint

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Excessive cytokine signalling frequently exacerbates lung tissue damage during respiratory viral infection. Type I and III interferons (IFN-α/β and IFN-λ) are host-produced antiviral cytokines and currently considered as COVID-19 therapy. Prolonged IFN-α/β responses can lead 5 to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, inducing localised antiviral immunity. Here we show that IFN signalling interferes with lung repair during influenza recovery, with IFN-λ driving these effects most potently. IFN-induced p53 directly reduces epithelial proliferation and differentiation, increasing disease severity and susceptibility to bacterial superinfections. Hence, excessive or prolonged IFN-production aggravates viral infection 10 by impairing lung epithelial regeneration. Therefore, timing and duration are critical parameters of endogenous IFN action, and should be considered carefully for IFN therapeutic strategies against viral infections like influenza and COVID-19. 15

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Section: Discussionmentioning

confidence: 74%

Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

Major

Crotta

Llorian

et al. 2020

Preprint

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“…Identification of patients with insufficient IFN production could define a high-risk population that could benefit from IFN-α or -β supplementation in conjunction with antiviral drugs when available. Alternatively, IFN-λ (Type III interferon) could be tested as recently proposed 34 , as the receptor is more specifically localized on epithelial cells, which may avoid potential systemic side effects with type I IFN. Conversely, inhibiting IFN production could be deleterious in these patients, reason why agents interfering with the IFN pathway, such as corticosteroids, anti-interferon antibody, JAK1/Tyk2 inhibitors or chloroquine, should be considered with great caution.…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

Hadjadj

Yatim

Barnabei

et al. 2020

Preprint

268

312

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“…In an animal model, treatment with IFN-λ2/IL-28A reversed the development of collagen-induced arthritis, also indicating an anti-inflammatory role in autoimmune responses [31]. However, in the contest of CRS associated with COVID-19, it cannot be excluded that type III IFN receptors are upregulated also in other cell types and that these cytokines could also contribute to the complex pathogenic process [32].…”

Section: Sars-cov-2 Infection and The Pathophysiology Of Cytokine Relmentioning

confidence: 99%

Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity

Picchianti-Diamanti

Rosado

Pioli

et al. 2020

IJMS

101

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On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient's clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.

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COVID-19 and emerging viral infections: The case for interferon lambda

Cited by 192 publications

References 20 publications

Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity

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