Two separate studies in mice suggest that a class of interferons being evaluated in clinical trials as a therapy for COVID-19 may increase susceptibility to bacterial infections, depending on how long patients are exposed to it, and when they receive it.
The results suggest that the timing and duration of this treatment may need to be carefully selected, as trials move forward, to avoid deleterious effects.
Interferons (IFNs) help fight viral infections in the lung. In particular, type III IFNs (IFN- λ) have attracted much attention, because, unlike other IFNs, they show antiviral effects without driving inflammatory responses.
Already, a clinical trial exploring the use of IFN-λ against SARS-CoV-2 has begun. Despite interest in the use of IFN-λ to treat viral infections, the long-term effects IFN-λ on lung physiology - and in possibly impairing bacterial control by the lung epithelium - remain largely overlooked.
Here, to directly evaluate whether SARS-CoV-2 induces IFNs, Achille Broggi and colleagues tested swabs of COVID-19 patients and healthy controls, as well as the bronchoalveolar lavage fluid of severe SARS-CoV-2-positive patients.
In the latter group, levels of type I and III interferons were high, the report. Next, to better understand the effects of IFN-λ signaling in the lung, Broggi, and colleagues studied the lungs of mice exposed to synthetic viral RNA.
In these animals, IFN-λ secreted by dendritic cells caused damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. In a separate study using a mouse model to investigate the dynamics of influenza virus infection, Jack Major et al. report that IFN signaling (especially that of IFN-λ) hampered lung repair.
This pair of papers suggests that the timing and duration of IFN-λ exposure are critical parameters underlying the success or failure of antiviral therapeutics, the authors say.
[O]ur data enjoin clinicians to carefully analyze the duration of IFN-λ administration and to take into consideration the severity of the disease when IFN-λ is used as a therapeutic agent against lung viral infections,"
Broggi and Colleagues, American Association for the Advancement of Science
"Optimal protection would be achieved by strong induction of IFN-stimulated genes early during infection to curb viral replication, followed by timely down-regulation of IFN responses, enabling efficient lung epithelial repair," says Major et al.
Broggi, A., et al. (2020) Type III interferons disrupt the lung epithelial barrier upon viral recognition. Science. doi.org/10.1126/science.abc3545.
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2020-06-12 06:27:00Z
CBMilAFodHRwczovL3d3dy5uZXdzLW1lZGljYWwubmV0L25ld3MvMjAyMDA2MTIvQS1jbGFzcy1vZi1pbnRlcmZlcm9ucy1iZWluZy10ZXN0ZWQtZm9yLUNPVklELTE5LW1heS1pbmNyZWFzZS1zdXNjZXB0aWJpbGl0eS10by1iYWN0ZXJpYWwtaW5mZWN0aW9ucy5hc3B40gGYAWh0dHBzOi8vd3d3Lm5ld3MtbWVkaWNhbC5uZXQvYW1wL25ld3MvMjAyMDA2MTIvQS1jbGFzcy1vZi1pbnRlcmZlcm9ucy1iZWluZy10ZXN0ZWQtZm9yLUNPVklELTE5LW1heS1pbmNyZWFzZS1zdXNjZXB0aWJpbGl0eS10by1iYWN0ZXJpYWwtaW5mZWN0aW9ucy5hc3B4
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