Are you confused about the role of type I interferons (IFN) in #SARS_CoV_2 infection?
Here is my speculation on what makes IFN-I helpful vs. harmful in #COVID19 patients - it comes down to timing and dose. A short thread.
All figures made by @BioRender & @annsea_park (1/n)
Here is my speculation on what makes IFN-I helpful vs. harmful in #COVID19 patients - it comes down to timing and dose. A short thread.
All figures made by @BioRender & @annsea_park (1/n)
In the best case scenario, a rapid and robust induction of IFN-I should result in viral control and mild disease. This may happen in young people, or with low viral exposure settings. For a discussion we wrote, please read this.
(2/n)
https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30290-0.pdf">https://www.cell.com/cell-host...
(2/n)
https://www.cell.com/cell-host-microbe/pdf/S1931-3128(20)30290-0.pdf">https://www.cell.com/cell-host...
In older adults or after high dose viral exposure, impaired IFN response early during infection results in enhanced viral replication, and prolonged levels of IFN-I and IFN-III responses that could result in pathological consequences and severe disease. (3/n)
Some papers supporting this scenario can be found here. (4/n)
https://immunology.sciencemag.org/content/5/49/eabd1554">https://immunology.sciencemag.org/content/5...
https://www.sciencedirect.com/science/article/pii/S009286742030489X?via%3Dihub
https://www.sciencedirect.com/science/a... href=" https://rupress.org/jem/article/217/12/e20201241/151999/Mouse-model-of-SARS-CoV-2-reveals-inflammatory
https://rupress.org/jem/artic... href=" https://www.nature.com/articles/s41586-020-2588-y
https://www.nature.com/articles/... href=" https://www.sciencedirect.com/science/article/pii/S1931312816300063?via%3Dihub
https://www.sciencedirect.com/science/a... href=" https://science.sciencemag.org/content/369/6504/706
https://science.sciencemag.org/content/3... href=" https://science.sciencemag.org/content/369/6504/712
https://science.sciencemag.org/content/3... href=" https://stke.sciencemag.org/content/10/509/eaan2392/tab-figures-data">https://stke.sciencemag.org/content/1...
https://immunology.sciencemag.org/content/5/49/eabd1554">https://immunology.sciencemag.org/content/5...
https://www.sciencedirect.com/science/article/pii/S009286742030489X?via%3Dihub
https://www.sciencedirect.com/science/a... href=" https://rupress.org/jem/article/217/12/e20201241/151999/Mouse-model-of-SARS-CoV-2-reveals-inflammatory
https://rupress.org/jem/artic... href=" https://www.nature.com/articles/s41586-020-2588-y
https://www.nature.com/articles/... href=" https://www.sciencedirect.com/science/article/pii/S1931312816300063?via%3Dihub
https://www.sciencedirect.com/science/a... href=" https://science.sciencemag.org/content/369/6504/706
https://science.sciencemag.org/content/3... href=" https://science.sciencemag.org/content/369/6504/712
https://science.sciencemag.org/content/3... href=" https://stke.sciencemag.org/content/10/509/eaan2392/tab-figures-data">https://stke.sciencemag.org/content/1...
Not all studies show this pattern. Here is a study that showed lower IFN-I levels in more severe COVID patients. It would be interesting to understand this difference. (5/n) https://science.sciencemag.org/content/369/6504/718">https://science.sciencemag.org/content/3...
In the setting of host genetic mutations in viral sensors, signaling molecules, adaptors, transcription factors; or in older people with neutralizing antibodies to IFN-I, little to no IFN-I is available. Uncontrolled virus replication can lead to very severe COVID-19. (6/n)
Papers supporting this scenario can be found here. (7/n)
https://science.sciencemag.org/content/early/2020/09/23/science.abd4585
https://science.sciencemag.org/content/e... href=" https://science.sciencemag.org/content/early/2020/09/29/science.abd4570
https://science.sciencemag.org/content/e... href=" https://jamanetwork.com/journals/jama/fullarticle/2768926">https://jamanetwork.com/journals/...
https://science.sciencemag.org/content/early/2020/09/23/science.abd4585
https://science.sciencemag.org/content/e... href=" https://science.sciencemag.org/content/early/2020/09/29/science.abd4570
https://science.sciencemag.org/content/e... href=" https://jamanetwork.com/journals/jama/fullarticle/2768926">https://jamanetwork.com/journals/...
Finally, recombinant IFN therapy, especially given early during infection, can shut down viral replication and promote recovery. Further, prophylactic treatment with rIFN might be useful in high risk groups. (8/n)
A number of clinical trials are under way to test whether IFN therapy can help #COVID-19 patients recover quickly from infection and disease. Thank you for reading! (End)
https://www.clinicaltrials.gov/ct2/results?cond=COVID-19&term=interferon&cntry=&state=&city=&dist=&Search=Search
https://www.clinicaltrials.gov/ct2/resul... href=" https://www.sciencemag.org/news/2020/07/can-boosting-interferons-body-s-frontline-virus-fighters-beat-covid-19
https://www.sciencemag.org/news/2020... href=" https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/interferons/">https://www.covid19treatmentguidelines.nih.gov/immune-ba...
https://www.clinicaltrials.gov/ct2/results?cond=COVID-19&term=interferon&cntry=&state=&city=&dist=&Search=Search
https://www.clinicaltrials.gov/ct2/resul... href=" https://www.sciencemag.org/news/2020/07/can-boosting-interferons-body-s-frontline-virus-fighters-beat-covid-19
https://www.sciencemag.org/news/2020... href=" https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/interferons/">https://www.covid19treatmentguidelines.nih.gov/immune-ba...