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Prof. Akiko Iwasaki Profile picture
@VirusesImmunity
Sep 30, 2020 • 9 tweets • 7 min read • Read on X
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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)
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)
cell.com/cell-host-micr…
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)

immunology.sciencemag.org/content/5/49/e…

sciencedirect.com/science/articl…

rupress.org/jem/article/21…

nature.com/articles/s4158…

sciencedirect.com/science/articl…

science.sciencemag.org/content/369/65…

science.sciencemag.org/content/369/65…

stke.sciencemag.org/content/10/509…
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)

science.sciencemag.org/content/369/65…
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)

science.sciencemag.org/content/early/…

science.sciencemag.org/content/early/…

jamanetwork.com/journals/jama/…
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)

clinicaltrials.gov/ct2/results?co…

sciencemag.org/news/2020/07/c…

covid19treatmentguidelines.nih.gov/immune-based-t…

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More from @VirusesImmunity

Prof. Akiko Iwasaki Profile picture
Jun 19
Sharing our new study by @keylas3, @SilvaJ_C, Rafael Bayarri Olmos et al (with T. Horvath & @PutrinoLab) showing that a passive transfer of IgG from patients with #longCOVID into mice recapitulates ⬆️ pain and other symptoms 🧵 (1/)

medrxiv.org/content/10.110…
Long COVID disease pathogenesis includes persistent SARS-CoV-2 virus, dysbiosis, herpesvirus reactivation, autoimmunity, and others. In this study, we focus on the role of autoantibodies. (2/) Image
Among the original Mount Sinai-Yale Long COVID study participants 👇🏼 (with @PutrinoLab), we focused on patients with high neurological symptom burden (n=55), and compared antibodies with convalescent controls (n=42) or uninfected controls (n=39). (3/)
nature.com/articles/s4158…
Read 20 tweets
Prof. Akiko Iwasaki Profile picture
Jun 19
What determines whether someone gets infected or not after exposure to SARS-CoV-2? A new study by Lindeboom et al examined this question with COVID-19 human challenge study. @BenIsraelow and I summarize their key findings in this News & Views 🧵 (1/)
nature.com/articles/d4158…
The study: 16 healthy young volunteers with no prior infection or vaccination were inoculated nasally with a low dose of pre-Alpha SARS-CoV-2 strain. Interestingly, only 6 had sustained infection, 3 had transient, and 7 had abortive infection at this dose. (2/) nature.com/articles/s4158…Image
The three infection outcomes allowed investigation of key features associated with susceptibility vs. resistance. Higher baseline expression of HLA-QA2 mRNA was associated with COVID resistance. Early nasal interferon I response was seen in those with transient infection. (3/) Image
Read 10 tweets
Prof. Akiko Iwasaki Profile picture
Apr 22
Preventing infection is the best way to avoid diseases like #PAIS. A new study from our team @tianyangmao, Jooyoung Kim, @marioph13 et al shows that a generic antibiotic neomycin acts on the host immune system in the👃🏽to trigger antiviral resistance. (1/)🧵
pnas.org/doi/10.1073/pn…
This work is inspired by @SmitaGopinath et al who showed that an antibiotic class called aminoglycosides has an unusual antiviral property. Aminoglycosides including neomycin trigger interferon-stimulated genes through a TLR3-dependent mechanism. (2/)
ncbi.nlm.nih.gov/pmc/articles/P…
In our current study, we showed that nasal application of neomycin in mice one day before infection reduces viral load and disease burden after the SARS-COV-2 challenge. @tianyangmao (3/) Image
Read 11 tweets
Prof. Akiko Iwasaki Profile picture
Mar 3
Delighted to share our latest work on #longCOVID - sex differences in symptoms and immune signatures. Led by @SilvaJ_C @taka_takehiro @wood_jamie_1 et al. with @LeyingGuan & @PutrinoLab. We find a striking inverse correlation btw testosterone levels and symptom burden👇🏼 (1/)

medrxiv.org/content/10.110…
This work leverages data from our recent Mount Sinai-Yale long COVID "MY-LC" study with the @PutrinoLab. This time, we asked the question, "Are there differences in symptoms and immune signatures of ♀️ vs. ♂️ with LC"? (2/)

nature.com/articles/s4158…
Image
While some symptoms were equally frequent in females and males, many were more frequent in females (e.g., swelling, headaches, muscle pain, cramps) than males. The top distinguishing symptoms of LC status by sex were hair loss in females and sexual dysfunction in males. (3/) Image
Read 16 tweets
Prof. Akiko Iwasaki Profile picture
Jan 13
In this prospective observational study, we examined changes in symptoms & immune phenotypes in vaccine-naïve people with #LongCovid after COVID-19 vaccination. Due to the timing of the initiation of this study, we were only able to recruit 16 people. However, the insights we gained are intriguing. Led by @connorbgrady, @bornali_27, @silva_JC, @hmkyale et al. (1/)
medrxiv.org/content/10.110…Image
This study was initiated in collaboration with @Survivor_Corps @dianaberrent based on their Facebook poll showing that 40% of respondents with self-reported Long COVID had mild to full symptom resolution after vaccination while 14% reported worsening of their symptoms. (2/)
doi.org/10.1101/2021.0…
In addition, evidence from other patient advocate groups, including @patientled and @longCovidSOS, and from @DanielGriffinMD, was emerging at the time on the impact of COVID vaccines in people with long COVID. (3/)
Read 19 tweets
Prof. Akiko Iwasaki Profile picture
Sep 25, 2023
So pleased to report that our Mount Sinai-Yale long COVID (MY-LC) paper with @putrinolab & others is now published!! Proud of the hard work of all who contributed. We found biological signatures that can distinguish people with vs. without #longCOVID (1/) nature.com/articles/s4158…
Question being asked: are there circulating cells & immune factors that are distinct in people with #longCOVID (LC) vs. those who recovered from COVID (convalescent control; CC) or those who never had COVID (healthy control; HC)? We studied 268 participants to address this. (2/) Image
Most participants were infected during the first wave in 2020, and studied on average about a year after the infection. Most were not hospitalized at acute phase and ~2/3 were female. We examined plasma factors, blood leukocytes & antibodies to SARS2, other viruses & self (3/) Image
Read 11 tweets

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