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Prof. Akiko Iwasaki Profile picture
@VirusesImmunity
Sep 30, 2020 • 9 tweets • 7 min read • Read on X
Scrolly
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
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
Prof. Akiko Iwasaki Profile picture
Aug 27, 2023
A short 🧵on a recent study by @MaggieLind2 with @MHitchingsEpi @datcummings Albert Ko et al. Data show that immunity induced by vaccines, prior infection or both (hybrid) protects against SARS-CoV-2 infection when viral exposure is low to moderate (1/)

nature.com/articles/s4146…
Question being asked: What is the risk of becoming *infected* with SARS-CoV-2 after developing immunity following a vaccine, prior infection, or both if exposure to the virus is very high, moderate, or low? They did not study the severity of symptoms. (2/)
How? The authors used the existing database of the Connecticut Department of Correction, where infection data based on high frequency of testing for SARS-CoV-2 on ~9300 residents across 13 facilities were available. (3/)
Read 9 tweets
Prof. Akiko Iwasaki Profile picture
May 5, 2023
A new study in @SciImmunology led by @AnisBarmada & Jon Klein @YaleIBIO with @lucasite_lab @InciYildirim11 @YalePediatrics teams explored immune signatures of people who developed myocarditis after mRNA vaccines. Here is what we found. 🧵 (1/)
science.org/doi/10.1126/sc…
Myocarditis is a rare adverse event that occurs most frequently in adolescent and young adult males after the second dose of mRNA vaccines. However, the underlying mechanisms remain unclear. (2/)

cdc.gov/vaccines/covid…
We considered three possible immune mechanisms of myocarditis.
1) Autoimmune/molecular mimicry
2) Hypersensitivity/eosinophilic type 2 immunity
3) Cytokine-mediated lymphocyte/macrophage activation
(3/)
Read 19 tweets

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