Prof. Akiko Iwasaki Profile picture
Apr 22 11 tweets 4 min read Read on X
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
Intranasal application of neomycin also protected mice against highly virulent influenza virus infection. @MiyuMoriyama (4/) Image
We could also treat mice already infected with SARS-CoV-2 with nasal application of neomycin 4 hours later, in a dose-dependent manner. This led to viral load reduction and increased survival. @tianyangmao (5/) Image
What about transmission? Hamsters trx 1 day earlier with neomycin were protected from catching the virus from an infected hamster in the same cage. Even if they did, their viral load was ⬇️. Thus, neomycin applied in the nose can shield the host from COVID transmission. @marioph13 (6/)Image
OK, but does this work in humans? Collaborating with @CDelaCruzMed, we ran a small randomized, double-blind, placebo-controlled trial involving healthy human volunteers, who applied OTC Neosporin (containing neomycin) (n=12) or placebo (vaseline) (n=7) twice daily into their noses with cotton swabs. (7/)Image
More than half of the human volunteers who applied Neosporin into their noses showed robust antiviral gene expression (interferon-stimulated genes) measured by nasal brush, compared to placebo controls. We believe we can ⬆️ efficacy with higher neomycin doses. (8/) Image
We acknowledge the limitations of the study and propose future improvements we can make. (9/) Image
In a nutshell, we showed that over-the-counter cheap generic antibiotic neomycin can be repurposed in nasal formulation to prevent & treat infection, block transmission, and reduce disease burden against a wide array of viruses. Since this is a host-directed strategy and virus-agnostic, it holds promise as a prophylactic strategy against any viral threat. (10/)
Here are the amazing people who made this study possible, and we are grateful for all the human volunteers who participated in the pilot trial. We are grateful to the @gatesfoundation for the encouragement and support of this research 🙏🏽 (end) Image

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More from @VirusesImmunity

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
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
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
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
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
Mar 21, 2023
Very excited that our PaxLC clinical trial on #longCOVID patients is now open, led by @hmkyale! This is a phase 2, 1:1 randomized, double-blind, placebo-controlled research study in 100 non-hospitalized highly symptomatic long COVID. (1/)

clinicaltrials.gov/ct2/show/NCT05…
We will be providing paxlovid or placebo pills in long haulers for 15 days. The primary outcome will be measured by asking the patients to fill out some questionnaires pre & post treatment. We will find out whether their health changes with paxlovid vs. placebo. (2/)
Before, during, and after treatment, we will do a deep dive immune profiling to see if any changes are detected due to Paxlovid. We will apply a similar strategy that we used in our study with @PutrinoLab to understand the immune and viral signatures (3/)

medrxiv.org/content/10.110…
Read 10 tweets

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