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/)
Intranasal application of neomycin also protected mice against highly virulent influenza virus infection. @MiyuMoriyama (4/)
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/)
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/)
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/)
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/)
We acknowledge the limitations of the study and propose future improvements we can make. (9/)
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)
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A new study led by @marioph13 in collaboration with the @WilenLab examines two bat coronaviruses that are the closest relatives of SARS-CoV-2 for their ability to infect, evade immunity and transmit between rodents. Some key takeaway points 🧵 (1/) nature.com/articles/s4156…
Here is a link to the accessible manuscript (2/) rdcu.be/dPjsA
We used the highest biosafety level available at Yale (BSL3+) to conduct the study and we did not introduce gain-of-function mutations into the bat viruses. No serial passaging of the viruses were done - to avoid adaptation. Grateful to @YaleEHS for all the support. (3/)
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/)
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/)
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…
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…
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/)
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/)
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/)
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/)
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…
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/)
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/)
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/)