Latest preprint by @tianyangmao et al shows that a stem-loop RNA RIG-I agonist in mice can
1) Block viral replication and disease when given early after SARS-CoV-2 infection (including VOCs)
2)Eliminate chronic infection in immunodeficient mice
We urgently need antiviral agents that can work against any viral threats. Here, we use a stem-loop RNA developed by @AnnaPyle to trigger interferon to stimulate antiviral state. Work by @MelissaLV14 et al demonstrated robust ISG induction in mice👇🏽 (2/)
First, we wanted to know if SLR can be used as a post-exposure prophylaxis. Mice infected with lethal dose of SARS-CoV-2 were treated with SLR 4 hours after exposure. SLR-treated mice had no detectable infectious virus 5 days later and most survived. (3/)
Next, we asked whether interferon signaling is required for the SLR-mediated protection. Mice injected with blocking antibodies to IFNAR were no longer protected by SLR from SARS-CoV-2 infection. Thus, SLR-mediated protection depends on IFN-I signaling. (4/)
How late can we administer SLR to observe protection? Compared to robust protection at 4 hours, injection of SLR 24 h and 48 h post exposure protected only partially, and at 72 h, no protection was observed. (Note: mouse disease course is accelerated compared to humans)(5/)
We also tested SLR in a mouse model of immunodeficiency. Here, we used RAG-deficient mice (devoid of T or B cells) that become persistently infected. In immunocompromised patients, prolonged SARS-CoV-2 infection has been widely reported (see @Primary_Immune’s tweets) (6/)
What is remarkable is that a single injection of SLR in persistently infected animal was able to eliminate infectious virus in most of the treated mice. Thus, in the absence of adaptive immunity, robust IFN response is sufficient to eliminate persistent virus infection 🤯 (7/)
Is SLR effective against the VOCs? SLR injection 4 hours post exposure with P.1, B.1.526, B.1.351 or B.1.1.7 led to significant protection from disease & death. Difference in effectiveness might reflect the IFN-resistance of these variants.
To sum up, the work led by @tianyangmao showed that a small RNA RIG-I agonist can be used in prophylactic, post exposure, and chronic infection settings to combat COVID-19. Since SLR works by triggering host innate immune defense, it works against a wide range of viruses. (9/)
To bring SLR to patients, @annapyle and I co-founded a company called #RIGImmune. For people interested in learning more about this technology, please attend the upcoming webinar hosted by @YaleOCR (10/)
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/)
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/)
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/)