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

🧵(1/)
biorxiv.org/content/10.110…
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/)

advances.sciencemag.org/content/4/2/e1…
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.

biorxiv.org/content/10.110…

(8/)
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/)

yale.zoom.us/webinar/regist…
As with all the work we do, this is a highly collaborative effort of many including @tianyangmao @BenIsraelow @carolilucas @VogelsChantal Olga Fedorova, Mallery Breban, Bridget Menasche, Huiping Dong, @MelissaLV14 @WilenLab Marie Landry @NathanGrubaugh @AnnaPyle 🙏🏼 (end)

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More from @VirusesImmunity

14 May
It’s finally happening! I will be giving a talk today at the #AAI2021 with Dr. Fauci and Dr. Saif in the session, COVID-19 and the Science of Pandemics (12-2PM ET).

My talk will be on “Protective vs. harmful immune responses in COVID-19”. See you there!

immunology2021.org/scientific-pro…
Amazing to listen to Dr. Fauci talk about the decades of basic research that led to the success of COVID vaccines. #AAI2021

“Effectiveness of the vaccines in real world setting is stunning - in every single age group.”
Exciting talk by Dr. Saif focuses on all things mucosal immunity! Secretory IgA, tissue-resident memory B cells and T cells are key to confer durable mucosal immunity. #AAI2021

SARS-CoV-2 infects not only respiratory mucosa, but also found in the gut, eyes and oral cavity.
Read 4 tweets
29 Apr
After many months of planning and hard work by so many (incl. @hmkyale @Dianaberrent @wade_schulz @CharleszYaleMed @Aaronmring @DaisySMassey @JeffGehlhausen), today, we are launching our research study to understand how vaccination may help improve #longcovid. 🧵 (1/n)

Pls RT🙏🏼
This study will examine how vaccines might improve the symptoms of #LongCovid. We are recruiting people with long covid (PCR+, Ab+, T-test+, or COVID diagnosed by medical doctor) who live in Connecticut, >18 years old, and have not received vaccines yet but are planning to. (2/n)
To participate in this study, you will be asked to complete 4 online surveys and provide blood and saliva 3 times at sites in New Haven Connecticut. If you are interested in participating, please email covidrecovery@yale.edu (3/n)
Read 10 tweets
10 Apr
New study by @MHitchingsEpi et al shows that an inactivated vaccine CoronaVac is effective against COVID-19 in a setting of epidemic P.1 variant transmission in Brazil 🇧🇷. A thread. (1/n)

medrxiv.org/content/10.110…
The authors conducted a matched test-negative case-control study to estimate the effectiveness of an
inactivated vaccine, CoronaVac, in healthcare workers in Manaus, where P.1 accounted for ~75% of the circulating virus.(2/n)
Vaccination with at least one dose was associated with an adjusted vaccine effectiveness of 49.6% (95% CI, 11.3 - 71.4) against symptomatic SARSCoV-2 infection >14 days after receiving the first dose. (3/n)
Read 8 tweets
9 Apr
An important thread from @PutrinoLab about why we should not be excluding PCR/Ab negative #LongCovid from analysis. So proud of @PutrinoLab for refusing to succumb to reviewers’ demand -which would have resulted in exclusion of data from underrepresented minorities. (1/)
I wish to highlight the importance of their study in this short thread and why I think it should be published ASAP. 84 people with long covid were examined for various symptoms in a retrospective cross-sectional observational study.(2/)

medrxiv.org/content/10.110…
First, look at the demographic data of those with #LongCovid. Compared to acute severe COVID (in older adults, male>female), long haulers appear more skewed towards women of younger age. (3/)
Read 7 tweets
26 Mar
How does COVID reinfection happen?

Our deep dive into the immune profiles during the 1st and 2nd infections. A case study.

Work led by @sneakyvirus1 @AndersonBrito_ Paul Turbin @peowenlu @BenIsraelow and Marwan Azar (1/)

medrxiv.org/content/10.110…
To address this question, we first looked at other confirmed cases of COVID reinfection. The number of such cases is limited due to the requirement for viral genome sequences in both infections. (2/)
We noted that very little information is available regarding the immune responses that developed during the first infection that can explain why someone would get reinfected. (3/)
Read 14 tweets
14 Mar
Are vaccines harmful or helpful for #longcovid?

@gushamilton and team asked through observational study of COVID patients post discharge - 82% with long lasting symptoms (>8 months). Symptoms compared 1 month post vaccination to the unvaccinated.🧵 (1/)

medrxiv.org/content/10.110…
When compared to matched unvaccinated participants (n=22), those who had receive a vaccine (n=44) had no worsening of symptoms. This is reassuring for people with long covid thinking about getting a vaccine. (2/)
In fact, a small overall improvement in Long Covid symptoms, with a decrease in worsening symptoms (5.6% vaccinated vs 14.2% unvaccinated) and increase in symptom resolution (23.2% vaccinated vs 15.4% unvaccinated)(p=0.035) was reported. This is encouraging 👍🏼 (3/)
Read 6 tweets

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