Happy to share our latest work by @YYexin et al. on antibody-mediated control of endogenous retroviruses in mice. In the process, we found “natural antibodies” with broad reactivity against enveloped viruses. Here is how “panviral” antibodies work 🧵(1/)

science.org/doi/10.1126/sc… Endogenous retroviruses (ERV) are remnants of genetic invaders that have integrated into our ancestors' genomes over millions of years. ERVs occupy ~8% of the human genome and are under constant host immune surveillance. (2/)
nature.com/articles/nrg31…
nature.com/articles/nrmic…

This time, we developed a nasal booster vaccine for influenza viruses. In this preprint, @MiyuMoriyama et al. show that nasal boosters with unadjuvanted hemagglutinin protein induce sterilizing immunity in mice against flu. (1/)
biorxiv.org/content/10.110… This work builds on the Prime and Spike vaccine strategy by @tianyangmao @BenIsraelow et al. against COVID where mRNA vaccine followed by nasal booster with recombinant spike protein established local immunity, ⬇️ infection & transmission in rodents. (2/)
science.org/doi/10.1126/sc…

Much-needed data on the genetics of #longCOVID in a new preprint by @23andMeResearch - GWAS of #LongCOVID identified 3 loci pointing to immune and thrombo-inflammatory mechanisms 🔥 @ninaadsc
1) HLA-DQA1–HLA-DQB
2) ABO
3) BPTF–KPAN2–C17orf58
(1/)
medrxiv.org/content/10.110… Among research participants who reported acute SARS-CoV2 infection, 64,384 participants reported to have experienced Long COVID and 178,537 participants did not. Their analytical cohort consisted of 54,390 cases and 124,777 controls 👇🏼 (2/)

Keynote talk by @MichaelPelusoMD. “#LongCovid is not a mystery anymore. Working with patients, I have optimism that we can figure this out.” #YaleCIISymposium An excellent framework in thinking about the pathogenesis of #LongCovid
@MichaelPelusoMD

Sharing this scoping review on "Post-Acute sequelae of COVID-19 in pediatric patients within the United States" by @ChrisMillerDO - an amazing @YalePediatrics infectious diseases fellow focused on research and treatment of #longcovidkids (1/)

sciencedirect.com/science/articl… Key findings:
- Most pediatric LC patients were adolescents.
- ♀>♂️
- 80% of pediatric LC patients started with a mild initial infection.
- Asthma, atopy, allergic rhinitis (type 2 immune diseases), and obesity were frequently reported pre-existing conditions. (2/)

An important study by F. Eun-Hyung Lee's team shows that long lived plasma cells (the source of long-term circulating antibodies) fail to establish after mRNA vaccination (even combined with SARS-CoV-2 infection). 🧵 (1/)
nature.com/articles/s4159… The longevity of antibody-mediated protection against infectious diseases rely on whether or not the vaccines can establish long lived plasma cells (LLPC) in the bone marrow. They are the source of circulating antibodies for years to decades. (2/)
nature.com/articles/s4159…

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

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/)

medrxiv.org/content/10.110… 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/)

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…

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…

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…

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…

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/)

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/)

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…

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/)

A very interesting paper from Dr. Mark Davis’ group shows that in response to the mRNA vaccine, CD8 T cell responses are attenuated in people who had prior COVID compared to uninfected people. What does this mean? (1/)

doi.org/10.1016/j.immu… Fei Gao, @VMallajosyula et al used SARS-CoV-2 pMHC-spheromers to detect viral antigen-specific CD8 and CD4 T cells from people who were vaccinated, infected or both. Spheromers are peptide-MHC multimers (12 units) that are more sensitive than conventional pMHC tetramers. (2/)

Does the innate immune system recognize metastatic cells and control their growth?

@weizmano et al found that type 2 dendritic cells and natural killer cells orchestrate very early immunity against metastatic cancer cells in the lung 👇🏽 (1/)

journals.aai.org/jimmunol/artic… Adaptive immune system is important to ultimately eliminate cancer cells. However, what happens in the first days after metastatic cells arrive in a target tissue? @weizmano looked at the first 3 days after metastasis and found leukocyte recruitment around the cancer cell. (2/)

A while ago, @MiyuMoriyama et al showed that SARS-CoV-2 variants suppress MHC I levels in infected cells to the same degree as the ancestral virus. Then came the Omicron variants. A short update. (1/) biorxiv.org/content/10.110…

https://twitter.com/VirusesImmunity/status/1522939444856193024

Since the original submission, @MiyuMoriyama, with the help of @NathanGrubaugh's team & @carolilucas, obtained and analyzed the ability of Omicron subvariants shown here 👇🏽 Miyu gated on spike-positive (infected) cells and compared MHC I levels to uninfected (S-) cells. (2/)

Very excited to share our latest research on immunological features of #LongCovid. Our 2+ year collaboration with @PutrinoLab with many other fantastic colleagues and patients - Mount Sinai Yale Long COVID (MY-LC) study by @sneakyvirus1 et al. 🧵(1/)

medrxiv.org/content/10.110… This work is led by the amazing @sneakyvirus1 with @wood_jamie_1 @_BlueJay3 @peowenlu @rahuldhodapkar @JeffGehlhausen @S_Tabachnikova from @aaronmring @david_van_dijk @PutrinoLab labs, with @hmkyale @SaadOmer3 @InciYildirim11 @RMedzhitov and @serimmune team & many others 👇🏽 (2/)

A brilliant & timely review by Prof. #DianeEGriffin on the persistence of viral RNA following RNA virus infection - which can be associated with late progressive disease or nonspecific lingering symptoms of post-acute infection syndromes (#PAIS). (1/)

dx.plos.org/10.1371/journa… First question addressed is WHERE viral RNA can persist. After a variety of RNA virus infection, viral RNA can persist not only in immune privileged sites (brain, eyes, and testes), but also in blood, lymphoid tissue, joints, respiratory tract, GI tissues, and kidney. (2/)