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/)

Please read our latest review by @jan_choutka et al. on “Unexplained post-acute infection syndromes”.

What a privilege to work with Jan Choutka, who is an #MECFS patient, expert and advocate. Grateful to @mhornig on her expertise/insights 🙏🏼 (1/)

nature.com/articles/s4159… With millions of #longCOVID patients, it is becoming better known that even a mild infection can lead to longterm debilitating health problems. SARS-CoV-2 joins the long list of other pathogens that cause post-acute infection syndrome (PAIS). (2/)

In this study, @MiyuMoriyama et al investigate how well SARS-CoV-2 variants of concern (VOC) suppress MHC I needed for recognition by cytotoxic T cells. This question is important to understand how well the virus limits CD8 killing 🧵(1/) @biorxivpreprint
biorxiv.org/content/10.110… CD8 T cells help fight off viral infection by detecting and killing infected cells. CD8 T cells detect MHC I + viral peptide on infected cells. One of the common tricks viruses use to avoid killing is to inhibit MHC I expression and presentation. (2/)

pubmed.ncbi.nlm.nih.gov/19498380/

A Phase 2 clinical trial of oral camostat mesylate during early phase of COVID-19 in outpatients reduced illness course (including fatigue) and prevented loss of smell and taste!
Work of fantastic colleagues at @YaleMed. (1/)

medrxiv.org/content/10.110… This randomized double-blind placebo-controlled phase 2 trial gave patients (within 3 days of testing PCR+) either oral camostat mesylate or placebo pills, 4x/day for 7 days. Note the lower smell/taste scores (meaning better ability to smell and taste) in camostat group (2/)

This new preprint by Stadler et al. integrated data from 37 randomized controlled trials to ask how the timing and dose of passive antibodies (monoclonal Ab & convalescent plasma) predict protection from SARS-CoV-2 disease. A short 🧵 (1/)

medrxiv.org/content/10.110… Timing: the study found that the earlier the patients were treated with monoclonal antibodies (mAb) or convalescent plasma (CP), the more effective the passive antibodies were in preventing the clinical outcome measured (indicated by right end of line). #TheEarlierTheBetter (2/)

What immune cell features are most predictive of COVID outcomes?
@mkuchroo @JcsHuang Patrick Wong et al used ML algorithm Multiscale PHATE to assign each immune cell type in COVID patients a mortality-likelihood score. Latest from @KrishnaswamyLab 💪🏼 (1/)
go.nature.com/3K0QCqi Based on the flow cytometry data on 54 million cells from COVID 168 patients, the low density granulocytes (neutrophils and eosinophils) were the most enriched cell types in patients who had fatal COVID, followed by inflammatory monocytes and certain B cell subsets. (2/)

“COVID toes” are swollen discolored toes (and fingers) that were seen in areas with high incidence of COVID-19, but the cause is unknown. This new study by @JeffGehlhausen et al shows lack of association between covid toes and SARS-CoV-2 infection. 🧵(1/)

pnas.org/content/119/9/… We enrolled 23 pandemic chilblains (PC) patients. While there is an association with community COVID cases (blue line) and PC (red bars), only 2 PC patients had evidence of infection by PCR or antibodies. We wondered if people may have missed the time window for testing +ve. (2/)

Vaccines that reduce infection & disease are needed to combat the pandemic. Here, @tianyangmao @BenIsraelow et al. describe our new mucosal booster strategy, Prime and Spike, to induce such immunity via nasal delivery of unadjuvanted spike vaccine 🧵 (1/)

biorxiv.org/content/10.110… Current COVID vaccines are given intramuscularly. This induces robust circulating antibodies and systemic T & B cell responses that block viral spread and disease. However, to better block infection, immunity has to be established at mucosal surfaces. (2/)
annualreviews.org/doi/10.1146/an…

So excited to be a part of this important study led by @michelle_monje on how significant longterm neurologic damage can occur after a mild respiratory-only SARS-CoV-2 infection. My own🧵on the findings of this study with relevance to #longCovid (1/)

biorxiv.org/content/10.110… How can a mild respiratory SARS-CoV-2 infection lead to longterm neurological symptoms? Possibilities include 1) direct infection of 🧠, 2) autoimmunity, and 3) inflammatory impact of infection distal to the 🧠. In this study, we focused on 3) 👇🏽 (2/)

CoronaVac is an inactivated SARS-CoV-2 vaccine approved for use in 48 countries. In collaboration with the Ministry of Health in Dominican Republic, we tested whether CoronaVac (2x) + Pfizer booster induces neutralizing Abs to Delta and Omicron. (1/)

medrxiv.org/content/10.110… We analyzed plasma samples from 101 participants in Dominican Republic (DR) who received the BNT162b2 booster >4 weeks after the 2x of CoronaVac. We compared them to samples from people at Yale who received 2x of BNT162b2.
⬆️ ⬆️ Ab induced by heterologous prime & boost.(2/)

This thread is about our new preprint on transposable element called long interspersed nuclear elements (LINE-1/L1). When expressed excessively in the cerebellum, L1 causes ataxia (impaired coordination).

A fascinating finding by @taka_takehiro 👇🏽 (1/)

biorxiv.org/content/10.110… Human genome is occupied in large part by transposable elements or jumping genes. LINE-1 occupies ~20% of our genome, compared to only 1.1% by exons. Some evolutionarily young LINE-1 are still active and are a rare cause of genetic diseases. (2/)

nejm.org/doi/full/10.10…

Our new study by @JieunOh9 @ericsongg @MiyuMoriyama et al shows that immune priming via intranasal route provides superior protection against heterologous respiratory virus challenge. The key is in inducing local secretory IgA with broader coverage. (1/)

science.org/doi/10.1126/sc… Mucosal surface epithelium expresses polymeric Ig receptor (pIgR), which transports dimeric IgA + J-chain secreted from plasma cells within the tissue, across to the luminal side. IgA dimer + J-Chain + part of pIgR is released as ‘secretory IgA’. Figure by @BioRender. (2/)

Today is #WorldAidsDay2021

Sharing our new review on "Impact of Chronic HIV Infection on SARS-CoV-2 Infection, COVID-19 Disease and Vaccines” by @YYexin. A short thread (1/)

link.springer.com/article/10.100… Despite a number of studies, whether HIV infected individuals are at higher risk of COVID-19 diagnosis, hospitalization, and mortality remains unclear due to variable results found in the population studies, cohort studies, and case series. (2/)