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This is a cross-sectional multi-dimensional immune phenotyping & patient surveys in people with or without LC, who got COVID during the 2020 first wave, on average more than a year from infection. Most were not-hospitalized, ♀ dominant, younger to middle age. (4/)
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This study was led and executed by my amazing colleague, @michelle_monje & her team + @PutrinoLab @MountSinaiNYC, @nathavindra et al. From our Yale team, I wish to highlight @peowenlu @ericsongg and others listed here 💪🏼 (14/)
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Very interesting. Vaccines can induce immune responses to clear persistent viral infection. Relevance to #longCOVID?
In this WAS patient;
1) mRNA vax (but not infection) induced antibody to the Spike
2) mRNA vax ⬆️ IFN-g secreting T cells
3) Vax cleared persistent 🦠 twitter.com/Primary_Immune…
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In contrast to autoantibodies, REAP detected elevation in IgG against herpesvirus antigens. In particular, antibody reactivity to glycoproteins and early antigens of Epstein-Barr virus, Varicella zoster virus were elevated in long COVID over other groups. (17/)
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“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/…
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However, REAP did find notably elevated autoantibodies to sodium ion transporters in a subset of Long COVID patients who displayed reactivities agains 6-9 different proteins of this family. Those with tinnitus and nausea had elevated levels of these AABs. (16/)
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This study found 39 breakthrough cases (85% alpha variant) in 1497 fully vaccinated healthcare workers. Most breakthrough cases were mild/asymptomatic, but 19% developed long COVID (>6 weeks); loss of smell, cough, fatigue, weakness, dyspnea, or myalgia.
nejm.org/doi/full/10.10…
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To achieve this goal, @peowenlu & @ericsongg used a mouse model developed by @BenIsraelow & @ericsongg in which we can control where the infection happens. Using AAV-hACE2 intratracheally, we can confine the SARS-CoV-2 infection only to the lungs. (3/)
rupress.org/jem/article/21…
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What other changes are happening in the brain of mice with mild respiratory infection? Within just 7 days of infection, we found a loss of ~1/3 of oligodendrocytes, which persisted for at least 7 weeks! Analysis by @ThisIsAnthonyFC and @AnnaGeraghty2 (12/)
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Somewhat unexpectedly, we also see that some of these cytokines remain elevated at 7 weeks post infection in both sera and CSF. Similarly elevated cytokines have been reported from the sera of long COVID patients by others, months after primary infection. (6/)
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The intranasal spike protein booster will also be much easier to administer (via nasal spray), quite stable (just protein) and is much more likely to be accepted by people who are hesitant of mRNA or those with needle phobia. (16/)
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Our latest study is about an immunocompromised patient with persistent COVID ➡️ treated with remdesivir but developed resistant mutation ➡️ was then cured by monoclonal Ab cocktail. Study by @gandhisk @sneakyvirus1 @epidememeology @marioph13 et al. (1/)
medrxiv.org/content/10.110…
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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
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Here is a piece I wrote with Dr. Albert Ko on why we need booster doses to maintain our immune responses against SARS-CoV-2. Help educate your immune system by being up to date with your booster doses to prevent severe COVID. @YaleCII @YaleSPH @YaleMed
time.com/6198402/covid-…
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Nasal Spray Booster Keeps COVID-19 at Bay - an excellent piece by Meghan Rosen.
So grateful to @HHMINEWS for stepping up and supporting our research efforts on COVID - on acute COVID, #longCOVID pathogenesis and vaccine strategies against SARS-CoV-2 🙏🏼
hhmi.org/news/nasal-spr…
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So what do systemic (serum) and local (cerebrospinal fluid; CSF) cytokines look like after this mild respiratory-only infection? Not surprisingly, we see many elevated cytokines 7 days after infection in the serum. We also see elevated cytokines in the CSF. (5/)
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To elicit mucosal immunity from scratch, live attenuated vaccines are often necessary, due to the need to introduce sufficient antigen and innate immune signals needed for priming via mucosal surfaces. Live vaccines are not safe for immunocompromised. (3/)
nature.com/articles/s4157…
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In fact, mice infected only in the respiratory tract show no evidence for weight loss (a disease measurement)(B),and no evidence of SARS-CoV-2 infection in the brain (C). (4/)
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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…
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What can lead to impaired neurogenesis in hippocampus? We looked into a chemokine called CCL11 (eotaxin-1) which was shown to reduce neurogenesis (Villeda et al). In our mice, CCL11 was elevated in the CSF 7 weeks after mild respiratory infection. (10/)
pubmed.ncbi.nlm.nih.gov/21886162/
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Several features significantly distinguished Long COVID (double negative B cells, serum galectin-1, various EBV epitopes) while others were negatively associated (serum cortisol, PD-1+ CD4+ TCM, and HSV1 and HSV2 motifs). (22/)
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Very important work by @PGTimmune and colleagues showing that repeated SARS-CoV-2 antigen exposure (infection and/or vaccines) does not lead to an exhausted T cell phenotype.
#GetBoosted
nature.com/articles/s4159… twitter.com/PGTimmune/stat…
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Q: Why can nasal vaccines do?
A:“Nasal sprays assemble a separate set of antibodies known as immunoglobulin A (IgA). These populate the spongy mucosal tissues of the nose, mouth and throat, where the COVID-causing coronavirus first lands." #PrimeandSpike
By @mvbroadfoot twitter.com/sciam/status/1…
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In #longCOVID patients, “exercise capacity was primarily limited by impaired systemic EO2 of such severity that what should have been an adequate increase in DO2 was insufficient to allow for an increase in VO2.” Via @YalePCCSM
sciencedirect.com/science/articl…
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So wonderful to see this work published! Timing is everything when it comes to immune control of COVID. Neutralizing antibody production is delayed in lethal COVID. By the brilliant @carolilucas @sneakyvirus1 & #YaleIMPACT team 💪🏼(1/n) twitter.com/NatureMedicine…
We study innate and adaptive immunity against viruses and study disease pathogenesis. #COVID19 #longCOVID #vaccines @HHMINEWS @YaleIBIO @YaleMed @YaleCII