Prof. Akiko Iwasaki Profile picture
Sep 25 11 tweets 4 min read Twitter logo Read on Twitter
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/) Image
Most participants were infected during the first wave in 2020, and studied on average about a year after the infection. Most were not hospitalized at acute phase and ~2/3 were female. We examined plasma factors, blood leukocytes & antibodies to SARS2, other viruses & self (3/) Image
Before we get to immune phenotype, the clinical symptom surveys by @PutrinoLab of these people alone were able to accurately differentiate those with vs. without long COVID with 94% accuracy. These survey instruments can be a great diagnostic tool for long COVID. (4/) Image
What biological factors did we find? Key findings = people with long COVID had 1) lower circulating cortisol, 2) higher activated B and cytokine-secreting T cells, 3) higher anti-Spike IgG, 4) higher EBV reactive Abs. No significant differences in # of autoantibodies. (5/) Image
Machine learning identified key immune factors that can distinguish those with long COVID. These factors included lower levels of cortisol, conventional DC1, central memory T and higher levels of EBV IgG, galectin-1, APRIL...etc. (6/) Image
What does this mean? The study is exploratory and signal seeking, not hypothesis testing. It is a first step in identifying biomarkers that can be used in the future to diagnose long COVID. To get there, we still need to validate these markers in external cohorts. (7/)
What are limitations of the study? They include small sample size, only analyzed autoantibodies to exoproteome, no T cell specificity analyzed, insights from the earlier variants and may not apply to Omicron...etc. (8/)
What are the strengths? Deep clinical and biological phenotyping of closely and explicitly matched long COVID and control groups. External cohort validation. New insights on EBV reactivation and Th2 correlation, hormonal dysregulation suggestive of HPA axis defects. (9/)
This study is a result of incredible dedication and hard work by the MY-LC team, headed by Jon Klein, @wood_jamie_1 @_BlueJay3 @rahuldhodapkar @peowenlu @JeffGehlhausen @S_Tabachnikova and many others, with senior co-authors, @DavidvanDijk19, Aaron Ring & @PutrinoLab (10/) Image
Most importantly, we are grateful for all the participants who contributed their time, effort, blood and medical information to better understand long COVID disease pathogenesis. Very grateful to all those involved 🙏🏽 (end)

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Prof. Akiko Iwasaki

Prof. Akiko Iwasaki Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @VirusesImmunity

Aug 27
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/)
How? The authors used the existing database of the Connecticut Department of Correction, where infection data based on high frequency of testing for SARS-CoV-2 on ~9300 residents across 13 facilities were available. (3/)
Read 9 tweets
May 5
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…
We considered three possible immune mechanisms of myocarditis.
1) Autoimmune/molecular mimicry
2) Hypersensitivity/eosinophilic type 2 immunity
3) Cytokine-mediated lymphocyte/macrophage activation
(3/)
Read 19 tweets
Mar 21
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/)
Before, during, and after treatment, we will do a deep dive immune profiling to see if any changes are detected due to Paxlovid. We will apply a similar strategy that we used in our study with @PutrinoLab to understand the immune and viral signatures (3/)

medrxiv.org/content/10.110…
Read 10 tweets
Mar 21
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/)
CD8 T cell responses to viral antigens were compared in people who received the mRNA vaccines to those with prior infection with SARS-CoV-2. The vaccine induced significantly better CD8 T cell immunity in both quantity and quality than the infection. (3/)
Read 10 tweets
Mar 8
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/) Image
Next, @weizmano used various mice with depletion in dendritic cell types and found that CD11b+ dendritic cells (but not monocytes, CD301b+, or DC1) were required to contain the rapid growth of metastatic cells. (3/) Image
Read 11 tweets
Dec 26, 2022
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…
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/)
Note that MHC I surface levels are only downregulated in the infected (S+) cells, but not in the uninfected cells (S-) in the same tissue culture wells. SARS-CoV-2 evades recognition of the infected cells by cytotoxic T cells but has no impact on the surrounding cells. (3/)
Read 5 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!

Ethereum

0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy

Bitcoin

3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us on Twitter!

:(