1/ Our newest COVID-19 immunology work is online today at Cell! @ljiresearch cell.com/cell/fulltext/…
2/ We aimed to better understand hospitalized COVID-19 cases by examining virus-specific immune responses all in the same people. SARS2-specific Helper T cells, killer T cells, and neutralizing antibodies.
3/ (I.e., measure the adaptive immune response in acute COVID-19 cases with virus-specific tools.)
4/ The three main findings are:
A) Coordinated adaptive immune responses (CD4, CD8, and antibodies together) were associated with reduced COVID-19 disease severity. The adaptive immune system fights the virus well when the 3 branches work together.
5/
B) T cells appear to do the heavy lifting in controlling an active SARS-CoV-2 infection. Virus-specific helper T cells (CD4) and virus-specific killer T cells (CD8) both were significantly associated with lower COVID-19 disease severity.
6/
B) Older people were much less likely to make a coordinated adaptive immune response. It appears that weak or absent T cell responses is a contributing risk factor for why older people are so much more susceptible to severe or fatal COVID-19.
7/ The susceptibility of older people to severe COVID-19 may be, in part, because older people have fewer ’naive’ (inexperienced) T cells, which can make it harder for them to recognize and fight a new virus.
cell.com/cell/fulltext/…
8/ We think this work fills an important piece of the COVID-19 puzzle. It looks like the adaptive immune responses are generally a good thing in the fight against this virus, and it is the absence of an adaptive immune response in some people that is a big problem in severe COVID
9/ The problem of older people making T cell responses highlights issues to consider in treatment of COVID-19 cases, and the importance of vaccines electing strong immune responses in older people against COVID-19.
10/ This was a big team effort by the Crotty lab,
@SetteLab , @EOSaphire , @ljiresearch, and UCSD Infectious Disease clinicians!

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More from @profshanecrotty

24 Sep
1/ There are several major aspects of what Scott Atlas is saying that are wrong.
2) There is no direct evidence that pre-existing T cell immunity affects COVID-19 infections. LJI researchers and other have proven that such T cells exist, but neither we nor anyone else have shown that the pre-existing T cells make COVID-19 better, worse, or no difference.
3) To say it another way, There is no direct evidence that crossreactive memory T cells to common cold viruses affects COVID-19.
Read 8 tweets
21 Sep
Crotty lab member of the week is Carolyn Rydyznski Moderbacher, PhD!
1. Carolyn is the lead author of our new COVID-19 immunology paper studying T cell and antibody responses in acute COVID-19 cases.
cell.com/cell/fulltext/…
@ljiresearch Image
2. Carolyn wasn’t planning on working on COVID-19, but she had developed excellent multi parameter flow cytometry panels for other human T cell studies, and AIM assays, and I needed her to take the lead on COVID-19 T cell work,
3. so she dropped her other project and has worked full time on COVID-19 for the past 6 months, trying to understand immunity to COVID-19. Culminating in the new paper. Image
Read 5 tweets
16 Sep
Our newest COVID-19 immunology work is online today at Cell! bit.ly/3mugShW
We aimed to better understand hospitalized COVID-19 cases by examining virus-specific immune responses all in the same people. SARS2-specific Helper T cells, killer T cells, and neutralizing antibodies.
(I.e., measure the adaptive immune response in acute COVID-19 cases with virus-specific tools.)
Read 10 tweets
8 Sep
1/ Crotty Lab member of the week: Yu (Alex) Kato
Alex led the work just published in @ImmunityCP on the multifaceted ways antigen valency affects B cell responses in vivo. That study is important for vaccine immunology, connecting vaccine designs to immunological rules. Image
2/ He used two photo intravital microscopy, custom engineered proteins, a variety of in vivo models manipulating antigen-specific B cells and CD4 T cells, and all kinds of flow cytometry to figure out this interesting and important puzzle. All told, it was almost 4 years of work!
3/ Alex has also been deeply involved in fantastically successful collaborations with Darrell Irvine's lab at MIT, including a novel vaccine delivery / adjuvant study in @NatureMedicine this year.
Read 4 tweets
31 Aug
1/ Our new paper is out: Multifaceted Effects of Antigen Valency on B Cell Responses In Vivo.
bit.ly/34MMKrJ
There is lots of excitement about nanoparticle vaccine designs, and a general consensus that multivalency is a good thing for vaccines. @ljiresearch @ImmunityCP Image
2/ But, mechanistic immunological understand of the impact of valency has been limited, for a variety of reasons. Here, we completed a four years study of valency and and affinity on antigen-specific B cell responses in vivo.
3/ We found that antigen valency dictates the magnitude and composition of B cell responses. Antigen valency alters breadth of B cell affinities recruited. And valency appears to modulate both the magnitude and the clonal compositions of GC responses.
Read 7 tweets
12 Aug
1/ There are various tweets misinterpreting COVID-19 “pre-existing immunity” and making dangerous claims about herd immunity. Since many of those claims refer to our scientific papers, we will reiterate the facts. @SetteLab @ljiresearch @ScienceMagazine @CellCellPress Image
2/ Our 1st scientific paper showed that ~50% of unexposed people have T cells that recognized SARS-CoV-2 already doi.org/10.1016/j.cell…. The most obvious conclusion was these were memory T cells from previous common cold coronavirus infections, but that was not directly shown. Image
3/ Our 2nd paper, very recently published, showed that these were memory T cells from previous common cold coronavirus infections doi.org/10.1126/scienc…. Five other labs have also published related findings doi.org/10.1038/s41577…
Read 14 tweets

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