Profile picture
, 8 tweets, 5 min read
My Authors
Read all threads
Several studies are coming out saying that blood LDH (lactate dehydrogenase) levels early in #COVID19 disease correlates with severe disease progression. This is a clue that #pyroptosis may be a the core of this disease (1/n).

medrxiv.org/content/10.110…
jci.org/articles/view/…
What is LDH? It is an enzyme found within the cytosol of nearly all cells. Ed Miao's group showed that LDH release is a reliable way to monitor #pyroptosis, a form of cell death that depends on inflammasomes leading to plasma membrane rupture. (2/n)

ncbi.nlm.nih.gov/pubmed/23852598
LDH is not released by apoptosis or even hyperactivation of macrophages. It requires pyroptosis and membrane rupture shown by @jkagan1 's group. (3/n)

sciencedirect.com/science/articl…
How might #SARSCoV2 induce pyroptosis? A study showed that #SARSCoV1's Orf8 triggers NLRP3 inflammasome activation and pyroptosis in macrophages. Whether #SARSCoV2 Orf8 also activate pyroptosis is unknown. (4/n)

ncbi.nlm.nih.gov/pubmed/31231549
While LDH correlates well with disease severity, this may not be the reason for severe disease. However, pyroptotic (pyro=fire, ptosis=falling) death is very immunogenic, releasing intracellular contents and can lead to blood clotting. (5/n)

ncbi.nlm.nih.gov/pubmed/31076358
Blood clotting is also associated with poor prognosis in #COVID19. (6/n)

ncbi.nlm.nih.gov/pubmed/32073213
There are other reasons why inflammasome inhibitors might be a promising approach - to increase host disease tolerance. Please see a nice thread by @padminipillai explaining this concept. (7/n)

I believe inflammasome inhibitors should be tested for #COVID19 treatment. I've said this before but I believe it is worth repeating here. I hope pharma companies working on developing such inhibitors for other disease indications can help 🙏🏽 (end)

nature.com/articles/d4157…
Missing some Tweet in this thread? You can try to force a refresh.

Enjoying this thread?

Keep Current with 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!

Twitter may remove this content at anytime, convert it as a PDF, save and print for later use!

Try unrolling a thread yourself!

how to unroll video

1) Follow Thread Reader App on Twitter so you can easily mention us!

2) Go to a Twitter thread (series of Tweets by the same owner) and mention us with a keyword "unroll" @threadreaderapp unroll

You can practice here first or read more on our help page!

Related hashtags

#COVID19 #pyroptosis #SARSCoV2 #SARSCoV1

More from @VirusesImmunity see all

Profile picture
Prof. Akiko Iwasaki
@VirusesImmunity
This is a cautionary tale of how anti-Spike antibody may make COVID disease worse. In this study, the authors show that anti-Spike IgG made SARS-CoV disease worse by switching macrophage from wound-healing to proinflammatory phenotype. A thread (1/n)

insight.jci.org/articles/view/…
When rhesus macaques were immunized with SARS-Spike MVA vaccine, high titers of neutralizing Ab (NAb) generated correlated with severe diffuse alveolar damage NOT protection upon i.n. challenge with SARS-CoV, despite reducing viral load. Loss of disease tolerance by S-IgG. (2/n)
Next, rhesus macaques injected with low or high dose of anti-Spike-IgG (passive transfer) and challenged with SARS developed worse disease. Thus, S-IgG alone can lead to SARS disease exacerbation. (3/n)
Read 8 tweets
Profile picture
Prof. Akiko Iwasaki
@VirusesImmunity
A few years ago, @HShin_Lab developed a new vaccine strategy called 'Prime & Pull' - T cells are pulled into target tissue with chemokines, as #HSV2 vaccine strategy. Now, @SmitaGopinath shows that topical aminoglycosides = potent 'Pull' agent 👇🏽(1/n)

jimmunol.org/content/early/…
This finding follows @SmitaGopinath's earlier work that aminoglycoside antibiotics applied to the genital mucosa induces potent interferon-stimulated genes including CXCL10. Effector CD8 T cell expressing CXCR3 are recruited to the tissue. (2/n)

nature.com/articles/s4156…
Single application aminoglycoside antibiotics are advantageous over recombinant chemokines because they are 1) approved for human use, 2) cheap, 3) effective. #HSV2 #vaccine

Prime & Pull also is very effective when used therapeutically @peowenlu. (3/n)

nature.com/articles/s4154…
Read 3 tweets
Profile picture
Prof. Akiko Iwasaki
@VirusesImmunity
There is a lot of talk about #herdimmunity. Vaccination is the only safe way to achieve it. In the absence of vaccine, we need to practice #SocialDistancing. @BioRender made this amazing infographic to explain how a hypothetical virus spreads through the population. (1/n)
Herd immunity describes indirect protection from infectious disease when a large % of people in a population is immune to the pathogen. The % threshold of immune individuals required for #herdImmunity depends on how contagious (R0) the pathogen is. (2/n)

pbs.org/wgbh/nova/arti…
#herdimmunity can be achieved either through vaccination or through natural infection. However, vaccination is the only safe way to achieve it. It also depends on how effective & long lasting immune response induced by the vaccine or infection to confer #herdimmunity. (3/n)
Read 7 tweets

Related threads

Profile picture
Elemi Fuentes 🇫️🇺️🇨️🇰️
@ElemiFuentes
1- I am getting sick of all these people that go like:
#COVIDー19 is a #hoax because I drove to a hospital and the parking lot/front entrance was empty.

Well genius, they are empty because everybody with minor surgery and non-life threatening conditions has been turned away in
2-In preparation of a crisis. That is way hallways are mostly empty. Visitors no longer can wait in halls.
3-Also, there is the fact that since ppl are at home, there are less car accidents and such that require hospitalizations.
4-People are not going to hospitals unless a real
5-Emergency is threatening their lives.
6-You have something called #Hippa Laws that prevent footage being shown from hospitals. Fortunately for you, same thing doesn't apply to Italy, Turkey, Spain, and others. So if you get a kick out of watching other suffers, get off American
Read 28 tweets
Profile picture
Gary Payinda, MD DDU FACEM
@GaryPayinda
1/ Forward of one US doctor's Covid experience. Self-proning, discharging multilobar pneumonia home, 20-30% survival rate for pts requiring intubation, it's necessary education for the rest of us that may face similar situations in a week or two.
2/ Hope UK and Europe will soon be coming out the other side of the covid case spike. #covid #covid19 #emergencymedicine

"Clinical course is predictable.

2-11 days after exposure (day 5 on average) flu like symptoms start.
3/
Common are fever, headache, dry cough, myalgias (back pain), nausea without vomiting, abdominal discomfort with some diarrhea, loss of smell, anorexia, fatigue.
Day 5 of symptoms- increased SOB, and bilateral viral pneumonia from direct viral damage to lung parenchyma.
Read 33 tweets
Profile picture
Lou Iren Leaf
@louandtongTTC
My husband and I have experienced a traumatizing event in the past 24 hours #covid #personalstory #threadstorytime
A few days ago, we made arrangements with my husband’s sister to have their travelling mom live with us for a bit during the quarantine period immediately after her arrival. My mother in law “officially” lived with my sister in law. And the latter has an immunocompromised child.
My MIL left the country to go to France in mid January this year. She usually arranges this type of trip yearly to be with her retired sisters who live there. This year they planned to go to a pacific island with a group in early March.
Read 18 tweets
Profile picture
Mikey Kay
@MikeyKayNYC
#COVIDー19 22 March 2020|

IMPORTANT THREAD.

Part 1

There’s important data coming out of Italy on confirmed cases & deaths due to COVID. This should be treated as an Indicator & Warning by all of us. Please watch & share. (Birds chirping in the background for moral support!)
2. #COVID19 Part 2

Reliable data source:

Coronavirus.jhu.edu
3. #COVIDー19 Part 3

Government policy & guidance needs to rapidly turn into a proactive stance to reassure us, the public, that there is a plan. What happens when, and it will happen, we get zero confirmed no new cases?
Read 6 tweets
Profile picture
Thomas Wood 🌊
@twoodiac
FWIW, I for one no longer believe the numbers of new cases being reported by the Republic of China, or the claim that the country has succeeded in suppressing #COVID-19.

I no longer find the numbers being reported (typically one of two new cases per day) to be believable. 1/17
The novel #coronavirus has a high transmission factor: is apparently mutating rapidly; and has a pathological profile that makes case tracing *very* difficult. (As for the latter factor, see Osterholm at 3:30+) 2/17 tinyurl.com/rp3ajaw
Furthermore, the Chinese numbers have always differed from the finding outside China that a significant number of young people become seriously ill from the virus, and that a large percentage of carriers are asymptomatic. 3/17
Read 19 tweets
Profile picture
Xihong Lin
@XihongLin
Analysis results of 25,000+ lab-confirmed COVID-19 cases in Wuhan till Feb 18: epidemiological characteristics and non-pharmaceutical Intervention effects. The key results are summarized below and hope they are useful for the strategies in US and others medrxiv.org/content/10.110…
1. In the absence of intervention (before 1/23), the effective reproductive number R=3.8>>1, and dropped to R=0.3 after the massive intervention on Feb 1(centralized quarantine and treatment of all confirmed and suspected cases). This intervention worked.
2. Various sensitivity analyses were done and the conclusion holds.
Read 24 tweets

Trending hashtags

#China #medtwitter #CoronaVirus #coronavirus #Covid_19 #COVID #waves #Washington #cases #telehealth #TablighiJamaat #COVIDー19 #Karnataka #Nanaimo #nCoV2019 #DTES #QuédateEnCasa #Nephtwitter #NewWestminster #database #COVID_19 #msm #socialdistancing #UK #Hippa

Embed code for your website

×
Follow Us on Twitter!

Did Thread Reader help you today?

Support us! We are indie developers!

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

Become a Premium Member ($3.00/month or $30.00/year) and get exclusive features!

Become Premium

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

Donate via Paypal Become our Patreon

Thank you for your support!