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Vipin M. Vashishtha Profile picture
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Jun 5 • 4 tweets • 2 min read
A significant number of COVID19 patients develop '#longCOVID', a condition defined by long-lasting debilitating, often neurological, symptoms. The pathophysiology of long COVID is unknown. 1/
Here comes a new Preprint that presents in-vivo evidence of widespread #neuroinflammation in long COVID, using a quantitative assessment, [18F]DPA-714 PET, in two long COVID patients. 2/
The researchers reanalyzed historical data from three matched healthy control subjects, for comparison purposes. Both patients with long COVID had widespread increases in [18F]DPA-714 binding throughout the brain. 3/
Quantitative measures of binding were increased on average by 121% and 76%, respectively. This implicates profound neuroinflammation in the pathophysiology of long COVID. 4/

medrxiv.org/content/10.110…

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More from @vipintukur

Vipin M. Vashishtha Profile picture
Jun 5
T-cell lymphopenia & functional impairment is a hallmark of severe acute #COVID19. How T-cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated. 1/
Noted T cell immunologist @fitterhappierAJ is saying…T-cells are damaged by Covid potentially undermining not just Covid immunity but immunity to other diseases. His views are further corroborated by the findings of a new study👇 2/
The extensive T-cell lymphopenia observed particularly in patients with severe COVID19 during acute infection had recovered 6 months after infection, which was accompanied by a normalization of functional T-cell responses to common viral antigens 3/
Read 12 tweets
Vipin M. Vashishtha Profile picture
May 3
COVID19 has demolished many ‘dogmas’ of the science. One such is our immense faith in the heroics of our T cells. Many believe they are the saviours—our last wall of defence against the severe disease…

I raised this issue last year👇 1/

However, the emergence of #Omicron, it seems has unveiled the true prowesses of the two arms of our immune system: humoral & cellular. And the stark reality soone became evident…

Wrote another piece early this year👇
2/
In fact, @fitterhappierAJ has been yelling constantly on the inadequacy of our T cell, particularly against this weird bug since the onset of the pandemic. Yet, people like @MonicaGandhi9 kept on harping about the virtues of the cellular responses. 3/

Read 4 tweets
Vipin M. Vashishtha Profile picture
Apr 7
Welcome sublineages of BA.2: (sublineages mean stuff clearly derived from known omicrons (BA.2 or BA.1.1. or whatever)

⚠️ BA.4 & BA.5 just got designated

➡️ BA.4 (S:L452R+486V +N:151S + orf9b:11F)

➡️ BA.5 (S:L452R+486V +M:D3N)

So BA.4 & BA.5 would be new omicrons! 1/
➡️ BA.* sublineages with S:L452R and S:F486V (79 sequences as of 2022-04-05, mainly South Africa)

➡️ Mutations on top of BA.2:

S: L452R, F486V
ORF7b: L11F*
N: P151S*
nuc: G12160A
*these two don't always seem to be picked up, G12160A is a better marker outside the spike 2/
➡️ Notably, 452 and 486 are two of the biggest antigenic sites that are not already hit by BA.2 mutations; 452R might knock out some of the same antibodies that 446S does in BA.1. 3/
Read 10 tweets
Vipin M. Vashishtha Profile picture
Apr 6
#Monocytes at the Center of #SARS2 triggered inflammation & severe #Covid19

#SARS2 can cause acute respiratory distress & death in some patients. Although severe #COVID19 disease is linked to exuberant inflammation, how #SARS2 triggers inflammation is not understood. 1/
Monocytes & macrophages are the key sentinel cells that sense invasive infection to form inflammasomes that activate inflammatory cascade by secreting caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) & release of potent inflammatory mediators. 2/
~6% of monocytes in COVID patients are infected w/ SARS2

Monocyte infection depends on uptake of Ab-opsonized virus by Fcγ receptors

SARS2 begins to replicate in monocytes, but infection is aborted & infectious virus is not detected in infected monocyte culture supernatants. 3/
Read 5 tweets
Vipin M. Vashishtha Profile picture
Apr 6
Protection by a 4th Dose of #BNT162b2 against #Omicron in #Israel:

➡️ Israeli MoH data, 1,252,331 persons 60 y/o or above, Study period: Jan 10-March 2, 2022

1/
➡️ Rate of confirmed infection & severe Covid as a function of time:

-Four-dose groups (8 days after receipt of a 4th dose)
-Three dose group: among persons who had received only 3 doses
-Internal control group: among persons who had received a 4th dose 3 to 7 days earlier 2/
➡️ Number of cases of *severe* Covid19 per 100,000 person-days:
-1.5 in four-dose groups,
-3.9 in the three-dose group,
-4.2 in the internal control group

3/
Read 6 tweets
Vipin M. Vashishtha Profile picture
Apr 5
Characterisation of a new recombinant, #XD (a Delta-Omicron recombinant)

➡️ The XD is a chimeric SARS2 virus having recombination of Delta AY.4 & Omicron BA.1.

➡️ The XD spike carries a larger fraction of the signature changes of BA.1, including the entirety of the RBD
1/ Image
There are two breakpoints, one at the beginning of spike & one within ORF 3a

➡️ Immune escape:

-With pseudovirus, only a small reduction in NAb titers ag #Delta compared to WT

-In contrast, both XD & BA.1 were barely neutralized by sera sampled 1 or 6 mo after 2 doses

2/
-The titers were all much higher 1 month after a 3rd immunization, although they displayed an 8-fold to 10-fold reduction in neutralization efficacy against both BA.1 and XD compared to the WT virus.

3/
Read 12 tweets

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