Vipin M. Vashishtha Profile picture
Apr 8, 2023 16 tweets 8 min read Read on X
The indian saga of XBB.1.16 #Arcturus

It has been a month when @siamosolocani 1st flagged this variant. Later, I started tracking it. We are still amid an ongoing surge, it’s time to take a stock of the situation: what we do know, what we don’t 1/

What do we know for sure!

1-XBB.1.16 has succeeded in creating a new, significant surge in India after a gap of >6 months. A feat that even BA.5, BQ.1 & XBB.1.5 failed to achieve!
2/ ImageImage
2-XBB.1.16 definitely has got a growth advantage & more fitter than other circulating XBBs & has even replaced some other similar sublineages like XBB.1.5 & XBB.1.9 3/
@vinodscaria Image
3-XBB.1.16 is definitely not a more pathogenic variant than other Omicron’s progenies

4-This variant is still evolving, adding few more mutations. But not all new mutations are beneficial to the virus (i.e. E180V). 4/ Image
5-The chances of XBB.1.16 leading a new, significant wave (i.e. the 4th wave) akin to Jan’ 22 BA.2 wave are remote 5/
@JPWeiland Image
6-The new surge in cases is yet to peak in India. According to @JPWeiland India is more than 2 weeks from peak cases. 6/ Image
And, now let’s see what we still don’t know:
1-How big this new surge would be?
2-What are the key factors responsible for making XBB.1.16 a more fitter variant than its contemporaries? Higher immune evasion?
Higher infectiousness, i.e. higher ACE2 binding? 7/
A new study by @SystemsVirology suggests:

-a higher infectiousness (~1.2-fold greater than that of XBB.1.5) 8/

Image
However, XBB.1.16 doesn’t have significantly greater immune evasion than XBB.1.5. 9/

@SystemsVirology Image
We know XBB.1.5 & XBB.1.16 have almost similar Spike barring a few Spike mutations. However, above study suggests that mutations in the non-Spike region may be responsible for increased viral growth of XBB.1.16 10/ Image
The above mentioned study & some early work done by @StuartTruvile in NSW, Australia points that XBB.1.16 is not more immune evasive than XBB.1.5. @StuartTurville calls it “super similar to XBB.1.5 in neut evasion”. 11/ Image
Now, If it's not immune evasion, is the growth advantage is because of stronger ACE2 binding then?

No, in fact, the entry into cells is similar as with Omicrons including XBB.1.5. @StuartTurville has shown this 👇 12/ Image
Most evolutionary biologists now agree to believe that the increased fitness is mainly due to changes at non-Spike region of this variant.
Acc to @LongDesertTrain ORF1a:L3829F is probably the key mute responsible for its advantage over XBB.1.9 13/ Image
As per @SolidEvidence mutation in NSP6 of ORF1ab may be behind this higher fitness 14/ Image
Now, most experts believe the extra mutations at ORF9b & ORF1a are responsible to give “teeth” to this variant.
ORF9b is thought to be involved with suppressing interferon response, so they might make the virus slightly fitter by counteracting the innate immune system. 15/ Image
We still don’t know whether XBB.1.16 will become a global thing replacing the existing dominant variant XBB.1.5. However, all the indications point it will. This is the current projection by @JPWeiland for the US (an update on the CDC graph) 16/ Image

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More from @vipintukur

Apr 2
Even after 5 yrs since its arrival, SARS-CoV-2 mutations keep emerging. A new variant LP.8.1 is rising. Almost 1 in 5 COVID cases in New South Wales are it. In the UK, it accounts for at least 3 in 5 cases. Just what is LP.8.1? Is it worrying? 1/ Image
LP.8.1 was first detected in July 2024. It’s a descendant of Omicron, specifically of KP.1.1.3, which is descended from JN.1, a subvariant that caused large waves of COVID infections around the world in late 2023 and early 2024. 2/ Image
The WHO designated LP.8.1 as a variant under monitoring in January. This was in response to its significant growth globally, and reflects that it has genetic changes which may allow the virus to spread more easily and pose a greater risk to human health. 3/ Image
Read 8 tweets
Apr 1
SARS-CoV-2 spike protein binds fibrinogen, causing thrombo-inflammation, according to a recent study. The virus must bind to fibrinogen, but why? Could this relationship help the virus evolve? Could this cause post-COVID heart attacks? 1/ Image
Scientists often think they grasp a virus's anatomy, tricks, and body movement. But occasionally, we discover something unexpected that radically transforms how we view an infection. 2/ Image
Some strategies are well documented: antigenic drift, glycan shielding, immune suppression. But every so often, we stumble upon a novel mechanism that redefines our understanding of viral pathogenesis. 3/ Image
Read 17 tweets
Mar 27
COVID-19 increases the risk of autoimmune diseases including rheumatoid arthritis and type 1 diabetes. The virus alters the immune system in unknown ways, making it difficult to design medicines to prevent post-COVID autoimmunity. 1/ Image
One leading hypothesis involves viral “molecular mimics”—proteins from the virus that resemble the body’s own proteins. These mimics may trigger an immune response against the virus but unintentionally cause the immune system to target healthy tissues as well. 2/ Image
Thanks to recent advancements in data analysis and machine learning, scientists have now identified a set of SARS-CoV-2-derived molecular mimics that may play a role in initiating autoimmune responses. 3/ Image
Read 10 tweets
Mar 27
mRNA-COVID-19 vaccines train the 'long-term memory' of immune system

Researchers have determined that the novel mRNA-COVID-19 vaccines not only induce acquired immune responses such as antibody production, but also cause persistent epigenetic changes in innate immune cells 1/ Image
Thus, vaccination with mRNA vaccines could lead to an enhanced immune response to future encounters with pathogens which are not specifically targeted by the vaccine. 2/ Image
These findings reveal that mRNA vaccines cause epigenetic 'training' of innate immune cells, sustaining immunological response. Epigenetic alterations may enable long-lasting innate immunity that enhances acquired immune system protection. 3/ Image
Read 12 tweets
Mar 26
In a proof-of-concept study, people with cognitive impairment in #LongCOVID were found to have asymmetrical glymphatic dysfunction in the left hemisphere of the brain which also correlated with disruption of the blood-brain barrier (BBB). 1/ Image
A group of researchers used special MRI techniques to assess perivascular spaces in the brain of 14 individuals with LongCOVID compared to 10 healthy controls. 2/ Image
A significant reduction in the DTI-ALPS index—a measure of glymphatic function—in the left hemisphere of LongCOVID patients was found, indicating impaired waste clearance in the brain. 3/ Image
Read 6 tweets
Mar 25
Sugar coatings aren't only for candies; they also help viruses, like the ones that cause COVID-19, hide from their hosts' immune system.

Now, researchers have developed a universal vaccine that targets coronaviruses and the sugars that they use as cover. 1/ Image
As demonstrated in animal studies, the vaccine removed sugar molecules from an area of a coronavirus spike protein that rarely mutates and created effective and plentiful antibodies to inactivate the virus. 2/ Image
Researchers say that the premise of this research is simple: it's an effective vaccine that targets more than one coronavirus at a time, which will allow individuals to receive a single shot for protection against multiple infectious agents. 3/ Image
Read 10 tweets

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