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/
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/
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
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/
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
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/
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/
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/
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/
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/
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/
As per @SolidEvidence mutation in NSP6 of ORF1ab may be behind this higher fitness 14/
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/
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/
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Could this molecule be 'checkmate' for SARS-CoV-2?
A research team has developed new drug candidates major protease blockers, AVI-4516 & AVI-4773 that show great promise against SARS-CoV-2 & potentially other coronaviruses that could cause future pandemics 1/
In preclinical testing, the compounds performed better than Paxlovid against SARS-CoV-2 and the Middle East Respiratory Syndrome (MERS) virus, which periodically causes deadly outbreaks around the world. 2/
These MPro blocking compounds could inhibit coronaviruses in general, giving us a head start against the next pandemic. We need to get them across the finish line and into clinical trials. 3/
➡️ A study has found that people with pandemic chilblains have an unusually strong immune response to SARS-CoV-2, driven by overactive plasmacytoid dendritic cells (pDCs) responding to TLR7 signals. 1/
Given the essential role of type I interferon in protective immunity against SARS2 & the association of chilblains with inherited type I interferonopathies, researchers hypothesized that excessive I-IFN responses to SARS2 might underlie the occurrence of chilblains 2/
They identified a transient I-IFN signature in chilblain lesions, accompanied by an acral infiltration of activated plasmacytoid dendritic cells (pDCs). Patients with chilblains were otherwise asymptomatic or had mild disease without seroconversion. 3/
Differential DNA methylation 7 months after SARS-CoV-2 infection
A NEW study detected associations between changes in DNA methylation in individuals who had even asymptomatic or mild SARS-CoV-2 infections as compared to their household controls after 7 moths of infection 1/
Aberrant DNA methylation patterns have been linked to various diseases, including cancer and metabolic disorders.
These changes resembled patterns seen in autoimmune or inflammatory diseases, suggesting long-term epigenetic remodeling even in mild cases. 2/
This study shows that even mild or symptom-free COVID-19 infections can cause lasting changes in how certain genes are turned on or off in the body, seven months after infection. 3/
New research reveals that calming the brain's immune cells may reduce Alzheimer's disease inflammation. The study highlights the importance of norepinephrine, which could lead to more targeted, early, and personalized treatments. 1/
Norepinephrine is a major signaling factor in the brain and affects almost every cell type. In the context of neurodegenerative diseases such as Alzheimer's disease, it has been shown to be anti-inflammatory. 2/
In this study, the researchers describe how enhancing norepinephrine's action on microglia can mitigate early inflammatory changes and neuronal injury in Alzheimer's models. 3/
➡️ A NEW study finds Metformin could prevent a form of acute myeloid leukemia (AML) in people at high risk of the disease.
Researchers investigated how metformin could prevent abnormal blood stem cells w/ genetic changes from progressing to AML 1/
Metformin impacts mitochondrial metabolism, & these pre-cancerous cells need this energy to keep growing. By blocking this process, researchers stop the cells from expanding & progressing towards AML, whilst also reversing other effects of mutated DNMT3A gene 2/
Thanks to recent advances, individuals at high risk of AML can be identified years in advance using blood tests and blood DNA analysis, but there's no suitable treatment that can prevent them from developing the disease. 3/
It has been reported that repeated administration of some COVID vaccines induces high IgG4 levels.
New research revealed a surprising IgE anti-RBD response after both natural infection & several SARS-CoV-2 vaccines. 1/
Presence of IgG4 & IgE in COVID-19 suggests that the virus may induce an “allergic-like” response to evade immune surveillance, leading to a shift from Th1 to Th2 cells, which promotes tolerance to the virus & potentially contributes to chronic infection & may be LongCovid 2/
An increase in IgG4 levels is typically associated w/ immunological tolerance & develops after prolonged exposure to antigens. While tolerance to an allergen benefits the host in Allergen Immunotherapy, in viral infection, it enables viral persistence rather than clearance 3/