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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#LongCOVID (LC) shares striking symptom overlap with hypermobility spectrum disorders (HSD/hEDS): fatigue, brain fog, dysautonomia, pain—especially in women.
➡️ A new case series explores whether some “intractable” LC may reflect undiagnosed hypermobility disorders.
➡️ Five women with persistent LC symptoms were evaluated at an hEDS/HSD clinic.
All met Beighton score criteria for hypermobility.
➡️ 4 diagnosed with hEDS, 1 with HSD
➡️ 3 had dysautonomia
None had prior hypermobility diagnoses. 1/
All patients carried MTHFR polymorphisms (C677T or A1298C)—recently linked to hEDS/HSD.
➡️ Several also showed features of mast cell activation, suggesting immune dysregulation may unmask latent connective tissue disorders after SARS-CoV-2 infection.
➡️ Targeted management (physical therapy, methylfolate/B12, mast cell stabilization, pain interventions) led to clinical improvement in all cases.
🔑 Takeaway: Consider hEDS/HSD in women with refractory Long COVID, especially with multisystem pain and dysautonomia. 2/
This case series suggests that some patients with severe, persistent #LongCOVID—especially women—may have previously undiagnosed hypermobility disorders (hEDS/HSD).
➡️ Five women with refractory LongCOVID symptoms were found to meet criteria for hypermobility, often with dysautonomia, mast cell–related features, and MTHFR polymorphisms.
➡️ Targeted management led to clinical improvement, highlighting the need to consider hEDS/HSD in patients with intractable Long COVID symptoms. 3/
🔥 A landmark study challenges the long-held belief that Alzheimer’s disease (AD) is irreversible.
➡️ Using advanced mouse models that mimic human AD pathology, researchers found that restoring and maintaining healthy levels of NAD⁺, a key cellular energy molecule, can not only prevent but also reverse advanced Alzheimer’s pathology and fully restore cognitive function in mice. 1/
The team showed that NAD⁺ deficiency is a central driver of AD pathology—leading to blood-brain barrier breakdown, neuroinflammation, oxidative damage, and impaired neurogenesis. 2/
➡️ By administering a compound that rebalances NAD⁺ (P7C3-A20), all these pathological features were reversed, and memory and cognitive function were recovered.
➡️ These effects were seen in both amyloid-driven and tau-driven models, with supporting evidence from human AD brain samples suggesting disrupted NAD⁺ homeostasis in patients. 3/
As we age, our immune system becomes less effective, partly because key cells called CD8⁺ T-cells have trouble forming long-lasting memory.
A new study shows that a process called autophagy — the cell’s way of cleaning out old or damaged components — plays a central role in this problem. 1/
When a T-cell divides, it can make two daughter cells with different future roles: one becomes a long-lived ‘memory T cell’ that helps protect against future infections, and the other becomes a short-lived ‘effector T cell’ that fights the immediate infection.
For this to happen, the cell must sort its internal parts unevenly during division. 2/
The researchers found that #autophagy helps clear out old mitochondria before division, allowing daughter cells to inherit different mitochondrial content.
➡️ This asymmetric inheritance is crucial for creating a mix of T-cells with distinct fates — including memory cells.
➡️ Without autophagy, old mitochondria aren’t cleared, the inheritance becomes symmetric, and the diversity in T-cell fates is lost.
➡️ This has major implications for understanding why immune memory weakens with age and may inform new strategies to boost T-cell immunity. 3/
A new review highlights how neurotropic viruses like SARS-CoV-2 reprogram the metabolism of brain immune cells — especially microglia and astrocytes — contributing to neuroinflammation and brain dysfunction.
➡️ Under normal conditions, glial cells use oxidative phosphorylation (OXPHOS) to support brain homeostasis and anti-inflammatory functions. But viral infection shifts them toward aerobic glycolysis, driving pro-inflammatory cytokine production and immune activation. 1/
This metabolic switch:
• increases inflammatory mediators (IL-1β, TNF-α)
• elevates oxidative stress
• impairs neuronal support
• disrupts the blood-brain barrier
All of which can exacerbate neuroinflammation and damage. 2/
For SARS-CoV-2 specifically, the viral S1 protein can cross the BBB and trigger microglial activation and inflammasome (NLRP3) signaling, which further promotes inflammation and potentially persistent neurological effects. 3/
Breakthrough in respiratory virus prevention (Flu, COVID & more)
➡️ Researchers have developed an AI-designed intranasal antiviral platform that could block multiple respiratory viruses—flu, COVID-19, and future variants—right at the entry point: the nose. 1/
The platform is based on interferon-lambda, a natural antiviral protein, redesigned using AI protein engineering to overcome major limitations: poor heat stability and rapid clearance from nasal mucosa.
➡️ Using AI, scientists strengthened unstable protein regions, improved solubility, and added glycoengineering—making the protein so robust it remained stable for 2 weeks at 50 °C. 2/
To keep it in the nose longer, the protein was packaged in nanoliposomes and coated with chitosan, greatly improving adhesion to nasal mucosa and penetration through thick mucus. 3/
New study in International Journal of Infectious Diseases highlights persistent immune alterations after SARS-CoV-2 infection—providing further biological evidence for #LongCOVID as a genuine post-infectious condition.
➡️ Researchers found lasting changes in immune activation and regulation, even months after recovery from acute COVID-19—suggesting the immune system does not fully reset after infection. 1/
Key findings point to chronic inflammation, altered cytokine responses, and immune imbalance, which may explain prolonged symptoms such as fatigue, pain, and neurocognitive complaints.
➡️ Importantly, these immune changes were seen independent of initial disease severity, reinforcing that even mild COVID-19 can have long-term immunological consequences. 2/
The study of >40,000 people shows that key immune cells (T cells, B cells, NK cells) dropped during widespread COVID infection and stayed below pre-pandemic levels for nearly 2 years. 3/