New study suggests #LongCOVID may involve disrupted cortisol rhythms, not just inflammation.

Patients showed:
• Reduced morning cortisol
• Elevated evening levels
• Flattened daily cortisol cycle

➡️ Indicating hypothalamic–pituitary–adrenal (HPA) axis dysfunction. 1/ Prospective study of post-COVID patients:

➡️ Compared with healthy controls,
✔ Long COVID patients had blunted morning cortisol peaks
✔ Higher evening cortisol
✔ Loss of normal circadian pattern

Blood cortisol alone failed to detect these changes. 2/

Brain Fog after COVID-19: What’s driving it?

➡️ New review highlights that persistent cognitive symptoms in COVID survivors are strongly linked to pro-inflammatory cytokines and blood–brain barrier (BBB) dysfunction.

➡️ Key culprits include IL-6, TNF-α, IL-1β, IL-8, IL-13 and MCP-1 — many remain elevated months after infection.

🔥 COVID-19 is not just a respiratory disease.

➡️ Evidence suggests cognitive impairment can occur due to:

• Systemic inflammation
• Neuroinflammation
• Microvascular injury
• Persistent immune activation
• BBB disruption

➡️ These mechanisms may explain prolonged attention, memory & executive dysfunction. 1/ Cytokine signature of cognitive impairment in #LongCOVID:

🔹 Acute phase → IL-6, IL-1β, CXCL10 rise
🔹 Post-acute → Persistent IL-6, TNF-α, MCP-1
🔹 Long phase (>6 months) → IL-6, IL-13, IL-8 linked with “brain fog”

Inflammation clearly outlives the infection.

➡️ Blood–brain barrier disruption appears central in post-COVID cognitive decline.

Markers suggesting BBB injury:
• GFAP
• Neurofilament light chain
• MMP-9
• S100β

➡️ BBB leakage may persist in patients with cognitive symptoms even >1 year. 2/

Post-COVID fatigue isn’t just subjective.
Using advanced MRI, researchers found real changes in brain blood flow and oxygen metabolism in people with Post-COVID-19 Syndrome (PCS) after mild infection.

➡️ Key finding:

PCS patients showed increased oxygen metabolism in the hippocampus (memory hub) but reduced metabolism in the anterior cingulate cortex (ACC) — despite no visible brain atrophy. 1/ Why this matters:

➡️ Higher hippocampal metabolism was linked to better cognitive performance, suggesting a compensatory response to maintain thinking and memory in PCS. 2/

Why do some people feel exhausted long after COVID-19?

➡️ New brain-imaging research shows that even after mild COVID, people with persistent fatigue can have subtle but real changes in brain structure.

➡️ These changes are not large or widespread, but tend to appear in connected brain networks, especially areas involved in attention, decision-making, and sensory processing. 1/
Importantly, the brain regions affected overlap with areas that naturally express TMPRSS2, a protein that helps SARS-CoV-2 enter cells — suggesting certain brain circuits may be more vulnerable to the virus. 2/

COVID-19 doesn’t just affect the lungs — it can disrupt how cells produce energy. New research shows that COVID-19 alters the genetic “switches” that control mitochondria, the structures that power our cells. 1/ By comparing people who died from severe COVID-19, those who recovered, and healthy individuals, researchers found lasting changes in how mitochondrial genes are regulated. These changes were most prominent in genes involved in energy production and metabolism. 2/

#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/

🔥 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/

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/

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/

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/

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/

A new Israeli study demonstrates why some people develop #LongCOVID.

➡️ By analysing immune responses, gene expression and plasma proteins in blood samples, scientists found that people with longCOVID show persistent chronic inflammation and disrupted immune signalling months after infection — patterns not seen in those who fully recovered. 1/ These immune differences help explain lingering symptoms — such as fatigue, brain fog and breathlessness — and point to specific inflammatory pathways that could be targeted for treatment. This work opens new avenues for better therapies for millions living with longCOVID. 2/

Can past COVID-19 weaken the body’s ability to fight tuberculosis?

➡️ A new study comparing immune responses to SARS-CoV-2 and Mycobacterium tuberculosis (MTB) suggests COVID-19 may dampen both antiviral and anti-TB immunity — even months later. 1/ Researchers tested immune cells from healthy individuals and COVID-19 survivors, both with and without latent TB infection (LTBI).

➡️ They stimulated the cells with SARS-CoV-2 Spike and MTB antigens and measured cytokine responses. 2/

A new study comparing immune profiles months after COVID-19 vs influenza shows that SARS-CoV-2 leaves behind distinct and longer-lasting immune abnormalities — very different from what is seen after flu. 1/ Post-COVID patients showed increased CXCR3 and CCR6 expression across multiple lymphocyte populations.

➡️ Punjabi This means their immune system is still sending signals for cells to migrate into tissues (especially the lungs) months after infection.

➡️ Persistent tissue-homing = prolonged inflammation. 2/

A new study provides some of the strongest evidence yet that mitochondrial dysfunction can directly cause #Parkinson’s disease, rather than being a consequence of neuron loss.

➡️ Researchers used a unique mouse model carrying a mutation in CHCHD2, a mitochondrial protein linked to a rare inherited form of Parkinson’s that closely mimics the common, late-onset form. 1/ Key Findings

➡️ Mutant CHCHD2 accumulates in mitochondria, making them swollen and structurally abnormal.

➡️ Cells shift away from normal energy production and develop oxidative stress due to buildup of reactive oxygen species (ROS).

➡️ Alpha-synuclein aggregation occurs after ROS rises, suggesting oxidative stress triggers Lewy body formation.

➡️ Human brain tissue from people with sporadic Parkinson’s showed CHCHD2 accumulation inside early alpha-synuclein aggregates, confirming relevance beyond the rare genetic form. 2/

New research in Cell Reports Medicine helps explain why women are more likely to develop #LongCOVID — and often experience more severe, persistent symptoms like fatigue, brain fog, and pain.

The key? Differences in the immune system, gut, and hormones. 1/ Researchers studied 78 people with LongCOVID (mostly mild initial cases) and compared them to 62 who recovered fully.

➡️ One year later, women with Long COVID showed clear biological differences — especially signs of gut inflammation and “leakiness.” 2/

Urine tells the story of #LongCOVID:

➡️ New study identifies a molecular fingerprint for #LongCOVID (PASC) — using just a urine test.

➡️ Researchers found 195 urinary peptides that can accurately distinguish Long COVID patients from healthy and ME/CFS controls (AUC > 0.95). 1/ Researchers used urinary peptidomics to identify a molecular fingerprint of post-acute sequelae of SARS-CoV-2 infection (PASC or LongCOVID).

➡️ Methods

-50 PASC patients (10 months post-infection) were compared with 50 controls (42 healthy + 8 with non-COVID ME/CFS).

-Capillary electrophoresis–mass spectrometry (CE–MS) was used to analyze urinary peptides.

-A support vector machine (SVM) model was built to distinguish PASC cases from controls. 2/

Understanding Long COVID

➡️ Long COVID isn’t one disease — it’s a complex web of immune, vascular, and metabolic dysfunctions.
From fatigue & brain fog to heart & lung complications, it stems from viral persistence, autoimmunity, and mitochondrial damage. 1/ Proposed mechanisms:

1️⃣ Persistent viral reservoirs or antigen remnants

2️⃣ Reactivation of latent viruses (e.g., EBV)

3️⃣ Immune dysregulation & autoimmunity

4️⃣ Endothelial injury and microclots

5️⃣ Gut microbiome imbalance

6️⃣ Mitochondrial dysfunction and energy metabolism impairment. 2/

Fathers’ COVID & offspring

➡️ New research shows that paternal SARS-CoV-2 infection before conception can alter sperm RNA — leading to anxiety-like behavior & brain gene changes in offspring.

A biological “memory” of infection may pass across generations. 1/ Beyond infection: inheritance

➡️ Male mice infected with SARS-CoV-2 fathered pups with altered hippocampal transcriptomes & higher anxiety.
Injecting sperm RNA from infected males reproduced the same effects — clear evidence of RNA-based inheritance. 2/

A new study provides new evidence to help us redefine steroid use in TB care

➡️ Given the renewed interest in the steroid dexamethasone, as a host-directed treatment during the COVID-19 pandemic, the Trinity College Dublin team provides evidence that treating patients with steroids may enhance the function of their macrophages to kill the mycobacteria, while diminishing pathways of inflammatory damage. 1/ The researchers goal was to determine whether dexamethasone impacts the macrophage's ability to fight TB. Although glucocorticoids can reactivate TB, they are paradoxically the only adjunctive host-directed therapies that are recommended by WHO for TB.

Steroids are given to patients alongside antimicrobials in certain circumstances; however, scientists don't fully understand the effect of these drugs on the immune system, especially innate immune cells such as macrophages. 2/

A NEW review explores how SARS-CoV-2 may influence cancer risk.

➡️ Unlike classical oncogenic viruses, it doesn’t insert viral oncogenes. Instead, its proteins:

-Inhibit tumor suppressors
-Activate growth, survival & inflammation pathways

👉 Potential role in cancer initiation & progression. 1/ Bioinformatic & experimental studies show direct interactions between viral proteins and host cellular components tied to cancer hallmarks.

➡️ These mechanisms could contribute to initiation, promotion, and progression of tumors, raising the possibility that SARS-CoV-2 may act as an oncovirus.

👇The figure illustrates various key oncogenic signaling molecules or pathways targeted by SARS-CoV-2 NSP, N, M and S protein. The activation of oncogenic pathways can lead to the conversion of a normal cell into a cancer cell. 2/