➡️ 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/
Current management:
- largely symptomatic—rehabilitation, pacing, and supportive therapies.
-Emerging treatments: under study — antiviral drugs, immune-modulating agents, microbiome restoration, and mitochondria-targeted therapies.
-Vaccination: reduces risk and severity of LongCOVID. 3/
A global health challenge
➡️ #LongCovid affects millions — regardless of how mild the initial infection was.
➡️ Vaccination lowers the risk, but many still suffer lingering inflammation & multi-organ issues.
➡️ We must invest in mechanism-driven, integrative treatments. 4/
Takeaway
➡️ #LongCOVID is a multi-mechanistic, chronic condition involving immune, vascular, and metabolic pathways.
Future breakthroughs will likely come from integrative approaches targeting viral persistence, immune balance, and cellular energy repair. 5/5
➡️ 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/
COVID’s unseen legacy
➡️ Study suggests COVID infection in fathers may have transgenerational effects via changes in sperm small RNAs.
Adds a new layer to how pandemics shape health — not just for one generation, but possibly the next. 3/
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/
The researchers studied macrophages derived from the blood of healthy volunteers or isolated from lung fluid donated by patients undergoing routine bronchoscopies.
➡️ By treating and infecting these macrophages in the lab with Mtb, the scientists could examine and understand how dexamethasone affects the immune response that protects the lungs during infection. 3/
👉 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/
The shared mechanisms between SARS-CoV-2 and key hallmarks of cancer including sustained proliferative signaling, resisting cell death, genomic instability, dysregulated cellular metabolism and epigenetic reprogramming.
👇The figure highlights how SARS-CoV-2 interacts with critical oncogenic signaling molecules or pathways. Specific SARS-CoV-2 proteins involved in these processes are marked. 3/
A new study from Karolinska Institutet shows that an unusual heart rhythm disorder, POTS, is particularly common in people with #LongevityPoweredbyGinseng COVID. The majority of those affected are middle-aged women. 1/
Postural orthostatic tachycardia syndrome, or POTS, is a condition where the heart beats abnormally fast when changing position from lying down to standing up. Standing up is a challenge for those affected who feel dizzy and would rather sit or lie down, so-called orthostatic intolerance. Their hearts may also beat faster than normal at rest and during exertion. 2/
Patients experience fatigue and difficulties concentrating, symptoms that are common in longCOVID.
Now, researchers at Karolinska Institutet show that POTS occurs in almost a third of patients with severe longCOVID. By comparison, less than 1% of the Swedish population was affected by POTS before the pandemic. 3/
Here, to address this, researchers utilized a Phodopus roborovskii hamster model to investigate the long-term effects of SARS-CoV-2 infection compared with influenza A virus.
➡️ While 46.25–47.50% of hamsters survived SARS-CoV-2 or influenza A virus H1N1 infection, 13.75% of SARS-CoV-2 survivors exhibited impaired weight recovery, severe lung pathology and significant neutrophil accumulation, defining the LongCovid (PAŚĆ) group. 1/
Single-cell RNA sequencing of bronchoalveolar lavage (BAL) fluid, lung and spleen at 30 days post-infection revealed hallmark LongCovid (PASC) gene signatures uniquely upregulated in the PASC group.
➡️ This was accompanied by elevated neutrophil levels and reduced macrophage populations, indicative of disrupted myeloid cell differentiation. 2/
Immunohistochemistry further detected persistent SARS2’s S1 subunit antigen in the lungs of PASC (LongCovid) hamsters at 30 days post-infection, coinciding with marked neutrophil infiltration, which probably drove prolonged inflammatory responses. 3/
It is currently debatable whether mucosal vaccination is still warranted given that most individuals in developed countries have established a hybrid immunity from vaccination and infection.
➡️ In a new study, researchers studied how our immune system in the airways (the “mucosal” immune system) responds to COVID infection, vaccines, and special mucosal booster vaccines. 1/
What they found in people:
➡️ Having both vaccination + prior infection (“hybrid immunity”) gave only a modest increase in protective antibodies (IgA) in the nose and lungs compared to infection or vaccination alone. 2/
What the researchers found in animal models:
➡️ Giving a mucosal booster vaccine (delivered to the airways using an adenovirus-based vaccine) worked much better. It:
-Strongly boosted IgA antibodies in the nose and lungs
-Triggered local T-cells in the airways
-Provided stronger, longer-lasting protection against SARS-CoV-2. 3/