Despite testing negative and being told they’re fine, millions of people recovering from infections like Covid-19, influenza and glandular fever are left battling crippling fatigue, brain fog, joint pain, gut issues and a strange crash after any physical effort — a pattern that’s becoming too common to ignore.

These symptoms are medically known as myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS).

Both the World Health Organization and the US Centers for Disease Control and Prevention officially classify ME/CFS as a brain disorder and post-viral fatigue syndrome.

Now, researchers from Stellenbosch University believe they may have found a common underlying factor linking ME/CFS and Long Covid: zombie-like cells hiding in our blood vessels.

Dr. Massimo Nunes, a Postdoctoral Research Fellow at Stellenbosch University, explained:“Uncovering how ME/CFS and Long Covid originate and evolve over time is essential to move beyond symptom management toward disease-modifying therapies.”

The Stellenbosch team’s latest hypothesis is based on a growing body of research into what happens to blood vessels after viral infections. It proposes that viruses like SARS-CoV-2 (which causes Covid-19), Epstein–Barr virus, and influenza A can infect the inner lining of blood vessels, known as endothelial cells.

Once infected, these cells enter a “senescent” state — they stop functioning normally but stay alive, releasing molecules that trigger inflammation and clotting, while resisting destruction by the immune system.

Prof. Resia Pretorius, Distinguished Professor in Physiological Sciences at Stellenbosch University, said: “The long-term economic and health burden of Long Covid is immense, and we’re seeing striking parallels with ME/CFS, a condition that has been historically neglected. Many Long Covid patients meet ME/CFS diagnostic criteria, highlighting the urgent need to recognize these overlapping diseases as serious physiological illnesses with real-world consequences.”

The phenomenon of cellular senescence isn’t new, but Stellenbosch’s research adds a new dimension by placing these “zombie” blood-vessel cells at the centre of disease progression in both ME/CFS and Long Covid.

These dysfunctional cells contribute to thickened blood, lower oxygen delivery to tissues and immune dysfunction — a combination that aligns with what many patients experience physically and cognitively.

Prof. Burtram Fielding, Dean of the Faculty of Sciences and Professor in the Department of Microbiology, Stellenbosch University, explained: “Long Covid refers to a range of symptoms and conditions that persist for weeks, months or even years after a Covid-19 infection. It is not a single illness, but rather a collection of new, returning or ongoing symptoms that vary from person to person.”

Dr. Nunes highlighted several studies showing the overlap between Long Covid and ME/CFS diagnostic criteria: “A systematic review and meta-analysis inferred that 51% of Long COVID patients meet the diagnostic criteria for ME/CFS, based on data from 1,973 individuals across 13 studies.

“Another review with 127,117 participants found 45% met chronic fatigue criteria. A smaller study of 465 patients found 58% met ME/CFS criteria. Even in a 42-patient sample, 42% matched the diagnosis,” Nunes said.

The research team believes that when blood-vessel cells become senescent, they disrupt circulation and immune responses in ways that echo what many patients report fatigue, cognitive dysfunction, gut issues and post-exertional crashes.

“We propose that when blood-vessel cells turn into ‘zombies’, they pump out substances that make blood thicker and prone to forming tiny clots. These clots slow down circulation, so less oxygen reaches muscles and organs. This is one reason people feel drained,” Dr. Nunes said.

During physical exertion, the problem worsens. Instead of relaxing, blood vessels tighten, leading to a drop in oxygen supply. In the brain, this may contribute to dizziness and brain fog. In the gut, weakened blood-vessel walls could allow bacteria and toxins to leak into the bloodstream, fuelling further inflammation.

Adding to this is immune system exhaustion. Senescent cells are typically cleared by healthy immune responses, but in Long Covid and ME/CFS patients, natural killer cells and macrophages appear sluggish or dysfunctional. The zombie cells send out signals that help them evade immune attack, creating a cycle that allows them to persist and perpetuate illness.

As part of the next phase of their research, the Stellenbosch team is now testing blood samples from patients to see if they trigger senescence in lab-grown endothelial cells. They’re also piloting non-invasive imaging techniques to detect these ageing blood-vessel cells in real time.

“Our aim is simple: find these ageing endothelial cells in real patients. Pinpointing them will inform the next round of clinical trials and open the door to therapies that target senescent cells directly, offering a route to healthier blood vessels and, ultimately, lighter disease loads,” Dr. Nunes said.

tracy-lynn.ruiters@inl.co.za

Weekend Argus 

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