For millions of people worldwide, recovering from COVID-19 is just the beginning. Lingering symptoms like fatigue, memory problems, and difficulty concentrating—collectively termed Long Covid—have left researchers scrambling to understand their root causes. A groundbreaking study now suggests these symptoms may be tied to physical changes in the brain, specifically swelling in a region critical for memory and focus. Let’s dive into the science behind this discovery and what it means for those affected.
The Brain Connection: Hippocampus Swelling in Long Covid and Chronic Fatigue
A 2025 study led by Griffith University in Australia has uncovered a striking link between Long Covid, Chronic Fatigue Syndrome (CFS), and structural changes in the brain. Using advanced MRI technology, researchers compared brain scans of 17 Long Covid patients, 29 CFS patients, and 15 healthy individuals. The results revealed that both Long Covid and CFS patients had significantly larger hippocampus volumes compared to the control group .
The hippocampus, a small seahorse-shaped region deep in the brain, plays a vital role in forming memories, regulating emotions, and maintaining spatial navigation. Swelling in this area could explain why many patients struggle with cognitive symptoms like brain fog, delayed responses, and forgetfulness. Dr. Kiran Thapaliya, the study’s lead author, emphasized that these changes correlate with symptom severity: “Hippocampal impairment may directly contribute to the daily challenges these patients face, from concentration issues to unrefreshing sleep”.
Why Does the Hippocampus Swell?
Researchers propose two theories:
- Neurogenesis: The brain might produce new neurons in response to inflammation or viral damage, leading to increased volume.
- Viral Persistence: Lingering SARS-CoV-2 particles could trigger immune responses that inflame brain tissue .
While the exact mechanism remains unclear, the overlap between Long Covid and CFS suggests shared biological pathways. Both conditions involve debilitating fatigue, post-exertional malaise (a worsening of symptoms after minimal activity), and cognitive dysfunction—symptoms now linked to measurable brain changes.
Beyond the Brain: The Systemic Impact of Long Covid
Long Covid isn’t just a neurological issue. Studies highlight its multisystem nature, affecting the heart, immune system, and cellular health:
- Cardiac Risks: Elevated troponin T levels—a marker of heart damage—have been found in Long Covid patients, particularly those with severe fatigue and post-exertional malaise .
- Telomere Shortening: Accelerated cellular aging, measured through shortened telomeres, is more common in Long Covid patients and may contribute to prolonged recovery times .
- Mitochondrial Dysfunction: Disruptions in energy production at the cellular level could explain the pervasive fatigue seen in both Long Covid and CFS .
These findings underscore that Long Covid is not a single condition but a spectrum of disorders. A 2025 Belgian study identified six distinct symptom clusters, with the most severe group mirroring CFS and showing persistent fatigue, pain, and sleep disturbances .
The Rising Tide of Chronic Fatigue Syndrome Post-Covid
Before the pandemic, Chronic Fatigue Syndrome (CFS) affected just 0.2–1% of the global population. Post-Covid, those numbers are soaring. A U.S.-based RECOVER study found that 4.5% of COVID-19 survivors develop ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) within six months of infection—a 15-fold increase compared to pre-pandemic rates.
Key Risk Factors:
- Gender and Age: Women and individuals aged 46–65 are disproportionately affected.
- Infection Severity: Even mild initial COVID-19 cases can lead to ME/CFS, debunking the myth that only severe infections cause long-term issues.
- Vaccination Status: Unvaccinated individuals face higher risks, though breakthrough cases still occur.
Dr. Suzanne Vernon, a lead researcher on the RECOVER study, notes: “The sheer scale of post-Covid ME/CFS cases is alarming. These patients often endure the most severe form of Long Covid, with symptoms that devastate their quality of life”.
Bridging the Gap: How Research Could Unlock Treatments
The parallels between Long Covid and CFS offer hope for unified treatments. For example:
- Exercise Intolerance: Both conditions involve post-exertional malaise, likely due to mitochondrial dysfunction or impaired oxygen uptake. Advanced exercise tests in ongoing studies aim to pinpoint these metabolic flaws.
- Immune Dysregulation: Elevated cytokines like IL-6 and TNF-alpha suggest chronic inflammation, a target for existing immunotherapies.
- Brain Imaging: High-resolution MRIs could help track hippocampal changes over time, offering biomarkers for diagnosis and treatment efficacy.
Researchers are also exploring repurposed drugs. For instance, low-dose naltrexone—a medication used for fibromyalgia—is being tested for its anti-inflammatory effects in Long Covid trials.
The Role of Mental Health and Stigma
While physical symptoms dominate discussions, mental health cannot be overlooked. A Saudi Arabian study found that 14.4% of Long Covid patients met clinical criteria for fatigue, with depression significantly amplifying their symptoms. However, dismissing these conditions as “all in the head” remains a harmful misconception. As Dr. Thapaliya stresses: “These are biological illnesses with measurable impacts on the brain and body. Stigma only delays care”.
Looking Ahead: A Call for Global Action
The World Health Organization estimates 65 million people now live with Long Covid, many of whom may never fully recover. Addressing this crisis requires:
- Funding: Less than 5% of the U.S. RECOVER initiative’s $1.8 billion budget is dedicated to studying causes, highlighting a critical need for investment in mechanistic research.
- Awareness: Public health campaigns must educate clinicians and the public about ME/CFS and Long Covid to reduce diagnostic delays.
- Collaboration: Shared data repositories, like those being built by RECOVER, could accelerate discoveries across borders.