Immune system dysfunction in ME/CFS and Long Covid
- Isabel Hemmings
- May 27
- 4 min read
Updated: Jun 3
Our immune system is designed to protect us from infections, eliminate damaged cells, and support healing. In healthy individuals, the immune response is tightly regulated—ramping up when needed and switching off once the threat is dealt with. But in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long Covid, that regulation can go awry.
Emerging evidence suggests that both conditions involve persistent immune dysregulation, low-grade inflammation, and a failure to resolve immune responses properly. This blog explores what this means, and how diet and lifestyle changes may support immune function in these conditions.
Understanding the immune response
Our immune system involves the innate immune system and the adaptive immune system and includes a number of different mechanisms through which we are able to respond to pathogens and infections as detailed below.
The immune response involves three key phases:
Immunosurveillance – the body’s early warning system, in which immune cells constantly patrol tissues to detect pathogens or abnormal cells.
Inflammatory response – if a threat is detected, a rapid release of cytokines and immune cells occurs, causing redness, heat, swelling, and sometimes pain or fever.
Resolution phase – the final and crucial step where the immune system deactivates, clears the inflammatory by-products, and restores balance.
ME/CFS and Long Covid, the body appears to get stuck somewhere between the second and third phases. Instead of resolving, inflammation lingers.
” ME/CFS has often been purported as an inflammatory disorder in which an infectious pathogen triggers an abnormal systemic immune response that persists beyond clearance of the infection” ((Poenaru, 2021)
|
Immune system dysfunction in ME/CFS and Long Covid
Research undertaken in both ME/CFS and in Long Covid has identified many ways which suggest how the immune system is dysregulated in these conditions, as summarised by the diagram shown below.
Diagram summarising how the immune system is dysregulated in ME/CFS and Long Covid (Information taken from Komaroff, 2017 and Davis, 2023)
The role of natural killer (NK) cells
One of the most consistent immune abnormalities found in ME/CFS is reduced activity of
Natural Killer (NK) cells. These are frontline immune cells that detect and destroy virus-infected cells. In ME/CFS:
NK cells are present but often dysfunctional.
Their cytotoxic activity—their ability to kill infected cells—is significantly reduced.
This can lead to chronic viral persistence and prolonged immune activation.
This compromised function may fluctuate over time and contributes to the “immune exhaustion” seen in many patients.
Long Covid and immune similarities
Research suggests there are many similarities between Long Covid and ME/CFS and Long Covid in terms of the effects on the immune system in these two conditions. Long Covid shares many of these immune traits with ME/CFS. Studies have found:
Elevated inflammatory markers such as interleukin-6 (IL-6) and TNF-alpha.
Changes in T-cell activation and exhaustion markers.
Increased autoantibodies, suggesting a possible autoimmune component.
Both conditions also show signs of mitochondrial dysfunction and disrupted energy metabolism, likely driven in part by chronic inflammation.
Several researchers have considered the similarities between Long Covid and ME/CFS with respect to the imact on the immune system of these conditions.
Diagram showing post-COVID condition and relationship with ME/CFS (Sukocheva 2021)
Diagram showing how post-acute COVID-19 symptoms resemble post-infectious ME/CFS (Poenaru, 2021)
How Nutrition Can Support Immune Resolution
While diet alone cannot "cure" immune dysregulation, it plays a powerful role in modulating inflammation and supporting immune resilience.
Anti-inflammatory diets focus on whole foods that nourish the body without overstimulating the immune system. These diets emphasise:
Oily fish for omega-3 fatty acids (EPA and DHA) which support the resolution phase of inflammation.
Colourful vegetables and fruits rich in antioxidants and polyphenols, which help reduce oxidative stress.
Olive oil, nuts, and seeds for healthy fats.
Legumes, wholegrains, and herbs for fibre and micronutrients that support gut and immune health.
On the flip side, it is helpful to reduce or avoid foods that contribute to immune imbalance, including:
Added sugars and sweetened drinks
Refined carbohydrates like white bread and pastries
Processed meats and ultra-processed snacks
Industrial seed oils (e.g., sunflower, soybean, corn oil)
Nutrients of note in Immune health
Several nutrients have been studied for their impact on immune function, especially in the context of fatigue-related conditions:
Omega-3 fatty acids: Found in oily fish, they produce pro-resolving lipid mediators like resolvins and protectins, which help turn off inflammation.
Vitamin D: Supports both innate and adaptive immunity. Low levels have been linked to worse outcomes in Covid-19 and may play a role in ME/CFS symptom severity.
Protein: Essential for building immune cells and antibodies. Chronic illness increases protein demands, making adequate intake even more important.
Zinc and Selenium: Critical for antiviral immunity and antioxidant defence.
Supporting resolution - more than just suppression
It's important to understand that healthy immune recovery does not mean suppressing inflammation entirely—it means resolving it. The resolution of inflammation is an active, nutrient-driven process. Nutrients like omega-3s, polyphenols, and glutathione precursors (like glycine and cysteine) help the body complete the immune response and return to homeostasis.
This concept is particularly important for people with ME/CFS and Long Covid, where incomplete resolution may underlie persistent symptoms.
Lifestyle factors that support the immune system
In addition to dietary changes, other lifestyle habits that support immune health include:
Restorative sleep - deep sleep enhances immune repair and memory.
Stress management -chronic stress activates inflammatory pathways and suppresses beneficial immune responses.
Gentle movement - while vigorous exercise is not recommended in these conditions, short, gentle stretching or walking may help support lymphatic flow and circulation
Sun exposure - 10–15 minutes of daily sun can support vitamin D levels (season and skin tone dependent).
Conclusion
ME/CFS and Long Covid are complex conditions with significant immune involvement. Nutrition can play an important role in reducing chronic inflammation, supporting the immune system and improving quality of life.
By adopting an anti-inflammatory approach, focusing on whole foods, and ensuring optimal intake of key nutrients, people with these conditions may support their immune systems in the long-term management of these challenging conditions.
References
Poenaru S, et al COVID-19 and post-infectious myalgic encephalomyelitis/chronic fatigue syndrome: a narrative review. Therapeutic Advances in Infectious Disease. 2021;8. doi:10.1177/20499361211009385
Komaroff, A.L 2017 Inflammation correlates with symptoms in chronic fatigue syndrome. PNAS https://doi.org/10.1073/pnas.1712475114
Hannah E Davis, 2023, Long COVID: major findings, mechanisms and recommendations. Nature Review.
Sukocheva, O. A, et al (2022). Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome. Jnl. of Advanced Research
Comments