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Is long COVID a new form of ME/CFS?

Dr Ilduara Pintos-Pascual and colleagues at the Hospital Universitario Puerta de Hierro Majadahonda in Madrid have recently published a review paper suggesting that long COVID reflects a collection of clinical signs and symptoms that match much of the clinical picture found in ME/CFS.

Such a suggestion will not surprise many ME/CFS sufferers, but there is ongoing debate in academic circles whether long COVID represents a new form of ME/CFS, or whether it is a distinct and different illness?

Around 10% of adults infected with SARS-CoV-2, and who survive a first episode of COVID-19, experience long-term clinical manifestations. These are symptoms that persist after the patient no longer tests positive for COVID-19 and is considered to have recovered.

These people can go on to experience lingering and debilitating symptoms such as fatigue, shortness of breath, joint pain, muscle pain, chest pain, cough, loss of taste and smell, headache, depression, anxiety, memory loss, concentration difficulties and insomnia. Apart from breathing and taste problems, most of these symptoms are the same as those reported in ME/CFS.

The Spanish researchers found that long COVID – or post-acute COVID syndrome (PACS) as it is increasingly being called in academic medicine – is the consequence of SARS-CoV-2 infection for some patients, and could be viewed as a form of ME/CFS.

While the exact cause of ME/CFS remains unclear, much research suggests that viral infections such as Epstein-Barr virus could be the likely cause or trigger for the disease, with a small percentage of infected individuals developing ME/CFS.

Apart from the symptom overlap between long COVID and ME/CFS, other important similarities include the higher number of female sufferers. Researchers studying long COVID are now grappling with trying to understand why women are more at risk than men, just as they have in ME/CFS.

Genetic factors could be involved in both diseases. The international COVID-19 Host Genetics Initiative is an open-science collaboration to share scientific methods and resources with research groups across the world, with the goal of mapping the genetic determinants of SARS-CoV-2 infection.

To date, no clear host genes have been identified to explain long COVID. Similarly, genetic research in ME/CFS has identified some interesting lines of enquiry, but has also found it difficult to pinpoint any clear genetic mutation responsible.

The Spanish review team found evidence of dysregulation of multiple body organs and systems, including the immune system, blood clotting, hormones, the autonomic nervous system, and more. COVID-19 clearly has profound effects on cells, tissues and organs all over the body, yet the virus is predominately a respiratory virus.

Researchers are trying to identify the exact biological mechanisms that lead to long COVID, but the leading hypothesis is that it is triggered by an abnormal response to infection. What ‘abnormal’ means is yet to be fully explained, but evidence continues to emerge of an immune response that leads to inflammation in many tissues and organs.

Perhaps the important question to be answered is why does this response not subside if the initial viral illness has been brought under control? Does COVID-19 begin some type of auto-immune disease?

The Spanish researchers conclude by suggesting that most long COVID sufferers will go on to meet criteria for ME/CFS, fibromyalgia or central sensitisation syndrome, and that the pathogenesis of the disease probably depends on many factors. They also state that the management of both long COVID and ME/CFS will require a multi-disciplinary team, and will most likely involve drugs and other forms of therapy, to reduce symptoms and improve quality of life.

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