Long COVID & ME/CFS

A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery. An international group of researchers have published a review of the themes arising from that meeting.

“It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/ chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes.”

Extract: Links with ME/CFS

The increased incidence of symptoms after COVID-19 compared to influenza suggests some specificity for the type of infection. However, there are also some similarities between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Like long COVID, this is associated with prior viral infection and often occurs in previously healthy and active people (predominantly females) (Poenaru et al., 2021).

The chronic presentation of both conditions is similar, with fatigue, brain fog and post-exertional malaise (PEM) (Singh et al., 2022), impacting on activities of daily living.

One study demonstrated that in those symptomatic with long COVID at 2 months, 85% still reported symptoms after 1 year (Tran et al., 2022). Long COVID can have a significant impact on patients’ lives after 6 months, which may, in some cases, represent evolution to an ME/CFS-like condition.

Symptoms of Long COVID (Tacquet)

Life-altering fatigue is very common in both populations and also in patients with chronic autoimmune (Davies et al., 2021) or neurological (Kluger et al., 2013) diseases. In some, this fatigue becomes severely disabling (van Ruitenbeek et al., 2019).

Patients with ME/CFS need daily management of activity levels in order to prevent PEM, which when severe, can lead individuals to become bed-bound, with symptoms such as severe postural orthostatic intolerance (POTS), sleep dysfunction, myalgia, cognitive dysfunction, dysautonomia, neuro-immuno-endocrine dysfunction, hyperacusis and photophobia (Carruthers et al., 2011; Stussman et al., 2020).

Similar to long COVID, the lack of a diagnostic test is a significant hurdle, with many patients diagnosed by excluding other conditions, or given a diagnosis of ME/CFS after a prolonged period of time (>10 years). Between 80% and 90% of patients never get a clear diagnosis (Komaroff et al., 1996).

Current ME/CFS management options are limited, with graded exercise therapy removed in 2021 from NICE guidance as a result of 50% of patients experiencing a deterioration of their conditions (Kujawski et al., 2020, 2021; NICE Guideline [NG206], 2021). Treatments for depression or other psychiatric illness have limited benefit.

Once ME/CFS is established, many patients never fully recover and are ‘forgotten’ by society. However, the burden on families is enormous, with many families taking on a life-long commitment as carers. A better understanding of long COVID, a prolonged condition with many of the same symptoms observed in ME/CFS, therefore presents an opportunity that may also help in understanding and managing patients with ME/CFS, with options for the development of therapeutic interventions in a potentially more homogeneous condition.

ME/CFS research can also help with understanding of underlying pathophysiological mechanisms, such as:

• dysregulated energy metabolism (Missailidis et al., 2020; Sweetman et al., 2020; Tomas et al., 2017, 2020),
• exercise-induced plasma metabolome alterations (Germain et al., 2022),
• dysbiotic gut (Morten et al., 2018; Xiong et al., 2021) and immune cell dysfunction (Milivojevic et al., 2020).

Evidence of metabolic dysregulation and prolonged immune dysregulation has also been found in long COVID patients (Phetsouphanh et al., 2022). This could potentially be due to viral persistence of SARS-CoV-2 or other viruses, though this has not been demonstrated in ME/CFS patients (Chang et al., 2021). SARS-CoV-2 persistence of 3–5 months has been reported in immunocompromised patients, but with no co-existing symptoms (Gaspar-Rodríguez et al., 2021), and this is an area of further study (Brodin et al., 2022).

lessons must be learnt from the poor management of ME/CFS patients

To progress, lessons must be learnt from the poor management of ME/CFS patients and long-term research programmes established to fully understand the biology behind long COVID and ME/CFS.

Certain insights may arise sooner in populations that have undergone particularly high levels of scrutiny of the disease course, progression and effects of interventions. These include individuals in elite athletics or the military, where physical fitness is key to success and resource-intensive monitoring of performance is routine.

From:

Long COVID: mechanisms, risk factors and recovery, by Ronan Astin, Amitava Banerjee, Mark R. Baker, Melanie Dani, Elizabeth Ford, James H Hull, Phang Boon Lim, Melitta McNarry, Karl Morten, Oliver O’Sullivan, Etheresia Pretorius, Betty Raman, Demetris S Soteropoulos, Maxime Taquet, Catherine N Hall in Experimental Physiology, Nov 2022 [https://doi.org/10.1113/EP090802]

Review abstract

Long COVID, the prolonged illness and fatigue suffered by a small proportion of those infected with SARS-CoV-2, is placing an increasing burden on individuals and society. A Physiological Society virtual meeting in February 2022 brought clinicians and researchers together to discuss the current understanding of long COVID mechanisms, risk factors and recovery.

This review highlights the themes arising from that meeting. It considers the nature of long COVID, exploring its links with other post-viral illnesses such as myalgic encephalomyelitis/ chronic fatigue syndrome, and highlights how long COVID research can help us better support those suffering from all post-viral syndromes.

Long COVID research started particularly swiftly in populations routinely monitoring their physical performance – namely the military and elite athletes. The review highlights how the high degree of diagnosis, intervention and monitoring of success in these active populations can suggest management strategies for the wider population.

We then consider how a key component of performance monitoring in active populations, cardiopulmonary exercise training, has revealed long COVID-related changes in physiology – including alterations in peripheral muscle function, ventilatory inefficiency and autonomic dysfunction.

The nature and impact of dysautonomia are further discussed in relation to postural orthostatic tachycardia syndrome, fatigue and treatment strategies that aim to combat sympathetic overactivation by stimulating the vagus nerve.

We then interrogate the mechanisms that underlie long COVID symptoms, with a focus on impaired oxygen delivery due to micro-clotting and disruption of cellular energy metabolism, before considering treatment strategies that indirectly or directly tackle these mechanisms. These include remote inspiratory muscle training and integrated care pathways that combine rehabilitation and drug interventions with research into long COVID healthcare access across different populations.

Overall, this review showcases how physiological research reveals the changes that occur in long COVID and how different therapeutic strategies are being developed and tested to combat this condition.