Nature report on Long Covid literature

Nature: Long COVID: major findings, mechanisms and recommendations

Nature has published a digest of the main literature on Long Covid and brought together some of the key findings. There is considerable mention of ME/CFS and the overlap with Long Covid.

The pathological/causative overlaps are described on pages 5-6
The treatment overlaps are described on pages 7-8
However, there are a few conclusions that I would not agree with
There is very similar information in the MEA (free download) guide to Long Covid and ME/CFS

Dr Charles Shepherd


In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process. Sections Introduction Major findings Diagnostic tools and treatments Impact of vaccines, variants and reinfections Challenges and recommendations Conclusions 1 Patient-Led Research Collaborative, New York, NY, USA. 2 Patient-Led Research Collaborative, Oakland, CA, USA. 3

Long COVID research has found mitochondrial dysfunction including loss of mitochondrial membrane potential and possible dysfunctional mitochondrial metabolism, altered fatty acid metabolism and dysfunctional mitochondriondependent lipid catabolism consistent with mitochondrial dysfunction in exercise intolerance, redox imbalance108, and exercise intolerance and impaired oxygen extraction. Microclots and hyperactivated platelets are found not only in individuals with long COVID but also in individuals with ME/CFS.

Research on ME/CFS shows associations between ME/CFS and premenstrual dysphoric disorder, polycystic ovarian syndrome, menstrual cycle abnormalities, ovarian cysts, early menopause and endometriosis. Pregnancy, postpartum changes, perimenopause and menstrual cycle fluctuations affect ME/CFS and influence metabolic and immune system changes. Long COVID research should focus on these relationships to better understand the pathophysiology.


Long COVID is a multisystemic illness encompassing ME/CFS, dysautonomia, impacts on multiple organ systems, and vascular and clotting abnormalities. It has already debilitated millions of individuals worldwide, and that number is continuing to grow. On the basis of more than 2 years of research on long COVID and decades of research on conditions such as ME/CFS, a significant proportion of individuals with long COVID may have lifelong disabilities if no action is taken. Diagnostic and treatment options are currently insufficient, and many clinical trials are urgently needed to rigorously test treatments that address hypothesized underlying biological mechanisms, including viral persistence, neuroinflammation, excessive blood clotting and autoimmunity

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