Some COVID-19 patients experience persistent chronic fatigue six months after infection, finds study

A team of scientists from Germany has recently revealed that almost 50% of patients present with moderate to severe chronic fatigue syndrome six months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study is currently available on the medRxiv* preprint server.


Infection with SARS-CoV-2 is associated with a wide variety of symptoms, ranging from mild fever and cough to severe pulmonary and cardiovascular complications. Although almost 80% of coronavirus disease 2019 (COVID-19) patients remain asymptomatic or mildly symptomatic, a growing pool of evidence indicates that a significant fraction of COVID-19 patients present with persistent symptoms referred to as ‘long COVID’. Most commonly reported symptoms of long COVID are fatigue, cognitive impairment, and post-exertional malaise (worsening of symptoms after minor physical or mental exertion).

In the current study, the scientists have investigated mild to moderate COVID-19 patients who present with persistent fatigue and other related symptoms. They have also investigated whether these patients meet the diagnostic criteria for chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), which is a neurological disease characterized by severe mental and physical fatigue, chronic pain, and sleep disorder.

Study design

A total of 42 COVID-19 patients presented with moderate to severe intensity chronic fatigue, exertion intolerance, cognitive dysfunction, and pain six months after SARS-CoV-2 infection were investigated in the study. All participants were diagnosed with mild to moderate COVID-19. A team of experienced clinical immunologists, rheumatologists, neurologists, and cardiologists was involved for an accurate diagnosis of ME/CFS in these patients based on the Canadian Consensus Criteria. The intensity and duration of post-exertional malaise (symptoms lasting for more than 14 hours) was considered to be the main diagnostic criterion for ME/CCFS.

Important observations

Of all enrolled patients, 32 had mild COVID-19 and 10 had moderate COVID-19 because of pneumonia. The numbers of male and female patients were 29 and 13, respectively, and the average age of the patients was 36 years (age range: 22 – 62 years).

Of 42 enrolled patients, 19 met the diagnostic criteria for ME/CFS and were found to have severe fatigue and functional impairment, severe stress intolerance, and hypersensitivity to noise, light, and temperature. The scientists categorized these patients as Chronic COVID-19 Syndrome/Chronic Fatigue Syndrome (CCS/CFS). The rest of the patients who were not diagnosed with ME/CFS mainly because of the relatively shorter duration of post-exertional malaise (2 – 10 hours) were referred to as CCS. The patients with ME/CFS showed significantly reduced hand grip strength than those without ME/CFS.

After 6 months of SARS-CoV-2 infection, all participants were found to have fatigue with different intensities. The most commonly observed symptoms were post-exertional malaise, cognitive impairment, and muscle pain. Although patients without ME/CFS exhibited less severe symptoms, most of them had severely impaired daily life activities. The majority of enrolled patients (n=28) were either unable to work or required a reduced work schedule because of post-COVID-19 symptoms.

In the study cohort, autonomic dysfunction was observed in most of the patients, with no significant difference in symptom intensity between patients with and without ME/CFS. The increase in systolic and diastolic blood pressure at standing position was significantly lower in patients with ME/CFS than those without it. Among patients with ME/CFS, four were diagnosed with postural tachycardia syndrome.         

Regarding biochemical parameters, only two patients in the entire study cohort showed mildly elevated C-reactive protein levels, indicating the absence of robust inflammatory response. Almost 50% of patients showed increased levels of interleukin 8 (IL-8), which is a clinical feature of severe COVID-19 patients. Moreover, a low level of mannose-binding lectin was observed in 22% of patients, indicating impaired immune functioning. An indication of autoimmune disorder was noticed in the study cohort as elevated levels of antinuclear antibody were found in 3 ME/CFS patients and 6 non-ME/CFS patients.

Study significance

The study reveals that even mildly affected COVID-19 patients can develop a severe chronic syndrome characterized by moderate to severe fatigue and exertion intolerance. Because most of the post-COVID symptoms considered in this study did not differ significantly between patients with and without ME/CFS, the scientists suggest that chronic COVID-19 syndrome is a more appropriate terminology than ME/CFS in defining long-term symptoms related to SARS-CoV-2 infection.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Sanchari Sinha Dutta

Written by

Dr. Sanchari Sinha Dutta

Dr. Sanchari Sinha Dutta is a science communicator who believes in spreading the power of science in every corner of the world. She has a Bachelor of Science (B.Sc.) degree and a Master's of Science (M.Sc.) in biology and human physiology. Following her Master's degree, Sanchari went on to study a Ph.D. in human physiology. She has authored more than 10 original research articles, all of which have been published in world renowned international journals.


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  1. Hani Aziz Hani Aziz United States says:

    I had over 6 months ago and I'm still suffering here and there with fatigue and foggy brain sometime especially after physical work Or mental work I feel very weak and tired do you guys have any suggesting solution I am 44 years old man. Thank you

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