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How common is chronic fatigue syndrome among long-term patients with COVID-19?




In a recent study posted on medrex sib*Preprint Server, Researchers have found myalgic encephalitis/chronic fatigue syndrome (ME/CFS) to be common in the 2019 long coronavirus disease (COVID-19).

Study: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is common in acute sequelae of SARS-CoV-2 infection (PASC): multidisciplinary clinic results after COVID-19. Image Credit: fizkes/Shutterstock
study: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is common in acute sequelae of SARS-CoV-2 infection (PASC): results of multidisciplinary clinics after COVID-19Image Credit: fizkes/Shutterstock


Although most patients recover from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within a few weeks, some patients present with debilitating symptoms that persist beyond the acute phase. The overall prevalence of acute sequelae of COVID-19 (PASC) is estimated at 0.43%.

The post-COVID-19 condition is increasingly being detected in asymptomatic and mild cases. PASC is characterized by postexercise malaise, brain fog, headache, sleep disturbance, dyspnea, and chest pain. In a multinational survey of more than 3,700 participants, post-exercise malaise, fatigue, and brain fog were most frequently reported six months after COVID-19.

These symptoms share similar characteristics with another often debilitating disease, ME/CFS. In her two small cohort studies of COVID-19 patients, nearly 45% of subjects met her diagnostic criteria for ME/CFS.

The pathobiological features of ME/CFS are not well defined, and many PASC patients with ME/CFS features may allow better characterization of both conditions.

About research

In the current study, researchers characterized a clinical cohort of PASC patients and determined the prevalence of the ME/CFS phenotype in long-term COVID based on the Institute of Medicine (IOM) 2015 criteria. 140 adults with a history of COVID-19 were referred to the multidisciplinary Stanford PACS Clinic from 18 May 2021 until he 1 February 2022.

Data on persistent symptoms from all patients were obtained from questionnaires and electronic health records (EHR) 7 days before the visit. The questionnaire included a) 29 commonly reported symptoms during acute COVID-19, b) symptom severity on a Likert scale, c) vaccination status, and d) post-COVID-19 functional status scale ( FSS) collected information.

demographics and radiology, laboratory results, vital signs, oxygen saturation, body mass index (BMI), heart rate measurements, and orthostatic blood pressure were obtained from the EHR. In addition, each patient received an identical questionnaire before their scheduled visit.

Patients presenting to the clinic more than 6 months after their COVID-19 diagnosis were analyzed for symptoms to determine if they met the IOM 2015 criteria for ME/CFS. Patients who had previously experienced ME/CFS or other conditions that accounted for fatigue pre-COVID-19 were excluded from the study.


Six of the 140 patients referred to the clinic were excluded due to incomplete questionnaires or lack of diagnostic test results for SARS-CoV-2. The median age of the remaining patients he was 47 years. Females (59%) and Caucasians (49.3%) were the most common. Seventeen patients were hospitalized during acute COVID-19. Two required intensive care. Sixty-two patients had severe predisposing comorbidities to her COVID-19.

Functional limitations were noted in 109 patients, including 45 subjects with severely impaired health. The median duration of symptoms at presentation was 285.5 days, and the median number of symptoms was 12 per patient. Fatigue, post-exercise malaise, restless sleep, brain fog, and daytime sleepiness were common.

Notably, the median number of symptoms was higher in women than in men, and fatigue, dysgeusia, and insomnia were more frequent in women. We found that there is a significant correlation. A principal component analysis revealed that fatigue, post-exercise malaise, brain fog, daytime sleepiness, and unrefreshing sleep were likely to occur simultaneously.

Symptoms persisted for more than 6 months in 105 patients, with fatigue, brain fog, post-exercise malaise, insomnia, daytime sleepiness, and unrefreshing sleep being the most common and severe. Forty-eight patients met her IOM criteria, and her final ME/CFS cohort (after exclusion) consisted of her 45 patients. Most patients in this cohort were female, healthy, and non-hospitalized (during acute COVID-19), and obesity was the most common complication. More than half of the cohort had significantly decreased function.


Most patients referred to the PASC clinic were not hospitalized or supported with oxygen during the acute phase of COVID-19. Females had significantly more symptoms than males. In conclusion, her 43% of patients with PASC and symptoms lasting more than 6 months met her criteria for ME/CFS. Her ME/CFS-PASC phenotype, like ME/CFS, was more common in non-hospitalized women.

The clinical similarities between ME/CFS-PASC and ME/CFS suggest a common pathobiology. Notably, these findings are from a single clinic in Northern California, are skewed toward specific populations, and have a low proportion of ethnic minorities. A large multicenter study is needed.

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .




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