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

In a recent study posted to the medRxiv* preprint server, researchers found that myalgic encephalitis/chronic fatigue syndrome (ME/CFS) was common in long coronavirus disease 2019 (COVID-19).

Background

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

The post-COVID-19 conditions are increasingly detected even in asymptomatic cases or those with mild disease. PASC is characterized by post-exertional malaise, brain fog, headaches, sleep disturbance, dyspnea, and chest pain.  In a multinational survey of more than 3,700 participants, post-exertional malaise, fatigue, and brain fog were reported most frequently six months after COVID-19.

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

The pathobiological features of ME/CFS are poorly defined, and many PASC patients with ME/CFS features might allow for better characterization of both conditions. 

About the study

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

Data about persistent symptoms from all patients were obtained via a questionnaire seven days before the visit and from electronic health records (EHRs). The questionnaire captured information on a) 29 symptoms commonly reported during acute COVID-19, b) severity of symptoms on the Likert scale, c) vaccination status, and d) post-COVID-19 functional status scale (FSS).

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

For patients whose clinic visits occurred more than six months after COVID-19 diagnosis, symptoms were analyzed to see if they fulfilled the IOM 2015 criteria for ME/CFS. Patients were excluded from the study if they had previously experienced ME/CFS or other condition(s) explaining pre-COVID-19 fatigue.

Findings

Six of the 140 patients referred to the clinic were excluded due to incomplete questionnaires or the lack of SARS-CoV-2 diagnostic test results. The median age of the remaining patients was 47 years. Most were females (59%) and White (49.3%). Seventeen patients were hospitalized during acute COVID-19; two required intensive care. Sixty-two patients had comorbidities predisposing them to severe COVID-19.

Functional limitations were noted in 109 patients, including 45 subjects with significantly compromised wellbeing. The median duration of symptoms at the initial clinic visit was 285.5 days, and the median number of symptoms was 12 per patient. Fatigue, post-exertional malaise, unrefreshing sleep, brain fog, and sleepiness during the day were common.

Notably, the median number of symptoms was greater in females than males, with fatigue, dysgeusia, and insomnia being more frequent among females. The authors found a significant correlation between the severity and frequency of symptoms. Principal component analysis revealed that fatigue, post-exertional malaise, brain fog, daytime sleepiness, and unrefreshing sleep were more likely to co-occur.

Symptoms persisted longer than six months for 105 patients, with fatigue, brain fog, post-exertional malaise, insomnia, daytime sleepiness, and unrefreshing sleep being the most common and severe. Forty-eight patients met the IOM criteria, and the final ME/CFS cohort (after exclusions) comprised 45 patients. Most patients in this cohort were females, healthy, and non-hospitalized (during acute COVID-19), with obesity as the most common comorbidity. More than half of the cohort had a significant decrease in their functionality.

Conclusions

Most patients referred to the PASC clinic had not been hospitalized or supported with oxygen during acute COVID-19. Females had significantly more symptoms than males. In conclusion, 43% of patients with PASC and symptoms for longer than six months met the criteria for ME/CFS. The ME/CFS-PASC phenotype, like ME/CFS, was more prevalent in non-hospitalized females.

The clinical similarities between ME/CFS-PASC and ME/CFS suggest common pathobiology. Notably, these findings are from a single clinic in Northern California with a bias towards specific populations and a lower proportion of minority populations. Thus, large multicenter studies with a diverse population are required to corroborate the results.

*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.

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.