Post-COVID-19 fatigue: A systematic review

Post-COVID-19 fatigue: A systematic review

Jian Joli¹, Patrizia Buck¹, Stephan Zipfel¹ and Andreas Stengel^1,2*

¹Department of Psychosomatic Medicine and Psychotherapy

This study is a systematic review examining post-COVID fatigue, including its symptoms, etiology, risk factors, and therapeutic approaches.

Post-COVID-19 Fatigue Overview ​

Post-COVID-19 fatigue is a prevalent long-term symptom experienced by individuals recovering from COVID-19, characterized by debilitating tiredness and other associated symptoms. ​ This systematic review aims to explore the symptoms, etiology, risk factors, and treatment approaches related to post-COVID-19 fatigue. ​

Symptoms and Prevalence of Post-COVID Fatigue ​

The most common symptoms reported by patients recovering from COVID-19 include fatigue, dyspnea, and depression.

• Fatigue is reported in 64% of patients. ​

• Other prevalent symptoms include dyspnea (40%), depression/anxiety (38%), arthralgia (24.3%), headache (21%), and insomnia (20%). ​

• Symptoms can persist for weeks to months after the initial infection. ​

Risk Factors Associated with Post-COVID Fatigue

Several risk factors have been identified that may contribute to the development of post-COVID fatigue.

• Older age, female sex, and severe clinical status during the acute phase of infection are significant risk factors.
• A high number of comorbidities and a prediagnosis of depression/anxiety also increase the risk.
• Potential autoimmune etiology is suspected in some cases.

Treatment Approaches for Post-COVID Fatigue ​

Various treatment methods have been explored for managing post-COVID fatigue, though many studies are small and uncontrolled.

• Chinese herbal formulations have shown improvement in breathlessness and fatigue.
• Molecular hydrogen inhalation has beneficial effects on physical and respiratory function.
• Hyperbaric oxygen therapy (HBOT) and enhanced external counterpulsation (EECP) have led to reported improvements in fatigue.
• A biweekly physical therapy course improved muscle strength and physical function.

Methodology of the Systematic Review ​

The systematic review followed established guidelines to ensure comprehensive and unbiased results. ​

• The review was registered with PROSPERO (CRD42022320676) and adhered to Cochrane and PRISMA guidelines. ​
• A systematic literature search was conducted across multiple databases, including PubMed and Cochrane Library. ​
• Studies included were original research focusing on adult patients with confirmed COVID-19 and post-COVID fatigue, excluding those in the acute phase or with chronic diseases. ​​

Definition and Measurement of Post-COVID-19 Fatigue

Post-COVID-19 fatigue was defined variably across studies, with some requiring persistent symptoms for at least 6 months. ​ Various scales were used to measure fatigue, including the PROMIS and Chalder fatigue scales. ​

• Elanwar et al. defined post-COVID-19 fatigue as persistent fatigue for at least 6 months. ​
• Other studies defined it as fatigue lasting at least 6 weeks post-recovery. ​
• Measurement scales included PROMIS, Chalder fatigue scale, and Borg scale. ​

Symptoms Associated with Post-COVID-19 Fatigue

Participants reported a range of symptoms related to fatigue, with varying frequencies. ​ Fatigue was consistently present, along with other symptoms such as brain fog, myalgia, and sleep disturbances. ​

• Fatigue was always present; anhedonia and brain fog reported by up to 81%. ​
• Myalgia reported by up to 55%; depression/anxiety by up to 47%.
• Insomnia and cognitive issues reported by up to 33% and 32%, respectively.

Etiology and Risk Factors for Fatigue ​

Several studies identified potential risk factors for post-COVID-19 fatigue, including age, gender, disease severity, and preexisting conditions. ​ Female patients and those with longer illness duration were particularly affected. ​

• Older age and female gender associated with higher fatigue risk. ​
• Longer duration of acute phase linked to increased fatigue. ​
• Comorbidities and preexisting depression/anxiety also identified as risk factors.

Therapeutic Approaches for Post-COVID-19 Fatigue

Various therapeutic approaches were explored in case reports, including enhanced external counterpulsation (EECP), physical therapy, and hyperbaric oxygen therapy. Some treatments showed promise in alleviating symptoms, though evidence is limited.

• EECP improved symptoms in a case report after 5 weeks of treatment. ​
• Physical therapy led to improved physical performance but did not enhance quality of life.
• Hyperbaric oxygen therapy reported benefits in fatigue and cognitive function after multiple sessions. ​

Conclusion and Future Directions

The review highlights the prevalence of post-COVID-19 fatigue and its multifactorial nature, suggesting a need for further research into effective treatments. A biopsychosocial model is proposed to understand the origins of fatigue, emphasizing the importance of addressing both physical and psychological factors. ​

• Fatigue is a common persistent symptom post-COVID-19.
• Future research should explore long-term effects and treatment efficacy.
• A biopsychosocial model may help in understanding and treating post-COVID-19 fatigue.