Review Fatigue in Post-Acute Sequelae of Coronavirus Disease 2019, 2023, Abbott et al

Key points

• According to recent data from the US Census Bureau and CDCs National Center for Health Statistics, 7.5% or one in 13 patients diagnosed with coronavirus disease 2019 (COVID-19) reported long-term symptoms.
  
  
• Because of the varied possible etiologies causing post-acute sequelae of COVID-19 (PASC) symptoms, there does not seem to be a single-laboratory evaluation, diagnostic test, or examination finding that will best identify the etiology of PASC symptoms.
  
  
• At this time, there is continued investigation into which medication, therapy program, diet, infusion, or supplement that would best improve PASC symptoms.
  

Introduction/history/definitions/background

As of July 19, 2022, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and its associated infectious disease coronavirus disease 2019 (COVID-19) have amassed over 600 million confirmed cases worldwide.1 Multiple authors cite significant underreporting of infections with true infection rates somewhere in the range of 2 to 20 times higher than documented.2,3 In the United States alone, these infections have led to nearly 5 million hospital admissions4 and over 1 million deaths.5 Hospitalization rates are widely variable with differences in virus variant, vaccination status, and age, though most estimates place the percentage of hospitalization in the single digits.6 Despite low incidence of hospitalization, most research to date has focused on sequelae and management of acute disease in patients hospitalized with severe disease.

Recently, attention has focused on long-term impacts of COVID-19. A clinical profile has emerged known as “long-COVID” to describe the prolonged impacts of infection. Commonly described sequelae include fatigue, post-exertional malaise, and cognitive dysfunction, although sufferers of long-COVID often experience a multitude of symptoms from various organ systems.7 This constellation of symptoms has been termed “Post-Acute Sequelae of COVID” (PASC).8 According to recent data from the US Census Bureau and centers for disease control and prevention (CDCs) National Center for Health Statistics, 7.5% or one in 13 patients diagnosed with COVID-19 reported long-term symptoms.a These individuals were more likely to be younger than 59 years, female, and Hispanic, comparatively. Long-COVID has been documented in less symptomatic nonhospitalized patients7,9,10 and among more severe cases that required hospitalization and critical care.

One of the most reported symptoms of long-COVID is fatigue.11,12 In general, fatigue is a subjective, nonspecific term that is pervasive in the outpatient setting with one in five primary care provider visits discussing the topic.13 Fatigue is often described as akin to feeling tired (reported more often by male patients) or depression/anxiety (reported more often by female patients).13 The etiology of fatigue can be physiologic, secondary, or chronic. Physiologic fatigue refers to day-to-day variation in energy levels and is often related to sleep patterns, exercise habits, and diet, among other factors. This form of fatigue improves with rest. Pathologic or secondary fatigue is attributable to a medical condition (eg, anemia) and often lasts greater than 1 month but less than 6 months and often improves with treatment of the underlying medical etiology. Chronic fatigue is defined as lasting greater than 6 months and not improving with rest or medical treatment. Another form of fatigue is “post-exertional malaise,” which refers to worsening of fatigue following physical, cognitive, or emotional stressors that under normal circumstances would not cause symptoms.14 Data from the International Committee on Fatigue Following Infection15 suggest that the rates of clinically significant post-COVID infection fatigue are in the range of 10% to 35% at 6 months after controlling for medical and psychiatric causes.

This high prevalence has drawn comparisons between the PASC and post-viral fatigue syndrome/myalgic encephalomyelitis and chronic fatigue syndrome (ME/CFS). Chronic fatigue syndrome is a constellation of symptoms that accompanies severe fatigue for a period of longer than 6 months. The etiology of this condition is debated with early discussions centered on post-viral sequelae16 and more recent criteria being updated to include considerations for a neurologic basis of disease. However, sources agree that ME/CFS encompasses a variety of organ systems with pathophysiology related to the metabolic, neurologic, and myofibrillar components.17 ME/CFS requires a thorough medical and psychological workup to rule out other etiologies (see Evaluation section [Box 1]). ME/CFS is often a debilitating constellation of symptoms and has led to an estimated loss of billions of dollars of productivity in both households and the labor force.18

Open access, https://www.sciencedirect.com/science/article/pii/S1047965123000293

 

Not sure why they aren't referencing the newer guideline,

"NICE published guidelines in 2007 to help quantify fatigue severity in the context of ME/CFS."

 

Also included in the special issue are —

Autonomic Dysfunction Related to Postacute SARS-CoV-2 Syndrome (2023)
Sequelae of COVID-19 and the Need for Post-COVID Rehabilitation (2023)
Neurologic and Neuromuscular Sequelae of COVID-19 (2023)
Immunologic and Autoimmune-Related Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Clinical Symptoms and Mechanisms of Disease (2023)