Severe, Persistent, Disruptive Fatigue Post-SARS-CoV-2 Disproportionately Affects Young Women, 2023, Price et al.

[SNT Gatchaman]

Severe, Persistent, Disruptive Fatigue Post-SARS-CoV-2 Disproportionately Affects Young Women
Jillian Kallman Price; Leyla de Avila; Maria Stepanova; Ali A Weinstein; Huong Pham; Wisna’odom Keo; Andrei Racila; Suzannah Gerber; Brian P Lam; Lynn H Gerber; Zobair M Younossi

Introduction: Post-acute SARS-CoV-2 (PASC) symptoms are often persistent, disruptive, and difficult to treat effectively. Fatigue is often among the most frequently reported symptoms and may indicate a more challenging road to recovery.

Purpose: To describe the natural history, symptomology, and risk profile of long-term post-acute SARS-CoV-2.

Patients and Methods: Participants treated for SARS-CoV-2 within a large, community health system in the US were enrolled prospectively in a longitudinal, observational PASC study examining participants at enrollment and 6 months. Medical history, symptom reporting, validated measures of cognition, and patient-reported outcomes (PROs), were performed for all participants and repeated during study follow-up visits.

Results: A total of 323 participants completed baseline evaluations. Sixty one participants indicated clinically significant fatigue (23.1% at baseline); a representative sample of 141 enrollees also completed a baseline Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in-depth fatigue reporting questionnaire, 37 had severe fatigue. The severely fatigued (FACIT-F ≤29.7) were significantly younger, female, had more anxiety and depression, had a higher resting heart rate, reported more sick days, and were less physically active post-COVID. They were more likely to have a diagnosis of chronic kidney disease (13.5% vs 2.9%) but less likely to have a history of cancer (8.1% vs 23.1). Participants who were severely fatigued reported health, diet, weight, and sleep were worse than those not severely fatigued post-COVID (p = 0.02 to 0.0002). Fatigue was significantly correlated with impairment of all PROs administered after COVID-19 infection.

Conclusion: Fatigue is a common symptom post-COVID-19 infection and is associated with lower reported well-being and function. Those with severe fatigue tended to be younger and female and have a past medical history of anxiety, depression, kidney disease, and more sedentary lifestyles.

Link | PDF (International Journal of General Medicine)

 

[SNT Gatchaman]

No new information, just another study counting symptoms and noting there's a problem.

Global prevalence of PASC is estimated at approximately 65 million people, and growing, worldwide. This presents an important challenge to the health care community. The prevalence of PASC, its myriad of symptoms, its persistence, impact on function and life roles presents a significant health risk for domestic and global populations.

Despite improvement in fatigue and other symptoms over the follow-up period, severe, disruptive fatigue seems to linger in a substantial number of patients with PASC. Our analysis suggests that the group likely to report severe, persistent fatigue are younger female patients who have a high symptom burden and especially report anxiety and depressive symptoms in addition to their fatigue. Additionally, the most impacted seem to be those with lower preCOVID exercise behaviors, and those for whom the acute infection highly disrupted previously functional healthy diet and exercise habits.

Does include a new variation on messing up ME/CFS —

Lingering fatigue is not unique to PASC. Post-viral fatigue has been reported in patients with Hepatitis C, Lyme Disease, and E-B virus among others and is often referred to as Chronic Fatigue/Myalgic Encephalomyelitis Syndrome (ME/CFS).

 

[Hutan]

The introduction sets up the findings (note, no references given for the idea that food and beverage, exercise etc choices etc affect PASC risk):

The prevalence of PASC and its various manifestations pose a significant challenge to patients and health care teams. Some evidence suggests that lifestyle health behaviors such as food and beverage choices, smoking, exercise, and sleep could help influence the progression of PASC. However, more evidence is needed to understand whether these factors are more influential in the development of PASC, and to what extent they can moderate recovery. Intervention strategies are needed to lessen the burden of PASC and may include diet, exercise/activity, and possible cognitive/behavioral treatments.

The participants had to be treated for Covid-19 by the health system - there's a bias there to people who were either more significantly affected or perhaps more anxious (for a range of reasons) about having the infection. They don't tell us how many of the people they treated agreed to be part of the study. There surely had to be some self-selection bias operating there.

Briefly, participants who were treated for SARS-CoV-2 between March 2020 and July 2022 within Inova Health System – a large, metropolitan, community health system in the northeastern U.S. – were invited to enroll in a post-acute SARS-CoV-2 (PASC) follow-up study examining post-COVID-19 recovery. Once enrolled, 323 participants’ data was collected at baseline and 6 months and continuing annual follow-ups with those experiencing persistent symptoms.

It isn't clear to me when 'baseline' is, apart from it's when the person was enrolled. It seems to be well after the acute illness as 41% of people at baseline had no symptoms.

This was at baseline:

Among the 58.2% reporting persistent symptoms, the nine top symptoms reported were fatigue (20.5%), memory difficulties (15.5%), shortness of breath (12.2%), general neurological symptoms (10.9%), loss of smell and/or taste (10.2%), musculoskeletal symptoms (8.6%), headache (8.3%), rash (7.6%), and mood disturbance (6.9%).

I'm not to sure what the denominator is in those percentages for symptoms (is it a percentage of the whole sample, or just of the 58% reporting persistent symptoms?). But regardless, with only 20.5% reporting fatigue and with 7.6% reporting a rash for example, these people are very variable in symptom presentation. It means it is very hard to draw any conclusions from this that might be relevant to ME/CFS.

And things get more complicated after the baseline with people dropping out of followups.

Additionally, the most impacted seem to be those with lower preCOVID exercise behaviors, and those for whom the acute infection highly disrupted previously functional healthy diet and exercise habits.

There is not enough evidence here to think that this statement applies to post-Covid ME/CFS. There are many reasons why people with lower preCovid exercise behaviours and/or who were severely affected by the infection might have lingering symptoms including fatigue that they attribute to the infection.

Global prevalence of PASC is estimated at approximately 65 million people, and growing, worldwide. This presents an important challenge to the health care community.9,17,24 The prevalence of PASC, its myriad of symptoms, its persistence, impact on function and life roles presents a significant health risk for domestic and global populations. Assessing which are modifiable should be a high priority. In our view, data collected from prospective, natural history studies using standard, reliable assessments, including PROs are critical to understanding this novel and emergent condition.

Looking at past medical history of anxiety and depression in more detail may also give us some understanding whether these diagnoses are overrepresented in our post-viral population with severe, persistent fatigue.

There is no consensus regarding the evaluation and treatment of fatigue. Our data support the finding of many other studies that fatigue is not an isolated symptom and may be associated with negative mood/affect, sedentary lifestyle, and metabolic dysregulation. This may compound the diminished social participation/social isolation that many reported during the pandemic, resulting in significant and extremified disparities in the work and social lives of persons with fatigue resulting from infection with COVID-19.30,36

These data may help inspire clinicians to include assessment of patient exercise and health behavior history in routine visits and especially in visits where patients seek treatment after viral infections. The association between regular exercise (30 minutes, 5x/week or a total of 150 minutes/week) and fewer symptoms and faster symptom resolution is striking. Targeting a manageable activity, such as pacing, may provide appropriate guidance for populations at risk and offer clinicians a recommendation for patients seeking medical attention for reasons other than SARS-CoV2 infection and its sequelae. As reported in our previous paper, this effect was also seen in mAb-treated patients.37 While our study did not include comprehensive assessments of diet and eating behavior, patient reports regarding the quality of their diet indicated that disruptions to diet may be associated with worse PASC symptom persistence.

In case it's not obvious, I'm less than impressed with this paper. It just adds more confusion to the existing confusion. The authors pat themselves on the back for their understanding of fatigue and yet the concept of PEM is not mentioned anywhere. And, having suggested that it's young women with high levels of anxiety and depression who don't exercise and don't eat well who are at risk, they then note the low representation of adults in the "18-20s age range" in their sample. I assume "20s" means 20 to 29. (edit - why would you present an age range as 18-20s rather than 18-29 other than to minimise the impact of the poor representation on the conclusion - a conclusion that even gets presented in the title?)

However, a significant strength of our study was the inclusion of patient-reported outcomes (PROs) at all visits -including fatigue via FACIT-F- which were both standardized and quantifiable.38 This study documents an association between patient reports of fatigue as a new symptom developed post-acute SARS-CoV-2 but does not establish causality. While our analysis identified that younger working age adults and specifically younger women were at higher risk for fatigue, our study also cannot speak to the magnitude and roles of fatigue, depression, and anxiety in the youngest of adults (age 18–20s), due to their low representation within our study cohort.

There is a difference between identifying fatigue and understanding fatigue. An added strength of our prospective, multi-visit, in-depth cohort study with face-to-face discussion of symptomatology is that the features of interest within our cohort – possible confounding variables also assessed using validated measures – provide clarity in differentiating fatigue from frequent co-traveling conditions. Unique to the literature, we are also trying to determine phenomenon that go along with fatigue with patient-reported outcomes to understand what may be impactful in people’s lives, including behavioral milieu, depression, sleep, and quality of life. This is informed by our experience examining both viral and metabolic drivers of fatigue prior to the advent of SARS-CoV-2 and PASC.