Fatigue and Mental Illness Symptoms in Long COVID: Protocol for a Prospective Cohort Multicenter Observational Study
Authors: Pires Ligia , Reis Cláudia , Mesquita Facão Ana Rita , Moniri Armin , Marreiros Ana , Drummond Marta , Berger-Estilita Joana 
Published: January 2024

Background
The aftermath of the COVID-19 pandemic continues to affect millions worldwide, resulting in persisting postvirus complaints and impacting peoples’ quality of life. Long COVID, characterized by lingering symptoms like fatigue and mental illness, can extend beyond a few months, necessitating further research to understand its implications.

Objective
This study aims to quantify the degree of physical and psychological fatigue in patients following COVID-19 infection and examine its correlation with mental health disorders.

Methods
Using a consecutive nonrandom sampling technique, we will conduct a prospective cohort multicenter observational study in 5 Portuguese hospitals. Symptomatic adult patients with previous COVID-19 attending follow-up consultations will be enrolled. We will include patients who had mild, moderate, and severe acute disease. We will assess clinical outcomes related to COVID-19, including the type of respiratory support such as high-flow nasal cannula, noninvasive ventilation, and invasive mechanical ventilation. The exclusion criteria will include previous severe psychiatric disorders confirmed by a psychiatrist; refusal or inability to respond to the questionnaire; concomitant neurological disorder; persistent fatigue symptoms during the 6 months before infection; and the need for invasive mechanical ventilation during COVID-19 infection due to a high prevalence of postintensive care syndrome. Our primary outcome is the prevalence of fatigue in patients with post–COVID-19 depression and/or anxiety, as measured by the Chalder Fatigue Scale (CFQ-11) and the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes will include an assessment of health-related quality of life via the EQ-5D questionnaire and an exploration of the prevalence of symptoms of posttraumatic stress disorder (PTSD) using the 14-item Posttraumatic Stress Scale (PTSS-14). We will also examine the association between mental health symptoms and the severity of acute COVID-19. The post–COVID-19 data will be collected at least 6 months after the positive test and no longer than 9 months during the clinical appointment.

Results
We expect our multicenter study on patients post COVID-19 to reveal a significant link between mental illness symptoms and both physical and psychological fatigue. Patients with heightened depression and anxiety may report increased levels of fatigue. Additionally, we expect to find persistent PTSD symptoms in a subset of participants, indicating the enduring psychological impact of the virus.

Conclusions
This study may underscore the need for integrated care addressing physical and mental health in patients post COVID-19. The observed connections emphasize the importance of considering mental well-being for long-term health outcomes. Despite study limitations, our findings contribute valuable insights for future treatment strategies and highlight the necessity for comprehensive mental health support in post–COVID-19 care. This research provides valuable insights into the mental health implications of COVID-19 and its impact on post–COVID-19 fatigue and the overall well-being of affected individuals.

Trial Registration
ClinicalTrials.gov NCT05323318; https://clinicaltrials.gov/study/NCT05323318

International Registered Report Identifier (IRRID)
DERR1-10.2196/51820