Association between fatigue and depressive symptoms in persons with post-COVID-19 condition: a post hoc analysis

Abstract

Objective

Post-COVID-19 Condition (PCC) is a prevalent, persistent and debilitating phenomenon occurring three or more months after resolution of acute COVID-19 infection. Fatigue and depressive symptoms are commonly reported in PCC. We aimed to further characterize PCC by assessing the relationship between fatigue and depressive symptom severity in adults with PCC.

Methods

A post hoc analysis was conducted on data retrieved from a randomized, double-blinded, placebo-controlled study evaluating vortioxetine for cognitive deficits in persons with PCC. We sought to determine the relationship between baseline fatigue [i.e. Fatigue Severity Scale (FSS) total score] and baseline depressive symptom severity [i.e. 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR-16) total score] in adults with PCC.

Results

The statistical analysis included baseline data from 142 participants. After adjusting for age, sex, education, employment status, history of major depressive disorder (MDD) diagnosis, self-reported physical activity, history of documented acute SARS-CoV-2 infection and body mass index (BMI), baseline FSS was significantly correlated with baseline QIDS-SR-16 (β = 0.825, p = .001)

Conclusion

In our sample, baseline measures of fatigue and depressive symptoms are correlated in persons living with PCC. Individuals presenting with PCC and fatigue should be screened for the presence and severity of depressive symptoms. Guideline-concordant care should be prescribed for individuals experiencing clinically significant depressive symptoms. Fatigue and depressive symptom severity scores were not pre-specified as primary objectives of the study. Multiple confounding factors (i.e. disturbance in sleep, anthropometrics and cognitive impairment) were not collected nor adjusted for in the analysis herein.

Trial registration

Unrestricted Research Grant from H. Lundbeck A/S, Copenhagen, Denmark. ClinicalTrials.gov Identifier: NCT05047952

Keywords:

• Long COVID
• Post COVID-19 condition
• post-acute sequelae SARS-CoV-2 infection
• fatigue
• depression
• major depressive disorder

Transparency

Declaration of financial/other relationships

Kayla M. Teopiz and Felicia Ceban have received fees from Braxia Scientific Corp. Dr. Roger Ho has received funding from the National University of Singapore iHeathtech Other Operating Expenses (A-0001415-09-00). Dr. Taeho Greg Rhee was supported in part by the National Institute on Aging (NIA) (#R21AG070666; R21AG078972), National Institute of Mental Health (#R21MH117438), National Institute on Drug Abuse (#R21DA057540) and Institute for Collaboration on Health, Intervention, and Policy (InCHIP) of the University of Connecticut. Dr. Rhee serves as a review committee member for Patient-Centered Outcomes Research Institute (PCORI) and Substance Abuse and Mental Health Services Administration (SAMHSA) and has received honoraria payments from PCORI and SAMHSA. Dr. Rhee has also served as a stakeholder/consultant for PCORI and received consulting fees from PCORI. Dr. Rhee serves as an advisory committee member for International Alliance of Mental Health Research Funders (IAMHRF). Dr. Rhee is currently a co-Editor-in-Chief of Mental Health Science and has received honorarium payments annually from the publisher, John Wiley & Sons, Inc.

Dr. Joshua D. Rosenblat has received research grant support from the Canadian Institute of Health Research (CIHR), Physician Services Inc (PSI) Foundation, Labatt Brain Health Network, Brain and Cognition discovery Foundation (BCDF), Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship and industry funding for speaker/consultation/research fees from iGan, Boehringer Ingelheim, Janssen, Allergan, Lundbeck, Sunovion and COMPASS. Dr. Rodrigo B. Mansur has received research grant support from the Canadian Institute of Health Research; Physicians’ Services Incorporated Foundation; the Baszucki Brain Research Fund; and the Academic Scholar Awards, Department of Psychiatry, University of Toronto. Dr. Roger S. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals,Viatris, Abbvie, Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. All other authors have nothing to disclose. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

RSM conceptualized the hypothesis, design and methodology of the primary clinical trial. KMT and RSM conceptualized the current post hoc analysis including hypothesis and methodology. Material preparation and data collection was performed by KMT and ATHK. Data analysis was performed by ATHK and GHL. ATHK, GHL and KMT prepared Tables 1–3. The first draft of the manuscript was written by KMT and RSM. All authors contributed to revisions of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The post hoc analysis herein was conducted on measures from a primary study sponsored by the Brain and Cognition Discovery Foundation (BCDF), a non-profit organization located in Toronto, Ontario, Canada. The authors would like to thank the volunteers and personnel at BCDF for their support in data management and administration.

Data availability statement

The data presented in this study are available upon request to the corresponding author.

Ethics statement

The study protocol was approved by Advarra, a local research ethics board that operates in compliance with Health Canada regulations (IRB#00000971). The clinical trial is registered on Clinicaltrials.gov (NCT05047952). The clinical trial was conducted in compliance with the guidelines of Good Clinical Practice and the Declaration of Helsinki^31,32. All participants in the study provided written informed consent prior to participation.

Additional information

Funding

The primary clinical trial was sponsored by the Brain and Cognition Discovery Foundation (BCDF) through an unrestricted research grant from H. Lundbeck A/S, Copenhagen, Denmark. BCDF operates as a non-profit research organization. The authors of this post hoc analysis did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.