Association of long COVID with health-related quality-of-life outcomes

ACTIV-2/A5401 Study Team; ACTIV-2/A5401 Participating Sites, Investigators, Study Personnel; Industry Representatives

doi:10.1038/s41598-026-36189-8

Association of long COVID with health-related quality-of-life outcomes

ACTIV-2/A5401 Study Team
, ACTIV-2/A5401 Participating Sites, Investigators, Study Personnel
, Industry Representatives

Department of Emergency Medicine

Brigham and Women’s Hospital
Harvard University
Sanofi SA
University of California at Los Angeles
University of North Carolina at Chapel Hill
University of Iowa
Stanford University
University of California at San Diego
Cornell University
New York Presbyterian Hospital
Washington University St. Louis
Wake Forest University
West Virginia University
Vida Clinical Studies
Valley Clinical Research Inc
Department of Veterans Affairs
University of Texas Southwestern Medical Center
University of Washington
University of Southern California
University of Pennsylvania
University of Kansas
University of Florida

Research output: Contribution to journal › Article › peer-review

Abstract

The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Participants who received blinded placebo in the ACTIV-2/A5401 outpatient COVID-19 treatment trial were included in an analysis of the association of long COVID with HrQOL (both pre-specified exploratory trial endpoints) 9 months after acute COVID-19. Long COVID was defined as presence of self-assessed COVID-19 symptoms and HrQOL was assessed with EQ-5D-5L and SF-36v2 questionnaires. Associations were evaluated by Fisher’s exact tests and Wilcoxon rank-sum tests. Of 546 participants, 13% had long COVID. Long COVID was associated with greater risk of reported problems in the EQ-5D-5L dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression (risk ratios 3.45–6.00, all p < 0.001) and worse self-reported health scores (median 80 vs. 95, p < 0.001). Participants with long COVID also had worse SF-36v2 composite physical and mental component scores (both p < 0.001) and individual SF-36 domain scores (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health; all p < 0.001). Associations were similar regardless of baseline (pre-COVID-19) medical history. Long COVID is associated with impaired HrQOL across multiple domains, highlighting the need to develop preventative and therapeutic interventions for this protean condition.

Original language	English
Article number	14229
Journal	Scientific Reports
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41598-026-36189-8
State	Published - Dec 2026

Keywords

Health-related quality-of-life
Long COVID

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10.1038/s41598-026-36189-8

Cite this

@article{ad4861a127ac4178b9b84c7215681e08,

title = "Association of long COVID with health-related quality-of-life outcomes",

abstract = "The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Participants who received blinded placebo in the ACTIV-2/A5401 outpatient COVID-19 treatment trial were included in an analysis of the association of long COVID with HrQOL (both pre-specified exploratory trial endpoints) 9 months after acute COVID-19. Long COVID was defined as presence of self-assessed COVID-19 symptoms and HrQOL was assessed with EQ-5D-5L and SF-36v2 questionnaires. Associations were evaluated by Fisher{\textquoteright}s exact tests and Wilcoxon rank-sum tests. Of 546 participants, 13\% had long COVID. Long COVID was associated with greater risk of reported problems in the EQ-5D-5L dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression (risk ratios 3.45{\textendash}6.00, all p < 0.001) and worse self-reported health scores (median 80 vs. 95, p < 0.001). Participants with long COVID also had worse SF-36v2 composite physical and mental component scores (both p < 0.001) and individual SF-36 domain scores (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health; all p < 0.001). Associations were similar regardless of baseline (pre-COVID-19) medical history. Long COVID is associated with impaired HrQOL across multiple domains, highlighting the need to develop preventative and therapeutic interventions for this protean condition.",

keywords = "Health-related quality-of-life, Long COVID",

author = "\{ACTIV-2/A5401 Study Team\} and \{ACTIV-2/A5401 Participating Sites, Investigators, Study Personnel\} and \{Industry Representatives\} and Gandhi, \{Malini M.\} and Carlee Moser and Currier, \{Judith S.\} and Justin Ritz and Eron, \{Joseph J.\} and Daar, \{Eric S.\} and Wohl, \{David A.\} and Fischer, \{William A.\} and Upinder Singh and Hughes, \{Michael D.\} and Smith, \{Davey M.\} and Evering, \{Teresa H.\} and Chew, \{Kara W.\} and Alem Haile and Rachel Presti and Hannah Seagle and Jamraus Fayssoux and Aimee Wilkin and Hannah Hazard-Jenkins and Midhun Malla and Matthew Caloura and Hisham Atriss and Derrick Williamson and Lisa Nakatani and Christopher Chow and Masoud Azizad and Mary Lewinski and Smith, \{David David Davey\} and Sanjay Mehta and Kimberly Turner-Gray and Smruthi Senthil and Jain, \{Mamta K.\} and Chris Jonsson and Sarah McGuffin and Ignacio, \{Rachel Bender\} and Mendez, \{Luis M.\} and Saahir Khan and Dube, \{Michael P.\} and William Short and Pablo Tebas and Loftis, \{Amy James\} and Jonathan Oakes and David Wohl and Chase Hall and Leslie Spikes and Mario Castro and Amna Riaz and Saniyyah Mahmoudi and Joshua Lynch and Brian Clemency",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026.",

year = "2026",

month = dec,

doi = "10.1038/s41598-026-36189-8",

language = "English",

volume = "16",

journal = "Scientific Reports",

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T1 - Association of long COVID with health-related quality-of-life outcomes

AU - ACTIV-2/A5401 Study Team

AU - ACTIV-2/A5401 Participating Sites, Investigators, Study Personnel

AU - Industry Representatives

AU - Gandhi, Malini M.

AU - Moser, Carlee

AU - Currier, Judith S.

AU - Ritz, Justin

AU - Eron, Joseph J.

AU - Daar, Eric S.

AU - Wohl, David A.

AU - Fischer, William A.

AU - Singh, Upinder

AU - Hughes, Michael D.

AU - Smith, Davey M.

AU - Evering, Teresa H.

AU - Chew, Kara W.

AU - Haile, Alem

AU - Presti, Rachel

AU - Seagle, Hannah

AU - Fayssoux, Jamraus

AU - Wilkin, Aimee

AU - Hazard-Jenkins, Hannah

AU - Malla, Midhun

AU - Caloura, Matthew

AU - Atriss, Hisham

AU - Williamson, Derrick

AU - Nakatani, Lisa

AU - Chow, Christopher

AU - Azizad, Masoud

AU - Lewinski, Mary

AU - Smith, David David Davey

AU - Mehta, Sanjay

AU - Turner-Gray, Kimberly

AU - Senthil, Smruthi

AU - Jain, Mamta K.

AU - Jonsson, Chris

AU - McGuffin, Sarah

AU - Ignacio, Rachel Bender

AU - Mendez, Luis M.

AU - Khan, Saahir

AU - Dube, Michael P.

AU - Short, William

AU - Tebas, Pablo

AU - Loftis, Amy James

AU - Oakes, Jonathan

AU - Wohl, David

AU - Hall, Chase

AU - Spikes, Leslie

AU - Castro, Mario

AU - Riaz, Amna

AU - Mahmoudi, Saniyyah

AU - Lynch, Joshua

AU - Clemency, Brian

PY - 2026/12

Y1 - 2026/12

N2 - The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Participants who received blinded placebo in the ACTIV-2/A5401 outpatient COVID-19 treatment trial were included in an analysis of the association of long COVID with HrQOL (both pre-specified exploratory trial endpoints) 9 months after acute COVID-19. Long COVID was defined as presence of self-assessed COVID-19 symptoms and HrQOL was assessed with EQ-5D-5L and SF-36v2 questionnaires. Associations were evaluated by Fisher’s exact tests and Wilcoxon rank-sum tests. Of 546 participants, 13% had long COVID. Long COVID was associated with greater risk of reported problems in the EQ-5D-5L dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression (risk ratios 3.45–6.00, all p < 0.001) and worse self-reported health scores (median 80 vs. 95, p < 0.001). Participants with long COVID also had worse SF-36v2 composite physical and mental component scores (both p < 0.001) and individual SF-36 domain scores (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health; all p < 0.001). Associations were similar regardless of baseline (pre-COVID-19) medical history. Long COVID is associated with impaired HrQOL across multiple domains, highlighting the need to develop preventative and therapeutic interventions for this protean condition.

AB - The association of long COVID with health-related quality-of-life (HrQOL) has not been well-characterized. Participants who received blinded placebo in the ACTIV-2/A5401 outpatient COVID-19 treatment trial were included in an analysis of the association of long COVID with HrQOL (both pre-specified exploratory trial endpoints) 9 months after acute COVID-19. Long COVID was defined as presence of self-assessed COVID-19 symptoms and HrQOL was assessed with EQ-5D-5L and SF-36v2 questionnaires. Associations were evaluated by Fisher’s exact tests and Wilcoxon rank-sum tests. Of 546 participants, 13% had long COVID. Long COVID was associated with greater risk of reported problems in the EQ-5D-5L dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression (risk ratios 3.45–6.00, all p < 0.001) and worse self-reported health scores (median 80 vs. 95, p < 0.001). Participants with long COVID also had worse SF-36v2 composite physical and mental component scores (both p < 0.001) and individual SF-36 domain scores (physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, and mental health; all p < 0.001). Associations were similar regardless of baseline (pre-COVID-19) medical history. Long COVID is associated with impaired HrQOL across multiple domains, highlighting the need to develop preventative and therapeutic interventions for this protean condition.

KW - Health-related quality-of-life

KW - Long COVID

UR - https://www.scopus.com/pages/publications/105038096193

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DO - 10.1038/s41598-026-36189-8

M3 - Article

C2 - 41857005

AN - SCOPUS:105038096193

SN - 2045-2322

VL - 16

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 14229

ER -

Association of long COVID with health-related quality-of-life outcomes

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Keywords

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