Association of Obstructive Sleep Apnea with Post-Acute Sequelae of SARS-CoV-2 Infection - 22/03/24

Doi : 10.1016/j.amjmed.2024.02.023

Stuart F. Quan, MD ^a,^b,^⁎ , Matthew D. Weaver, PhD ^a,^b, Mark É. Czeisler, PhD ^c,^d,^e, Laura K. Barger, PhD ^a,^b, Lauren A. Booker, PhD ^e,^f, Mark E. Howard, MBBS, PhD ^e,^g,^h, Melinda L. Jackson, PhD ^d,^e, Rashon I. Lane, PhD ^a, Christine F. McDonald, MBBS, PhD ^e,^h,^i,^j, Anna Ridgers, MBBS ^e,^h,ⁱ, Rebecca Robbins, PhD ^a,^b, Prerna Varma, PhD ^d, Joshua F. Wiley, PhD ^d, Shantha M.W. Rajaratnam, PhD ^a,^b,^d,^e, Charles A. Czeisler, MD, PhD ^a,^b
^a Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Mass
^b Division of Sleep Medicine
^c Francis Weld Peabody Society, Harvard Medical School, Boston, Mass
^d School of Psychological Sciences, Turner Institute for Brain and Mental Health, Monash University, Melbourne, Victoria, Australia
^e Institute for Breathing and Sleep, Austin Health, Heidelberg, Victoria, Australia
^f University Department of Rural Health, La Trobe Rural Health School, La Trobe University, Bendigo, Victoria, Australia
^g Turner Institute for Brain and Mental Health, Monash University, Clayton, Victoria, Australia
^h Department of Medicine, The University of Melbourne, Victoria, Australia
ⁱ Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Victoria, Australia
^j Faculty of Medicine, Monash University, Melbourne, Victoria, Australia

^⁎Requests for reprints should be addressed to Stuart F. Quan, MD, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, 221 Longwood Ave., Boston, MA 02115. E-mail address:Division of Sleep and Circadian DisordersBrigham and Women's Hospital221 Longwood Ave.BostonMA02115

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Abstract

Background

Obstructive sleep apnea is associated with COVID-19 infection. Less clear is whether obstructive sleep apnea is a risk factor for the development of post-acute sequelae of SARS-CoV-2 infection (PASC).

Study Design

Cross-sectional survey of a general population of 24,803 US adults to determine the association of obstructive sleep apnea with PASC.

Results

COVID-19 infection occurred in 10,324 (41.6%) participants. Prevalence of persistent (>3 months post infection) putative PASC-related physical and mental health symptoms ranged from 6.5% (peripheral edema) to 19.6% (nervous/anxious). In logistic regression models, obstructive sleep apnea was associated with all putative PASC-related symptoms with the highest adjusted odds ratios being fever (2.053) and nervous/anxious (1.939). In 4 logistic regression models of overall PASC derived from elastic net regression, obstructive sleep apnea was associated with PASC (range of adjusted odds ratios: 1.934-2.071); this association was mitigated in those with treated obstructive sleep apnea. In the best fitting overall model requiring ≥3 symptoms, PASC prevalence was 21.9%.

Conclusion

In a general population sample, obstructive sleep apnea is associated with the development of PASC-related symptoms and a global definition of PASC. Treated obstructive sleep apnea mitigates the latter risk. The presence of 3 or more PASC symptoms may be useful in identifying cases and for future research.

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Keywords : COVID-19, Long COVID, Obstructive sleep apnea, PASC, Post-acute sequelae of SARS-CoV-2 infection

Plan

Introduction

Methods

Study Design and Participants

	Funding: This work was supported by the Centers for Disease Control and Prevention. MÉC was supported by an Australian-American Fulbright Fellowship, with funding from The Kinghorn Foundation. The salary of LKB, CAC, RR, and MDW were supported, in part, by National Institute for Occupational Safety and Health (NIOSH) R01 OH011773 and National Heart, Lung, and Blood Institute (NHLBI) R56 HL151637. RR also was supported in part by NHLBI K01 HL150339.
	Conflicts of Interest: MDW reports institutional support from the US Centers for Disease Control and Prevention, National Institutes of Occupational Safety and Health, Delta Airlines, and the Puget Sound Pilots; as well as consulting fees from the Fred Hutchinson Cancer Center and the University of Pittsburgh. LKB reports institutional support from the US Centers for Disease Control and Prevention, National Institutes of Occupational Safety and Health, Delta Airlines, and the Puget Sound Pilots; as well as honorariums from the National Institutes of Occupational Safety and Health, University of Arizona and University of British Columbia. MÉC reported personal fees from Vanda Pharmaceuticals Inc., research grants or gifts to Monash University from WHOOP, Inc., Hopelab, Inc., CDC Foundation, and the Centers for Disease Control and Prevention. SMWR reported receiving grants and personal fees from the Cooperative Research Centre for Alertness, Safety, and Productivity, receiving grants and institutional consultancy fees from Teva Pharma Australia and institutional consultancy fees from Vanda Pharmaceuticals, Circadian Therapeutics, BHP Billiton, and Herbert Smith Freehills. SFQ has served as a consultant for Best Doctors, Bryte Foundation, Jazz Pharmaceuticals, Apnimed, and Whispersom. RR reports personal fees from SleepCycle AB; Rituals Cosmetics BV; Sonesta Hotels International, LLC; Ouraring Ltd; AdventHealth; and With Deep, LLC. CAC serves as the incumbent of an endowed professorship provided to Harvard Medical School by Cephalon, Inc. and reports institutional support for a Quality Improvement Initiative from Delta Airlines and Puget Sound Pilots; education support to Harvard Medical School Division of Sleep Medicine and support to Brigham and Women's Hospital from: Jazz Pharmaceuticals PLC, Inc, Philips Respironics, Inc., Optum, and ResMed, Inc.; research support to Brigham and Women's Hospital from Axome Therapeutics, Inc., Dayzz Ltd., Peter Brown and Margaret Hamburg, Regeneron Pharmaceuticals, Sanofi SA, Casey Feldman Foundation, Summus, Inc., Takeda Pharmaceutical Co., LTD, Abbaszadeh Foundation, CDC Foundation; educational funding to the Sleep and Health Education Program of the Harvard Medical School Division of Sleep Medicine from ResMed, Inc., Teva Pharmaceuticals Industries, Ltd., and Vanda Pharmaceuticals; personal royalty payments on sales of the Actiwatch-2 and Actiwatch-Spectrum devices from Philips Respironics, Inc; personal consulting fees from Axome, Inc., Bryte Foundation, With Deep, Inc. and Vanda Pharmaceuticals; honoraria from the Associated Professional Sleep Societies, LLC for the Thomas Roth Lecture of Excellence at SLEEP 2022, from the Massachusetts Medical Society for a New England Journal of Medicine Perspective article, from the National Council for Mental Wellbeing, from the National Sleep Foundation for serving as chair of the Sleep Timing and Variability Consensus Panel, for lecture fees from Teva Pharma Australia PTY Ltd. and Emory University, and for serving as an advisory board member for the Institute of Digital Media and Child Development, the Klarman Family Foundation, and the UK Biotechnology and Biological Sciences Research Council. CAC has received personal fees for serving as an expert witness on a number of civil matters, criminal matters, and arbitration cases, including those involving the following commercial and government entities: Amtrak; Bombardier, Inc.; C&J Energy Services; Dallas Police Association; Delta Airlines/Comair; Enterprise Rent-A-Car; FedEx; Greyhound Lines, Inc./Motor Coach Industries/FirstGroup America; PAR Electrical Contractors, Inc.; Puget Sound Pilots; and the San Francisco Sheriff's Department; Schlumberger Technology Corp.; Union Pacific Railroad; United Parcel Service; Vanda Pharmaceuticals. CAC has received travel support from the Stanley Ho Medical Development Foundation for travel to Macao and Hong Kong; equity interest in Vanda Pharmaceuticals, With Deep, Inc, and Signos, Inc.; and institutional educational gifts to Brigham and Women's Hospital from Johnson & Johnson, Mary Ann and Stanley Snider via Combined Jewish Philanthropies, Alexandra Drane, DR Capital, Harmony Biosciences, LLC, San Francisco Bar Pilots, Whoop, Inc., Harmony Biosciences LLC, Eisai Co., LTD, Idorsia Pharmaceuticals LTD, Sleep Number Corp., Apnimed, Inc., Avadel Pharmaceuticals, Bryte Foundation, f.lux Software, LLC, Stuart F. and Diana L. Quan Charitable Fund. CAC interests were reviewed and are managed by the Brigham and Women's Hospital and Mass General Brigham in accordance with their conflict of interest policies. No other disclosures were reported.
	Authorship: All authors have seen and approved the manuscript. SFQ: Writing - review & editing, original draft, Methodology, Investigation, Formal analysis, Conceptualization; MDW: Writing - review & editing, Methodology, Investigation, Formal analysis, Data curation; MÉC: Writing - review & editing, Methodology, Investigation, Funding acquisition; LKB: Writing - review & editing; LAB: Writing - review & editing; MEH: Writing - review & editing, Investigation, Data curation; MLJ: Writing - review & editing; RIL: Writing - review & editing; CFM: Writing - review & editing; AR: Writing - review & editing; RR: Writing - review & editing; PV: Writing - review & editing; JFW: Writing - review & editing; SMWR: Writing - review & editing, Funding acquisition; CAC: Writing - review & editing, Funding acquisition. A preprint of this manuscript has posted on medRxiv: 2023.12.30.23300666v1.