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Multicenter Study
. 2024 Jul 1;7(7):e2423555.
doi: 10.1001/jamanetworkopen.2024.23555.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection

Elizabeth R Unger  1 , Jin-Mann S Lin  1 , Lauren E Wisk  2 , Huihui Yu  3 , Michelle L'Hommedieu  2 , Helen Lavretsky  4 , Juan Carlos C Montoy  5 , Michael A Gottlieb  6 , Kristin L Rising  7   8 , Nicole L Gentile  9   10   11 , Michelle Santangelo  12 , Arjun K Venkatesh  3   13 , Robert M Rodriguez  5 , Mandy J Hill  14 , Rachel E Geyer  10 , Efrat R Kean  7 , Sharon Saydah  15 , Samuel A McDonald  16   17 , Ryan Huebinger  14 , Ahamed H Idris  16 , Jocelyn Dorney  3 , Bala Hota  18 , Erica S Spatz  3   19 , Kari A Stephens  10   20 , Robert A Weinstein  12   21 , Joann G Elmore  2 ; Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) Group
Collaborators, Affiliations
Multicenter Study

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection

Elizabeth R Unger et al. JAMA Netw Open. .

Abstract

Importance: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Objective: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness.

Design, setting, and participants: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration-approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023.

Exposure: COVID-19 status (positive vs negative) at enrollment.

Main outcome and measures: The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms.

Results: A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19-positive (range, 2.8%-3.7%) and COVID-19-negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19-positive and COVID-19-negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]).

Conclusions and relevance: In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection-like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Wisk reported receiving grants from the Centers for Disease Control and Prevention (CDC) and US Department of Health and Human Services during the conduct of the study. Dr Lavretsky reported receiving grants from the National Center for Complementary and Integrative Health, National Institute of Mental Health, US Department of Defense, and Patient-Centered Outcomes Research Institute (PCORI) outside the submitted work and royalties for books published by Oxford University Press and Johns Hopkins University Press. Dr Montoy reported receiving grants from the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) during the conduct of the study and from the CDC outside the submitted work. Dr Gottlieb reported receiving grants from the CDC during the conduct of the study. Dr Rising reported receiving grants from the CDC during the conduct of the study and from the National Institutes of Health outside the submitted work. Dr Gentile reported receiving grants from the CDC during the conduct of the study and being the primary care medical director of the COVID Aftercare, Recovery, and Support (CAReS) Clinic at the University of Washington. Dr Venkatesh reported receiving grants from the CDC during the conduct of the study and from the Society for Academic Emergency Medicine Foundation outside the submitted work. Dr Huebinger reported receiving grants from the CDC during the conduct of the study. Dr Idris reported receiving grants from the CDC during the conduct of the study. Dr Spatz reported receiving grant funding from the CDC; US Food and Drug Administration to support projects within the Yale University–Mayo Clinic Center of Excellence in Regulatory Science and Innovation; National Heart, Lung, and Blood Institute; and PCORI. Dr Stephens reported receiving grants from the CDC during the conduct of the study. Dr Weinstein reported receiving grants from the CDC during the conduct of the study. Dr Elmore reported receiving grants from the CDC during the conduct of the study and serving as editor-in-chief of adult primary care for UpToDate and as director of the National Clinician Scholars Program at the University of California, Los Angeles. No other disclosures were reported.

Figures

Figure.
Figure.. Weighted Marginal Effect Estimates for the Association Between Index COVID-19 Status and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Outcomes
MIRR indicates marginal incidence rate ratio; MOR, marginal odds ratio.
See this image and copyright information in PMC

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