Dolphin
Senior Member (Voting Rights)
Open Access Article
Alaa Ghali
1,*<i></i>,
Christian Lavigne
2<i></i>,
Maria Ghali
3,4,†<i></i> and
Valentin Lacombe
5,†<i></i>
1
Outpatient Department, Doue-En-Anjou Hospital, F-49700 Doue-En-Anjou, France
2
Department of Internal Medicine and Clinical Immunology, Angers University Hospital, F-49100 Angers, France
3
Department of General Medicine, University of Angers, F-49000 Angers, France
4
POPS, SFR ICAT, University of Angers, F-49000 Angers, France
5
Department of Internal and Polyvalent Medicine, Haut-Anjou Hospital, F-53200 Chateau-Gontier, France
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Clin. Med. 2026, 15(8), 2948; https://doi.org/10.3390/jcm15082948
Submission received: 7 February 2026 / Revised: 28 March 2026 / Accepted: 8 April 2026 / Published: 13 April 2026
(This article belongs to the Special Issue POTS, ME/CFS and Long COVID: Recent Advances and Future Direction)
Post-exertional malaise (PEM), which is the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is also reported in a proportion of patients with post-COVID-19 syndrome (PCS). Our objective was to identify determinants that may be linked to the emergence of PEM in PCS patients.
Methods:
Patients fulfilling the World Health Organization definition for PCS who attended the post-COVID unit of the Internal Medicine Department of Angers University Hospital, France, between June 2020 and December 2023 were included retrospectively. Their medical records were reviewed to extract information on COVID-19 infection history, characteristics of post-exertional malaise (PEM), fatigue severity, and relevant epidemiological variables.
Results:
The study included 220 patients, grouped according to whether post-exertional malaise was present (PCS/PEM+) or absent (PCS/PEM–). PEM was observed in 26.4% of patients and was significantly linked to earlier COVID onset in 2020/2021 (OR 5.68 (95% CI: 1.66–19.45), p = 0.006), as well as higher fatigue levels (OR 2.07 (95% CI: 1.22–3.50), p = 0.007).
Conclusions:
Patients who contracted COVID-19 during the pre-Omicron period reported PEM more frequently than those infected in later waves. This observation could reflect differences in viral characteristics following the emergence of the Omicron variant; however, alternative explanations—such as increasing vaccination coverage, accumulating post-infectious immunity, or other unmeasured factors—cannot be ruled out. Based on the observed link between PEM and symptom severity, PCS patients should be systematically assessed for the presence of PEM.
Keywords:
post-COVID-19 syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; post-exertional malaise; pre-omicron phase; vaccination
Post-Exertional Malaise in Post-COVID-19 Syndrome: A Shift in the Frequency Across Pandemic Phases
byAlaa Ghali
1,*<i></i>,
Christian Lavigne
2<i></i>,
Maria Ghali
3,4,†<i></i> and
Valentin Lacombe
5,†<i></i>
1
Outpatient Department, Doue-En-Anjou Hospital, F-49700 Doue-En-Anjou, France
2
Department of Internal Medicine and Clinical Immunology, Angers University Hospital, F-49100 Angers, France
3
Department of General Medicine, University of Angers, F-49000 Angers, France
4
POPS, SFR ICAT, University of Angers, F-49000 Angers, France
5
Department of Internal and Polyvalent Medicine, Haut-Anjou Hospital, F-53200 Chateau-Gontier, France
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Clin. Med. 2026, 15(8), 2948; https://doi.org/10.3390/jcm15082948
Submission received: 7 February 2026 / Revised: 28 March 2026 / Accepted: 8 April 2026 / Published: 13 April 2026
(This article belongs to the Special Issue POTS, ME/CFS and Long COVID: Recent Advances and Future Direction)
Abstract
Background:Post-exertional malaise (PEM), which is the cardinal feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is also reported in a proportion of patients with post-COVID-19 syndrome (PCS). Our objective was to identify determinants that may be linked to the emergence of PEM in PCS patients.
Methods:
Patients fulfilling the World Health Organization definition for PCS who attended the post-COVID unit of the Internal Medicine Department of Angers University Hospital, France, between June 2020 and December 2023 were included retrospectively. Their medical records were reviewed to extract information on COVID-19 infection history, characteristics of post-exertional malaise (PEM), fatigue severity, and relevant epidemiological variables.
Results:
The study included 220 patients, grouped according to whether post-exertional malaise was present (PCS/PEM+) or absent (PCS/PEM–). PEM was observed in 26.4% of patients and was significantly linked to earlier COVID onset in 2020/2021 (OR 5.68 (95% CI: 1.66–19.45), p = 0.006), as well as higher fatigue levels (OR 2.07 (95% CI: 1.22–3.50), p = 0.007).
Conclusions:
Patients who contracted COVID-19 during the pre-Omicron period reported PEM more frequently than those infected in later waves. This observation could reflect differences in viral characteristics following the emergence of the Omicron variant; however, alternative explanations—such as increasing vaccination coverage, accumulating post-infectious immunity, or other unmeasured factors—cannot be ruled out. Based on the observed link between PEM and symptom severity, PCS patients should be systematically assessed for the presence of PEM.
Keywords:
post-COVID-19 syndrome; myalgic encephalomyelitis/chronic fatigue syndrome; post-exertional malaise; pre-omicron phase; vaccination