Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: A case report

Abstract

Background

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a neurological adverse effect after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccinations. However, clinicians do not recognize the condition well, and no case report has shown a full recovery.

Case Presentation

We present a 65‐year‐old Japanese female who experienced severe fatigue, postexertional malaise, orthostatic intolerance, and various symptoms after her third SARS‐CoV‐2 vaccination. Following thorough examinations and excluding other potential diagnoses, she met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The symptoms persisted for 30 months and improved ultimately with comprehensive treatment and a self‐management strategy, including pacing management, pharmacological treatments, and psychiatric interventions to support those struggling with the despair over the devastating symptoms.

Conclusion

This case report describes ME/CFS following the SARS‐CoV‐2 vaccination and its full recovery. It illustrates the importance of considering the differential diagnosis of psychiatric disorders and addressing the condition through psychiatric interventions. Our findings provide new insights into treating ME/CFS and the vaccination‐related adverse effects.

BACKGROUND

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by multiple symptoms and debilitating fatigue that can significantly hinder daily activities for more than 6 months. ¹ Most of the patients were previously healthy and socially active before the onset of the neurological disease that suddenly impairs social function, which can be triggered by viral infection, other infectious diseases, or vaccinations. ² , ³ A systematic review and meta‐analysis of ME/CFS showed that the prevalence is 0.89% (95% confidence interval 0.60–1.33). ⁴ Although the involvement of immunological mechanisms was suspected, ⁵ with increased attention to this devastating syndrome in recent years, ⁶ diagnosing ME/CFS remains challenging due to the lack of identified etiology and specific diagnostic tests; current diagnoses rely on clinical criteria. ⁷ , ⁸ , ⁹ , ¹⁰ Additionally, it is often misdiagnosed as a psychiatric disorder, such as major depressive disorder (MDD), due to medically unexplained symptoms. ¹¹

During the coronavirus disease 2019 (COVID‐19) pandemic, ME/CFS was reported to resemble the lingering effects of COVID‐19 referred to as “long COVID.” ¹² , ¹³ After the widespread administration of vaccinations for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), there were reports of adverse effects resembling long COVID symptoms. ¹⁴ Neurological adverse effects after the SARS‐CoV‐2 vaccination were identified, ¹⁵ , ¹⁶ and Mundorf and colleagues reported that 131 patients out of 191 patients with the symptoms after the SARS‐CoV‐2 vaccination met the clinical criteria of ME/CFS, including several other dysautonomia syndromes. ¹⁷ However, a detailed medical survey of clinicians by the Ministry of Health, Labor and Welfare reported only one patient with possible ME/CFS among 212 patients with the symptoms after SARS‐CoV‐2 vaccination, ¹⁸ which indicates the possibility that the condition was not well recognized. Moreover, while there is a Japanese case‐series study showing one patient with ME/CFS developing after the first BNT162 vaccination, ¹⁹ no cases of complete recovery from the condition have been reported. Therefore, we report a case of ME/CFS after the third SARS‐CoV‐2 vaccination and complete recovery over a 25‐month follow‐up period.

CASE PRESENTATION

A 65‐year‐old Japanese female received her third vaccination for SARS‐CoV‐2 (mRNA‐1273). She experienced no adverse effects to the first and second doses of the BNT162 vaccine. The day after the third vaccination, she began to experience a slight fever, fatigue, loss of taste, decreased appetite, weight loss, nonrestorative sleep, palpitations, shortness of breath, neck and shoulder stiffness, and excessive sweating with minimal exertion. Additionally, she experienced significant difficulty concentrating and was unable to watch television. These symptoms persisted for a year and prevented her from performing household chores, which her husband had to manage entirely. Her symptom progression and treatment course are shown in Figure 1. Two weeks after the onset of symptoms, she visited our internal medicine department. Although evaluations included physical examinations, laboratory blood and urine tests, an electrocardiogram, abdominal ultrasonography, a contrast‐enhanced chest and abdomen computed tomography scan, and brain magnetic resonance imaging, no definitive cause was identified. However, mild liver function abnormalities were noted, which had not been previously noted. After several visits, she was informed that her symptoms came from the vaccination and no specific treatment was available. The informing led to a fear that she might never recover, the discontinuation of treatment at our hospital, and seeking care at multiple medical institutions. For several months, she was bedridden and had water placed beside her pillow for convenience.

Figure 1.

Symptom progression and treatment course for the patient with myalgic encephalomyelitis/chronic fatigue syndrome after the third severe acute respiratory syndrome coronavirus 2 vaccination.

Three months after the third vaccination, she developed herpes zoster. After this time, she was sometimes able to return to work. However, after standing for 1 or 2 h, she experienced palpitations, shortness of breath, and feelings of faintness. Her coworkers noticed that her face appeared markedly pale and her hands turned white. While lying down provided some relief from these symptoms, her recovery was inconsistent; she would sometimes feel better by the following day, while at other times, she remained bedridden for several days. Throughout the year, her symptoms persisted and she was able to work fewer than half of the days in a month, struggling to remain at her job until noon. Although she could manage personal tasks somewhat, she had difficulty maintaining an everyday social life and spent more than 50% of the day in bed. On the other hand, she did not experience persistent symptoms such as a sore throat, olfactory dysfunction, lymphadenopathy, photophobia, and phonophobia during the follow‐up period.

Eleven months after the third vaccination, the patient was suspected of having a psychiatric disorder and visited the psychiatric department of our hospital. Her developmental and educational history was unremarkable, and she had no previous psychiatric history. Although her symptoms persisted, clinical examination and further evaluations revealed no abnormalities, including liver function issues, that could explain her condition. The specific pattern of her symptoms suggested postexertional malaise (PEM) and orthostatic intolerance. Depressive mood was observed in response to the physical symptoms for a year, but it was not always persistent. There was no sense of worthlessness or suicidal ideation, and she expressed motivation for work. She felt distressed due to the symptoms that emerged after the vaccination, and the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text Revision, were not met. After excluding other potential diagnoses, she met the diagnostic criteria for ME/CFS. While there is no evidenced‐based radical treatment for ME/CFS and PEM, the most common treatment strategy aimed to relieve PEM, which balances energy and rests to reduce the frequency or severity of episodes of PEM, is called pacing. Therefore, pacing with information about the diseases, education for self‐management, and emotional support were incorporated. She was advised to engage in leisure activities and avoid overexerting herself with household chores or work. She was encouraged not to dwell excessively on her symptoms, to take time for herself, and to find the path to recovery, under the clinician's guidance. She was also required to report detailed daily activities every week for 2 months, while activity diaries were not introduced. Additionally, hochuekkito, a Japanese herbal (Kampo) medicine (7.5 g/day), and tandospirone (15 mg/day) were prescribed.

Two weeks after visiting the department, she experienced PEM after taking a long trip for recreation and was advised to avoid overexerting herself even with leisure activities. Twelve months after the third vaccination, she restarted taking walks around the neighborhood and vegetable gardening at home, which she had been unable to do for a year. Her symptoms gradually improved, and she said, “I was feeling rushed. I can see a clear sky now”. Although her symptoms occasionally appeared, she developed self‐management skills and began working every other day. Fourteen months after the third vaccination, the patient experienced a new‐onset headache that persisted for a month, leading to increased anxiety. The headache was alleviated after advising her to pace herself, offering supportive psychotherapy, and encouraging a commitment to recovery. Her symptoms gradually improved with the coping strategy, allowing her to return to work just as before the third vaccination. Thirty months after the third vaccination, her taste dysfunction finally improved, and all symptoms were entirely resolved. By the time this report was written, 6months had passed since her full recovery, with no signs of relapse or recurrence.

DISCUSSION

This case report is the first to detail the symptom progression of ME/CFS that developed after the third SARS‐CoV‐2 vaccination. ME/CFS has not been well‐known among clinicians as an adverse effect after the SARS‐CoV‐2 vaccination, and patients are frequently referred to psychiatry due to suspicions of psychiatric disorders such as MDD from other departments. This patient was also referred to psychiatry; however, the primary symptoms were distinctly physical, particularly those characteristic of ME/CFS, which met the four international clinical diagnostic criteria for ME/CFS: the Fukuda criteria, ⁷ the Revised Canadian Consensus Criteria, ⁸ the International Consensus Criteria, ⁹ and the Institute of Medicine. ¹⁰ Awareness of the condition is warranted for improving patient outcomes and preventing long‐term disabilities.

The patient did not meet the clinical diagnosis or the criteria for MDD, ²⁰ representing distress that should be differentiated from a form of MDD. Due to the physical symptoms, this was considered a secondary psychological response and was understandable. A recent Mendelian randomization study showed no gene causal evidence between MDD and ME/CFS. ²¹ In fact, however, a retrospective study showed that the suicide risk among patients with ME/CFS was almost sevenfold higher than in the general population of England and Wales. ²² While ME/CFS is not directly linked to MDD, the persistent symptoms and the despair over the possibility that it may not be curable can lead to it. From a historical theory, the debilitating symptoms and severe deconditioning of ME/CFS were considered to result from patients' fears and avoidance behaviors. ²² , ²³ As a result, patients tended to avoid the perceived stigma of the illness being seen as “just a psychological issue” or “a matter of attitude,” which discouraged them from seeking psychiatric treatment. Psychiatrists can distinguish whether the symptoms are due to a psychiatric disorder or not, offer empathy for those suffering from undiagnosed or misdiagnosed other diseases, and provide psychiatric intervention for the distress.

We report the comprehensive treatment and self‐management strategy, including a pacing strategy and psychiatric intervention based on supportive psychotherapy. PEM significantly reduces quality of life and is one of the most severe symptoms experienced by patients with ME/CFS, and a symptom management approach like pacing is essential. ²⁴ Pacing is a physical therapy strategy that enables patients to increase or decrease their activity levels according to their daily condition, not to trigger PEM. ²⁵ Patients and clinicians collaboratively determine the activity limits that can be tolerated. ² , ³ On the other hand, based on the large randomized control study, there was a more designed behavior therapy, a combination of cognitive behavioral therapy and graded exercise therapy. ²⁶ However, that study has faced criticism from both patients and clinicians regarding its methodology and the controversial disease theory. ²⁷ , ²⁸ , ²⁹ The exercise routines may exacerbate PEM and potentially harm patients, leading the United States Centers for Disease Control and Prevention not to recommend it. ³⁰ It is important to discuss and determine patients' tolerable activity limits through a mutual decision‐making process. ² , ³ , ³⁰

We also prescribed hochuekkito and tandospirone to reduce the debilitating fatigue and anxiety. Hochuekkito is anticipated to be beneficial for patients with cancer, ³¹ long COVID, ³² , ³³ and ME/CFS after the SARS‐CoV‐2 infection to alleviate fatigue. ³⁴ A study in a mouse model of ME/CFS showed that hochuekkito reduced neuroinflammation, ³⁵ and the medication may help mitigate fatigue and support overall recovery. Although various medicines have ever been tested, no standardized pharmacological treatment exists for this condition, including antidepressants. ³⁶ However, if patients' distress deteriorates, psychiatrists can carry out pharmacological interventions while carefully monitoring for potential adverse effects.

CONCLUSION

This case report highlights the occurrence of ME/CFS following the SARS‐CoV‐2 vaccination and details the patient's complete recovery. It emphasizes the importance of considering ME/CFS in the differential diagnosis among patients experiencing adverse effects of the SARS‐CoV‐2 vaccination. While the severity and conditions of each patient vary, our findings shed new light on the treatment of ME/CFS and the vaccination‐related adverse effects. Psychiatrists can provide valuable interventions to help those struggling with devastating symptoms and the associated despair over the condition.

AUTHOR CONTRIBUTIONS

Isaku Kurotori treated the patient, reviewed the literature, and drafted the manuscript. All authors reviewed the draft and approved the final version.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

ETHICS APPROVAL STATEMENT

This report was conducted according to the principles of the Declaration of Helsinki.

PATIENT CONSENT STATEMENT

Informed written consent was obtained from the patient for this report.

CLINICAL TRIAL REGISTRATION

N/A.

Kurotori I, Sasao W, Abe M. Recovery from Myalgic Encephalomyelitis/Chronic Fatigue syndrome developed after severe acute respiratory syndrome coronavirus 2 vaccination: a case report. Psychiatry Clin Neurosci Rep. 2025;4:e70111. 10.1002/pcn5.70111

DATA AVAILABILITY STATEMENT

Research data are not shared. The participant in this study did not provide written consent for their data to be shared publicly, therefore, due to the sensitive nature of the research, research data are not shared.