Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post‐COVID‐19 [ME/CFS], 2025, Nakajima et al

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Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post‐COVID‐19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report

Kan Nakajima, Nobutaka Ayani, Teruyuki Matsuoka, Kenya Kasahara, Yoshiyuki Nakajima, Haruki Ikawa, Riki Kitaoka, Tatsuhiko Akimoto, Jin Narumoto

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Background
The COVID‐19 pandemic has led to an increase in post‐acute sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), potentially mediated by dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. Corticosteroids are occasionally administered to ameliorate fatigue symptoms in ME/CFS; however, their psychiatric adverse effects, particularly in individuals with preexisting mood disorders, necessitate careful consideration.

Case Presentation
We report the case of a 32‐year‐old woman with bipolar disorder who developed ME/CFS following COVID‐19 infection.

Initial corticosteroid therapy with betamethasone and prednisolone, agents with potent glucocorticoid receptor (GR) activity, resulted in a manic episode with psychotic features, necessitating psychiatric hospitalization. Although mood stabilization was achieved with olanzapine and valproate, corticosteroid withdrawal subsequently led to metabolic alkalosis and hypoxemia, secondary to hypothalamic hypoadrenalism.

Following a comprehensive endocrinological assessment, physiological replacement therapy with hydrocortisone, characterized by relatively higher mineralocorticoid receptor (MR) activity and lower GR potency, was initiated, resulting in the resolution of physical symptoms without destabilization of psychiatric status.

Conclusion
The clinical course suggests that GR‐dominant corticosteroids may exacerbate psychiatric instability in patients with mood disorders. Simultaneously, MR‐favoring agents, such as hydrocortisone, may offer a safer therapeutic alternative for managing HPA axis dysfunction.

This case underscores the critical role of receptor selectivity in corticosteroid therapy, particularly in patients with comorbid psychiatric conditions, and highlights the necessity for individualized treatment strategies that integrate both endocrine and neuropsychiatric considerations.

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[Utsikt]

I think the authors are confused about what ME/CFS is. This is their description of it:

Post-COVID has a variety of symptoms, one of which is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), characterized by chronic fatigue that does not improve with adequate rest.

Graded exercise therapy and cognitive behavioral therapy have been shown to alleviate ME/CFS symptoms, while corticosteroids have demonstrated partial efficacy in improving symptoms.4

4 = Interventions for the treatment and management of chronic fatigue syndrome: a systematic review
P Whiting et al. JAMA. 2001.

Interventions for the treatment and management of chronic fatigue syndrome: a systematic review - PubMed

Overall, the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies. Interventions which have shown promising results include cognitive behavioral therapy and graded...

pubmed.ncbi.nlm.nih.gov

There is nothing in the case presentation about ME/CFS. Fatigue is only mentioned here:

In May 2022, she contracted COVID-19, which was followed by persistent fatigue and malaise. A rash was observed on her hands and feet, which was considered unlikely to be a drug reaction, although lamotrigine was discontinued at her request. In August 2023, she was hospitalized for worsening depressive symptoms and started quetiapine; however, this was discontinued due to liver dysfunction, and olanzapine (OLZ) 5 mg/day was initiated, which improved her symptoms. After discharge, she continued the same dose of OLZ, and her mental status remained stable despite persistent fatigue, leading to a diagnosis of post-COVID syndrome.

This is mentioned in the introduction:

In this case report, we describe a patient with bipolar disorder who developed ME/CFS following COVID-19 infection.

And this is from the discussion:

We hypothesized the following sequence of events. First, COVID-19 led to hypothalamic dysfunction, causing hypothalamic hypoadrenalism and contributing to ME/CFS onset. Next, PSL and BMS were used to treat ME/CFS, improving physical symptoms but worsening psychiatric symptoms of bipolar disorder. Despite a gradual reduction in PSL, the patient still experienced severe physical symptoms due to hypothalamic hypoadrenalism.

Blind administration of corticosteroids in patients with ME/CFS is not advisable; however, corticosteroid replacement therapy may be warranted in cases where patients have conditions such as hypothalamic hypoadrenalism. Therefore, evaluating hypothalamic function may contribute to improving the quality of ME/CFS treatment.