# Post-COVID-19 fatigue: A systematic review.
> COVID-19後疲労に関する系統的レビュー：症状・病因・リスク因子および介入アプローチの概観


## Abstract

Persistent fatigue following SARS-CoV-2 infection ranks among the most frequently reported long-term complaints. This systematic review searched PubMed, Web of Science, Cochrane Library, and PsycInfo, ultimately including 20 studies of moderate-to-high methodological quality encompassing 5,629 adult participants (aged 18–65). Identified risk factors included older age, female sex, severe acute-phase illness, a high comorbidity burden, and a prior diagnosis of depression or anxiety; an autoimmune etiology was also hypothesized. Various interventions were examined, mostly in small uncontrolled settings: a Chinese herbal formulation reduced breathlessness and fatigue; molecular hydrogen (H2) inhalation was associated with improvements in physical capacity (6-minute walk test) and respiratory function; hyperbaric oxygen and enhanced external counterpulsation also yielded fatigue relief; and an 8-week biweekly program combining aerobic exercise, strengthening, diaphragmatic breathing, and mindfulness improved muscle strength and physical function. The authors conclude that larger, well-controlled trials are needed to establish the efficacy of physical and psychological interventions for post-COVID-19 fatigue.

### Mechanism

H2 inhalation is proposed to exert antioxidant and anti-inflammatory effects, potentially contributing to the observed improvements in physical capacity and respiratory function in post-COVID-19 patients.

## Bibliographic

- **Authors**: Joli J, Buck P, Zipfel S, Stengel A
- **Journal**: Front Psychiatry
- **Year**: 2022
- **PMID**: [36032234](https://pubmed.ncbi.nlm.nih.gov/36032234/)
- **DOI**: [10.3389/fpsyt.2022.947973](https://doi.org/10.3389/fpsyt.2022.947973)
- **PMC**: [PMC9403611](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403611/)
- **Study type**: review
- **Delivery route**: inhalation
- **Effect reported**: positive

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 36032234. https://h2-papers.org/en/papers/36032234
> **Source**: PubMed PMID [36032234](https://pubmed.ncbi.nlm.nih.gov/36032234/)