Review Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review 2024 Patil et al

Andy

Retired committee member
Abstract

Background
Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed. Epigenetics has helped elucidating the pathophysiology of several health conditions and it might help unravelling inter-individual differences in patients with PACS and long-COVID. As accumulating research is exploring epigenetic mechanisms in PACS and long-COVID, we systematically summarized the available literature on the topic.

Methods
We interrogated five databases (Medline, Embase, Web of Science, Scopus and medXriv/bioXriv) and followed PRISMA and SWiM guidelines to report our results.

Results
Eight studies were included in our review. Six studies explored DNA methylation in PACS and/or long-COVID, while two studies explored miRNA expression in long-COVID associated with lung complications. Sample sizes were mostly small and study quality was low or fair. The main limitation of the included studies was a poor characterization of the patient population that made a homogeneous synthesis of the literature challenging. However, studies on DNA methylation showed that mechanisms related to the immune and the autonomic nervous system, and cell metabolism might be implicated in the pathophysiology of PACS and long-COVID.

Conclusion
Epigenetic changes might help elucidating PACS and long-COVID underlying mechanisms, aid subgrouping, and point towards tailored treatments. Preliminary evidence is promising but scarce. Biological and epigenetic research on long-COVID will benefit millions of people suffering from long-COVID and has the potential to be transferable and benefit other conditions as well, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We urge future research to employ longitudinal designs and provide a better characterization of included patients.

Open access, https://www.cambridge.org/core/jour...matic-review/BCF992CF0E491FC0AD0FEDC3A8AFFD4B
 
Quote from the review:
research focussing on the epigenetics of PACS and long-COVID is scarce and mostly of low quality. Sample sizes are generally quite small, and the clinical description of the included populations is rather superficial. In addition, different studies used different biological matrices and/or methods to explore the same mechanism (e.g. Illumina array-based assays vs. whole-genome bisulphite sequencing for DNA methylation). In fact, different studies showed different results, and firm conclusions cannot be drawn on the exact underlying epigenetic mechanisms.

In the discussion section the reviewers refer to ME/CFS:
Research on long-COVID can learn a lot from the knowledge obtained from studies on ME/CFS over the past decades (Ref. 45). In turn, current research on long-COVID will benefit patients with ME/CFS (Ref. 46). Given the expected huge prevalence of long-COVID (and thus the possibility to recruit patients for research purposes), results from studies on patients with long-COVID should be widely transferred to the ME/CFS field
 
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