LEF1-AS1 Deregulation in the Peripheral Blood of Patients with Persistent Post-COVID Symptoms, 2025, Madè et al.

[SNT Gatchaman]

LEF1-AS1 Deregulation in the Peripheral Blood of Patients with Persistent Post-COVID Symptoms
Madè, Alisia; Piella, Santiago Nicolas; Ranucci, Marco; Gaetano, Carlo; Renna, Laura Valentina; Cardani, Rosanna; Spinetti, Gaia; Milani, Valentina; Martelli, Fabio

Long COVID denotes the persistence of symptoms after acute SARS-CoV-2 infection lasting for at least two months without another identifiable cause. Affecting an estimated 15% of COVID-19 patients, long COVID manifests in a wide range of symptoms. Despite extensive research on its one-year effects, limited data exist beyond 12 months. Due to the different manifestations of long COVID, its diagnosis can be challenging. Identifying potential mechanistic contributors and biomarkers would be highly valuable. Recent studies have highlighted the potential of noncoding RNAs (ncRNAs) as biomarkers for disease stratification in COVID-19. Specifically, we have recently identified miR-144-3p and a subset of lncRNAs as candidates for assessing disease severity and outcomes in COVID-19.

This nested case–control study extends such investigations to 98 long COVID patients recruited 18 months after hospitalization, exploring the relationship between circulating ncRNA expression and persistent symptoms. While miR-144-3p, HCG18, and lncCEACAM21 expression did not differ between symptomatic and asymptomatic patients, LEF1-AS1 was downregulated in the peripheral blood mononuclear cells (PBMCs) of symptomatic patients. Of note, multiple LEF1-AS1 isoforms and LEF1 sense transcript levels were reduced and negatively correlated with relevant clinical markers.

While further studies are needed, our discoveries offer new perspectives on the diagnosis and management of persistent long COVID.

Link | PDF (International Journal of Molecular Sciences) [Open Access]

 

[SNT Gatchaman]

For this study, 98 patients hospitalized at IRCCS Policlinico San Donato because of mild to severe COVID-19 were enrolled in the “long COVID” protocol to assess symptoms persistent after hospitalization.

LEF1 is Lymphoid Enhancer Binding Factor 1
LEF1-AS1 is LEF1 Antisense RNA 1

GeneCards —

LEF1
LEF1-AS1

 

[wigglethemouse]

LEF1-AS1 was downregulated in the peripheral blood mononuclear cells (PBMCs) of symptomatic patients.

LEF1 was found decresead in this Long Covid study
Persistent Activation of Chronic Inflammatory Pathways in Long Covid, 2024, Aid et al.

NK cells

• Genes associated with natural killer function such as KLRC4, KLRC1, KLRC2 and transcription factors such LEF1, GATA6, BACH2 were decreased in the LC group compared with the CC and uninfected control groups

 

[Hutan]

It looks like an interesting molecule

Aliases for LEF1
Lymphoid Enhancer Binding Factor 1 2 3 5
Lymphoid Enhancer-Binding Factor 1 2 3 4
TCF1ALPHA 2 3 5
TCF7L3 2 3 5
TCF10 2 3 5
T Cell-Specific Transcription Factor 1-Alpha 3 4
TCF1-Alpha 3 4
LEF-1 3 4

Regulates T-cell receptor alpha enhancer function (PubMed:19653274). Required for IL17A expressing gamma-delta T-cell maturation and development, via binding to regulator loci of BLK to modulate expression

Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein that is expressed in pre-B and T cells. It binds to a functionally important site in the T-cell receptor-alpha (TCRA) enhancer and confers maximal enhancer activity.

It belongs to a family of proteins with roles in DNA transcription. There are different isoforms that seem to have different roles, and it has different roles in different tissues.

BUT, the 98 participants (all hospitalised during their Covid infection and all described as Long Covid) are divided into two groups - no major physical symptoms and major physical symptoms. The major physical symptoms group has a mean age of 71 versus the 58 in the No MPS group (p=0.005). The percentage of males is also significantly different. There are big differences in some health metrics e.g. former smoker (58% vs 30%), hypertension (58% vs 36%), atrial fibrillation (17% vs 2%).


Green is the no major physical symptoms, red is the major physical symptoms. A lot of one group looks like the other group, when it comes to levels of this protein. Yes, there's a group with lower levels, but perhaps that is something to do with age or a comorbidity severity.

 

[Hutan]

With respect to new symptoms present at 18 months, some of the most marked from Table 2

persistent fatigue (75% in MPS group; 0% in No MPS group)
shortness of breath (71% vs 0%)
arthralgia (42% vs 12%)
brain fog (12.5% vs 6%)
difficulties in concentrating (27% vs 8%)
memory dysfunction (46% to 16%)
dizziness and balance disorders (44% vs 4%)

I note the significant percentage of reported new joint pain. We have seen this in post-infection syndromes e.g. also after Chikungnya. @Jonathan Edwards has suggested that joint pain is common, and so it might not mean much. And that is particularly possible in this elderly group. But, we have seen it reported a number of times.


The groups don't differ markedly in many of the symptoms but do differ in a whole lot of other important ways - pretty much the opposite of what we would be hoping for in a study assessing biomarkers for a disease. So, it's a bit messy and only a handful of the MPS group had lower levels of LEF1.