LEF1-AS1 Deregulation in the Peripheral Blood of Patients with Persistent Post-COVID Symptoms

Abstract: Long COVID denotes the persistence of symptoms after acute SARS-CoV-2 infection lasting for at least two months without another identifiable cause. Affecting anestimated 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. Dueto the different manifestations of long COVID, its diagnosis can be challenging. Identifyingpotential mechanistic contributors and biomarkers would be highly valuable. Recent studies have highlighted the potential of noncoding RNAs (ncRNAs) as biomarkers for diseasestratification in COVID-19. Specifically, we have recently identified miR-144-3p and a subsetof lncRNAs as candidates for assessing disease severity and outcomes in COVID-19. Thisnested case–control study extends such investigations to 98 long COVID patients recruited18 months after hospitalization, exploring the relationship between circulating ncRNAexpression and persistent symptoms. While miR-144-3p, HCG18, and lncCEACAM21expression did not differ between symptomatic and asymptomatic patients, LEF1-AS1 wasdownregulated in the peripheral blood mononuclear cells (PBMCs) of symptomatic patients. Of note, multiple LEF1-AS1 isoforms and LEF1 sense transcript levels were reducedand negatively correlated with relevant clinical markers. While further studies are needed,our discoveries offer new perspectives on the diagnosis and management of persistentlong COVID.