Association of LEF1-AS1 with cardiovascular and neurological complications of COVID-19

A significant proportion of COVID-19 patients develop long-term complications, particularly cardiovascular and neurological issues. Even though risk factors for developing complications after COVID-19 have been identified, a biomarker to predict these complications could enable personalized healthcare and potentially reduce the disease burden. Easily measurable in the blood, the long noncoding RNA LEF1-AS1 has recently been associated with in-hospital mortality following SARS-CoV - 2 infection and holds potential as a biomarker for disease severity in COVID-19 patients. Consequently, we examined LEF1-AS1's ability to predict cardiovascular and neurological complications after COVID-19. LEF1-AS1 has been measured in the blood by quantitative PCR in 104 primo-infected participants from the Predi-COVID cohort within 3 days post clinical PCR-confirmed COVID-19 diagnosis. Among them, 35 participants (34 %) reported at least one persistent cardiovascular symptom and at least one persistent neurological or ocular symptom in a self-administered questionnaire 12 months after COVID-19 diagnosis. Blood levels of LEF1-AS1 at baseline in these patients were lower (p = 0.019) compared to those who did not report symptoms. Lower LEF1-AS1 levels were associated with symptoms with an odds ratio of 0.48 (95 % confidence interval 0.28-0.83) in a logistic regression model adjusted for age, sex, comorbidity, and moderate disease severity at baseline. LEF1-AS1 expression was positively correlated with the frequency of naïve T cells and negatively correlated with the frequency of effector memory T cells among total CD8+ T cells, revealing a potential association between LEF1-AS1 and CD8+ T-cell differentiation following SARS-CoV-2 infection. In conclusion, blood levels of LEF1-AS1 can potentially help in predicting 12-month cardiovascular and neurological complications in COVID-19 patients, though this finding requires validation in larger cohorts.