ABSTRACT
COVID-19 may induce short- and long-term cognitive failures after recovery, but the underlying risk factors are still controversial. Here, we investigated whether (i) the odds of experiencing persistent cognitive failures differ based on the patients' disease course severity and sex at birth; and (ii) the patients' electrolytic profile in the acute stage represents a risk factor for persistent cognitive failures. We analysed data from 204 patients suffering from COVID-19 and hospitalised during the first pandemic wave. According to the 7-point WHO-OS scale, their disease course was classified as severe or mild. We investigated the presence of persistent cognitive failures collected after hospital discharge, while electrolyte profiles were collected during hospitalisation. The results showed that females who suffered from a mild course compared to a severe course of COVID-19 had a higher risk of presenting with persistent mental fatigue after recovery. Furthermore, in females who suffered from a mild course of COVID-19, persistent mental fatigue was related to electrolyte imbalance, in terms of both hypo- and hypernatremia, during hospitalisation in the acute phase. These findings have important implications for the clinical management of hospitalised COVID-19 patients. Attention should be paid to potential electrolyte imbalances, mainly in females suffering from mild COVID-19.
ABSTRACT
BACKGROUND: COVID-19 has a wide spectrum of clinical manifestations and given its impact on morbidity and mortality, there is an unmet medical need to discover endogenous cellular and molecular biomarkers that predict the expected clinical course of the disease. Recently, epigenetics and especially DNA methylation have been pointed out as a promising tool for outcome prediction in several diseases. METHODS AND RESULTS: Using the Illumina Infinium Methylation EPIC BeadChip850K, we investigated genome-wide differences in DNA methylation in an Italian Cohort of patients with comorbidities and compared severe (n = 64) and mild (123) prognosis. Results showed that the epigenetic signature, already present at the time of Hospital admission, can significantly predict risk of severe outcomes. Further analyses provided evidence of an association between age acceleration and a severe prognosis after COVID-19 infection. The burden of Stochastic Epigenetic Mutation (SEMs) has been significantly increased in patients with poor prognosis. Results have been replicated in silico considering COVID-19 negative subjects and available previously published datasets. CONCLUSIONS: Using original methylation data and taking advantage of already published datasets, we confirmed in the blood that epigenetics is actively involved in immune response after COVID-19 infection, allowing the identification of a specific signature able to discriminate the disease evolution. Furthermore, the study showed that epigenetic drift and age acceleration are associated with severe prognosis. All these findings prove that host epigenetics undergoes notable and specific rearrangements to respond to COVID-19 infection which can be used for a personalized, timely, and targeted management of COVID-19 patients during the first stages of hospitalization.