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Introduction: Long-COVID is a multisystem disease characterized by a varied presentation of symptoms. According to most recent research, the most common symptom of long-COVID is fatigue, which up to this date lacks a universally accepted definition. This study aimed to investigate neurocognitive and physical manifestations of neurological long-COVID, particularly fatigue and its relation with autonomic disfunction, cognitive impairment (known as, brain fog), and depressive symptoms. Furthermore, the study provided insights into predictors of fatigue in long-COVID., Methods: The included patients (n=141) were referred to the neuro-long-COVID ambulatory service of Trieste from 30 September 2021-02 March 2022. Patients were given self-reporting questionnaires to screen for fatigue, autonomic dysfunction, cognitive impairment and depressive symptoms. The questionnaires adopted for these conditions to be assessed were Fatigue Severity Scale (FSS), COMPASS-31, Prospective-Retrospective Memory Questionnaire (PRMQ), and Beck Depression Inventory (BDI). Participants were divided into two groups, fatigued and non-fatigued patients, based on FSS scoring (scores > 4.67 indicate fatigued patients). The questionnaire scores of the two groups were then compared., Results: Fatigued patients had significantly higher scores in COMPASS (p<0.001, Cohen's d=1.077), BDI (p<0.001, Cohen's d=0.862), and PRMQ ( p<0.001, Cohen's d=1.159). Furthermore, the multivariate regression analysis showed that predictors of fatigue in long-COVID were symptomatological burden in acute infection (OR=1.38, 95 % CI 1.020-1.887, p=0.037) and in long-COVID (OR=1.78, 95 % CI 1.133-2.2824, p=0.013), COMPASS-31>16 (OR=3.44, 95 % CI 1240-9.560, p=0.018) and BDI>15 (OR=5.1, 95 % CI 1.715-15.164, p=0.003)., Conclusion: This study showed associations between fatigue, dysautonomia and depression, as well as with symptom burden in acute and long-COVID., (Copyright © 2024. Published by Elsevier B.V.)

"Long-COVID" is a clinical entity that consists of persisting post-infectious symptoms that last for more than three months after the onset of the first acute COVID-19 symptoms. Among these, a cluster of neurological persisting symptoms defines Neuro-Long-COVID. While the debate about the pathogenesis of Long-COVID is still ongoing, sex differences have been individuated for both the acute and the chronic stage of the infection. We conducted a retrospective study describing sex differences in a large sample of patients with Neuro-Long-COVID. Demographic and clinical data were collected in a specifically designed Neuro-Long-Covid outpatient service. Our sample included 213 patients: 151 were females and 62 were males; the mean age was similar between females (53 y, standard deviation 14) and males (55 y, standard deviation 15); no significant differences was present between the demographic features across the two groups. Despite the prevalence of the specific chronic symptoms between male and females showed no significant differences, the total number of females accessing our service was higher than that of males, confirming the higher prevalence of Neuro-Long-COVID in female individuals. Conversely, a worse acute phase response in males rather than females was confirmed by a significant difference in the rates of acute respiratory symptoms (p = 0.008), dyspnea (p = 0.018), respiratory failure (p = 0.010) and the consequent need for ventilation (p = 0.015), together with other acute symptoms such as palpitations (p = 0.049), headache (p = 0.001) and joint pain (p = 0.049). Taken together, these findings offer a subgroup analysis based on sex-dependent characteristics, which can support a tailored-medicine approach., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Figures are original and not previously published., (Copyright © 2022. Published by Elsevier B.V.)