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Objective: To investigate the persistence of symptoms compatible with COVID-19 in a real-file prospective cohort of patients at 12 months from hospital discharge. Methods: Longitudinal, prospective, single-center, cohort telephone follow-up (FU) study in a Tertiary Care Hospital. All consecutive patients >18 years admitted for COVID-19 were prospectively enrolled in a telephone FU program aimed at monitoring symptoms after 1,3,6,9 and 12 months from hospital discharge. The survey screened for somatic (fatigue, dyspnea, dyspnea, palpitations, cough, chest pain, abdominal pain, ageusia, anosmia, bowel symptoms) and psycho-emotional (insomnia, confusion, altered sense of reality, loss of appetite, fear, and depression) and frailty. Only patients with 12 months FU data were analyzed. Prevalence and factors associated with symptoms were the main outcomes. Frailty was defined by the presence of ≥3 indicators: weakness, slowness/impaired mobility, weight-loss, low physical activity, and exhaustion. Results: At 12 months, 40.5% of patients reported at least one symptom. The most common somatic ones were fatigue, exertional dyspnea, cough, bowel complaints while the most common psycho-emotional were insomnia, confusion, fear, and depression. Age, gender, gender, frailty, multiple symptoms at baseline and chronic obstructive pulmonary disease (COPD) were associated with symptoms persistence. Furthermore, frailty, COPD and multiple symptoms at baseline were associated with increased risk of somatic symptoms at 12 months, while age and gender were associated with psycho-emotional ones. Conclusions: Burden of the long COVID-19 symptoms decreased over time but remained as high as 40% at 12 months with important gender and functional differences, highlighting potential patient categories who may benefit from specific follow up strategies.