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Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.