In 2022, three antiviral drugs—molnupiravir, remdesivir and nirmatrelvir/ritonavir—were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the involvement of 1118 patients, with complete follow-up data, treated between the 5th of January and the 3rd of October 2022 at Santa Maria Goretti’s hospital in Latina, Central Italy. A univariable and a multivariable analysis were performed on clinical and demographic data and composite outcome, the persistence of symptoms at 30 days and time to negativization, respectively. The three antivirals showed a similar effectiveness in containing the progression of the infection to severe COVID-19 and a good tolerability in the absence of serious adverse effects. Persistence of symptoms after 30 days was more common in females than males and less common in patients treated with molnupiravir and nirmatrelvir/r. The availability of different antiviral molecules is a strong tool and, if correctly prescribed, they can have a significant role in changing the natural history of infection for frail persons, in which vaccination could be not sufficient for the prevention of severe COVID-19.
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