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(1) Background: Computed tomography (CT) plays a paramount role in the characterization and follow-up of COVID-19. Several score systems have been implemented to properly assess the lung parenchyma involved in patients suffering from SARS-CoV-2 infection, such as the visual quantitative assessment score (VQAS) and software-based quantitative assessment score (SBQAS) to help in managing patients with SARS-CoV-2 infection. This study aims to investigate and compare the diagnostic accuracy of the VQAS and SBQAS with two different types of software based on artificial intelligence (AI) in patients affected by SARS-CoV-2. (2) Methods: This is a retrospective study; a total of 90 patients were enrolled with the following criteria: patients' age more than 18 years old, positive test for COVID-19 and unenhanced chest CT scan obtained between March and June 2021. The VQAS was independently assessed, and the SBQAS was performed with two different artificial intelligence-driven software programs (Icolung and CT-COPD). The Intraclass Correlation Coefficient (ICC) statistical index and Bland-Altman Plot were employed. (3) Results: The agreement scores between radiologists (R1 and R2) for the VQAS of the lung parenchyma involved in the CT images were good (ICC = 0.871). The agreement score between the two software types for the SBQAS was moderate (ICC = 0.584). The accordance between Icolung and the median of the visual evaluations (Median R1-R2) was good (ICC = 0.885). The correspondence between CT-COPD and the median of the VQAS (Median R1-R2) was moderate (ICC = 0.622). (4) Conclusions: This study showed moderate and good agreement upon the VQAS and the SBQAS; enhancing this approach as a valuable tool to manage COVID-19 patients and the combination of AI tools with physician expertise can lead to the most accurate diagnosis and treatment plans for patients.