Background: The aim of the present study was to investigate and compare the relationship between the anatomical distribution of pulmonary lesions in computed tomography scan of patients with COVID-19. Materials and Methods: This is a cross-sectional study that was performed in 2020–2021 in Isfahan on 300 patients infected with COVID-19 pneumonia. We collected data on the age, gender, and comorbidities of patients. In addition, we gathered data on the clinical manifestations of the patients from their medical records. Results: We noted a significant decline in symptoms such as fever and sputum production in the second and third peak in comparison to the first peak (P < 0.05). Moreover, cough and muscular pain were higher in the second and third peaks compared to the first peak (P < 0.05). Cough was the most common clinical manifestation related to the peripheral distribution of the involvements, bilateral lung disease, and right lower lobe (RLL) involvements in the first peak. In the second COVID-19 peak, fever and cough were the most common clinical findings, respectively, that were mostly associated with peripheral distribution and left lower lobe involvement. Conclusion: Cough was the most common clinical manifestation related to the peripheral distribution of the involvements, bilateral lung disease, and RLL involvements in the first peak. In the second COVID-19 peak, fever and cough were the most common clinical findings.