SARS-CoV-2 has acquired many mutations that influence the severity of COVID-19’s course or the risk of developing long COVID. In 2022, the dominant SARS-CoV-2 variant was Omicron. This study aimed to compare the course of COVID-19 in the periods before and during the dominance of the Omicron variant. Risk factors for developing long COVID were also assessed. This study was based on stationary visits of patients after COVID-19 and follow-up assessments after 3 months. Clinical symptoms, comorbidities, and vaccination status were evaluated in 1967 patients. Of the analyzed group, 1308 patients (66.5%) were affected by COVID-19 in the period before the Omicron dominance. The prevalence of long COVID was significantly lower among patients of the Omicron group (47.7% vs. 66.9%, p < 0.001). The risk of long COVID was higher for women (OR: 1.61; 95% CI: 1.31, 1.99]) and asthmatics (OR: 1.46; 95% CI: 1.03, 2.07]). Conclusively, infection during the Omicron-dominant period was linked to a lower risk of developing long COVID. Females are at higher risk of developing long COVID independent of the pandemic period. Individuals affected by COVID-19 in the Omicron-dominant period experience a shorter duration of symptoms and reduced frequency of symptoms, except for coughing, which occurs more often.