SARS-CoV-2 infection leads to prolonged repercussions, the Post-COVID Conditions (PCC), which represent a global health challenge. PCC prevalence varies, making it difficult to understand its true impact and risk factors. Understanding its magnitude and associated elements is crucial to support effective public policies.

To calculate the frequency of PCC in a city in the interior of São Paulo and identify associated risk factors, including demographic variables, clinical variables (acute COVID-19), pre-existing diseases, and vaccination status.

Cross-sectional study with 3,088 individuals selected by randomization from approximately 50,000 mild, moderate, or severe COVID-19 cases notified in Botucatu, São Paulo, between January 2020 and May 2022. Secondary data were extracted from e-SUS Notifica and SIVEP-Gripe reports. Participants were contacted by telephone. Statistical analysis used chi-square test, independent t-test, and logistic regression (p < 0.05).

Among those included, 697 (22.6%) reported PCC. Age and proportion of asymptomatic individuals in the acute phase were homogeneous between groups with and without PCC. In the PCC group, there was a higher proportion of women (62.7% vs 55.1%, p < 0.001), hospitalized individuals (8.2% vs 5.6%, p = 0.013), unvaccinated individuals (48.2% vs 43.6%), and those with pre-existing comorbidities (16.8% vs 12.6%, p = 0.005). Among these, there was a higher proportion of cardiovascular diseases (9.4% vs 6.4%, p = 0.008) and obesity (1.8% vs 0.7%, p = 0.015) in the PCC group. In the same group, acute-phase symptoms such as cough, fever, anosmia, and headache were more frequent (p < 0.05) than in the group without PCC. In multivariate analysis, female sex was a significant risk factor for PCC (OR = 1.441; 95% CI: 1.205–1.724), and a higher number of vaccine doses was a protective factor (OR = 0.871; 95% CI: 0.811–0.937). The presence of symptoms during the acute phase was associated with the outcome (OR = 0.913; 95% CI: 0.725–1.150).

PCC are a relevant problem in the interior of São Paulo, affecting more than one fifth of the population. Identifying female sex as a risk factor and complete vaccination as a protective factor highlights the importance of differentiated prevention and management strategies to mitigate the long-term impact of the pandemic.