Objective To investigate the status of frailty in patients with coronavirus disease 2019 (COVID-19), and to analyze the influence of COVID-19 disease on the prevalence of frailty. Methods This study was conducted using a cross-sectional survey method. COVID-19 patients admitted to a centralized isolation point in Guangzhou were selected for an questionnaire survey by “questionnaire star”, between November and December 2022. The questionnaire included the general information questionnaire, Tilburg Frailty Indicator (TFI), the COVID-19 symptom scale and Mental Resilience Scale (RS-11). Multi-model logistic regression analysis was used to explore the influence of COVID-19 on the occurrence of debilitation. Results A total of 667 questionnaires were distributed, of which 594 were valid, with an effective rate of 89.1%. There were 150 patients (25.3%) were frail, 444 patients (74.7%) were non-frail, and 51 patients (8.6%) were newly frail after infected COVID-19. The median TFI score before COVID-19 was 3 (2, 4) points, 16.7% (99/594) were in a weak state. The median TFI score after COVID-19 was 3 (2, 5) points, 25.3% (150/594) were in a weak state. There were statistically significant differences in TFI scores (Z=−6.596, P＜0.001) and the incidence of debilitation (χ2=351.648, P＜0.001) before and after COVID-19. The results of multivariate logistic regression analysis showed that after controlling disease factors, demographic factors and psychosocial factors, the score of the COVID-19 symptom score was always the influencing factor of COVID-19 patients. The overall change trend of COVID-19 symptom score was statistically significant (P<0.001). Conclusions The COVID-19 symptom score is an important risk factor or predictor of frailty in patients with COVID-19. As the level of COVID-19 symptom score increases, the risk of frailty in COVID-19 patients increases.