Introduction The coronavirus disease 2019 (COVID-19) pandemic is a serious public health event and poses a global health threat. To study the specific antibody responses would contribute to a better understanding of COVID-19. Methods We collected complete follow-up data from 777 patients with pathogen-confirmed COVID-19 with corresponding immunoglobulin G and M (IgG/IgM) testing results. Results Overall, the positive rates of IgG and IgM in severe patients were slightly higher than those in non-severe patients. In addition, higher IgG levels were detected in severe patients compared to non-severe patients (P = 0.026). Through further analysis, differences in IgG were only significant in serum samples taken in the first 14 days of disease onset (P < 0.001). On the basis of analysis of antibody expression levels at different time points in 74 patients who had undergone more than three detection tests, we found that the differences in IgG levels between the severe/non-severe patients were more pronounced than those of IgM. On multivariate logistic regression, after adjusting for cofactors, the higher anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) IgG levels observed in the first 14 days of disease onset were independently associated with severe COVID-19 disease (odds ratio (OR) = 1.368, 95% confidence interval (CI) 1.138-1.645). Conclusion We observed differences in antibody responses among patients with different severity of COVID-19. A high IgG level in the first 14 days of disease may be positively associated with disease severity.