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Aim The aim of this study was to describe the frequency of post-vaccination SARS-CoV-2 infection and to compare SARS-CoV-2 IgG antibody levels between patients with severe obesity and individuals without obesity after two doses of the BNT162b2 vaccine. Methods One hundred two consecutive patients with severe obesity seen in the obesity outpatient clinic and 54 individuals without obesity who visited a vaccination outpatient clinic were included in the study. Inactivated Severe Adult Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG levels of these two groups were measured four weeks after administration of two doses of BNT162b2 vaccine. SARS-CoV-2 infection was defined as a PCR-confirmed infection documented in hospital records during the 12-month follow-up after completion of two-dose BNT162b2 vaccination. PCR testing was performed only when participants presented to the hospital with clinical suspicion of COVID-19 and was not conducted as routine screening. Clinical characteristics, protective measures and contact history were also queried. Results There was a statistically significant difference in SARS-CoV-2 infection rates after vaccination between the patients with severe obesity (n=28, 27%) and individuals without obesity (n=3, 5%) (p=0.001). In patients with severe obesity, SARS-CoV-2 IgG levels after BNT162b2 vaccination were lower in the group with SARS-CoV-2 infection than in the group without SARS-CoV-2 infection [2697 (1096-8955); 8103 (2208-26903) AUml, respectively] (p=0.008). The antibody levels of those with severe fatigue were lower than those without these complaints [2440 (365-4447); 8955 (2440-16317) AUml, respectively] (p=0.03). A loss of taste or smell was observed in 75% of patients with severe obesity but was not observed in individuals without obesity (p=0.03). In patients with severe obesity, those with taste/smell loss had statistically significantly lower SARS-CoV-2 IgG titres than those without severe obesity [2568 (400-4830); 9526 (2611-16810) AUml, p: 0.02]. Multiple logistic regression analysis revealed a correlation between body mass index (BMI) and having had a SARS-CoV-2 infection after BNT162b2 vaccination (p = 0.028, Exp(B) = 1.072). There was no need for hospitalisation due to SARS-CoV-2 infection and there were no deaths in either group. Conclusion Patients with severe obesity had higher rates of SARS-CoV-2 infection after BNT162b2 vaccination compared to individuals without obesity. SARS-CoV-2 IgG levels were lower in patients with severe obesity after BNT162b2 vaccination. Based on these findings, given the higher frequency of post-vaccination infections in the patients with severe obesity, timely booster vaccination policies may be particularly important for this population. Severe obesity, SARS-CoV-2, BNT162b2, SARS-CoV-2 IgG, breakthrough infection. Key points The rate of SARS-CoV-2 infection after vaccination was higher in patients with severe obesity than in individuals without obesity. It has been found that antibody levels are lower in patients with severe fatigue symptoms than in patients without these symptoms. Loss of taste or smell was observed at a high rate (75%) in the group with severe obesity, but not in individuals without obesity. In this study, there were no hospitalisations or deaths after vaccination with BNT162b2 in patients with severe obesity. Body mass index (BMI) has been found to negatively affect the likelihood of contracting SARS-CoV-2 infection after receiving the BNT162b2 vaccine. In our study, we emphasise the importance of vaccination in patients with severe obesity.