Investigation of immune complex formation in cases with COVID-19 infection and different vaccine applications

Objective: Many case reports have linked post-COVID-19 infection with type III hypersensitivity reactions. Consequently, there has been a discussion about the potential triggering of type III hypersensitivity reactions following COVID-19 vaccinations. In our study, we aim to investigate the relationship between COVID-19 and/or its vaccinations and type III hypersensitivity reactions. Methods: We collected serum samples from 135 subjects within 7-14 days. The subjects included unvaccinated individuals, those with different vaccination statuses, those who had recovered from COVID-19, and subjects with varying vaccination statuses who had not contracted COVID-19. We used the PEG precipitation method to qualitatively assess the presence of immune complexes in the collected serum samples. For quantitative analysis, we used the ELISA method to measure SARS-CoV-2 Spike RBD/SARS-CoV-2 IgG, C3a, C5a, and IL-6, and the IFA method for ANCA. Hematological analysis for WBC, neutrophils, and platelets was conducted using a Coulter principle-based hematology analyzer. xxiii Results: No significant difference in the presence of immune complexes was observed between symptomatic and asymptomatic groups based on the clinical course in individuals who had recovered from COVID-19. However, in individuals with different vaccination statuses who had recovered from COVID-19, a significantly higher presence of immune complexes was found in the heterologous vaccine group (p=0.042). There was no significant difference in the presence of immune complexes between the groups that received ≤3 doses and >3 doses among individuals with different vaccination statuses who had recovered from COVID-19. Although no significant difference was found when comparing individuals who had recovered from COVID-19 based on different types of vaccination, the highest presence of immune complexes was observed in the 2CV+2BNT group with 4 (26.7%) positive cases. No significant differences were found in the presence of immune complexes based on age and gender. Due to the small number of immune complex-positive cases in our other parameters, we were unable to perform statistical calculations. However, a multivariate analysis based on the presence of immune complexes in all subjects revealed that the mean levels of WBC and neutrophils were highly significant (p=0.003 and p=0.013, respectively, with WBC/OR: 5.880 and Neutrophil/OR: 2.655). Conclusions: Our findings indicate that immune complexes may develope after COVID-19 infection and/or vaccination. This may lead to an increase in certain immune molecules as part of the associated pathophysiological process. Furthermore, although only observed in a small number of cases, our results suggest that higher vaccine dosages may also have a proactive role in this process.