Comprehensive genomic, immunological and clinical analysis of COVID-19 vaccine breakthrough infections: a prospective, comparative cohort study (preprint)

ABSTRACT

Objectives: As the COVID-19 pandemic is still ongoing and SARS-CoV-2 variants are circulating worldwide, an increasing number of breakthrough infections have been detected despite the good efficacy of COVID-19 vaccines. Methods: A prospective, comparative cohort study was conducted in Beijing Ditan Hospital to evaluate the clinical, immunological and genomic characteristics of COVID-19 breakthrough infections. Data on 88 COVID-19 breakthrough cases (vaccinated group) and 41 unvaccinated cases (unvaccinated group) from June 1 to August 20, 2021 were extracted from a cloud database. Among these 129 COVID-19 cases, we successfully sequenced 33 whole genomes, including 16 from the vaccinated group and 17 from the unvaccinated group. Results: Asymptomatic and mild cases predominated in both groups, but 2 patients developed severe disease in the unvaccinated group. Between the two groups, the median time of viral shedding in the vaccinated group were significantly lower than those in the unvaccinated group (p = 0.003). A comparison of dynamic IgG titres of cases in the two groups indicated that IgG titres in the vaccinated group showed a significantly increasing trend (P =0.028). The CD4+T lymphocyte count was lower in the unvaccinated group, and there was a significant difference between the two groups (p=0.018). In the vaccinated group, the number of moderate cases who received Sinopharm BBIBP (42 cases) was significantly higher than those who received Sinovac Coronavac (p=0.020). Whole-genome sequencing revealed 23 cases of delta variants, including 15 patients from the vaccinated group. However, no significant difference was observed in either the RT-qPCR results or viral shedding time. Conclusions: COVID-19 vaccine breakthrough infections were mainly asymptomatic and mild, the IgG titres were significantly higher and increased rapidly, and the viral shedding was short. Delta variants may be more likely to cause breakthrough infections, and vaccination may not reduce the viral loads and shedding time.