This is a comprehensive investigation of the pathophysiological changes, including detailed immunological alterations in people after COVID-19 vaccination. Results indicated that vaccination, in addition to stimulating the generation of neutralizing antibodies, also influenced various health indicators including those related to diabetes, renal dysfunction, cholesterol metabolism, coagulation problems, electrolyte imbalance, in a way as if the volunteers experienced an infection. scRNA-seq of PBMCs from volunteers before and after vaccination revealed dramatic changes in immune cell gene expression, not only echoing some of the clinical laboratory measures but also suggestive of increased NF-κB-related inflammatory responses, which turned out to be mainly taking place in classical monocytes. Vaccination also increased classical monocyte contents. Moreover, the gene set positively contributing to MVS scores, also known to be associated with severe symptom development, was highly expressed in monocytes. Type I interferon (IFN-α/β) responses, supposedly beneficial against COVID-19, were downregulated after vaccination. In addition, the negative MVS genes were highly expressed in lymphocytes (T, B, and NK cells), yet showed reduced expression after vaccination. Together, these data suggested that after vaccination, at least by day 28, other than generation of neutralizing antibodies, people’s immune systems, including those of lymphocytes and monocytes, were perhaps in a more vulnerable state.

The analyses presented in this study, particularly, scRNA-seq of PBMCs had not been performed for previous vaccine evaluations, whether the changes in immune system function-related genes were COVID-19-specific or could be generally applied to other vaccines or other types of COVID-19 vaccines remained to be determined. However, these types of detailed analyses should be overall beneficial to vaccine development and applications. Our study postulates that it is imperative to consider the potential long-term impact of vaccination to certain medical conditions34 or to general human health

https://www.nature.com/articles/s41421-021-00329-3