Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines

“Abstract: Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders…

Discussion: 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 …

Our study postulates that it is imperative to consider the potential long-term impact of vaccination to certain medical conditions or to general human health.”