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.

Highlights

  • The COVID-19 pandemic has profoundly affected humanity

  • We found that coagulation profiles changed significantly after vaccination, in the short-term (7 days) after the 1st inoculation, coagulation profiles were leaning toward shorter Prothrombin Time (PT), whereas the long-term (28 and 42 days) effect was toward activated partial thromboplastin time (APTT) and PT prolongation (Fig. 2e)

  • CCL3 expression, significantly decreased in many T-cell subtypes but not NK cells after vaccination (Supplementary Fig. S3c). This is a comprehensive investigation of the pathophysiological changes, including detailed immunological alterations in people after COVID-19 vaccination

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Summary

Introduction

The development of COVID-19 vaccines in various forms has been underway in an unprecedented and accelerated manner. Vaccine research has been focused on whether or not vaccination could generate neutralizing antibodies to protect against viral infections, whereas short-term and long-term influences of the various newly developed vaccines to human pathophysiology and other perspectives of the human immune system have not been fully investigated. With the development of large-scale single-cell mRNA sequencing (scRNA-seq) technology, systematic investigation of people’s immune system function with precision became possible, primarily through scRNA-seq of peripheral blood mononuclear cells (PBMCs). During the COVID-19 pandemic, a large body of studies using scRNA-seq of PBMCs had revealed detailed changes in gene expression in different immune cell subtypes including different types of T and B cells, NK cells, monocytes, dendritic cells, etc. During the COVID-19 pandemic, a large body of studies using scRNA-seq of PBMCs had revealed detailed changes in gene expression in different immune cell subtypes including different types of T and B cells, NK cells, monocytes, dendritic cells, etc. during and

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