Disturbance of Adaptive Immunity System Was Accompanied by a Decrease in Plasma Short-Chain Fatty Acid for Patients Hospitalized During SARS-CoV-2 Infection After COVID-19 Vaccination

Abstract

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to disorders of immune function and a decrease in the diversity of intestinal flora. We aimed to explore the changes of circulating immune cell subsets and the plasma level of intestinal short-chain fatty acids (SCFAs) in patients with Coronavirus disease 2019 (COVID-19), further understanding the pathogenesis of COVID-19.

Methods

The study included 83 newly diagnosed COVID-19 patients and 39 non-COVID-19 controls. All have completed a full course of vaccination against SARS-CoV-2. The levels of peripheral lymphocyte subsets and plasma cytokines were detected by flow cytometry. Targeted metabolomics was used to explore the level of SCFAs in plasma.

Results

Compared with the non-COVID-19 group, COVID-19 patients showed a decrease in CD19⁺B cells, CD4⁺T cells, CD8⁺T cells, NK cells, CD4⁺CD8⁺T cells and CD4^–CD8^–T cells (all p<0.001) and concomitantly an increase in sIL-2R, IL-6 and IL-10 (all p<0.005). These alterations were more pronounced in those critical patients. In addition, COVID-19 patients had lower levels of propanoic acid (PA), butyric acid (BA), isobutyric acid (IBA) and isohexanoic acid (ICA) (all p<0.01). Among them, the level of ICA is positively correlated with the absolute number of immune cells.

Conclusion

Our study suggests the immune cell subsets in COVID-19 patients who had completed vaccination were still severely disturbed and concomitantly lower SCFAs, especially in severe patients with poor prognosis. Lower levels of plasma SCFAs may contribute to lymphopenia in COVID-19. The potential relationship between plasma SCFAs and immune cell reduction provides a new direction for the treatment of COVID-19.

Keywords:

• coronavirus disease 2019
• severe acute respiratory syndrome coronavirus 2
• adaptive immunity
• short-chain fatty acids

Data Sharing Statement

The research article data used to support the findings of this study are available from the corresponding author upon request.

Ethics Approval

The study was approved by the Ethics Committee of the Second Affiliated Hospital of Shanxi Medical University (number: 2022-KY-063).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that there is no conflict of interest regarding the publication of this article.

Additional information

Funding

This work was supported by the Scientific Research Project of Health commission of Shanxi Province (2019044), the Research Project Supported by Shanxi Scholarship Council of China (2020-191), the Science and Technology Innovation Project of Shanxi Province (2020SYS08), the Project of Central Guides Local Science and Technology Development Funds (YDZJSX2022C031) and the Foundation of Shanxi Key Laboratory for immunomicroecology (202104010910012).