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

Zhaojun Liang,1,2 Nan Wang,1,2 Chunxue Fan,1,2 Lili Shang,1,2 Yaping Zhang,1,2 Chong Gao,3 Jing Luo1,2 1Division of Rheumatology, Department of Medicine, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory for Immunomicroecology, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Jing Luo, Email [email protected]: 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

Keywords

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