SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism

Yukai Jing,Quan Gong,Zhiwei Sui,Peng Zhou,Ying Chen,Andrés A Herrada,Masato Kubo,Lisa S Westerberg,Chaohong Liu,Zhiping Xu,Bing Zheng,Zhongxin Lu,Chan-Sik Park,Yu Hu,Pamela Pui-Wah Lee,Heng Mei,Li Luo,Wei Xiao

doi:10.1038/s41392-021-00749-3

Abstract

The SARS-CoV-2 infection causes severe immune disruption. However, it is unclear if disrupted immune regulation still exists and pertains in recovered COVID-19 patients. In our study, we have characterized the immune phenotype of B cells from 15 recovered COVID-19 patients, and found that healthy controls and recovered patients had similar B-cell populations before and after BCR stimulation, but the frequencies of PBC in patients were significantly increased when compared to healthy controls before stimulation. However, the percentage of unswitched memory B cells was decreased in recovered patients but not changed in healthy controls upon BCR stimulation. Interestingly, we found that CD19 expression was significantly reduced in almost all the B-cell subsets in recovered patients. Moreover, the BCR signaling and early B-cell response were disrupted upon BCR stimulation. Mechanistically, we found that the reduced CD19 expression was caused by the dysregulation of cell metabolism. In conclusion, we found that SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism, which may provide a new intervention target to cure COVID-19.

Highlights

At the end of 2019, a new coronavirus (SARS-CoV-2) was identified as the causative pathogen of the severe acute respiratory infection named COVID-19
These results indicate that SARS-CoV-2 infection may alter the immune phenotype and function of B cells through inhibition of CD19 expression
SARS-CoV-2 infection alters the B-cell receptor (BCR) signaling and B-cell metabolism in recovered COVID-19 patients CD19 is a critical regulator of BCR signaling, B-cell development, and humoral immune response

Summary

Introduction

At the end of 2019, a new coronavirus (SARS-CoV-2) was identified as the causative pathogen of the severe acute respiratory infection named COVID-19. Patients infected with SARS-CoV-2 present vastly different clinical manifestations ranging from asymptomatic forms to life-threatening pathologies including Acute Respiratory. Evidence suggests that the so-called “cytokine storm”, uncontrolled activation of the inflammatory response, significantly contributes to the occurrence of ARDS. Emerging evidence suggests that the metabolic composition of serum from COVID-19 patients is significantly altered in comparison to healthy individuals and that specific changes correlate with disease severity.[7] Among other biochemicals, the levels of the TCA cycle component malate, the urea cycle component carbamoyl phosphate, and guanosine monophosphate have been suggested to change with disease progression.[8]

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