STTT Huazhong University of Science and Technology Liu Chaohong/Lu Zhongxin reveals the underlying mechanism of immunodeficiency in patients recovering from new coronavirus infection

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iNatureSARS-CoV-2 infection can cause severe immune interruption
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However, it is not clear whether the disrupted immune regulation still exists and whether it is related to recovered COVID-19 patients
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On September 22, 2021, Huazhong University of Science and Technology Liu Chaohong and Lu Zhongxin jointly published an online report entitled "SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells in Signal Transduction and Targeted Therapy (IF=18.
19)" Via enhancing B-cell metabolism" research paper, this study characterized the B cell immune phenotype of 15 recovered COVID-19 patients, and found that the healthy control group and recovered patients had similar B cell numbers before and after BCR stimulation, but The frequency of PBC in patients was significantly increased compared to healthy controls before stimulation
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However, after receiving BCR stimulation, the percentage of non-switched memory B cells in recovered patients decreased, but there was no change in healthy controls
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Interestingly, the study found that CD19 expression was significantly reduced in almost all B cell subpopulations of recovered patients
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In addition, BCR signals and early B cell responses are disrupted after BCR stimulation
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In terms of mechanism, the study found that the decrease in CD19 expression is caused by cell metabolism disorders
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In conclusion, the study found that SARS-CoV-2 infection down-regulates the expression of CD19 in B cells by enhancing B cell metabolism, leading to immunodeficiency in recovered patients, which may provide a new intervention target for curing COVID-19
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At the end of 2019, a new type of coronavirus (SARS-CoV-2) was identified as the pathogen of severe acute respiratory infection COVID-19
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Patients infected with SARS-CoV-2 present distinct clinical manifestations, ranging from asymptomatic forms to life-threatening pathologies, including acute respiratory distress syndrome (ARDS)
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There is evidence that the so-called "cytokine storm", that is, the uncontrolled activation of the inflammatory response, significantly promotes the occurrence of ARDS
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Similar to other diseases that trigger cytokine storms, suppressing the inflammatory immune response may improve the outcome of severe SARS-CoV-2 infection
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Inflammation is associated with increased glycolytic activity and is the main metabolic pathway involved in different activated immune cells
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Immune cells secrete lactic acid as the end product of glycolysis.
Increased blood lactic acid and slow lactic acid clearance are associated with increased mortality from sepsis
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Lactic acid is not only an end product of metabolism, it can also be absorbed by various cell types and affect signal transduction and metabolism
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Therefore, an overactive immune response will lead to changes in metabolic serum components, which may affect further immune responses
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In addition, liver dysfunction and other processes can lead to metabolic abnormalities during viral infection
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Emerging evidence shows that compared with healthy individuals, the metabolic composition of COVID-19 patients' serum has undergone significant changes, and certain changes are related to the severity of the disease
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Among other biochemical substances, the levels of TCA cycle components malic acid, urea cycle components carbamoyl, phosphate and guanosine monophosphate are thought to change as the disease progresses
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It is not yet clear how immune cells and B cells respond specifically to these metabolic changes
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However, there is increasing evidence that the metabolic environment plays an important role in directing the fate and function of B cells
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Changes in glucose concentration, the acquisition of short-chain fatty acids, oxygen supply and other metabolic changes profoundly affect the survival of B cells.
Therefore, it is conceivable that the specific metabolic environment of COVID-19 patients will change the biology of B cells
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The role of B cells in the progression of COVID-19 disease seems to be multifaceted and not yet fully understood
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Recently, it has been reported that patients with agammaglobulinemia lacking B cells have a better prognosis, while patients with common variable immunodeficiency (CVID) with dysfunction of B cells have a more severe disease
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Although the number of patients in this study is limited, observations indicate that B cells may worsen the disease during the acute phase of infection by aggravating inflammation
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On the other hand, specific B cell subpopulations may play a protective role in the initial stage of infection by producing protective natural antibodies
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Finally, the formation of memory B cells and long-lived plasma cells is a key factor in determining the level of protection in the case of repeated encounters of the virus
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The purpose of this study is to evaluate the signal characteristics of B cells from COVID-19 patients
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In addition, the study sought to analyze the metabolic composition of serum obtained from COVID-19 patients and determine how changes in the abundance of specific metabolites affect B cell receptor signaling
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The study found that the cytokine environment and metabolic environment of COVID-19 patients shape the signal transduction of the B cell population
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