SARS-CoV-2 infection causes immunodeficiency in recovered patients by downregulating CD19 expression in B cells via enhancing B-cell metabolism.
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 Distress Syndrome (ARDS).
Evidence suggests that the so-called “cytokine storm”, uncontrolled activation of the inflammatory response, significantly contributes to the occurrence of ARDS.
Similar to other diseases in which a cytokine storm is triggered, dampening of the inflammatory immune response may improve the outcome of a severe SARS-CoV-2 infection.1,2
Inflammation is associated with increased glycolytic activity3 and is the primary metabolic pathway engaged by different activated immune cells.4,5
Lactate as the end product of glycolysis is secreted by immune cells and elevated blood lactate and slow lactate clearance are associated with increased mortality in sepsis patients.6
Lactate is not only a metabolic end product, but can also be taken up by various cell types and affect both signaling and metabolism.3
Therefore, the hyperactive immune response leads to an altered metabolic serum composition potentially affecting further immune responses. Moreover, hepatic dysfunction and other processes can contribute to metabolic abnormalities during viral infection.
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
How immune cells and B cells in particular respond to these metabolic changes is currently unknown. However, accumulating evidence suggests that the metabolic environment plays a major role in directing B-cell fate and function.9
Changes in glucose concentration, access to short-chain fatty acids, oxygen availability, and other metabolic alterations profoundly affect B-cell survival, activation, and differentiation.9
Thus, it is conceivable that the specific metabolic environment in COVID-19 patients alters B-cell biology.
The role of B cells in COVID-19 disease progression appears to be multifaceted and is not fully understood yet. It has been recently reported that agammaglobulinemia patients who lack B cells have a more favorable disease outcome, whereas patients with common variable immune deficiency (CVID) whose B cells are dysfunctional present with a more severe form of the disease.10
Although the number of patients in this study was limited, the observation suggests that B cells may worsen the disease in the acute phase of the infection possibly by aggravating inflammation. On the other hand, specific B-cell subsets may play a protective role during the initial phases of infection by producing protective natural antibodies.
Lastly, the formation of memory B cells and long-lived plasma cells is a crucial factor determining the level of protection in the case of a repeated virus encounter.
The study findings were published in the peer reviewed journal: Signal Transduction And Targeted Therapy (Nature)
Numerous past studies have shown that the SARS-CoV-2 infection causes has caused immune disruption in a variety of ways. and reported that COVID-19 patients had decreased lymphocyte counts and increased counts of myeloid cells in peripheral blood.
Many recent reports show lymphopenia with drastically reduced numbers of both CD4+ and CD8+ T cells in moderate and severe COVID-19 cases.
Flow cytometry analysis of PBMCs from symptomatic COVID-19 patients has shown a significant influx of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing, activated CD4+ T cells and CD14+ HLA-DRlo inflammatory monocytes (IMs).
Others studies have also shown reduced numbers of NK cells in the PBMC of COVID-19 patients, which is associated with the severity of the disease.