Table 1.
Comparison between pathophysiological aspects of bacterial sepsis in humans, severe COVID-19, and B-1a cell studies in CLP/sepsis and other inflammatory diseases
| Pathophysiological aspects | Bacterial sepsis | Severe COVID-19 | B-1a cells |
|---|---|---|---|
| Stimuli | Bacteria | SARS-CoV2 | Bacteria, virus |
| Hyperimmune response | Early stage (hyperdynamic phase) (22) | At the onset (6) | Release TNF-α, IL-3, induce Th17 cells (10) |
| Immunosuppression | Late stage (hypodynamic phase) (22) | Early or late stage (17, 24) | Release IL-10, TGFβ which can induce immunosuppression; regulates T cell and macrophage functions (10) |
| Lymphocytosis/lymphocytopenia | Occurs at different stages of sepsis (22, 25) | At the onset and after recovery (20) | Decreased in CLP/sepsis (13) |
| Neutrophilia/infiltration in lungs | Yes (22) | Yes (5, 7) | Controls neutrophil infiltration in lungs (19) |
| Cytokine storm/hyperinflammation | Yes (22) | Yes (18) | Regulates pro-inflammatory cytokines through IL-10, GM-CSF, natural IgM (10) |
| NET formation | Yes (in blood and lungs) (26) | Yes (in lungs) (5) | Inhibits production of MPO (a component of NETs) (19) |
| Apoptosis | Yes (T cells, B cells, endothelial cells) (27) | Yes (T cells, B cells) (20, 21) | Increase phagocytosis of apoptotic cells (10) |
| Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) | Yes (28) | Yes (29) | Attenuates CLP/sepsis-induced ALI (19) |
| IgM/convalescent plasma therapy | IgM therapy improves the outcomes in mice, but in human, IgM therapy is refractory (30) | Convalescent plasma therapy improves the outcomes (8), while a randomized clinical trial shows that convalescent plasma does not improve the outcomes (31) | Transfer of IgM in secretory IgM deficient mice or B-1a cell deficient mice improves CLP/sepsis (23) |
| Therapeutic approaches and experimental interventions | Supportive, antibiotics, anti-inflammatory cytokines, IL-7, IL-15, anti-PD-1, steroids, anticytokine or immunolodulatory drugs, adjunctive and immunoglobulin therapies (32, 33) | Supportive, antiviral drugs like Ribavirin, Remdesivir, and Favipiravir. Chloroquine, Hydroxichloroquine, corticosteroids, anticytokine, or immunolodulatory drugs (8) | Adoptive transfer of B-1a cells at the time of CLP/sepsis induction was beneficial* (13) |
*
B-1a cells and IRA B cells have only recently been identified in humans, and have not yet been studies in neither sepsis nor COVID-19.