Table 1.
Potential similarities in innate and adaptive immune mechanisms against malaria and COVID-19.
| Malaria | References | COVID-19 | References | |
|---|---|---|---|---|
| Innate immunity | Pattern recognition receptors (e.g., TLRs) expressed by immune cells and STAT1/STAT2-IRF9 pathway contribute to recognition and engulfment of infected erythrocytes | (46, 47) | Pattern recognition receptors (e.g., TLRs) present on immune cells and the JAK-STAT pathway are the first to identify the virus | (50, 86) |
| Innate immune response begins with involving neutrophils, macrophages, dendritic cells and natural killer cells resulting in a sharp blowout of pro-inflammatory cytokines including (IFN) that induce inflammation to inhibit parasite growth | (41, 53) | Viral innate immune cells are efficient in producing IFNs involved in blocking cell proliferation, apoptosis, and immunomodulation. | (63, 87) | |
| These pro-inflammatory cytokines are regulated by anti-inflammatory cytokines because they can lead to severe malaria and death when unregulated | (41, 53) | Secretion of cytokines and chemokines, which attract the immune cells to the lungs, was increased, hence causing ARDS, which is fatal to severely ill individuals | (65) | |
| Interferon-alpha and beta regulate the pro-inflammatory function of interferon-gamma, thereby preventing chaotic inflammatory response that can lead to severe disease | (60) | Secretion of cytokines and chemokines, which attract the immune cells to the lungs, was increased, hence causing ARDS, which is fatal to severely ill individuals | (88) | |
| NK cells are involved in the direct destruction of parasitized RBCs and the production of pro-inflammatory cytokines early in malaria infection | (43, 53) | NK cells display an anti-SARS-CoV-2 activity and showed to limit tissue fibrosis during early infection | (89) | |
| The dual role of IFN signalling in human malaria where increased amounts of IFN-1 improve anti-parasite responses by increasing IFNAR1 signalling in the early stages of infection while exacerbated IFN-1/IFNAR1 signalling later in infection increases vulnerability to severe disease | (61) | Signalling by interferon (IFN) affects COVID-19 pathology in both protective and harmful ways. A multi-omics biosignature associated with varying levels of 12 different type I, II, and III IFNs has been defined in a systemic IFN signalling in hospitalized COVID-19 patients | (64) | |
| Adaptive immunity | Activation of CD4 cells, resulting in cell-mediated and antibody-mediated immunity, respectively | (41) | Humoral response against SARS-CoV-2 involves a strong CD4+ T-cell response and the crucial production of IgG, IgA and IgM. | (74) |
| Antibodies produced prevent merozoites invasion of RBCs and the cytoadherence of parasitized RBCs on the endothelium which could result in opsonization and subsequent phagocytosis, complement-mediated cell destruction or antibody-dependent cell-mediated destruction of parasitized RBCs | (41) | Antibody-Dependent Enhancement (ADE) occurs through non-neutralizing antibody enhanced the mechanism of viral entry that results in atypical activation of immune cells | (90) | |
| Immunoglobin G is the major antibody that prompts this cascade of immune reactions. In some malaria-endemic areas, high levels of circulating immunoglobin G have been associated with lower malaria risks | (76, 77) | IgG antibodies had higher viral clearance. A vigorous antibody response leads to disease severity while a weak response is associated with the elimination of the virus | (78) | |
| CD8+ TC lymphocytes are activated through antigen cross-presentation by DCs. IFN-γ-producing CD8+ T cells operate on inflammation and cytotoxicity (perforin and granzyme B mediated) functions | (91) | CD8+ TC lymphocytes, including memory cells, recognize SARS-CoV-2 epitopes and cross-reactive epitopes from related coronaviruses. Cytotoxicity to virus-infected cells mediated through granzyme and perforin | (92) |