Abstract
The pandemic of coronavirus disease 2019 (COVID-19), a disease which causes severe lung injury and multiple organ damage, presents an urgent need for new drugs. The case severity and fatality of COVID-19 are associated with excessive inflammation, namely, a cytokine storm. Metformin, a widely used drug to treat type 2 diabetes (T2D) mellitus and metabolic syndrome, has immunomodulatory activity that reduces the production of proinflammatory cytokines using macrophages and causes the formation of neutrophil extracellular traps (NETs). Metformin also inhibits the cytokine production of pathogenic Th1 and Th17 cells. Importantly, treatment with metformin alleviates various lung injuries in preclinical animal models. In addition, a recent proteomic study revealed that metformin has the potential to directly inhibit SARS-CoV-2 infection. Furthermore, retrospective clinical studies have revealed that metformin treatment reduces the mortality of T2D with COVID-19. Therefore, metformin has the potential to be repurposed to treat patients with COVID-19 at risk of developing severe illness. This review summarizes the immune pathogenesis of SARS-CoV-2 and addresses the effects of metformin on inhibiting cytokine storms and preventing SARS-CoV-2 infection, as well as its side effects.
Highlights
In recent decades, the world has experienced outbreaks of newly emerging viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), H5N1 virus, pandemic H1N1 virus, and H7N9 virus [1,2,3,4]
Single-cell analysis of bronchoalveolar lavage fluid shows that patients with mild COVID-19 have an expansion of clonal CD8 T cells, whereas patients with severe disease have a decline in T cells and NK cells and a concomitant increase in inflammatory FCN1+ macrophages [28]
Excessive inflammation is involved in the development of severe COVID-19
Summary
The world has experienced outbreaks of newly emerging viruses, including severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), H5N1 virus, pandemic H1N1 virus, and H7N9 virus [1,2,3,4]. A recent autopsy study of patients with COVID-19 shows that SARS-CoV-2 infection is detected in CD169+ macrophages that express the ACE2 molecule and produce IL-6. The infection of these CD169+ macrophages correlated with lymphocyte apoptosis in the spleen and lymph nodes. Single-cell analysis of bronchoalveolar lavage fluid shows that patients with mild COVID-19 have an expansion of clonal CD8 T cells, whereas patients with severe disease have a decline in T cells and NK cells and a concomitant increase in inflammatory FCN1+ macrophages [28] These observations suggest that weak adaptive immunity may result in an inadequate ability to control viral infection. The cascade of innate immune responses results in uncontrolled inflammation [20] (Figure 1)
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