Macrophage activation syndrome in COVID-19

Abstract

The novel coronavirus epidemic is characterized by high rates of morbidity and relatively high mortality. Laboratory test results in patients include leukopenia, an increase in liver function tests and ferritin levels reaching hundreds, and sometimes thousands of units. These data remind us about the macrophage activation syndrome (MAC). Secondary hemophagocytic lymphohistiocytosis syndrome, MAC, which pathogenesis is based on a defect in the mechanisms of T-cell cytotoxicity and decreased level of natural killer cells associated with the defect in the perforin-encoding gene as well as hyperproduction of a number of cytokines – interleukin (IL)-1â, tumor necrosis factor-á, etc. by T-lymphocytes and histiocytes, indirectly leading to the activation of macrophages and production of proinflammatory cytokines, in particular IL-6 hyperproduction. MAC is one of "hyperferritinemic syndromes". These disorders have similar clinical and laboratory manifestations, and they also respond to similar treatments, suggesting that hyperferritinemia may be involved in the overall pathogenesis and is characterized by elevated ferritin level and cytokine storm. Despite the fact that data on the immune and inflammatory status in patients with COVID-19 have only started to appear, it is already clear that hyperinflammation and coagulopathy affect the disease severity and increase the risk of death in patients infected with SARS-CoV-2. Hence, understanding the pathogenesis of the novel coronavirus infection can help in its early diagnostics and treatment.

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

“…Complex networks of cells, cytokines, and signaling pathways are involved in hyperinflammation and cytokine storm [5]. Macrophages are major cytokine producers [137][138][139][140]. Our data demonstrate that MSCs and A1AT can individually suppress cytokine release from inflamed macrophages and monocytes (Figure 1-2 and Figure S1-7), confirming previously reported results [19,[33][34][35][36].…”

“…Our data show that MSCs and A1AT reduce the production of cytokines, ROS, and NETs from neutrophils (Figure 3 and Figure S8), with combination therapy, again exceeding the performance of each individual component. IFNγ release from T cells is crucial to activating macrophages [137][138][139][140]. We show that the combination of MSCs and A1AT can significantly suppress TNFα and IFNγ production by T cells (Figure S6).…”

Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

“…A complex network of cells, cytokines, and signaling pathways are involved in hyperinflammation and cytokine storm 1 . Macrophages are major cytokine producers [142][143][144][145] . Our data demonstrate that MSCs and A1AT can individually suppress cytokine release from inflamed macrophages and monocytes (Fig.…”

“…S8), with combination therapy, again exceeding the performance of each individual component. IFNγ release from T cells is crucial to activating macrophages [142][143][144][145] . We show that the combination of MSCs and A1AT can significantly suppress TNFα and IFNγ production by T cells (fig.…”

“…Cytokines IFNγ, IL1, IL6, TNFα, and IL18 play a central role in hyperinflammation 1 . IFNγ is mainly produced by T cells and NK cells and is critical for activating macrophages [142][143][144][145] . A recent study finds that IFNγ and TNFα synergistically induce cytokine shock, MODS, and mortality in mice 164 .…”