The Role of Macrophages in the Pathogenesis of SARS-CoV-2-Associated Acute Respiratory Distress Syndrome.

Macrophages are cells that mediate both innate and adaptive immunity reactions, playing a major role in both physiological and pathological processes. Systemic SARS-CoV-2-associated complications include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, and pneumonia. These are predominantly effects of massive macrophage activation that collectively can be defined as macrophage activation syndrome. In this review we focus on the role of macrophages in COVID-19, as pathogenesis of the new coronavirus infection, especially in cases complicated by ARDS, largely depends on macrophage phenotypes and functionalities. We describe participation of monocytes, monocyte-derived and resident lung macrophages in SARS-CoV-2-associated ARDS and discuss possible utility of cell therapies for its treatment, notably the use of reprogrammed macrophages with stable pro- or anti-inflammatory phenotypes.

Host sphingolipids: Perspective immune adjuvant for controlling SARS-CoV-2 infection for managing COVID-19 disease.

Sphingolipids are potent bioactive agents involved in the pathogenesis of various respiratory bacterial infections. To date, several sphingolipid derivatives are known, but S1P (Sphingosine-1-phosphate) and Ceramide are the best-studied sphingolipid derivatives in the context of human diseases. These are membrane-bound lipids that influence host-pathogen interactions. Based on these features, we believe that sphingolipids might control SARS-CoV-2 infection in the host. SARS-CoV-2 utilizes the ACE-II receptor (Angiotensin-converting enzyme II receptor) on epithelial cells for its entry and replication. Activation of the ACE-II receptor is indirectly associated with the activation of S1P Receptor 1 signaling which is associated with IL-6 driven fibrosis. This is expected to promote pathological responses during SARS-CoV-2 infection in COVID-19 cases. Given this, mitigating S1P signaling by application of either S1P Lyase (SPL) or S1P analog (Fingolimod / FTY720) seems to be potential approach for controlling these pathological outcomes. However, due to the immunosuppressive nature of FTY720, it can modulate hyper-inflammatory responses and only provide symptomatic relief, which may not be sufficient for controlling the novel COVID-19 infection. Since Th1 effector immune responses are essential for the clearance of infection, we believe that other sphingolipid derivatives like Cermaide-1 Phosphate with antiviral potential and adjuvant immune potential can potentially control SARS-CoV-2 infection in the host by its ability in enhancing autophagy and antigen presentation by DC to promote T cell response which can be helpful in controlling SARS-CoV-2 infection in novel COVID-19 patients.