Severe Acute Lung Injury Related to COVID-19 Infection: A Review and the Possible Role for Escin

Abstract

Acute lung injury (ALI) represents the most severe form of the viral infection sustained by coronavirus disease 2019 (COVID-19). Today, it is a pandemic infection, and even if several compounds are used as curative or supportive treatment, there is not a definitive treatment. In particular, antiviral treatment used for the treatment of several viral infections (eg, hepatitis C, HIV, Ebola, severe acute respiratory syndrome-coronavirus) are today used with a mild or moderate effect on the lung injury. In fact, ALI seems to be related to the inflammatory burst and release of proinflammatory mediators that induce intra-alveolar fibrin accumulation that reduces the gas exchange. Therefore, an add-on therapy with drugs able to reduce inflammation, edema, and cell activation has been proposed as well as a treatment with interferon, corticosteroids or monoclonal antibodies (eg, tocilizumab). In this article reviewing literature data related to the use of escin, an agent having potent anti-inflammatory and anti-viral effects in lung injury, we suggest that it could represent a therapeutic opportunity as add-on therapy in ALI related to COVID-19 infection.

Keywords: COVID-19; acute lung injury; coronavirus-2; escin; pneumonia.

Figure 1

The immune and inflammatory responses in coronavirus infections. In the immune response, macrophages present SARS‐CoV‐2 antigens to T cells that activate, differentiate, and release chemokines and cytokines such as interleukin (IL)‐1, IL‐6, IL‐8, IL‐21, tumor necrosis factor‐β (TNF‐β), and monocyte chemotactic protein‐1 (MCP‐1), causing the cytokine storm that recruits lymphocytes and leukocytes to the site of infection. Whether it is in an infected cell or in an immune cell, nuclear factor kappa B (NF‐κB) activation itself may play an important role in immune response and acute inflammatory lung injury. ACE2, angiotensin‐converting enzyme 2; PAMPs, pathogen‐associated molecular patterns; PRRs, pattern recognition receptors; TLR4, Toll‐like receptor 4.

Figure 2

Chemical structure of escin. Escin is a natural mixture of triterpene saponins extracted from seeds of Aesculus hippocastanum. It mainly consists of A, B, C, and D escin, of which A and B are the main components that belong to β‐escin.