Oral Administration of Water‐Soluble Curcumin Complex Prevents <scp>ARDS</scp> With the Potential for <scp>COVID</scp>‐19 Treatment

Acute respiratory distress syndrome (ARDS)-a form of severe lung injury-is often caused by conditions such as pneumonia, sepsis, and COVID-19. COVID-19, which enters cells through the angiotensin-converting enzyme 2 (ACE2) receptor, has complications varying from mild infection to ARDS and death. Curcumin, a naturally occurring and safe anti-inflammatory compound, has previously been formulated as a water-soluble curcumin (CDC) to improve solubility and stability under physiologic conditions. CDC administration has been shown to improve cell survival and reduce inflammation, injury, and mortality in models of severe Klebsiella pneumoniae (KP) infection. This study aims to further evaluate the potential of CDC in treating COVID-19, particularly complicated by ARDS. Lung samples from post-mortem KP and COVID-19 patients were evaluated for relevant markers with immunohistochemistry. Separately, mice inoculated with KP with or without CDC were evaluated for injury, inflammation, and expression of ACE2, STAT-3, CXCL-10, and IFN-α. Mice treated with LPS with or without CDC were also evaluated similarly. Lung samples from KP patients had significantly higher ACE2 expression than normal lungs. Postmortem lung samples from COVID-19 patients exhibited intense ACE2 staining compared to normal human lungs. Administration of CDC substantially reduced ACE2 expression at serum, gene, and protein levels after KP and LPS infection. Furthermore, CDC administration reduced the levels of STAT-3, as well as the chemokine CXCL10, and interferon IFN-α in KP-infected mice. In vitro, data showed CDC administration reduced ACE2 and STAT3 expression in human lung epithelial cells following KP. Furthermore, administering CDC after LPS led to a significant decrease in injury, inflammation, and ACE2 levels. Based on the promising effects of CDC on these relevant markers, a proposal to use curcumin as a supportive therapy to treat ARDS and COVID-19 to save lives is being considered.