Do Changes in ACE-2 Expression Affect SARS-CoV-2 Virulence and Related Complications: A Closer Look into Membrane-Bound and Soluble Forms.

The SARS-CoV-2 virus utilizes angiotensin converting enzyme (ACE-2) for cell entry and infection. This enzyme has important functions in the renin-angiotensin aldosterone system to preserve cardiovascular function. In addition to the heart, it is expressed in many tissues including the lung, intestines, brain, and kidney, however, its functions in these organs are mostly unknown. ACE-2 has membrane-bound and soluble forms. Its expression levels are altered in disease states and by a variety of medications. Currently, it is not clear how altered ACE-2 levels influence ACE-2 virulence and relevant complications. In addition, membrane-bound and soluble forms are thought to have different effects. Most work on this topic in the literature is on the SARS-CoV virus that has a high genetic resemblance to SARS-Co-V-2 and also uses ACE-2 enzyme to enter the cell, but with much lower affinity. More recent studies on SARS-CoV-2 are mainly clinical studies aiming at relating the effect of medications that are thought to influence ACE-2 levels, with COVID-19 outcomes for patients under these medications. This review paper aims to summarize what is known about the relationship between ACE-2 levels and SARS-CoV/SARS-CoV-2 virulence under altered ACE-2 expression states.

Dexamethasone and transdehydroandrosterone significantly reduce pulmonary epithelial cell injuries associated with mechanical ventilation.

Many patients who suffer from pulmonary diseases cannot inflate their lungs normally, as they need mechanical ventilation (MV) to assist them. The stress associated with MV can damage the delicate epithelium in small airways and alveoli, which can cause complications resulting in ventilation-induced lung injuries (VILIs) in many cases, especially in patients with acute respiratory distress syndrome (ARDS). Therefore, efforts were directed to develop safe modes for MV. In our work, we propose a different approach to decrease injuries of epithelial cells (EpCs) upon MV. We alter EpCs' cytoskeletal structure to increase their survival rate during airway reopening conditions associated with MV. We tested two anti-inflammatory drugs dexamethasone (DEX) and transdehydroandrosterone (DHEA) to alter the cytoskeleton. Cultured rat L2 alveolar EpCs were exposed to airway reopening conditions using a parallel-plate perfusion chamber. Cells were exposed to a single bubble propagation to simulate stresses associated with mechanical ventilation in both control and study groups. Cellular injury and cytoskeleton reorganization were assessed via fluorescence microscopy, whereas cell topography was studied via atomic force microscopy (AFM). Our results indicate that culturing cells in media, DEX solution, or DHEA solution did not lead to cell death (static cultures). Bubble flows caused significant cell injury. Preexposure to DEX or DHEA decreased cell death significantly. The AFM verified alteration of cell mechanics due to actin fiber depolymerization. These results suggest potential beneficial effects of DEX and DHEA for ARDS treatment for patients with COVID-19. They are also critical for VILIs and applicable to future clinical studies.NEW & NOTEWORTHY Preexposure of cultured cells to either dexamethasone or transdehydroandrosterone significantly decreases cellular injuries associated with mechanical ventilation due to their ability to alter the cell mechanics. This is an alternative protective method against VILIs instead of common methods that rely on modification of mechanical ventilator modes.

Microfluidic-based virus detection methods for respiratory diseases.

With the recent SARS-CoV-2 outbreak, the importance of rapid and direct detection of respiratory disease viruses has been well recognized. The detection of these viruses with novel technologies is vital in timely prevention and treatment strategies for epidemics and pandemics. Respiratory viruses can be detected from saliva, swab samples, nasal fluid, and blood, and collected samples can be analyzed by various techniques. Conventional methods for virus detection are based on techniques relying on cell culture, antigen-antibody interactions, and nucleic acids. However, these methods require trained personnel as well as expensive equipment. Microfluidic technologies, on the other hand, are one of the most accurate and specific methods to directly detect respiratory tract viruses. During viral infections, the production of detectable amounts of relevant antibodies takes a few days to weeks, hampering the aim of prevention. Alternatively, nucleic acid-based methods can directly detect the virus-specific RNA or DNA region, even before the immune response. There are numerous methods to detect respiratory viruses, but direct detection techniques have higher specificity and sensitivity than other techniques. This review aims to summarize the methods and technologies developed for microfluidic-based direct detection of viruses that cause respiratory infection using different detection techniques. Microfluidics enables the use of minimal sample volumes and thereby leading to a time, cost, and labor effective operation. Microfluidic-based detection technologies provide affordable, portable, rapid, and sensitive analysis of intact virus or virus genetic material, which is very important in pandemic and epidemic events to control outbreaks with an effective diagnosis.