Studies show that inhaled microspheres reduce the infectious effect of SARS-CoV-2

The rapid outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a pandemic of Coronavirus Disease 2019 (COVID-19). COVID-19 continues to spread around the world. An estimated 15% of patients with immunodeficiency, primarily due to rapid viral vascular leakage and subsequent disseminated viremia, were found to develop severe cases.Control Viral load It is essential to reduce the mortality rate of COVID-19 and improve the treatment of serious illnesses.

study: Inhaled ACE2 Manipulated Microfluidic Microfluidics for Intratracheal Neutralization of COVID-19 and Cytokine Storm Sedation.. Image Credit: Kateryna Kon / Shutterstock

Background

With vaccine Neutralizing antibody The current strategy for combating SARS-CoV2 infection. These treatments prevent the spike (S) protein from binding to the host angiotensin converting enzyme II (ACE-2) receptor. While these approaches work, they have some inherent problems. Vaccines are not an urgent solution as they take time to develop.

The upper respiratory tract contains a wide range of ACE-2 expressing cells and is often ignored as a route of infection. Viruses in the upper respiratory tract, especially delta mutants, are released into saliva and enter the environment, causing rapid human contamination. Current strategies target specific viral species rather than the affected host cells. Therefore, neutralizing antibodies or vaccine-resistant viruses emerge due to SARS-CoV-2 mutations. Ignoring upper respiratory tract infections highlights the fact that current vaccines and neutralizing antibodies are inadequate.

Existing approaches do not effectively block SARS-CoV-2 infection and replication in the upper respiratory tract, especially in the nasopharynx. This passage acts as the first site of SARS-CoV-2 invasion, showing higher viral load and then passing the infection to the lungs. Existing treatment options are also focused solely on eliminating SARS-CoV-2 itself, ignoring other important factors such as anti-inflammatory interventions, especially in patients with immune disorders.

New research published in Matter It develops inhaled microfluidic microfluidics with cells genetically engineered from cells that overexpress ACE2 receptors and macrophages.

New research

Scientists have developed a microfluidic microsphere-based inhalation aerosol (iAE-PMS) to prevent SARS-CoV-2 infection, inspired by the process of viral infection from a host perspective. It is manufactured using an FDA-approved dual camouflage methacrylate hyaluronate hydrogel microsphere with a bioactive membrane from the ACE2 receptor. The great advantage of iAE-PMS is related to its ability to be distributed simultaneously throughout the respiratory system, including the nasopharynx, trachea, bronchi and alveoli.

HEK293-ACE2 cells with high levels of ACE2 expression were successfully constructed using the imported ACE2 gene vector. Subsequently, the human ACE2 gene was inserted into the PCNDA3.1-3XFlag-C vector. This generated the ACE2-PCNDA3.1-3XFlag-C vector and introduced it into HEK293-ACE2 cells. Scientists have confirmed high levels of ACE2 expression in HEK293-ACE2 cells by immunofluorescence imaging and quantitative analysis.

Major NSInding

Scientists have observed that the protective activity of iAE-PMS against viral infections increased from 9.28% to 91.33%. This was 10 times more effective than the blank control. Fulminant inflammation and direct SARS-CoV-2 infection are also important in the treatment of COVID-19 and cannot be ignored to save the lives of critically ill patients. The researchers conducted an in vitro study that observed promising results regarding the effect of iAE-PMS on the broad-spectrum neutralization of inflammatory cytokines, including TNF-α, IL-1b, and IL-6.

In addition, inhaled aerosols can significantly reduce lung damage by providing a regulated landscape of immune cells that have infiltrated the lungs. The lung-damaging microenvironment is composed of M1 macrophages, neutrophils, and cytotoxic T cells. Aerosols were administered in vivo (intratracheal) to mice with acute pneumonia. Scientists have observed that aerosols significantly relieve hyperinflammatory conditions by draining the lymph nodes and spleen. This improved the survival rate from 7.35% to 56.74%. Therefore, iAE-PMS may be a powerful strategy for treating patients with severe COVID-19 by non-invasive selective lung topical administration.

Graphical abstraction: Inhaled ACE2 Manipulated Microfluidic Microfluidics for Intratracheal Neutralization of COVID-19 and Cytokine Storm Sedation

Conclusion

The SARS-CoV-2 pandemic continues to spread around the world, and its trajectory is still quite uncertain.Gain protection against viruses throughout the airways and calm afterwards Cytokine storm The main challenges that scientists are working on remain.

In this study, scientists have developed an inhaled microfluidic microsphere. This demonstrated the ability to significantly reduce the effects of SARS-CoV-2 infection in vitro and in vivo throughout the respiratory system. In the acute pneumonia model, microspheres showed a significant therapeutic effect and reduced acute mortality. These are promising results in advocating new and powerful synergistic strategies for treating severely ill COVID-19 patients.