Mucosal delivery of IFN is an excellent strategy for post-exposure COVID-19 prevention.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a beta coronavirus that causes the epidemic of coronavirus disease-19 (COVID-19) and is an infectious disease of over 111 million worldwide. To date, about 2.46 million people have died. SARS-CoV-2 uses the entry receptor angiotensin converting enzyme 2 (ACE2) to infect host cells with clinical outcomes ranging from asymptomatic infection to severe symptoms and death. Viruses, as shown by the therapeutic benefits provided by immunomodulators, including corticosteroids, while multiple host factors such as age and gender contribute to serious illness and adverse clinical outcomes A large immune response to the virus plays an important role.

However, the immunopathogenicity of COVID-19 is not yet completely clear. Identifying host cells that promote viral invasion and characterizing their response to infection are important for understanding the etiology of COVID-19 and improving treatment. Studies have shown that the nasal epithelium is an important gateway to the SARS-CoV-2 virus. Viral shedding Contributes to higher viral transmissibility and pathological features, including olfactory dysfunction from the nasopharynx. Nasal epithelial cells are early viral target cells that can elicit a systemic immune response and affect clinical outcomes.

All these factors underscore the need for further analysis of host virus interactions in nasal cells. The ACE2 receptor is regulated by interferon (IFN), which represents a complex relationship between tropism and IFN signaling. Type I and type III IFNs play an important role in human antiviral innate immunity and are involved in SARS-CoV-2 defense. Sensitivity to severe or deadly COVID-19 has been shown to be associated with deleterious variants of the IFNAR gene and IFN-I blocking autoantibodies.

Comprehensive characterization of SARS-CoV-2 response in human nasal epithelial cells

British and German researchers recently reported a comprehensive characterization of the SARS-CoV-2 response in human nasal epithelial cells, revealing a predominant response for IFN-I / III. Recombinant IFN-I / III treatment was also found to effectively block SARS-CoV-2 replication. This suggests that mucosal delivery of IFN may be an excellent strategy for post-exposure prophylaxis.The survey will be published on the preprint server bioRxiv*.

The ISG response governs the proteome of SARS-CoV-2 infected nasal ALI cultures. Functional annotation network for proteins with different expression.

Researchers have applied proteomics and single-cell RNA sequencing to a primary cell model of human nasal epithelium differentiated at the gas-liquid interface. The results showed that type I and type III IFNs and interferon-stimulated gene products govern the host response.

“Our findings that exogenous IFN-I or IFN-III can potently induce antiviral status in nasal cells are consistent with its apparent protective effect in patients and early-stage clinical trials.”

This immune response was significantly delayed in onset compared to viral gene expression and was unable to substantially affect SARS-CoV-2 replication. However, when IFNb or IFN1 was provided prior to infection, they elicited a good antiviral response that effectively restricted SARS-CoV-2 replication and maintained the integrity of the epithelial barrier. These findings suggest that nasal delivery of recombinant IFN may be a potential chemical prophylaxis strategy for SARS-CoV-2 infection.

“It is also worth noting that while all cell types contain the SARS-CoV-2 protein, immunoassay intensity is greater in ciliated cells and also contains more virion-like structures per cell. I will. “

Challenges in vaccine coverage and efficacy may require the need for targeted chemoprevention strategies

This is an important observation that highlights the therapeutic value of chemical prophylaxis.Already tested in a small clinical trial in China, but difficult to evaluate because there was no control in this trial Effectiveness of This approach.

Vaccination is the best approach for mass prophylaxis of COVID-19, but inadequate vaccine distribution, coverage, efficacy against mild or asymptomatic diseases, and the emergence of more infectious variants It is a serious challenge and requires targeted chemical prevention strategies to prevent viral infections.

These strategies include post-exposure prophylaxis of contact with COVID-19 patients and help avoid the need for self-isolation and pre-exposure prophylaxis for high-risk encounters, such as in healthcare facilities.

“Our data suggest that the application of IFNb to the nasal mucosa may have an important role to play in this situation, arguing for an urgent clinical assessment of this approach. “

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.