ABSTRACT
The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production and potential for delivery via inhalation. Here, we characterize the RBD-specific nanobody W25, which we previously isolated from an alpaca, and show superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike surface glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. Furthermore, we show that W25 also binds the spike protein from the emerging, more infectious Omicron BA.2 lineage with picomolar affinity. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse prioritization of W25 for further clinical development.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
Purpose Awake Tracheal Intubation (ATI) can be performed in cases where there is potential for difficult airway management. It is considered an aerosol generating procedure and is a source of concern to healthcare workers due to the risk of transmission of airborne viral infections, such as SARS–CoV-2. At present, there is a lack of data on the quantities, size distributions and spread of aerosol particles generated during such procedures.Methods This was a volunteer observational study which took place in an operating room of a university teaching hospital. Optical particle sizers were used to provide real time aerosol characterisation during a simulated ATI performed with concurrent high-flow nasal oxygen therapy. The particle sizers were positioned at locations that represented the different locations of clinical staff in an operating room during an ATI.Results The greatest concentration of patient derived aerosol particles was within 0.5–1.0 m of the subject and along their midline, 2242 #/cm3. As the distance, both radial and longitudinal, from the subject increased, the concentration decreased towards ambient levels, 36.92 ± 5.12 #/cm3. Patient derived aerosol particles < 5µm in diameter remained entrained in the exhaled aerosol plume and fell to the floor or onto the subject. Patient derived particles > 5µm in diameter broke away from the exhaled plume and spread radially throughout the operating room.Conclusions Irrespective of distance and ventilation status, full airborne protective equipment should be worn by all staff when ATI is being performed on patients with suspected viral respiratory infections.