ABSTRACT
Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.
Subject(s)
COVID-19 , Animals , Antibodies, Monoclonal , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , Cricetinae , Humans , Mesocricetus , Neutralization Tests , SARS-CoV-2ABSTRACT
The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.
Subject(s)
COVID-19 , Olfactory Receptor Neurons , Animals , COVID-19/complications , Cricetinae , Olfactory Mucosa/metabolism , Olfactory Receptor Neurons/metabolism , SARS-CoV-2 , Post-Acute COVID-19 SyndromeABSTRACT
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting billions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, we developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. We find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. We also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.
Subject(s)
Anosmia/virology , COVID-19/pathology , Olfactory Mucosa/pathology , Animals , Anosmia/pathology , Behavior, Animal , COVID-19/complications , Chlorocebus aethiops , Cricetinae , Disease Models, Animal , Female , Mesocricetus , Recovery of Function , Vero CellsABSTRACT
Olfactory dysfunction is one of the most frequent and specific symptoms of coronavirus disease 2019 (COVID-19). Information on the damage and repair of the neuroepithelium and its impact on olfactory function after COVID-19 is still incomplete. While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the ongoing worldwide outbreak of COVID-19, little is known about the changes triggered by SARS-CoV-2 in the olfactory epithelium (OE) at the cellular level. Here, we report profiles of the OE after SARS-CoV-2 infection in golden Syrian hamsters, which is a reliable animal model of COVID-19. We observed severe damage in the OE as early as 3 days postinoculation and regionally specific damage and regeneration of the OE within the nasal cavity; the nasal septal region demonstrated the fastest recovery compared to other regions in the nasal turbinates. These findings suggest that anosmia related to SARS-CoV-2 infection may be fully reversible.