Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice.

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.

Development of an organ procurement team in South Australia in response to COVID-19.

BACKGROUND: Due to the nature of border closures and quarantine requirements in Australia during the COVID-19 pandemic, the feasibility of interstate travel for organ retrieval created complex logistics. An organ procurement service in South Australia, to procure heart and lungs of local donors, was commenced to mitigate the impact of the travel restrictions imposed due to COVID-19. The purpose of this review was to examine the initial data and feasibility of the service. METHODS: A single unit, multi-site retrospective review from April 2020-August 2021 of all organ retrievals undertaken by the Flinders Medical Centre cardiothoracic service across Adelaide metropolitan area. Data was prospectively collected and analysed from the DonateLife South Australian centralized database. All data was de identified. RESULTS: A total of 25 organ procurements had been undertaken across 17 months since commencing the program. Total of 9 hearts and 16 bilateral lungs were procured with median age of donor of hearts 49 years (IQR 35.5-51. 5) and 60 years (IQR 44-72) for lung donation. Six organs were donated after determination of circulatory death and 19 after neurological determination of death. Median ischaemic time for heart donation was 4.4 h (IQR 3.0-5.8) and lung donation 4.4 h (IQR 3.4-6.1). All organs procured by the local South Australian team were successfully transplanted at the recipient site. Recipient sites included 8 in Victoria, 10 in New South Wales, 4 in Western Australia and 3 in Queensland. CONCLUSIONS: The necessity of flexibility within the field of cardiothoracic surgery is evident during the COVID-19 pandemic. The implementation of an organ retrieval service in South Australia has been successful with no apparent increased risk to successful transplant outcomes.

Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy.

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2-associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.