A Comparison of Clinical Characteristics of Infections with SARS-CoV-2 Omicron Subvariants BF.7.14 and BA.5.2.48 - China, October-December 2022.

What is already known about this topic?: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, the clinical manifestations resulting from different SARS-CoV-2 variants may demonstrate significant variation. What is added by this report?: We conducted a comparative analysis of the clinical features associated with SARS-CoV-2 Omicron subvariants BF.7.14 and BA.5.2.48 infections. The results of our study indicate that there are no substantial differences in clinical manifestations, duration of illness, healthcare-seeking behaviors, or treatment between these two subvariants. What are the implications for public health practice?: Timely identification of alterations in the clinical spectrum is crucial for researchers and healthcare practitioners in order to enhance their comprehension of clinical manifestations, as well as the progression of SARS-CoV-2. Furthermore, this information is beneficial for policymakers in the process of revising and implementing appropriate countermeasures.

Risk evaluation and mitigation strategies for newly detected SARS-CoV-2 Omicron BF.7 subvariant: A brief report.

Mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are always going on. The pathogenic characteristics of a virus are influenced by mutations in the viral genome. Therefore, the recently identified Omicron BF.7 subvariant might harm humans. Here we aimed to evaluate the potential risks of this newly detected variant and identify possible mitigation strategies. The frequent mutation associated with SARS-CoV-2 makes it more concerning compared to other viruses. The Omicron variant of SARS-CoV-2 has unique changes in the structural amino acid. Thus, Omicron subvariants are different from other coronavirus variants in terms of viral spread, disease severity, vaccine neutralization capacity, and immunity evade. Moreover, Omicron subvariant BF.7 is an offspring of BA.4 and BA.5. Similar S glycoprotein sequences are present among BF.7, BA.4, and BA.5. There is a change in the R346T gene in the receptor binding site of Omicron BF.7 than other Omicron subvariants. This BF.7 subvariant has created a limitation in current monoclonal antibody therapy. Omicron has mutated since it emerged, and the subvariants are improving in terms of transmission as well as antibody evasion. Therefore, the healthcare authorities should pay attention to the BF.7 subvariant of Omicron. The recent upsurge may create havoc all of a sudden. Scientists and researchers across the world should monitor the nature and mutations of SARS-CoV-2 variants. Also, they should find ways to fight the current circulatory variants and any future mutations.

Intranasal Boosting with Spike Fc-RBD of Wild-Type SARS-CoV-2 Induces Neutralizing Antibodies against Omicron Subvariants and Reduces Viral Load in the Nasal Turbinate of Mice.

The emergence of new immune-evasive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and subvariants outpaces the development of vaccines specific against the dominant circulating strains. In terms of the only accepted immune correlate of protection, the inactivated whole-virion vaccine using wild-type SARS-CoV-2 spike induces a much lower serum neutralizing antibody titre against the Omicron subvariants. Since the inactivated vaccine given intramuscularly is one of the most commonly used coronavirus disease 2019 (COVID-19) vaccines in developing regions, we tested the hypothesis that intranasal boosting after intramuscular priming would provide a broader level of protection. Here, we showed that one or two intranasal boosts with the Fc-linked trimeric spike receptor-binding domain from wild-type SARS-CoV-2 can induce significantly higher serum neutralizing antibodies against wild-type SARS-CoV-2 and the Omicron subvariants, including BA.5.2 and XBB.1, with a lower titre in the bronchoalveolar lavage of vaccinated Balb/c mice than vaccination with four intramuscular doses of inactivated whole virion vaccine. The intranasally vaccinated K18-hACE2-transgenic mice also had a significantly lower nasal turbinate viral load, suggesting a better protection of the upper airway, which is the predilected site of infection by Omicron subvariants. This intramuscular priming and intranasal boosting approach that achieves broader cross-protection against Omicron variants and subvariants may lengthen the interval required for changing the vaccine immunogen from months to years.

Comparative analysis of SARS-CoV-2 Omicron BA.2.12.1 and BA.5.2 variants.

The initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants, BA.1 and BA.2, are being progressively displaced by BA.5 in many countries. To provide insight on the replacement of BA.2 by BA.5 as the dominant SARS-CoV-2 variant, we performed a comparative analysis of Omicron BA.2.12.1 and BA.5.2 variants in cell culture and hamster models. We found that BA.5.2 exhibited enhanced replicative kinetics over BA.2.12.1 in vitro and in vivo, which is evidenced by the dominant BA.5.2 viral genome detected at different time points, regardless of immune selection pressure with vaccine-induced serum antibodies. Utilizing reverse genetics, we constructed a mutant SARS-CoV-2 carrying spike F486V substitution, which is an uncharacterized mutation that concurrently discriminates Omicron BA.5.2 from BA.2.12.1 variant. We noticed that the 486th residue does not confer viral replication advantage to the virus. We also found that 486V displayed generally reduced immune evasion capacity when compared with its predecessor, 486F. However, the surge of fitness in BA.5.2 over BA.2.12.1 was not due to stand-alone F486V substitution but as a result of the combination of multiple mutations. Our study upholds the urgency for continuous monitoring of SARS-CoV-2 Omicron variants with enhanced replication fitness.

Genomic surveillance of SARS-CoV-2 positive passengers on flights from China to Italy, December 2022.

With numbers of COVID-19 cases having substantially increased at the end of 2022 in China, some countries have started or expanded testing and genomic surveillance of travellers. We report screening results in Italy in late December 2022 of 556 flight passengers in provenance from two Chinese provinces. Among these passengers, 126 (22.7%) tested SARS-CoV-2 positive. Whole genome sequencing of 61 passengers' positive samples revealed Omicron variants, notably sub-lineages BA.5.2.48, BF.7.14 and BQ.1.1, in line with data released from China.

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.