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.

Cellular Sensors and Viral Countermeasures: A Molecular Arms Race between Host and SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic that has caused disastrous effects on the society and human health globally. SARS-CoV-2 is a sarbecovirus in the Coronaviridae family with a positive-sense single-stranded RNA genome. It mainly replicates in the cytoplasm and viral components including RNAs and proteins can be sensed by pattern recognition receptors including toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs) that regulate the host innate and adaptive immune responses. On the other hand, the SARS-CoV-2 genome encodes multiple proteins that can antagonize the host immune response to facilitate viral replication. In this review, we discuss the current knowledge on host sensors and viral countermeasures against host innate immune response to provide insights on virus-host interactions and novel approaches to modulate host inflammation and antiviral responses.

The spike receptor-binding motif G496S substitution determines the replication fitness of SARS-CoV-2 Omicron sublineage.

The replication and pathogenicity of SARS-CoV-2 Omicron BA.2 are comparable to that of BA.1 in experimental animal models. However, BA.2 has rapidly emerged to overtake BA.1 to become the predominant circulating SARS-CoV-2 variant worldwide. Here, we compared the replication fitness of BA.1 and BA.2 in cell culture and in the Syrian hamster model of COVID-19. Using a reverse genetics approach, we found that the BA.1-specific spike mutation G496S compromises its replication fitness, which may contribute to BA.1 being outcompeted by BA.2 in the real world. Additionally, the BA.1-unique G496S substitution confers differentiated sensitivity to therapeutic monoclonal antibodies, which partially recapitulates the immunoevasive phenotype of BA.1 and BA.2. In summary, our study identified G496S as an important determinant during the evolutionary trajectory of SARS-CoV-2.

Pathogenicity, transmissibility, and fitness of SARS-CoV-2 Omicron in Syrian hamsters.

The in vivo pathogenicity, transmissibility, and fitness of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron (B.1.1.529) variant are not well understood. We compared these virological attributes of this new variant of concern (VOC) with those of the Delta (B.1.617.2) variant in a Syrian hamster model of COVID-19. Omicron-infected hamsters lost significantly less body weight and exhibited reduced clinical scores, respiratory tract viral burdens, cytokine and chemokine dysregulation, and lung damage than Delta-infected hamsters. Both variants were highly transmissible through contact transmission. In noncontact transmission studies Omicron demonstrated similar or higher transmissibility than Delta. Delta outcompeted Omicron without selection pressure, but this scenario changed once immune selection pressure with neutralizing antibodies-active against Delta but poorly active against Omicron-was introduced. Next-generation vaccines and antivirals effective against this new VOC are therefore urgently needed.

A Multimodal Data Driven Rehabilitation Strategy Auxiliary Feedback Method: A Case Study.

In Industry 4.0, medical data present a trend of multisource development. However, in complex information networks, an information gap often exists in data exchange between doctors and patients. In the case of diseases with complex manifestations, doctors often perform qualitative analysis, which is macroscopic and fuzzy, to present treatment recommendations for patients. Improving the reliability of data acquisition and maximizing the potential of data, require attention. To solve these problems, a multimodal data-driven rehabilitation strategy auxiliary feedback method is proposed. In this study, depth sensor and functional near-infrared spectroscopy (fNIRS) were used to obtain ethology and brain function data, and skeleton tracking analysis and ethology discrete statistics were performed to assist the diagnostic feedback of rehabilitation strategies. This study takes rhythm rehabilitation training of autistic children as a case, and results show that the multimodal data-driven rehabilitation strategy auxiliary feedback method can provide effective feedback for individuals or groups. The proposed auxiliary decision method increases the dimension of data analysis and improves the reliability of analysis. Through discrete statistical results, the potential of data are maximized, thereby assisting the proposed rehabilitation strategy diagnostic feedback.