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Our review found the effective reproduction number and basic reproduction number of the Omicron variant elicited 3.8 and 2.5 times higher transmissibility than the Delta variant, respectively. The Omicron variant has an average basic and effective reproduction number of 8.2 and 3.6.

Background The COVID-19 pandemic is caused by the betacoronavirus SARS-CoV-2. In November 2021, the Omicron variant was discovered and immediately classified as a variant of concern (VOC), since it shows substantially more mutations in the spike protein than any previous variant, especially in the receptor-binding domain (RBD). We analyzed the binding of the Omicron RBD to the human angiotensin-converting enzyme-2 receptor (ACE2) and the ability of human sera from COVID-19 patients or vaccinees in comparison to Wuhan, Beta, or Delta RBD variants. Methods All RBDs were produced in insect cells. RBD binding to ACE2 was analyzed by ELISA and microscale thermophoresis (MST). Similarly, sera from 27 COVID-19 patients, 81 vaccinated individuals, and 34 booster recipients were titrated by ELISA on RBDs from the original Wuhan strain, Beta, Delta, and Omicron VOCs. In addition, the neutralization efficacy of authentic SARS-CoV-2 wild type (D614G), Delta, and Omicron by sera from 2× or 3× BNT162b2-vaccinated persons was analyzed. Results Surprisingly, the Omicron RBD showed a somewhat weaker binding to ACE2 compared to Beta and Delta, arguing that improved ACE2 binding is not a likely driver of Omicron evolution. Serum antibody titers were significantly lower against Omicron RBD compared to the original Wuhan strain. A 2.6× reduction in Omicron RBD binding was observed for serum of 2× BNT162b2-vaccinated persons. Neutralization of Omicron SARS-CoV-2 was completely diminished in our setup. Conclusion These results indicate an immune escape focused on neutralizing antibodies. Nevertheless, a boost vaccination increased the level of anti-RBD antibodies against Omicron, and neutralization of authentic Omicron SARS-CoV-2 was at least partially restored. This study adds evidence that current vaccination protocols may be less efficient against the Omicron variant.

The COVID-19 pandemic remains a global health threat and novel antiviral strategies are urgently needed. SARS-CoV-2 employs the cellular serine protease TMPRSS2 for entry into lung cells, and TMPRSS2 inhibitors are being developed for COVID-19 therapy. However, the SARS-CoV-2 Omicron variant, which currently dominates the pandemic, prefers the endo/lysosomal cysteine protease cathepsin L over TMPRSS2 for cell entry, raising doubts as to whether TMPRSS2 inhibitors would be suitable for the treatment of patients infected with the Omicron variant. Nevertheless, the contribution of TMPRSS2 to the spread of SARS-CoV-2 in the infected host is largely unclear. In this study, we show that the loss of TMPRSS2 strongly reduced the replication of the Beta variant in the nose, trachea and lung of C57BL/6 mice, and protected the animals from weight loss and disease. The infection of mice with the Omicron variant did not cause disease, as expected, but again, TMPRSS2 was essential for efficient viral spread in the upper and lower respiratory tract. These results identify the key role of TMPRSS2 in SARS-CoV-2 Beta and Omicron infection, and highlight TMPRSS2 as an attractive target for antiviral intervention.

The Coronavirus disease 2019 (COVID-19) pandemic poses a great threat to global public health. The original wild-type strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has genetically evolved, and several variants of concern (VOC) have emerged. On 26 November 2021, a new variant named Omicron (B.1.1.529) was designated as the fifth VOC, revealing that SARS-CoV-2 has the potential to go beyond the available therapies. The high number of mutations harboured on the spike protein make Omicron highly transmissible, less responsive to several of the currently used drugs, as well as potentially able to escape immune protection elicited by both vaccines and previous infection. We reviewed the latest publication and the most recent available literature on the Omicron variant, enlightening both reasons for concern and high hopes for new therapeutic strategies.

Background The Omicron variant (B.1.1.529) is estimated to be more transmissible than previous strains of SARS-CoV-2 especially among children, potentially resulting in croup which is a characteristic disease in children. Current coronavirus disease 2019 (COVID-19) cases among children might be higher because (i) school-aged children have higher contact rates and (ii) the COVID-19 vaccination strategy prioritizes the elderly in most countries. However, there have been no reports confirming the age-varying susceptibility to the Omicron variant to date. Methods We developed an age-structured compartmental model, combining age-specific contact matrix in South Korea and observed distribution of periods between each stage of infection in the national epidemiological investigation. A Bayesian inference method was used to estimate the age-specific force of infection and, accordingly, age-specific susceptibility, given epidemic data during the third (pre-Delta), fourth (Delta driven), and fifth (Omicron driven) waves in South Korea. As vaccine uptake increased, individuals who were vaccinated were excluded from the susceptible population in accordance with vaccine effectiveness against the Delta and Omicron variants, respectively. Results A significant difference between the age-specific susceptibility to the Omicron and that to the pre-Omicron variants was found in the younger age group. The rise in susceptibility to the Omicron/pre-Delta variant was highest in the 10–15 years age group (5.28 times [95% CI, 4.94–5.60]), and the rise in susceptibility to the Omicron/Delta variant was highest in the 15–19 years age group (3.21 times [95% CI, 3.12–3.31]), whereas in those aged 50 years or more, the susceptibility to the Omicron/pre-Omicron remained stable at approximately twofold. Conclusions Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the Omicron variant of SARS-CoV-2 tends to propagate more easily among children than the pre-Omicron strains.

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 responsible for the global COVID-19 pandemic has caused almost 760 million confirmed cases and 7 million deaths worldwide, as of end-February 2023. Since the beginning of the first COVID-19 case, several virus variants have emerged: Alpha (B1.1.7), Beta (B135.1), Gamma (P.1), Delta (B.1.617.2) and then Omicron (B.1.1.529) and its sublineages. All variants have diversified in transmissibility, virulence, and pathogenicity. All the newly emerging SARS-CoV-2 variants appear to contain some similar mutations associated with greater \"evasiveness\" of the virus to immune defences. From early 2022 onward, several Omicron subvariants named BA.1, BA.2, BA.3, BA.4, and BA.5, with comparable mutation forms, have followed. After the wave of contagions caused by Omicron BA.5, a new Indian variant named Centaurus BA.2.75 and its new subvariant BA.2.75.2, a second-generation evolution of the Omicron variant BA.2, have recently been identified. From early evidence, it appears that this new variant has higher affinity for the cell entry receptor ACE-2, making it potentially able to spread very fast. According to the latest studies, the BA.2.75.2 variant may be able to evade more antibodies in the bloodstream generated by vaccination or previous infection, and it may be more resistant to antiviral and monoclonal antibody drug treatments. In this manuscript, the authors highlight and describe the latest evidences and critical issues have emerged on the new SARS-CoV-2 variants.

Symptoms are currently used as testing indicators for SARS-CoV-2 in England. In this study, we analysed national contact tracing data for England (NHS Test and Trace) for the period 1 December to 28 December 2021 to explore symptom differences between the variants, Delta and Omicron. We found that at least one of the symptoms currently used as indicators (fever, cough and loss of smell and taste) were reported in 61.5% of Omicron cases and 72.2% in Delta cases, suggesting that these symptoms are less predictive of Omicron infections. Nearly 40% of Omicron infections did not report any of the three key indicative symptoms, reinforcing the importance of the entire spectrum of symptoms for targeted testing. After adjusting for potential confounding factors, fever and cough were more commonly associated with Omicron infections compared to Delta, showing the importance of considering age and vaccination status when assessing symptom profiles. Sore throat was also more commonly reported in Omicron infections, and loss of smell and taste more commonly reported in Delta infections. Our study shows the value of continued monitoring of symptoms associated with SARS-CoV-2, as changes may influence the effectiveness of testing policy and case ascertainment approaches.

We report wastewater surveillance for SARS-CoV-2 variants of concern by using mutation-specific, real-time PCR and rapid nanopore sequencing. This surveillance might be useful for an early warning in a scenario in which a new variant is emerging, even in areas that have low virus incidences.

The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has rapidly become the dominant strain, with an unprecedented number of mutations within its spike gene. However, it remains unknown whether these variants have alterations in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies and entry inhibitors. In this study, we found that Omicron spike has evolved to escape neutralization by three-dose inactivated-vaccine-elicited immunity but remains sensitive to an angiotensin‐converting enzyme 2 (ACE2) decoy receptor. Moreover, Omicron spike could use human ACE2 with a slightly increased efficiency while gaining a significantly increased binding affinity for a mouse ACE2 ortholog, which exhibits limited binding with wild-type (WT) spike. Furthermore, Omicron could infect wild-type C57BL/6 mice and cause histopathological changes in the lungs. Collectively, our results reveal that evasion of neutralization by vaccine-elicited antibodies and enhanced human and mouse ACE2 receptor engagement may contribute to the expanded host range and rapid spread of the Omicron variant. IMPORTANCE The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Compared with the ancestor strain isolated in early 2020, the spike protein of Omicron utilizes the human ACE2 receptor with enhanced efficiency while gaining the ability to utilize mouse ACE2 for cell entry. Moreover, Omicron could infect wild-type mice and cause pathological changes in the lungs. These results reveal that antibody evasion, enhanced human ACE2 utilization, and an expanded host range may contribute to its rapid spread.

Background & objectives: COVID-19 cases have been rising rapidly in countries where the SARS-CoV-2 variant of concern (VOC), Omicron (B.1.1.529) has been reported. We conducted a study to describe the epidemiological and clinical characteristics and outcomes of COVID-19 patients with 'S' gene target failure (SGTF, suspected Omicron). Furthermore, their clinical outcomes with COVID-19 patients with non-SGTF (non-Omicron) were also compared. Methods: This study was conducted in Tamil Nadu, India, between December 14, 2021 and January 7, 2022 among patients who underwent reverse transcription-PCR testing for SARS-CoV-2 in four laboratories with facilities for S gene screening. Consecutively selected COVID-19 patients with SGTF were telephonically contacted, seven and 14 days respectively after their date of positive result to collect information on the socio-demographic characteristics, previous history of COVID-19, vaccination status and clinical course of illness along with treatment details. To compare their outcomes with non-SGTF patients, one randomly suspected non-Omicron case for every two suspected Omicron cases from the line-list were selected, matching for the date of sample collection and the testing laboratory. Results: A total of 1175 SGTF COVID-19 patients were enrolled for this study. Almost 6 per cent (n=72) reported a history of previous infection. 141 (13.5%) suspected Omicron cases were non-vaccinated, while 148 (14.2%) and 703 (67.4%) had received valid one and two doses of COVID-19 vaccines, respectively. Predominant symptoms reported included fever (n=508, 43.2%), body pain (n=275, 23.4%), running nose (n=261, 22.2%) and cough (n=249, 21.2%). Five (0.4%) of the 1175 suspected Omicron cases required oxygen supplementation as compared to ten (1.6%) of the 634 suspected non-Omicron cases. No deaths were reported among omicron suspects, whereas there were four deaths among suspected non-Omicron cases. Interpretation & conclusions: Majority of the suspected Omicron cases had a mild course of illness. The overall severity of these cases was less compared to the suspected non-Omicron cases.