In case of the Delta variant infected animals, mean weight loss of -779%, -1339% and -1134% were observed on 3, 5 and 7 DPI, respectively. Alpha and no titers against B.1, Beta and Delta. Interpretation This preliminary data shows that Omicron (R346K) variant contamination can produce moderate to severe lung disease comparable to that of the Delta variant and the neutralizing antibodies produced in response to Omicron (R346K) variant contamination shows poor neutralizing ability against other co-circulating SARS-CoV-2 variants like Delta which necessitates caution as it may lead to increased cases of reinfection. Funding This study was supported by Indian Council Rabbit Polyclonal to NF-kappaB p105/p50 (phospho-Ser893) of Medical Research as an intramural grant (COVID-19) to ICMR-National Institute of Virology, Pune. We analyzed the pathogenesis, disease severity and immune response generated in Syrian hamsters by Omicron (R346K) variant and compared the same with the Delta variant in hamsters. We also studied the neutralization potential CMP3a of Omicron (R346K) infected hamster sera with other Variant of Concerns like Alpha, Beta and Delta. Implications of all the available evidence Our findings shows that Omicron variant with R364K mutation replicates to high levels in respiratory CMP3a tract and is capable of inducing lung disease in hamsters. We found no evidence of prolonged computer virus shedding in hamsters. The model can be used to assess the efficacy of countermeasures against Omicron variant. Neutralizing antibody response generated against the Omicron (R346K) variant was found poor in neutralizing the earlier as well as currently circulating SARS-CoV-2 VOCs. The findings suggest that the pathogenicity of the circulating Omicron variant lineages could differ. Alt-text: Unlabelled box Introduction The emergence of SARS-CoV-2 Variants of Concerns (VOCs) has caused the most severe crisis and challenge to the public health worldwide. The situation has worsened yet again with the recent emergence of highly mutated and super spreading, Omicron variant (B.1.1.529) in the month of November 2021.1 As of March 22nd 2022, the variant has been reported from 164 countries.1 Increased incidences of COVID-19 cases were reported from countries where Omicron variant has become dominant.1,2 The variant constitutes for more than 99% of the SARS-CoV-2 sequences deposited in the Global Initiative on Sharing Avian Influenza Data (GISAID) database as on the third week of March 2022.1 Hundreds of thousands of people are getting infected with Omicron daily, hence there is an urgent need to deduce the properties of this VOC. Omicron variant possess around 26 to 32 mutations in the spike protein including mutations associated with CMP3a increased receptor binding and immune escape house.3 The major descendant lineages identified for the Omicron variant includes BA.1, BA.1.1, BA.2 and BA.3 of which BA.1 and BA.1.1 together contributes to the maximum cases reported around globe.1,4,5 These lineages has been further subdivided into multiple sublineages.4 BA.2 lineage is becoming a dominant lineage across the world now.1 Apart from this some recombinant variants of Delta and Omicron variant are CMP3a also being reported and has been given pango lineage designations recently as XD, XE and XF.1 The preliminary data available on the phenotypic characteristics of the Omicron variant shows increased transmissibility, risk of reinfection, reduced disease severity and need for hospitalization.1 More data needs to be assessed accounting to the population immunity and other co-morbid conditions to understand the severity of Omicron infection in humans. The studies around the humoral antibody responses have reported a reduction in the neutralizing antibody titers to the.