key: cord-0786672-chia0lu6 authors: Rissmann, Melanie; Noack, Danny; van Riel, Debby; Schmitz, Katharina S.; de Vries, Rory D.; van Run, Peter; Lamers, Mart M.; GeurtsvanKessel, Corine H.; Koopmans, Marion P. G.; Fouchier, Ron A. M.; Kuiken, Thijs; Haagmans, Bart L.; Rockx, Barry title: Pulmonary lesions following inoculation with the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant in Syrian golden hamsters date: 2022-03-15 journal: bioRxiv DOI: 10.1101/2022.03.15.484448 sha: a3fc4e35fdf07b6ce1b306c8b08c3185037546a8 doc_id: 786672 cord_uid: chia0lu6 The Omicron BA.1 (B.1.1.529) SARS-CoV-2 variant is characterized by a high number of mutations in the viral genome, associated with immune-escape and increased viral spread. It remains unclear whether milder COVID-19 disease progression observed after infection with Omicron BA.1 in humans is due to reduced pathogenicity of the virus or due to pre-existing immunity from vaccination or previous infection. Here, we inoculated hamsters with Omicron BA.1 to evaluate pathogenicity and kinetics of viral shedding, compared to Delta (B.1.617.2) and to animals re-challenged with Omicron BA.1 after previous SARS-CoV-2 614G infection. Omicron BA.1 infected animals showed reduced clinical signs, pathological changes, and viral shedding, compared to Delta-infected animals, but still showed gross- and histopathological evidence of pneumonia. Pre-existing immunity reduced viral shedding and protected against pneumonia. Our data indicate that the observed decrease of disease severity is in part due to intrinsic properties of the Omicron BA.1 variant. All staining steps were performed at room temperature for one hour. Plaque assay analysis 116 was performed using ImageQuant TL 8.2 software (GE Healthcare). 118 Nasal turbinates, trachea and lungs were fixed in 4% neutral-buffered formalin, embedded in 119 paraffin, and sectioned at 4 µm. Sections of all tissue samples were stained with hematoxylin 120 and eosin for histopathological analysis, and consecutive sections were stained by 121 immunohistochemistry for SARS-CoV-2 antigen expression, as described previously [16] . with no significant differences between the two groups ( Figure 1G ). 145 Despite the fact that Omicron BA.1 infected animals did not show weight loss, gross 146 postmortem examination at 5 dpi revealed single or multiple foci of pulmonary 147 consolidation, visible as well-delimited, slightly raised, dark red areas, covering 50-90% of 148 the lung surface (Figure 2A) . Due to animal-to-animal variation, no clear differences in within the olfactory mucosa were found to be positive for viral antigen (Figure 3) . 172 Furthermore, respiratory epithelial cells were occasionally found to carry viral antigen in 177 Besides of pulmonary lesions and the presence of viral antigen, respiratory tissue was also A Novel Coronavirus from Patients with Pneumonia in 271 The variant 275 gambit: COVID-19's next move Emergence of new SARS-CoV-2 Variant of Concern 277 529) -highlights Africa's research capabilities, but exposes major knowledge 278 gaps, inequities of vaccine distribution, inadequacies in global COVID-19 response and 279 control efforts Heavily mutated Omicron variant puts scientists on alert Omicron Variant (B.1.1.529): Infectivity, Vaccine 282 Breakthrough, and Antibody Resistance An infectious SARS-CoV-2 B.1.1.529 Omicron 284 virus escapes neutralization by therapeutic monoclonal antibodies Early assessment of the clinical severity of the SARS-286 CoV-2 omicron variant in South Africa: a data linkage study Milder disease with Omicron: is it the virus or the pre-existing immunity? The omicron (B.1.1.529) SARS-CoV-2 variant of 290 concern does not readily infect Syrian hamsters SARS-CoV-2 Omicron virus causes 292 attenuated disease in mice and hamsters Divergent SARS CoV-2 Omicron-reactive 294 Intranasal fusion inhibitory lipopeptide prevents 296 direct-contact SARS-CoV-2 transmission in ferrets Detection of 2019 novel coronavirus (2019-nCoV) 298 by real-time RT-PCR Human organoid systems reveal in 300 vitro correlates of fitness for SARS-CoV-2 B.1.1.7 Comparative pathogenesis of COVID-19, MERS, and 302 SARS in a nonhuman primate model Pathogenesis and transmission of SARS-CoV-2 in golden 304 hamsters Decreased severity of disease during the first global 306 omicron variant covid-19 outbreak in a large hospital in tshwane, south africa Measuring infectious SARS-CoV-2 in clinical 309 samples reveals a higher viral titer:RNA ratio for Delta and Epsilon vs. Alpha variants variant Delta with Omicron: Unprecedented Spike in COVID-19 Cases Associated with Fewer 313 Admissions and Comparable Upper Respiratory Viral Loads The SARS-CoV-2 Omicron (B.1.1.529) variant exhibits 315 altered pathogenicity, transmissibility, and fitness in the golden Syrian hamster model SARS-CoV-2 Neutralizing Human Antibodies 318 Protect Against Lower Respiratory Tract Disease in a Hamster Model SARS-CoV-2 Omicron efficiently infects 321 human airway, but not alveolar epithelium Omicron BA.1 and BA.2 are antigenically distinct 323 SARS-CoV-2 variants Acknowledgments: 328 We thank J.M. Fentener van Vlissingen, Ingeborg van Middelkoop, Rianne Stam, Vincent 329 Duiverman and Vincent Vaes for assistance with the animal studies.