SARS-CoV-2 Omicron variant replication in human respiratory tract ex vivo

Chan, Martin C.W.; Hui, K.; Ho, John W.; Cheung, Man-Chun; Ng, Ktp; Ching, Rachel Hiu Ha; Lai, Ka-Ling; Kam, T. L.; Gu, Haogao; Sit, Ko‐Yung; Hsin, Michael; Au, Wing‐Kuk; Peiris, Malik; Nicholls, John M.

doi:10.21203/rs.3.rs-1189219/v1

Cited by 37 publications

(49 citation statements)

References 34 publications

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“…However, these findings collectively suggest that differences in viral factors between the Omicron and the Delta variants, such as differences in viral tropism or virulence factors, might be driving the observed relative reductions in disease severity. Recent ex vivo studies demonstrate higher replication of the Omicron variant in the human upper respiratory tract as compared to the small airways of the lung [24], consistent with animal experiments suggesting that disease from infection with the Omicron variant might be confined to the large airway [25].…”

Section: Discussionsupporting

confidence: 63%

Clinical outcomes associated with Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in southern California

Lewnard

Hong

Patel

et al. 2022

Preprint

119

103

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Background: The Omicron (B.1.1.529) variant of SARS-CoV-2 has rapidly achieved global dissemination, accounting for most infections in the United States by December 2021. Risk of severe outcomes associated with Omicron infections, as compared to earlier SARS-CoV-2 variants, remains unclear. Methods: We analyzed clinical and epidemiologic data from cases testing positive for SARS-CoV-2 infection within the Kaiser Permanente Southern California healthcare system from November 30, 2021 to January 1, 2022, using S gene target failure (SGTF) as assessed by the ThermoFisher TaqPath ComboKit assay as a proxy for Omicron infection. We fit Cox proportional hazards models to compare time to any hospital admission and hospital admissions associated with new-onset respiratory symptoms, intensive care unit (ICU) admission, mechanical ventilation, and mortality among cases with Omicron and Delta (non-SGTF) variant infections. We fit parametric competing risk models to compare lengths of hospital stay among admitted cases with Omicron and Delta variant infections. Results: Our analyses included 52,297 cases with SGTF (Omicron) and 16,982 cases with non-SGTF (Delta [B.1.617.2]) infections, respectively. Hospital admissions occurred among 235 (0.5%) and 222 (1.3%) of cases with Omicron and Delta variant infections, respectively. Among cases first tested in outpatient settings, the adjusted hazard ratios for any subsequent hospital admission and symptomatic hospital admission associated with Omicron variant infection were 0.48 (0.36-0.64) and 0.47 (0.35-0.62), respectively. Rates of ICU admission and mortality after an outpatient positive test were 0.26 (0.10-0.73) and 0.09 (0.01-0.75) fold as high among cases with Omicron variant infection as compared to cases with Delta variant infection. Zero cases with Omicron variant infection received mechanical ventilation, as compared to 11 cases with Delta variant infections throughout the period of follow-up (two-sided p<0.001). Median duration of hospital stay was 3.4 (2.8-4.1) days shorter for hospitalized cases with Omicron variant infections as compared to hospitalized patients with Delta variant infections, reflecting a 69.6% (64.0-74.5%) reduction in hospital length of stay. Conclusions: During a period with mixed Delta and Omicron variant circulation, SARS-CoV-2 infections with presumed Omicron variant infection were associated with substantially reduced risk of severe clinical endpoints and shorter durations of hospital stay.

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Section: Discussionsupporting

confidence: 63%

Clinical outcomes associated with Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in southern California

Lewnard

Hong

Patel

et al. 2022

Preprint

119

103

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“…While these results are consistent with the very preliminary clinical data in humans suggesting that B.1.1.529 causes a more transmissible yet possibly milder respiratory infection 40,41 , the basis for the attenuation in rodents remains unknown. One pre-print study suggests that B.1.1.529 replicates faster in the human bronchus and less in lung cells, which may explain its greater transmissibility and putative lower disease severity 42 ; although it remains unclear if these observations extend to rodents, we observed less infection of hamster bronchial cells in vivo with B.1.1.529 Omicron than B.1.617.2 Delta virus. We also measured lower viral burden in nasal washes and turbinates in 129 mice compared to other SARS-CoV-2 strains.…”

Section: Discussionmentioning

confidence: 52%

The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters

Diamond

Halfmann

Maemura³

et al. 2021

Preprint

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Despite the development and deployment of antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. The recent emergence of B.1.1.529, the Omicron variant1,2, which has more than 30 mutations in the spike protein, has raised concerns for escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in pre-clinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of multiple B.1.1.529 Omicron isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2) expressing mice and hamsters. Despite modeling and binding data suggesting that B.1.1.529 spike can bind more avidly to murine ACE2, we observed attenuation of infection in 129, C57BL/6, and BALB/c mice as compared with previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. Although K18-hACE2 transgenic mice sustained infection in the lungs, these animals did not lose weight. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease, and pathology with B.1.1.529 also were milder compared to historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from multiple independent laboratories of the SAVE/NIAID network with several different B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

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“…A team of researchers in Hong Kong compared the replication competency and cellular tropism of all Covid variants in ex vivo explant cultures of human bronchus and lung. They demonstrated that Omicron replicated more rapidly in the bronchus than any other SARS-CoV-2 strain but less e ciently in the lung parenchyma [20]. This nding might be a probable reason for reduced severity in Omicron infections.…”

Section: Discussionmentioning

confidence: 99%

Omicron SARS-CoV-2 Variant of Concern: A Review on its Transmissibility, Immune Evasion, Reinfection, and Severity

Maqbool

Mahmud

2022

Preprint

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Background: Omicron, the new Covid-19 variant, has already become dominant in many countries and is spreading at an unprecedented speed. The objective of this study was to review the existing literature on Omicron’s transmissibility, immune evasion, reinfection, and severity.Method: A literature search was performed in “PubMed”, “Web of Science”, “Scopus”, "ScienceDirect", “Google Scholar”, “medRxiv”, and “bioRxiv”. Data were extracted from articles that reported at least one of transmissibility, immune evasion, reinfection, and severity related to Omicron.Findings: We found that Omicron spreads faster than any other previous variants. This higher transmissibility can be ascribed to its more extraordinary ability to evade immunity developed by both vaccinations and previous infections. However, we found that infections by Omicron are significantly less severe compared to infections by Delta and other previous variants. We observed a significantly lower incidence of hospitalization, intensive care unit, and mechanical ventilator use, a shorter median hospital stay, and lower fatality rates in Omicron infections than Delta and other variants.Conclusion: Omicron might be less severe than other VOCs. However, its immune evasiveness and faster spread pose an enormous threat to the global healthcare system.

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SARS-CoV-2 Omicron variant replication in human respiratory tract ex vivo

Cited by 37 publications

References 34 publications

Clinical outcomes associated with Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in southern California

Clinical outcomes associated with Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in southern California

The SARS-CoV-2 B.1.1.529 Omicron virus causes attenuated infection and disease in mice and hamsters

Omicron SARS-CoV-2 Variant of Concern: A Review on its Transmissibility, Immune Evasion, Reinfection, and Severity

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