Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5

Unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants imposes us to continuous control measurement. Given the rapid spread, new Omicron subvariant named BA.5 is urgently required for characterization. Here we analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1 comprehensively. Although in vitro growth kinetics of BA.5 is comparable among the Omicron subvariants, BA.5 become much more fusogenic than BA.1 and BA.2. The airway-on-a-chip analysis showed that the ability of BA.5 to disrupt the respiratory epithelial and endothelial barriers is enhanced among Omicron subvariants. Furthermore, in our hamster model, in vivo replication of BA.5 is comparable with that of the other Omicrons and less than that of the ancestral B.1.1. Importantly, inflammatory response against BA.5 is strong compared with BA.1 and BA.2. Our data suggest that BA.5 is still low pathogenic compared to ancestral strain but evolved to induce enhanced inflammation when compared to prior Omicron subvariants.

[1]  R. Webby,et al.  Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents , 2022, Nature.

[2]  H. Date,et al.  SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression , 2022, Science advances.

[3]  J. Zahradník,et al.  Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5 , 2022, Cell.

[4]  O. Pybus,et al.  Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa , 2022, Nature Medicine.

[5]  Fei Shao,et al.  BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection , 2022, Nature.

[6]  P. Klenerman,et al.  Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum , 2022, Cell.

[7]  Takeshi Noda,et al.  Cell response analysis in SARS-CoV-2 infected bronchial organoids , 2022, Communications Biology.

[8]  K. Ishii,et al.  Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike , 2022, Cell.

[9]  A. Kaneda,et al.  Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant , 2022, Nature.

[10]  Frances E. Muldoon,et al.  Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity , 2022, Nature.

[11]  Shinji Watanabe,et al.  Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants , 2022, Med.

[12]  T. Ndung’u,et al.  Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization , 2021, Nature.

[13]  P. Maes,et al.  Considerable escape of SARS-CoV-2 Omicron to antibody neutralization , 2021, Nature.

[14]  Fei Shao,et al.  Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies , 2021, bioRxiv.

[15]  A. Telenti,et al.  Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift , 2021, Nature.

[16]  Y. Kawaoka,et al.  Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation , 2021, Nature.

[17]  K. Maeda,et al.  Usability of Polydimethylsiloxane-Based Microfluidic Devices in Pharmaceutical Research Using Human Hepatocytes. , 2021, ACS biomaterials science & engineering.

[18]  J. Zahradník,et al.  SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity , 2021, Cell Host & Microbe.

[19]  Rani K. Powers,et al.  A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics , 2021, Nature Biomedical Engineering.

[20]  Vivek V. Thacker,et al.  Rapid endotheliitis and vascular damage characterize SARS‐CoV‐2 infection in a human lung‐on‐chip model , 2021, EMBO reports.

[21]  S. Lesellier,et al.  Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model , 2021, bioRxiv.

[22]  Thomas M. Keane,et al.  Twelve years of SAMtools and BCFtools , 2020, GigaScience.

[23]  J. Qin,et al.  Biomimetic Human Disease Model of SARS‐CoV‐2‐Induced Lung Injury and Immune Responses on Organ Chip System , 2020, Advanced science.

[24]  Fumihiro Kato,et al.  Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells , 2020, Proceedings of the National Academy of Sciences.

[25]  Jia Gu,et al.  fastp: an ultra-fast all-in-one FASTQ preprocessor , 2018, bioRxiv.

[26]  Yutaka Suzuki,et al.  Long-term expansion of alveolar stem cells derived from human iPS cells in organoids , 2017, Nature Methods.

[27]  M. Jiménez-Navarro,et al.  Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve , 2016, PloS one.

[28]  S. Muro,et al.  Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells , 2015, Stem cell reports.

[29]  Masahiro Yamamoto,et al.  Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles , 2014, PLoS pathogens.

[30]  S. Ogawa,et al.  Generation of Alveolar Epithelial Spheroids via Isolated Progenitor Cells from Human Pluripotent Stem Cells , 2014, Stem cell reports.

[31]  Pablo Cingolani,et al.  © 2012 Landes Bioscience. Do not distribute. , 2022 .

[32]  Richard Durbin,et al.  Fast and accurate long-read alignment with Burrows–Wheeler transform , 2010, Bioinform..