SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues

Or Alfi, Marah Hamdan, Ori Wald, Arkadi Yakirevitch, Ori Wandel, Esther Oiknine-Djian, Ben Gvili, Hadas Knoller, Noa Rozendorn, Hadar Golan Berman, Sheera Adar, Olesya Vorontsov, Michal Mandelboim, Zichria Zakay-Rones, Menachem Oberbaum, Amos Panet, Dana G. Wolf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC-a difference, which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Notably, blocking the innate immune signaling restored Omicron replication in the lung tissues. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron.

Original languageEnglish
Article number1583
JournalViruses
Volume14
Issue number7
DOIs
StatePublished - Jul 2022

Funding

FundersFunder number
Hadassah France Association
Israel Science Foundation530/18, 1728/20
Ministry of Science and Technology, Israel3-16964

    Keywords

    • COVID-19
    • Omicron
    • SARS-CoV-2
    • interferon response
    • lung organ culture
    • nasal organ culture
    • organ culture

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