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.
Keywords: COVID-19; Omicron; SARS-CoV-2; interferon response; lung organ culture; nasal organ culture; organ culture.
【저자키워드】 COVID-19, SARS-CoV-2, omicron, interferon response, lung organ culture, nasal organ culture, organ culture, 【초록키워드】 innate immune response, Antiviral, VoC, susceptibility, lung involvement, variant, SARS-CoV-2 variant, interferon, Delta, lung, nasal, omicron, Replication, Culture, respiratory tract, pathogenicity, interferon response, Clinical severity, Signaling, innate immune, Interaction, organ culture, tissue, tissues, lung tissue, lung tissues, organ, mucosal surfaces, mucosal surface, ex vivo infection, reduced, characterized, question, restored, raising, 【제목키워드】 Human, response, concern, enhanced, Restricted,