Human Nasal and Lung Tissues Infected <i>Ex Vivo</i> with SARS-CoV-2 Provide Insights into Differential Tissue-Specific and Virus-Specific Innate Immune Responses in the Upper and Lower Respiratory Tract
Or Alfi, Arkadi Yakirevitch, Ori Wald, Ori Wandel, Uzi Izhar, Esther Oiknine‐Djian, Yuval Nevo, Sharona Elgavish, Elad Dagan, Ory Madgar, Gilad Feinmesser, Eli Pikarsky, Michal Bronstein, Olesya Vorontsov, Wayne B. Jonas, John A. Ives, Joan Walter, Zichria Zakay‐Rones, Menachem Oberbaum, Amos Panet, Dana G. Wolf
Abstract
In order to reduce the late-phase morbidity and mortality of COVID-19, there is a need to better understand and target the earliest stages of SARS-CoV-2 infection in the human respiratory tract. Here, we have studied the initial steps of SARS-CoV-2 infection and the consequent innate immune responses within the natural multicellular complexity of human nasal mucosal and lung tissues. Comparing the global innate response patterns of nasal and lung tissues infected in parallel with SARS-CoV-2 and influenza virus, we found distinct virus-host interactions in the upper and lower respiratory tract, which could determine the outcome and unique pathogenesis of SARS-CoV-2 infection. Studies in the nasal mucosal infection model can be employed to assess the impact of viral evolutionary changes and evaluate new therapeutic and preventive measures against SARS-CoV-2 and other human respiratory pathogens.