| Autor: |
Zhang W; University of Melbourne., Chua B; University of Melbourne., Selva K; University of Melbourne., Kedzierski L; Peter Doherty Institute for Infection and Immunity., Ashhurst T; The University of Sydney., Haycroft E; University of Melbourne., Shoffner S; University of Michigan., Hensen L; Peter Doherty Institute for Infection and Immunity., Boyd D; St. Jude Children's Research Hospital., James F; Austin Hospital., Mouhtouris E; Austin Hospital., Kwong J; Austin Health., Chua K; Austin Hospital., Drewett G; Austin Hospital., Copaescu A; Austin Hospital., Dobson J; Austin Hospital., Rowntree L; Peter Doherty Institute for Infection and Immunity., Habel J; University of Melbourne., Allen L; University of Melbourne., Koay HF; University of Melbourne., Neil J; University of Melbourne., Gartner M; University of Melbourne., Lee C; University of Michigan., Andersson P; Doherty Institute., Seemann T; Doherty Institute., Sherry N; University of Melbourne., Amanat F; Icahn School of Medicine at Mount Sina., Krammer F; Icahn School of Medicine at Mount Sinai., Londrigan S; University of Melbourne at the Peter Doherty Institute for Infection and Immunity., Wakim L; University of Melbourne., King N; Charles Perkins Centre, University of Sydney., Godfrey D; University of Melbourne., Mackay L; University of Melbourne., Thomas P; St. Jude Children's Research Hospital., Nicholson S; Doherty Institute., Arnold K; University of Michigan-Ann Arbor., Chung A; University of Melbourne., Holmes N; Austin Hospital., Smibert O; Austin Hospital., Trubiano J; Austin Hospital., Gordon C; Austin Hospital., Nguyen T; University of Melbourne., Kedzierska K; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. |
| Abstrakt: |
Although the respiratory tract is the primary site of SARS-CoV-2 infection and the ensuing immunopathology, respiratory immune responses are understudied and urgently needed to understand mechanisms underlying COVID-19 disease pathogenesis. We collected paired longitudinal blood and respiratory tract samples (endotracheal aspirate, sputum or pleural fluid) from hospitalized COVID-19 patients and non-COVID-19 controls. Cellular, humoral and cytokine responses were analysed and correlated with clinical data. SARS-CoV-2-specific IgM, IgG and IgA antibodies were detected using ELISA and multiplex assay in both the respiratory tract and blood of COVID-19 patients, although a higher receptor binding domain (RBD)-specific IgM and IgG seroconversion level was found in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples was detected only when high levels of RBD-specific antibodies were present. Strikingly, cytokine/chemokine levels and profiles greatly differed between respiratory samples and plasma, indicating that inflammation needs to be assessed in respiratory specimens for the accurate assessment of SARS-CoV-2 immunopathology. Diverse immune cell subsets were detected in respiratory samples, albeit dominated by neutrophils. Importantly, we also showed that dexamethasone and/or remdesivir treatment did not affect humoral responses in blood of COVID-19 patients. Overall, our study unveils stark differences in innate and adaptive immune responses between respiratory samples and blood and provides important insights into effect of drug therapy on immune responses in COVID-19 patients. |
