Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity
Type
PreprintAuthor/s
Zhang, WujiChua, Brendon Y.
Selva, Kevin J.
Kedzierski, Lukasz
Ashhurst, Thomas M.
Haycroft, Ebene R.
Shoffner, Suzanne K.
Hensen, Luca
Boyd, David F.
James, Fiona
Mouhtouris, Effie
Kwong, Jason C.
Chua, Kyra Y. L.
Drewett, George
Copaescu, Ana
Dobson, Julie E.
Rowntree, Louise C.
Habel, Jennifer R.
Allen, Lilith F.
Koay, Hui-Fern
Neil, Jessica A.
Gartner, Matthew
Lee, Christina Y.
Andersson, Patiyan
Seemann, Torsten
Sherry, Norelle L.
Amanat, Fatima
Krammer, Florian
Londrigan, Sarah L.
Wakim, Linda M.
King, Nicholas J.C.
Godfrey, Dale I.
Mackay, Laura K.
Thomas, Paul G.
Nicholson, Suellen
Arnold, Kelly B.
Chung, Amy W.
Holmes, Natasha E.
Smibert, Olivia C.
Trubiano, Jason A.
Gordon, Claire L.
Nguyen, Thi H.O.
Kedzierska, Katherine
Abstract
ABSTRACT 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 ...
See moreABSTRACT 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.
See less
See moreABSTRACT 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.
See less
Date
2021Share