Immune responses in COVID-19 respiratory tract and blood reveal mechanisms of disease severity
Res Sq.
2021-08;
Wuji Zhang, Brendon Chua, Kevin Selva, Lukasz Kedzierski, Thomas Ashhurst, Ebene Haycroft, Suzanne Shoffner, Luca Hensen, David Boyd, Fiona James, Effie Mouhtouris, Jason Kwong, Kyra Chua, George Drewett, Ana Copaescu, Julie Dobson, Louise Rowntree, Jennifer Habel, Lilith Allen, Hui-Fern Koay, Jessica Neil, Matthew Gartner, Christina Lee, Patiyan Andersson, Torsten Seemann, Norelle Sherry, Fatima Amanat, Florian Krammer, Sarah Londrigan, Linda Wakim, Nicholas King, Dale Godfrey, Laura Mackay, Paul Thomas, Suellen Nicholson, Kelly Arnold, Amy Chung, Natasha Holmes, Olivia Smibert, Jason Trubiano, Claire Gordon, Thi Nguyen, Katherine Kedzierska
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)-spec... More
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.
