SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity

• Published in: Nature communications Vol. 13; no. 1; p. 2774
• Main Authors: Zhang, Wuji, Chua, Brendon Y., Selva, Kevin J., Kedzierski, Lukasz, Ashhurst, Thomas M., Haycroft, Ebene R., Shoffner-Beck, 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 J., Lee, Christina Y., Andersson, Patiyan, Khan, Sadid F., Blakeway, Luke, Wisniewski, Jessica, McMahon, James H., Vine, Erica E., Cunningham, Anthony L., Audsley, Jennifer, Thevarajan, Irani, 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/21; 13/31; 631/250/2152; 631/250/255/2514; 631/326/596/4130; 692/699/255/2514; Antibodies, Viral; Blood; Chemokines; Chemotherapy; Coronaviruses; COVID-19; Cytokines; Dexamethasone; Drug therapy; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunity; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Infections; Interferon; Interleukin 12; Leukocytes (neutrophilic); multidisciplinary; Neutralization; Pathogenesis; Patients; Peripheral blood; Respiratory System; Respiratory tract; Respiratory tract diseases; SARS-CoV-2; Science; Science (multidisciplinary); Seroconversion; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Spike Glycoprotein, Coronavirus; Sputum; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30088-y

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19. The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.