IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals

• Published in: Nature communications Vol. 12; no. 1; pp. 2133 - 9
• Main Authors: Stanczak, Michal A., Sanin, David E., Apostolova, Petya, Nerz, Gabriele, Lampaki, Dimitrios, Hofmann, Maike, Steinmann, Daniel, Krohn-Grimberghe, Marvin, Thimme, Robert, Mittler, Gerhard, Waller, Cornelius F., Pearce, Edward J., Pearce, Erika L.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.04.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 38; 45; 631/250/127/1213; 631/326/596/4130; 692/308/174; 82/80; Adolescent; Adult; Aged; Alveoli; Antibodies; Antibodies, Viral - immunology; Asthma; Bronchus; CD14 antigen; CD4 antigen; Cell activation; Child; Child, Preschool; Chronic infection; Chronic obstructive pulmonary disease; Coronaviruses; Correlation; COVID-19; COVID-19 - immunology; COVID-19 - virology; Female; Fever; Glycoproteins; Humanities and Social Sciences; Humans; IL-1β; Immune response; Immune system; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulin M; Infections; Interleukin 23; Interleukin 6; Interleukin-33 - immunology; Interleukin-33 - metabolism; Lung diseases; Lymphocytes; Lymphocytes T; Male; Middle Aged; Monocytes; multidisciplinary; Observational studies; Pathogenesis; Respiratory diseases; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 - physiology; Science; Science (multidisciplinary); Seroepidemiologic Studies; Serology; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Spike glycoprotein; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; TLR7 protein; Toll-like receptors; Tumor necrosis factor; Viral diseases; Young Adult
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-22449-w

Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We perform an observational study to investigate seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5–79 years). Seropositivity for SARS-CoV-2 Spike glycoprotein aligns with PCR results that confirm the previous infection. Anti-Spike IgG/IgM titers remain high 60 days post-infection and do not strongly associate with symptoms, except for fever. We analyze PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist-activation reveals an increased population of IL-6 + TNF - IL-1β + monocytes, while SARS-CoV-2 peptide stimulation elicits IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlates with CD4 + T cell activation in PBMCs from convalescent subjects and is likely due to T cell-mediated effects on IL-33-producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 reveals a population of IL-33-producing cells that increases with the disease. Together these findings show that IL-33 production is linked to SARS-CoV-2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity. Our understanding of the immune response to SARS-CoV-2 infection is still incomplete. Here, the authors find that IL-33, produced during immune recall potentially by CD14 + monocytes, correlates with CD4 + T cell activation, anti-SARS-CoV-2 antibody titer, and disease severity in a cohort of convalescent individuals professionally exposed to the virus.