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

Nat Commun. 2021 Apr 9;12(1):2133. doi: 10.1038/s41467-021-22449-w.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Viral / immunology*
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunoglobulin G / immunology*
  • Interleukin-33 / immunology*
  • Interleukin-33 / metabolism
  • Male
  • Middle Aged
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • Seroepidemiologic Studies
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Young Adult

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Interleukin-33
  • Spike Glycoprotein, Coronavirus
  • spike glycoprotein, SARS-CoV