ABSTRACT
BackgroundThe reliable detection of the T-cell mediated response to COVID-19 or COVID-19 vaccination is important for individual patient care and for monitoring the immune response e.g. in COVID-19 vaccine trials in a standardized fashion. MethodsWe used blood samples from health care workers (HCW) with or without history of COVID-19 to define test accuracy of a novel interferon-release assay. Usefulness of qualitative and quantitative results after COVID-19 vaccination was examined in HCW receiving homologous or heterologous vaccination regimens. For a real-life performance evaluation, we analysed interferon-response to complete vaccination in 149 patients receiving immunosuppressive or immune modulating therapies. ResultsUsing a double-cut-off strategy integrating the result of background stimulation the assay had a specificity of 100%. Sensitivity of the IGRA was 83.5 and 100% in HCW after SARS-CoV-2 infection more or less than 6 months ago. Quantitative results showed significant differences between first and second vaccine dose, but no difference between homologous and heterologous vaccination regimen. The majority of immunocompromised patients showed no immune response or isolated T-cell or antibody response to complete vaccination. ConclusionsThe novel IGRA proved to be a highly specific and sensitive tool to detect the SARS-CoV-2 specific T-cell response to COVID-19 as well as COVID-19 vaccination. In perspective, it may serve as a standardized tool in COVID-19 vaccine trials and in clinical care of immunosuppressed patients.
ABSTRACT
Our understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We investigated 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 aligned with PCR results that confirmed previous infection. Anti-spike IgG titers remained high 60 days post-infection and did not associate with symptoms, but spike-specific IgM did associate with malaise and fever. We found limited household transmission, with children of infected individuals seldomly seropositive, highlighting professional exposure as the dominant route of infection in our cohort. We analyzed PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist-activation revealed an increased population of IL-6+TNF-IL-1{beta}+ monocytes, while SARS-CoV-2 peptide stimulation elicited IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlated with CD4+ T cell activation in PBMCs from convalescent subjects, and was 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 revealed a population of IL-33-producing cells that increases with 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.