A 10h00
For IPBS colleagues, the seminar will take place in the seminar room (max 20 people). Due to the COVID-19-related situation, the seminar is NOT open to persons outside the IPBS.
Coronavirus disease 2019 (Covid-19) is characterized by distinct patterns of disease progression implying diverse host immune responses. We performed an integrated immune analysis on a cohort of fifty Covid19 patients with various disease severity, in both plasma and the nasopharynx, which reflects the initial site of infection. Using state-of-the-art technologies including ultra-sensitive digital Elisa (Simoa) to measure low levels of interferons (IFN), mass cytometry (CyTOF), ultrasensitive droplet based digital PCR (ddPCR), Nanostring nCounter technology and an ultrasensitive innovative antibody detection technic (S-Flow), we identified a unique phenotype in severe and critical patients. It consisted of a profoundly impaired type I IFN response characterized by low IFN-α production and activity, associated with a persistent blood viral load, an exacerbated inflammatory response, and a strong SARS-CoV2-specific antibody response. Inflammation was partially driven by the transcriptional factor NFκB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These inflammatory cytokines in all patient groups were significantly correlated with circulating viral levels, which was not associated with systemic type I interferon responses. Furthermore, we determine that while plasma inflammatory cytokine levels were a hallmark of COVID-19 regardless of disease severity, cytokines present in the nasopharynx allowed a better categorization of disease severity. In addition to expected inflammatory markers this also included locally regulated growth factors and chemokines suggesting viral induced mucosal tissue dysregulation. We propose that type-I IFN deficiency in the blood could be a hallmark of severe Covid-19 and provide a rationale for combined therapeutic approaches which may be further optimized with a better understanding of infected tissue immune responses.
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