PMC:7402624 / 53777-55814 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7402624","sourcedb":"PMC","sourceid":"7402624","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7402624","text":"To interrogate the immune response patterns of COVID-19 hospitalized patients, we studied a cohort of ~125 COVID-19 patients. We used high dimensional flow cytometry to perform deep immune profiling of individual B and T cell populations, with temporal analysis of immune changes during infection, and combined this profiling with extensive clinical data to understand the relationships between immune responses to SARS-CoV2 and disease severity. Using this approach, we made several key findings. First, a defining feature of COVID-19 disease in hospitalized patients was heterogeneity of the immune response. Many COVID-19 patients displayed robust CD8 T cell and/or CD4 T cell activation and proliferation and PB responses, though a considerable subgroup of patients (~20%) had minimal detectable response compared to controls. Furthermore, even within those patients who mounted detectable B and T cell responses during COVID-19 disease, the immune characteristics of this response were heterogeneous. By deep immune profiling, we identified three immunotypes in hospitalized COVID-19 patients including: (1) patients with robust activation and proliferation of CD4 T cells, relative lack of cTfh, together with modest activation of TEMRA-like as well as highly activated or exhausted CD8 T cells and a signature of T-bet+ PB; (2) Tbetbright effector-like CD8 T cell responses, less robust CD4 T cell responses, and Ki67+ PB and memory B cells; and (3) an immunotype largely lacking detectable lymphocyte response to infection, suggesting a failure of immune activation. UMAP embedding further resolved the T cell activation immunotype, suggesting a link between CD4 T cell activation, Immunotype 1, and increased severity score. Although differences in age and race existed between the cohorts and could impact some immune variables, the major UMAP relationships were preserved even when correcting for these variables. Thus, these immunotypes may reflect fundamental differences in the ways patients respond to SARS-CoV2 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