Expanding on observations made in smaller patient cohorts, researchers studying immune responses of 125 hospitalized COVID-19 patients identified distinct immune profiles -- "Immunotypes" -- and showed how these signatures correlated with disease severity. "By localizing patients on an immune topology map," Divij Mathew and colleagues say, "we can begin to infer which types of therapeutic interventions may be most useful in specific patients." As the global COVID-19 pandemic continues, researchers continue to investigate the characteristics of the human immune response in fighting it. Whether there is a common profile of immune dysfunction in critically ill COVID-19 patients remains a question. To date, studies investigating this are limited, reporting on single patients or small cohorts. Seeking to expand upon them, and also to better connect immune features in COVID-19 patients with clinical features of disease, Mathew and colleagues performed a high dimensional flow cytometry analysis on immune cells in blood from 125 COVID-19 patients at two points during their first week of hospitalization. Mathew and colleagues also collected clinical data on their patient cohort. Combining the flow cytometric and clinical data, they report several key findings, including that a defining feature of COVID-19 disease in this group is variability in immune response. At the same time, they found certain stable immune response signatures in subsets of their patients, which changed over time in consistent ways. Some of these patterns, like impaired CD8 T cell activation, were associated with worse disease outcomes. Mathew et al. ultimately defined three immune response signatures, or Immunotypes, in this cohort, associated with poor clinical trajectories versus improving health. "These Immunotypes may reflect fundamental differences in the ways patients respond to SARS-CoV2 infection," they say. They note that their "findings provoke the idea of the tailoring clinical treatments or future immune-based clinical trials to patients whose immunotype suggests greater potential benefit."