The “topology” of the immune response to COVID-19


High dimensional analysis of immune phenotypes with clinical data reveals distinct COVID19 patient immunotypes. (A) NIH ordinal scale for COVID-19 clinical severity. (B) Frequencies of major immune subsets. Significance determined by unpaired Wilcoxon test with BH correction: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001. (C) Heatmap of indicated immune parameters by row; donor type, disease severity, and mortality indicated across top. (D) UMAP projection of aggregated flow cytometry data. (E) Transformed UMAP projection; density contours drawn separately for healthy donor (HD), recovered donor (RD), and COVID-19 subjects (see Methods). (F) Bars represent mean of UMAP Component 1. Dots represent individual subjects; bars shaded by subject group and/or severity score. (Source: Mathew et al., 2020)

A recent article in Science used high dimensional cytometry to investigate the network of immune cell interactions and how they are connected in patients with COVID-19. Peripheral immune cells were analysed from 125 hospitalised patients with confirmed SARS-CoV-2 infection, 36 non-hospitalised patients who had recovered from infection and 60 healthy individuals. The authors found three “immunotypes”:

  • Immunotype 1: activated CD4+ T cells with proliferative capacity, a relative lack of circulating T follicular helper cells along with highly activated or exhausted CD8 T cells. This category was correlated with more severe disease.
  • Immunotype 2: a Tbetbright CD8 T cell responses, less robust CD4 T cell responses, and Ki67+ memory B cells.
  • Immunotype 3: evidence of a failure of immune activation, with immune cells lacking any detectable response to infection and represented about 20% of COVID-19 patients and may represent those individuals who failed to make a robust T and B cell response to SARS-CoV-2.

By connecting and integrating the immunotypes with the trajectory of disease severity change over time, the authors created a topology of immune cell phenotypes with severity of disease and conclude: “This study provides a compendium of immune response data and also an integrated framework as a “map” for connecting immune features to disease.

Journal Article: Mathew et al., 2020. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science

Summary by Clive Gray



International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids FoundationStellenbosch University