Digital Spatial Profiler Identifies Diverse Immune Responses within COVID-19 Patients

The Massachusetts General Hospital-led study utilized the GeoMx Digital Spatial Profiler (DSP) platform from NanoString Technologies, Inc. (Seattle, WA, USA) to uncover the new information in patients’ responses to SARS-CoV-2 infection.

These learnings identifying the relationship between viral location and immune response have the potential to be applied towards future therapeutic and clinical applications. COVID-19 is still poorly understood within the scientific community, and outcomes vary greatly across individual patients. Research efforts have been challenged by the scarcity of patient-derived tissue samples, as well as the necessity of fixing such samples prior to analysis to reduce the risk of viral transmission. However, the ability of GeoMx DSP to perform high-plex, spatial profiling of formalin-fixed paraffin-embedded (FFPE) samples enables researchers to gather more information from each precious sample and rapidly evaluate the body’s response to infection.

In the study, FFPE autopsy samples from patients with SARS-CoV-2 infection were analyzed with the GeoMx DSP, using the >1,800+ plex GeoMx COVID-19 Immune Response Atlas and a 79-plex GeoMx protein assay. GeoMx DSP revealed high intra- and inter-patient heterogeneity in the abundance and localization of immune markers. A critical step prior to quantitative profiling with GeoMX DSP is to determine the cells that contain the SAR-CoV-2 virus. Those cells are grouped into regions of interest with high and low viral loads using RNAscope SARs-CoV-2 probes from Advanced Cell Diagnostics (ACD), a Bio-techne brand. Immune cell types were classified in each region of interest, uncovering spatial relationships between the virus location and immune cell abundance, which may have therapeutic implications.

“This study detected differences in immunoregulatory markers that were not identified using traditional immunohistochemical staining and whole slide analysis, illustrating the importance of high-plex spatial analysis,” said Joe Beechem, chief scientific officer and SVP of R&D for NanoString. “The ability of GeoMx DSP to perform robust, highly sensitive spatial profiling of FFPE samples was critical to enable researchers to gather more information from clinically relevant samples.”

“We now have the ability to better understand the diversity of SARS-CoV-2 infections in patient lung samples using the unprecedented spatial transcriptomic and proteomic analysis that the GeoMx Digital Spatial Profiler provides,” said David Ting, Associate Clinical Director for Innovation at the Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School. “We hope these findings, along with continued spatial analysis of infected tissue samples, will inform the design of prospective interventional trials.”

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